Colon and Rectal

Prostate cancer (PC) is the most commonly and newly diagnosed nonskin cancer and the second leading cause of cancer death in men in the United States. About 191,930 cases and about 33,330 deaths from PC were expected for the year 2020.¹ About 1 in 41 men will die of PC. Most men diagnosed with PC are aged > 65 years and do not die of their disease. The 5-year survival rate of localized and regional disease is nearly 100%, and disease with distant metastases is 31%. As a result, more than 3.1 million men in the United States who have been diagnosed with PC are still alive today.¹ Among veterans, there is a substantial population living with PC. Skolarus and Hawley reported in 2014 that an estimated 200,000 veterans with PC were survivors and 12,000 were newly diagnosed.²

In PC, skeletal strength can be affected by several factors, such as aging, malnutrition, androgen-deprivation therapy (ADT), and bone metastasis.^3,4 In fact, most men can live the rest of their life with PC by using strategies to monitor and treat it, once it shows either radiographic or chemical signs of progression.⁵ ADT is the standard of care to treat hormone-sensitive PC, which is associated with significant skeletal-related adverse effects (AEs).^6,7

Men undergoing ADT are 4 times more likely to develop substantial bone deficiency, Shahinian and colleagues found that in men surviving 5 years after PC diagnosis, 19.4% of those who received ADT had a fracture compared with 12% in men who did not (P < .001). The authors established a significant relation between the number of doses of gonadotropin-releasing hormone given in the first 12 months and the risk of fracture.⁸ Of those who progressed to metastatic disease, the first metastatic nonnodal site is most commonly to the bone.⁹ Advanced PC is characterized by increased bone turnover, which further raises concerns for bone health and patient performance.¹⁰

Skeletal-related events (SREs) include pathologic fracture, spinal cord compression, palliative radiation, or surgery to bone, and change in antineoplastic therapy secondary to bone pain. The concept of bone health refers to the prevention, diagnosis, and treatment of idiopathic, pathogenic, and treatment-related bone loss and delay or prevention of SREs.^6,11 Guidelines and expert groups have recommended screening for osteoporosis at the start of ADT with bone mineral density testing, ensuring adequate calcium and vitamin D intake, modifying lifestyle behaviors (smoking cessation, alcohol moderation, and regular exercise), and prescribing bisphosphonates or receptor-activated nuclear factor κ-B ligand inhibitor, denosumab, for men with osteoporosis or who are at general high-fracture risk.^12,13 The overuse of these medications results in undue cost to patients as well as AEs, such as osteonecrosis of the jaw (ONJ), hypocalcemia, and bone/joint pains.^14-17 There are evidence-based guidelines for appropriate use of bisphosphonates and denosumab for delay and prevention of SREs in the setting of advanced PC.¹⁸ These doses also typically differ in frequency to those of osteoporosis.¹⁹ We summarize the evidence and guidance for health care providers who care for patients with PC at various stages and complications from both disease-related and treatment-related comorbidities.

Bone-Strengthening Agents

Overall, there is evidence to support the use of bone-strengthening agents in patients with osteopenia/osteoporosis in the prevention of SREs with significant risk factors for progressive bone demineralization, such as lifestyle factors and, in particular, treatments such as ADT. Bone-remodeling agents for treatment of bony metastasis have been shown to provide therapeutic advantage only in limited instances in the castration-resistant PC (CRPC) setting. Hence, in patients with hormone-sensitive PC due to medication-related AEs, treatment with bone-strengthening agents is indicated only if the patient has a significant preexisting risk for fracture from osteopenia/osteoporosis (Table). The Figure depicts an algorithm for the management of bone health in men with PC who are being treated with ADT.

Denosumab and bisphosphonates have an established role in preventing SREs in metastatic CRPC.²⁰ The choice of denosumab or a bisphosphonate typically varies based on the indication, possible AEs, and cost of therapy. There are multiple studies involving initiation of these agents at various stages of disease to improve both time to progression as well as management of SREs. There is a lack of evidence that bisphosphonates prevent metastatic-bone lesions in castration-sensitive PC; therefore, prophylactic use of this agent is not recommended in patients unless they have significant bone demineralization.^21,22

Bone Health in Patients

Nonmetastatic Hormone-Sensitive PC

ADT forms the backbone of treatment for patients with local and advanced metastatic castration-sensitive PC along with surgical and focal radiotherapy options. Cancer treatment-induced bone loss is known to occur with prolonged use of ADT. The ZEUS trial found no prevention of bone metastasis in patients with high-risk localized PC with the use of ZA in the absence of bone metastasis. A Kaplan-Meier estimated proportion of bone metastases after a median follow-up of 4.8 years was found to be not statistically significant: 14.7% in the ZA group vs 13.2% in the control/placebo group.²⁹ The STAMPEDE trial showed no significant overall survival (OS) benefit with the addition of ZA to ADT vs ADT alone (HR, 0.94; 95% CI, 0.79-1.11; P = .45), 5-year survival with ADT alone was 55% compared to ADT plus ZA with 57% 5-year survival.³⁰ The RADAR trial showed that at 5 years in high Gleason score patients, use of ZA in the absence of bone metastasis was beneficial, but not in low- or intermediate-risk patients. However, at 10-year analysis there was no significant difference in any of the high-stratified groups with or without ZA.³¹

The PR04 trial showed no effect on OS with clodronate compared with placebo in nonmetastatic castration-sensitive PC, with a HR of 1.12 (95% CI, 0.89-1.42; P = .94). The estimated 5-year survival was 80% with placebo and 78% with clodronate; 10-year survival rates were 51% with placebo and 48% with clodronate.³² Data from the HALT trial showed an increased bone mineral density and reduced risk of new vertebral fractures vs placebo (1.5% vs 3.9%, respectively) in the absence of metastatic bone lesions and a reduction in new vertebral fractures in patients with nonmetastatic PC.³³ Most of these studies showed no benefit with the addition of ZA to nonmetastatic PC; although, the HALT trial provides evidence to support use of denosumab in patients with nonmetastatic PC for preventing vertebral fragility fractures in men receiving ADT.

Metastatic Hormone-Sensitive PC

ZA is often used to treat men with metastatic castration-sensitive PC despite limited efficacy and safety data. The CALGB 90202 (Alliance) trial authors found that the early use of ZA was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the ZA group (95% CI, 24.2-40.3) and 29.8 months in the placebo group (stratified HR, 0.97; 95% CI, 0-1.17; 1-sided stratified log-rank P = .39).³⁴ OS was similar between the groups (HR, 0.88; 95% CI, 0.70-1.12; P = .29) as were reported AEs.³⁴ Results from these studies suggest limited benefit in treating patients with metastatic hormone-sensitive PC with bisphosphonates without other medical indications for use. Additional studies suggest similar results for treatment with denosumab to that of bisphosphonate therapies.³⁵

Nonmetastatic CRPC

Reasonable interest among treating clinicians exists to be able to delay or prevent the development of metastatic bone disease in patients who are showing biochemical signs of castration resistance but have not yet developed distant metastatic disease. Time to progression on ADT to castration resistance usually occurs 2 to 3 years following initiation of treatment. This typically occurs in patients with rising prostate-specific antigen (PSA). As per the Prostate Cancer Working Group 3, in the absence of radiologic progression, CRPC is defined by a 25% increase from the nadir (considering a starting value of ≥ 1 ng/mL), with a minimum rise of 2 ng/mL in the setting of castrate serum testosterone < 50 ng/dL despite good adherence to an ADT regimen, with proven serologic castration either by undetectable or a near undetectable nadir of serum testosterone concentration. Therapeutic implications include prevention of SREs as well as time to metastatic bone lesions. The Zometa 704 trial examined the use of ZA to reduce time to first metastatic bone lesion in the setting of patients with nonmetastatic CRPC.³⁶ The trial was discontinued prematurely due to low patient accrual, but initial analysis provided information on the natural history of a rising PSA in this patient population. At 2 years, one-third of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastasis and OS were not reached. Baseline PSA and PSA velocity independently predicted a shorter time to first bone metastasis, metastasis-free survival, and OS.³⁶

Denosumab was also studied in the setting of nonmetastatic CRPC in the Denosumab 147 trial. The study enrolled 1432 patients and found a significantly increased bone metastasis-free survival by a median of 4.2 months over placebo (HR, 0.85; 95% CI, 0.73-0.98; P = .03). Denosumab significantly delayed time to first bone metastasis (HR, 0.84; 95% CI, 0.71-0.98; P = .03). OS was similar between groups (HR, 1.01; 95% CI, 0.85-1.20; P = .91). Rates of AEs and serious AEs were similar between groups, except for ONJ and hypocalcemia. The rates of ONJ for denosumab were 1%, 3%, 4% in years 1,2, 3, respectively; overall, < 5% (n = 33). Hypocalcemia occurred in < 2% (n = 12) in denosumab-treated patients. The authors concluded that in men with CRPC, denosumab significantly prolonged bone metastasis–free survival and delayed time-to-bone metastasis.³⁷ These 2 studies suggest a role of receptor-activated nuclear factor κ-B ligand inhibitor denosumab in patients with nonmetastatic CRPC in the appropriate setting. There were delays in bony metastatic disease, but no difference in OS. Rare denosumab treatment–related specific AEs were noted. Hence, denosumab is not recommended for use in this setting.

Metastatic CRPC

Castration resistance typically occurs 2 to 3 years following initiation of ADT and the most common extranodal site of disease is within the bone in metastatic PC. Disease progression within bones after ADT can be challenging given both the nature of progressive cancer with osteoblastic metastatic lesions and the prolonged effects of ADT on unaffected bone. The Zometa 039 study compared ZA with placebo and found a significant difference in SREs (38% and 49%, respectively; P .03). No survival benefit was observed with the addition of ZA. Use of other bisphosphonates pamidronate and clodronate did not have a similar degree of benefit.^38,39

A phase 3 study of 1904 patients found that denosumab was superior to ZA in delaying the time to first on-study SRE (HR, 0.82; 95% CI, 0.71-0.95) and reducing rates of multiple SREs (HR, 0.82; 95% CI, 0.71-0.94).⁴⁰ This was later confirmed with an additional study that demonstrated treatment with denosumab significantly reduced the risk of developing a first symptomatic SRE, defined as a pathologic fracture, spinal cord compression, necessity for radiation, or surgery (HR, 0.78; 95% CI, 0.66-0.93; P = .005) and first and subsequent symptomatic SREs (rate ratio, 0.78; 95% CI, 0.65-0.92; P = .004) compared with ZA.²⁸ These findings suggest a continued role of denosumab in the treatment of advanced metastatic CRPC from both control of bone disease as well as quality of life and palliation of cancer-related symptoms.

Radium-223 dichloride (radium-223) is an α-emitting radionuclide for treatment of metastatic CRPC with bone metastasis, but otherwise no additional metastatic sites. Radium-223 is a calcium-mimetic that preferentially accumulates into areas of high-bone turnover, such as where bone metastases tend to occur. Radium-223 induces apoptosis of tumor cells through double-stranded DNA breaks. Studies have shown radium-223 to prolong OS and time-to-first symptomatic SRE.⁴¹ The ERA-223 trial showed that when radium-223 was combined with abiraterone acetate, there was an increase in fragility fracture risk compared with placebo combined with abiraterone. Data from the study revealed that the median symptomatic SRE-free survival was 22.3 months (95% CI, 20.4-24.8) in the radium-223 group and 26.0 months (21.8-28.3) in the placebo group. Concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 was associated with increased fracture risk. Osteoporotic fractures were the most common type of fracture in the radium-223 group and of all fracture types, differed the most between the study groups.⁴²

Conclusions

Convincing evidence supports the ongoing use of bisphosphonates and denosumab in patients with osteoporosis, significant osteopenia with risk factors, and in patients with CRPC with bone metastasis. Bone metastases can cause considerable morbidity and mortality among men with advanced PC. Pain, fracture, and neurologic injury can occur with metastatic bone lesions as well as with ADT-related bone loss. Prevention of SREs in patients with PC is a reasonable goal in PC survivors while being mindful of managing the risks of these therapies.

Prostate cancer (PC) is the most commonly and newly diagnosed nonskin cancer and the second leading cause of cancer death in men in the United States. About 191,930 cases and about 33,330 deaths from PC were expected for the year 2020.¹ About 1 in 41 men will die of PC. Most men diagnosed with PC are aged > 65 years and do not die of their disease. The 5-year survival rate of localized and regional disease is nearly 100%, and disease with distant metastases is 31%. As a result, more than 3.1 million men in the United States who have been diagnosed with PC are still alive today.¹ Among veterans, there is a substantial population living with PC. Skolarus and Hawley reported in 2014 that an estimated 200,000 veterans with PC were survivors and 12,000 were newly diagnosed.²

In PC, skeletal strength can be affected by several factors, such as aging, malnutrition, androgen-deprivation therapy (ADT), and bone metastasis.^3,4 In fact, most men can live the rest of their life with PC by using strategies to monitor and treat it, once it shows either radiographic or chemical signs of progression.⁵ ADT is the standard of care to treat hormone-sensitive PC, which is associated with significant skeletal-related adverse effects (AEs).^6,7

Men undergoing ADT are 4 times more likely to develop substantial bone deficiency, Shahinian and colleagues found that in men surviving 5 years after PC diagnosis, 19.4% of those who received ADT had a fracture compared with 12% in men who did not (P < .001). The authors established a significant relation between the number of doses of gonadotropin-releasing hormone given in the first 12 months and the risk of fracture.⁸ Of those who progressed to metastatic disease, the first metastatic nonnodal site is most commonly to the bone.⁹ Advanced PC is characterized by increased bone turnover, which further raises concerns for bone health and patient performance.¹⁰

Skeletal-related events (SREs) include pathologic fracture, spinal cord compression, palliative radiation, or surgery to bone, and change in antineoplastic therapy secondary to bone pain. The concept of bone health refers to the prevention, diagnosis, and treatment of idiopathic, pathogenic, and treatment-related bone loss and delay or prevention of SREs.^6,11 Guidelines and expert groups have recommended screening for osteoporosis at the start of ADT with bone mineral density testing, ensuring adequate calcium and vitamin D intake, modifying lifestyle behaviors (smoking cessation, alcohol moderation, and regular exercise), and prescribing bisphosphonates or receptor-activated nuclear factor κ-B ligand inhibitor, denosumab, for men with osteoporosis or who are at general high-fracture risk.^12,13 The overuse of these medications results in undue cost to patients as well as AEs, such as osteonecrosis of the jaw (ONJ), hypocalcemia, and bone/joint pains.^14-17 There are evidence-based guidelines for appropriate use of bisphosphonates and denosumab for delay and prevention of SREs in the setting of advanced PC.¹⁸ These doses also typically differ in frequency to those of osteoporosis.¹⁹ We summarize the evidence and guidance for health care providers who care for patients with PC at various stages and complications from both disease-related and treatment-related comorbidities.

Bone-Strengthening Agents

Overall, there is evidence to support the use of bone-strengthening agents in patients with osteopenia/osteoporosis in the prevention of SREs with significant risk factors for progressive bone demineralization, such as lifestyle factors and, in particular, treatments such as ADT. Bone-remodeling agents for treatment of bony metastasis have been shown to provide therapeutic advantage only in limited instances in the castration-resistant PC (CRPC) setting. Hence, in patients with hormone-sensitive PC due to medication-related AEs, treatment with bone-strengthening agents is indicated only if the patient has a significant preexisting risk for fracture from osteopenia/osteoporosis (Table). The Figure depicts an algorithm for the management of bone health in men with PC who are being treated with ADT.

Denosumab and bisphosphonates have an established role in preventing SREs in metastatic CRPC.²⁰ The choice of denosumab or a bisphosphonate typically varies based on the indication, possible AEs, and cost of therapy. There are multiple studies involving initiation of these agents at various stages of disease to improve both time to progression as well as management of SREs. There is a lack of evidence that bisphosphonates prevent metastatic-bone lesions in castration-sensitive PC; therefore, prophylactic use of this agent is not recommended in patients unless they have significant bone demineralization.^21,22

Bone Health in Patients

Nonmetastatic Hormone-Sensitive PC

ADT forms the backbone of treatment for patients with local and advanced metastatic castration-sensitive PC along with surgical and focal radiotherapy options. Cancer treatment-induced bone loss is known to occur with prolonged use of ADT. The ZEUS trial found no prevention of bone metastasis in patients with high-risk localized PC with the use of ZA in the absence of bone metastasis. A Kaplan-Meier estimated proportion of bone metastases after a median follow-up of 4.8 years was found to be not statistically significant: 14.7% in the ZA group vs 13.2% in the control/placebo group.²⁹ The STAMPEDE trial showed no significant overall survival (OS) benefit with the addition of ZA to ADT vs ADT alone (HR, 0.94; 95% CI, 0.79-1.11; P = .45), 5-year survival with ADT alone was 55% compared to ADT plus ZA with 57% 5-year survival.³⁰ The RADAR trial showed that at 5 years in high Gleason score patients, use of ZA in the absence of bone metastasis was beneficial, but not in low- or intermediate-risk patients. However, at 10-year analysis there was no significant difference in any of the high-stratified groups with or without ZA.³¹

The PR04 trial showed no effect on OS with clodronate compared with placebo in nonmetastatic castration-sensitive PC, with a HR of 1.12 (95% CI, 0.89-1.42; P = .94). The estimated 5-year survival was 80% with placebo and 78% with clodronate; 10-year survival rates were 51% with placebo and 48% with clodronate.³² Data from the HALT trial showed an increased bone mineral density and reduced risk of new vertebral fractures vs placebo (1.5% vs 3.9%, respectively) in the absence of metastatic bone lesions and a reduction in new vertebral fractures in patients with nonmetastatic PC.³³ Most of these studies showed no benefit with the addition of ZA to nonmetastatic PC; although, the HALT trial provides evidence to support use of denosumab in patients with nonmetastatic PC for preventing vertebral fragility fractures in men receiving ADT.

Metastatic Hormone-Sensitive PC

ZA is often used to treat men with metastatic castration-sensitive PC despite limited efficacy and safety data. The CALGB 90202 (Alliance) trial authors found that the early use of ZA was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the ZA group (95% CI, 24.2-40.3) and 29.8 months in the placebo group (stratified HR, 0.97; 95% CI, 0-1.17; 1-sided stratified log-rank P = .39).³⁴ OS was similar between the groups (HR, 0.88; 95% CI, 0.70-1.12; P = .29) as were reported AEs.³⁴ Results from these studies suggest limited benefit in treating patients with metastatic hormone-sensitive PC with bisphosphonates without other medical indications for use. Additional studies suggest similar results for treatment with denosumab to that of bisphosphonate therapies.³⁵

Nonmetastatic CRPC

Reasonable interest among treating clinicians exists to be able to delay or prevent the development of metastatic bone disease in patients who are showing biochemical signs of castration resistance but have not yet developed distant metastatic disease. Time to progression on ADT to castration resistance usually occurs 2 to 3 years following initiation of treatment. This typically occurs in patients with rising prostate-specific antigen (PSA). As per the Prostate Cancer Working Group 3, in the absence of radiologic progression, CRPC is defined by a 25% increase from the nadir (considering a starting value of ≥ 1 ng/mL), with a minimum rise of 2 ng/mL in the setting of castrate serum testosterone < 50 ng/dL despite good adherence to an ADT regimen, with proven serologic castration either by undetectable or a near undetectable nadir of serum testosterone concentration. Therapeutic implications include prevention of SREs as well as time to metastatic bone lesions. The Zometa 704 trial examined the use of ZA to reduce time to first metastatic bone lesion in the setting of patients with nonmetastatic CRPC.³⁶ The trial was discontinued prematurely due to low patient accrual, but initial analysis provided information on the natural history of a rising PSA in this patient population. At 2 years, one-third of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastasis and OS were not reached. Baseline PSA and PSA velocity independently predicted a shorter time to first bone metastasis, metastasis-free survival, and OS.³⁶

Denosumab was also studied in the setting of nonmetastatic CRPC in the Denosumab 147 trial. The study enrolled 1432 patients and found a significantly increased bone metastasis-free survival by a median of 4.2 months over placebo (HR, 0.85; 95% CI, 0.73-0.98; P = .03). Denosumab significantly delayed time to first bone metastasis (HR, 0.84; 95% CI, 0.71-0.98; P = .03). OS was similar between groups (HR, 1.01; 95% CI, 0.85-1.20; P = .91). Rates of AEs and serious AEs were similar between groups, except for ONJ and hypocalcemia. The rates of ONJ for denosumab were 1%, 3%, 4% in years 1,2, 3, respectively; overall, < 5% (n = 33). Hypocalcemia occurred in < 2% (n = 12) in denosumab-treated patients. The authors concluded that in men with CRPC, denosumab significantly prolonged bone metastasis–free survival and delayed time-to-bone metastasis.³⁷ These 2 studies suggest a role of receptor-activated nuclear factor κ-B ligand inhibitor denosumab in patients with nonmetastatic CRPC in the appropriate setting. There were delays in bony metastatic disease, but no difference in OS. Rare denosumab treatment–related specific AEs were noted. Hence, denosumab is not recommended for use in this setting.

Metastatic CRPC

Castration resistance typically occurs 2 to 3 years following initiation of ADT and the most common extranodal site of disease is within the bone in metastatic PC. Disease progression within bones after ADT can be challenging given both the nature of progressive cancer with osteoblastic metastatic lesions and the prolonged effects of ADT on unaffected bone. The Zometa 039 study compared ZA with placebo and found a significant difference in SREs (38% and 49%, respectively; P .03). No survival benefit was observed with the addition of ZA. Use of other bisphosphonates pamidronate and clodronate did not have a similar degree of benefit.^38,39

A phase 3 study of 1904 patients found that denosumab was superior to ZA in delaying the time to first on-study SRE (HR, 0.82; 95% CI, 0.71-0.95) and reducing rates of multiple SREs (HR, 0.82; 95% CI, 0.71-0.94).⁴⁰ This was later confirmed with an additional study that demonstrated treatment with denosumab significantly reduced the risk of developing a first symptomatic SRE, defined as a pathologic fracture, spinal cord compression, necessity for radiation, or surgery (HR, 0.78; 95% CI, 0.66-0.93; P = .005) and first and subsequent symptomatic SREs (rate ratio, 0.78; 95% CI, 0.65-0.92; P = .004) compared with ZA.²⁸ These findings suggest a continued role of denosumab in the treatment of advanced metastatic CRPC from both control of bone disease as well as quality of life and palliation of cancer-related symptoms.

Radium-223 dichloride (radium-223) is an α-emitting radionuclide for treatment of metastatic CRPC with bone metastasis, but otherwise no additional metastatic sites. Radium-223 is a calcium-mimetic that preferentially accumulates into areas of high-bone turnover, such as where bone metastases tend to occur. Radium-223 induces apoptosis of tumor cells through double-stranded DNA breaks. Studies have shown radium-223 to prolong OS and time-to-first symptomatic SRE.⁴¹ The ERA-223 trial showed that when radium-223 was combined with abiraterone acetate, there was an increase in fragility fracture risk compared with placebo combined with abiraterone. Data from the study revealed that the median symptomatic SRE-free survival was 22.3 months (95% CI, 20.4-24.8) in the radium-223 group and 26.0 months (21.8-28.3) in the placebo group. Concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 was associated with increased fracture risk. Osteoporotic fractures were the most common type of fracture in the radium-223 group and of all fracture types, differed the most between the study groups.⁴²

Conclusions

Convincing evidence supports the ongoing use of bisphosphonates and denosumab in patients with osteoporosis, significant osteopenia with risk factors, and in patients with CRPC with bone metastasis. Bone metastases can cause considerable morbidity and mortality among men with advanced PC. Pain, fracture, and neurologic injury can occur with metastatic bone lesions as well as with ADT-related bone loss. Prevention of SREs in patients with PC is a reasonable goal in PC survivors while being mindful of managing the risks of these therapies.

Prostate cancer (PC) is the most commonly and newly diagnosed nonskin cancer and the second leading cause of cancer death in men in the United States. About 191,930 cases and about 33,330 deaths from PC were expected for the year 2020.¹ About 1 in 41 men will die of PC. Most men diagnosed with PC are aged > 65 years and do not die of their disease. The 5-year survival rate of localized and regional disease is nearly 100%, and disease with distant metastases is 31%. As a result, more than 3.1 million men in the United States who have been diagnosed with PC are still alive today.¹ Among veterans, there is a substantial population living with PC. Skolarus and Hawley reported in 2014 that an estimated 200,000 veterans with PC were survivors and 12,000 were newly diagnosed.²

In PC, skeletal strength can be affected by several factors, such as aging, malnutrition, androgen-deprivation therapy (ADT), and bone metastasis.^3,4 In fact, most men can live the rest of their life with PC by using strategies to monitor and treat it, once it shows either radiographic or chemical signs of progression.⁵ ADT is the standard of care to treat hormone-sensitive PC, which is associated with significant skeletal-related adverse effects (AEs).^6,7

Men undergoing ADT are 4 times more likely to develop substantial bone deficiency, Shahinian and colleagues found that in men surviving 5 years after PC diagnosis, 19.4% of those who received ADT had a fracture compared with 12% in men who did not (P < .001). The authors established a significant relation between the number of doses of gonadotropin-releasing hormone given in the first 12 months and the risk of fracture.⁸ Of those who progressed to metastatic disease, the first metastatic nonnodal site is most commonly to the bone.⁹ Advanced PC is characterized by increased bone turnover, which further raises concerns for bone health and patient performance.¹⁰

Skeletal-related events (SREs) include pathologic fracture, spinal cord compression, palliative radiation, or surgery to bone, and change in antineoplastic therapy secondary to bone pain. The concept of bone health refers to the prevention, diagnosis, and treatment of idiopathic, pathogenic, and treatment-related bone loss and delay or prevention of SREs.^6,11 Guidelines and expert groups have recommended screening for osteoporosis at the start of ADT with bone mineral density testing, ensuring adequate calcium and vitamin D intake, modifying lifestyle behaviors (smoking cessation, alcohol moderation, and regular exercise), and prescribing bisphosphonates or receptor-activated nuclear factor κ-B ligand inhibitor, denosumab, for men with osteoporosis or who are at general high-fracture risk.^12,13 The overuse of these medications results in undue cost to patients as well as AEs, such as osteonecrosis of the jaw (ONJ), hypocalcemia, and bone/joint pains.^14-17 There are evidence-based guidelines for appropriate use of bisphosphonates and denosumab for delay and prevention of SREs in the setting of advanced PC.¹⁸ These doses also typically differ in frequency to those of osteoporosis.¹⁹ We summarize the evidence and guidance for health care providers who care for patients with PC at various stages and complications from both disease-related and treatment-related comorbidities.

Bone-Strengthening Agents

Overall, there is evidence to support the use of bone-strengthening agents in patients with osteopenia/osteoporosis in the prevention of SREs with significant risk factors for progressive bone demineralization, such as lifestyle factors and, in particular, treatments such as ADT. Bone-remodeling agents for treatment of bony metastasis have been shown to provide therapeutic advantage only in limited instances in the castration-resistant PC (CRPC) setting. Hence, in patients with hormone-sensitive PC due to medication-related AEs, treatment with bone-strengthening agents is indicated only if the patient has a significant preexisting risk for fracture from osteopenia/osteoporosis (Table). The Figure depicts an algorithm for the management of bone health in men with PC who are being treated with ADT.

Denosumab and bisphosphonates have an established role in preventing SREs in metastatic CRPC.²⁰ The choice of denosumab or a bisphosphonate typically varies based on the indication, possible AEs, and cost of therapy. There are multiple studies involving initiation of these agents at various stages of disease to improve both time to progression as well as management of SREs. There is a lack of evidence that bisphosphonates prevent metastatic-bone lesions in castration-sensitive PC; therefore, prophylactic use of this agent is not recommended in patients unless they have significant bone demineralization.^21,22

Bone Health in Patients

Nonmetastatic Hormone-Sensitive PC

ADT forms the backbone of treatment for patients with local and advanced metastatic castration-sensitive PC along with surgical and focal radiotherapy options. Cancer treatment-induced bone loss is known to occur with prolonged use of ADT. The ZEUS trial found no prevention of bone metastasis in patients with high-risk localized PC with the use of ZA in the absence of bone metastasis. A Kaplan-Meier estimated proportion of bone metastases after a median follow-up of 4.8 years was found to be not statistically significant: 14.7% in the ZA group vs 13.2% in the control/placebo group.²⁹ The STAMPEDE trial showed no significant overall survival (OS) benefit with the addition of ZA to ADT vs ADT alone (HR, 0.94; 95% CI, 0.79-1.11; P = .45), 5-year survival with ADT alone was 55% compared to ADT plus ZA with 57% 5-year survival.³⁰ The RADAR trial showed that at 5 years in high Gleason score patients, use of ZA in the absence of bone metastasis was beneficial, but not in low- or intermediate-risk patients. However, at 10-year analysis there was no significant difference in any of the high-stratified groups with or without ZA.³¹

The PR04 trial showed no effect on OS with clodronate compared with placebo in nonmetastatic castration-sensitive PC, with a HR of 1.12 (95% CI, 0.89-1.42; P = .94). The estimated 5-year survival was 80% with placebo and 78% with clodronate; 10-year survival rates were 51% with placebo and 48% with clodronate.³² Data from the HALT trial showed an increased bone mineral density and reduced risk of new vertebral fractures vs placebo (1.5% vs 3.9%, respectively) in the absence of metastatic bone lesions and a reduction in new vertebral fractures in patients with nonmetastatic PC.³³ Most of these studies showed no benefit with the addition of ZA to nonmetastatic PC; although, the HALT trial provides evidence to support use of denosumab in patients with nonmetastatic PC for preventing vertebral fragility fractures in men receiving ADT.

Metastatic Hormone-Sensitive PC

ZA is often used to treat men with metastatic castration-sensitive PC despite limited efficacy and safety data. The CALGB 90202 (Alliance) trial authors found that the early use of ZA was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the ZA group (95% CI, 24.2-40.3) and 29.8 months in the placebo group (stratified HR, 0.97; 95% CI, 0-1.17; 1-sided stratified log-rank P = .39).³⁴ OS was similar between the groups (HR, 0.88; 95% CI, 0.70-1.12; P = .29) as were reported AEs.³⁴ Results from these studies suggest limited benefit in treating patients with metastatic hormone-sensitive PC with bisphosphonates without other medical indications for use. Additional studies suggest similar results for treatment with denosumab to that of bisphosphonate therapies.³⁵

Nonmetastatic CRPC

Reasonable interest among treating clinicians exists to be able to delay or prevent the development of metastatic bone disease in patients who are showing biochemical signs of castration resistance but have not yet developed distant metastatic disease. Time to progression on ADT to castration resistance usually occurs 2 to 3 years following initiation of treatment. This typically occurs in patients with rising prostate-specific antigen (PSA). As per the Prostate Cancer Working Group 3, in the absence of radiologic progression, CRPC is defined by a 25% increase from the nadir (considering a starting value of ≥ 1 ng/mL), with a minimum rise of 2 ng/mL in the setting of castrate serum testosterone < 50 ng/dL despite good adherence to an ADT regimen, with proven serologic castration either by undetectable or a near undetectable nadir of serum testosterone concentration. Therapeutic implications include prevention of SREs as well as time to metastatic bone lesions. The Zometa 704 trial examined the use of ZA to reduce time to first metastatic bone lesion in the setting of patients with nonmetastatic CRPC.³⁶ The trial was discontinued prematurely due to low patient accrual, but initial analysis provided information on the natural history of a rising PSA in this patient population. At 2 years, one-third of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastasis and OS were not reached. Baseline PSA and PSA velocity independently predicted a shorter time to first bone metastasis, metastasis-free survival, and OS.³⁶

Denosumab was also studied in the setting of nonmetastatic CRPC in the Denosumab 147 trial. The study enrolled 1432 patients and found a significantly increased bone metastasis-free survival by a median of 4.2 months over placebo (HR, 0.85; 95% CI, 0.73-0.98; P = .03). Denosumab significantly delayed time to first bone metastasis (HR, 0.84; 95% CI, 0.71-0.98; P = .03). OS was similar between groups (HR, 1.01; 95% CI, 0.85-1.20; P = .91). Rates of AEs and serious AEs were similar between groups, except for ONJ and hypocalcemia. The rates of ONJ for denosumab were 1%, 3%, 4% in years 1,2, 3, respectively; overall, < 5% (n = 33). Hypocalcemia occurred in < 2% (n = 12) in denosumab-treated patients. The authors concluded that in men with CRPC, denosumab significantly prolonged bone metastasis–free survival and delayed time-to-bone metastasis.³⁷ These 2 studies suggest a role of receptor-activated nuclear factor κ-B ligand inhibitor denosumab in patients with nonmetastatic CRPC in the appropriate setting. There were delays in bony metastatic disease, but no difference in OS. Rare denosumab treatment–related specific AEs were noted. Hence, denosumab is not recommended for use in this setting.

Metastatic CRPC

Castration resistance typically occurs 2 to 3 years following initiation of ADT and the most common extranodal site of disease is within the bone in metastatic PC. Disease progression within bones after ADT can be challenging given both the nature of progressive cancer with osteoblastic metastatic lesions and the prolonged effects of ADT on unaffected bone. The Zometa 039 study compared ZA with placebo and found a significant difference in SREs (38% and 49%, respectively; P .03). No survival benefit was observed with the addition of ZA. Use of other bisphosphonates pamidronate and clodronate did not have a similar degree of benefit.^38,39

A phase 3 study of 1904 patients found that denosumab was superior to ZA in delaying the time to first on-study SRE (HR, 0.82; 95% CI, 0.71-0.95) and reducing rates of multiple SREs (HR, 0.82; 95% CI, 0.71-0.94).⁴⁰ This was later confirmed with an additional study that demonstrated treatment with denosumab significantly reduced the risk of developing a first symptomatic SRE, defined as a pathologic fracture, spinal cord compression, necessity for radiation, or surgery (HR, 0.78; 95% CI, 0.66-0.93; P = .005) and first and subsequent symptomatic SREs (rate ratio, 0.78; 95% CI, 0.65-0.92; P = .004) compared with ZA.²⁸ These findings suggest a continued role of denosumab in the treatment of advanced metastatic CRPC from both control of bone disease as well as quality of life and palliation of cancer-related symptoms.

Radium-223 dichloride (radium-223) is an α-emitting radionuclide for treatment of metastatic CRPC with bone metastasis, but otherwise no additional metastatic sites. Radium-223 is a calcium-mimetic that preferentially accumulates into areas of high-bone turnover, such as where bone metastases tend to occur. Radium-223 induces apoptosis of tumor cells through double-stranded DNA breaks. Studies have shown radium-223 to prolong OS and time-to-first symptomatic SRE.⁴¹ The ERA-223 trial showed that when radium-223 was combined with abiraterone acetate, there was an increase in fragility fracture risk compared with placebo combined with abiraterone. Data from the study revealed that the median symptomatic SRE-free survival was 22.3 months (95% CI, 20.4-24.8) in the radium-223 group and 26.0 months (21.8-28.3) in the placebo group. Concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 was associated with increased fracture risk. Osteoporotic fractures were the most common type of fracture in the radium-223 group and of all fracture types, differed the most between the study groups.⁴²

Conclusions

Convincing evidence supports the ongoing use of bisphosphonates and denosumab in patients with osteoporosis, significant osteopenia with risk factors, and in patients with CRPC with bone metastasis. Bone metastases can cause considerable morbidity and mortality among men with advanced PC. Pain, fracture, and neurologic injury can occur with metastatic bone lesions as well as with ADT-related bone loss. Prevention of SREs in patients with PC is a reasonable goal in PC survivors while being mindful of managing the risks of these therapies.

Substance use disorders (SUDs) are an important but understudied aspect of treating patients diagnosed with cancer. Substance use can affect cancer treatment outcomes, including morbidity and mortality.^1,2 Additionally, patients with cancer and SUD may have unique psychosocial needs that require close attention and management. There is a paucity of data regarding the best approach to treating such patients. For example, cocaine use may increase the cardiovascular and hematologic risk of some traditional chemotherapy agents.^3,4 Newer targeted agents and immunotherapies remain understudied with respect to SUD risk.

Although the US Department of Veterans Affairs (VA) has established helpful clinical practice guidelines for the treatment of SUD, there are no guidelines for treating patients with SUD and cancer.⁵ Clinicians have limited confidence in treatment approach, and treatment is inconsistent among oncologists nationwide even within the same practice. Furthermore, it can be challenging to safely prescribe opioids for cancer-related pain in individuals with SUD. There is a high risk of SUD and mental health disorders in veterans, making this population particularly vulnerable. We report a case of a male with metastatic pancreatic cancer, severe opioid use disorder (OUD) and moderate cocaine use disorder (CUD) who received pain management and cancer treatment under the direction of a multidisciplinary team approach.

Case Report

A 63-year-old male with a medical history of HIV treated with highly active antiretroviral therapy (HAART), compensated cirrhosis, severe OUD, moderate CUD, and sedative use disorder in sustained remission was admitted to the West Haven campus of the VA Connecticut Healthcare System (VACHS) with abdominal pain, weight loss and fatigue. He used heroin 1 month prior to his admission and reported regular cocaine and marijuana use (Table 1). He was diagnosed with HIV in 1989, and his medical history included herpes zoster and oral candidiasis but no other opportunistic infections. Several months prior to this admission, he had an undetectable viral load and CD4 count of 688.

At the time of this admission, the patient was adherent to methadone treatment. He reported increased abdominal pain. Computed tomography (CT) showed a 2.4-cm mass in the pancreatic uncinate process, multiple liver metastases, retroperitoneal lymphadenopathy, and small lung nodules. A CT-guided liver biopsy showed adenocarcinoma consistent with a primary cancer of the pancreas. Given the complexity of the case, a multidisciplinary team approach was used to treat his cancer and the sequelae safely, including the oncology team, community living center team, palliative care team, and interprofessional opioid reassessment clinic team (ORC).

Cancer Treatment

Chemotherapy with FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) was recommended. The first cycle of treatment originally was planned for the outpatient setting, and a peripherally inserted central catheter (PICC) line was placed. However, after a urine toxicology test was positive for cocaine, the PICC line was removed due to concern for possible use of PICC line for nonprescribed substance use. The patient expressed suicidal ideation at the time and was admitted for psychiatric consult and pain control. Cycle 1 FOLFIRINOX was started during this admission. A PICC line was again put in place and then removed before discharge. A celiac plexus block was performed several days after this admission for pain control.

Given concern about cocaine use increasing the risk of cardiac toxicity with FOLFIRINOX treatment, treating providers sconsulted with the community living center (CLC) about possible admission for future chemotherapy administration and pain management. The CLC at VACHS has 38 beds for rehabilitation, long-term care, and hospice with the mission to restore each veteran to his or her highest level of well-being. After discussion with this patient and CLC staff, he agreed to a CLC admission. The patient agreed to remain in the facility, wear a secure care device, and not leave without staff accompaniment. He was able to obtain a 2-hour pass to pay bills and rent. During the 2 months he was admitted to the CLC he would present to the VACHS Cancer Center for chemotherapy every 2 weeks. He completed 6 cycles of chemotherapy while admitted. During the admission, he was transferred to active medical service for 2 days for fever and malaise, and then returned to the CLC. The patient elected to leave the CLC after 2 months as the inability to see close friends was interfering with his quality of life.

Upon being discharged from the CLC, shared decision making took place with the patient to establish a new treatment plan. In collaboration with the patient, a plan was made to admit him every 2 weeks for continued chemotherapy. A PICC line was placed on each day of admission and removed prior to discharge. It was also agreed that treatment would be delayed if a urine drug test was positive for cocaine on the morning of admission. The patient was also seen by ORC every 2 weeks after being discharged from the CLC.

Imaging after cycle 6 showed decreased size of liver metastases, retroperitoneal lymph nodes, and pancreas mass. Cancer antigen 19-9 (CA19-9) tumor marker was reduced from 3513 U/mL pretreatment to 50 U/mL after cycle 7. Chemotherapy cycle 7 was delayed 6 days due to active cocaine and heroin use. A repeat urine was obtained several days later, which was negative for cocaine, and he was admitted for cycle 7 chemotherapy. Using this treatment approach of admissions for every cycle, the patient was able to receive 11 cycles of FOLFIRINOX with clinical benefit.

Palliative Care/Pain Management

Safely treating the patient’s malignant pain in the context of his OUD was critically important. In order to do this the palliative care team worked closely alongside ORC, is a multidisciplinary team consisting of health care providers (HCPs) from addiction psychiatry, internal medicine, health psychology and pharmacy who are consulted to evaluate veterans’ current opioid regimens and make recommendations to optimize both safety and efficacy. ORC followed this particular veteran as an outpatient and consulted on pain issues during his admission. They recommended the continuation of methadone at 120 mg daily and increased oral oxycodone to 30 mg every 6 hours, and then further increased to 45 mg every 6 hours. He continued to have increased pain despite higher doses of oxycodone, and pain medication was changed to oral hydromorphone 28 mg every 6 hours with the continuation of methadone. ORC and the palliative care team obtained consent from the veteran and a release of Information form signed by the patient to contact his community methadone clinic for further collaboration around pain management throughout the time caring for the veteran.

Even with improvement in disease based on imaging and tumor markers, opioid medications could not be decreased in this case. This is likely in part due to the multidimensional nature of pain. Careful assessment of the biologic, emotional, social, and spiritual contributors to pain is needed in the management of pain, especially at end of life.⁶ Nonpharmacologic pain management strategies used in this case included a transcutaneous electrical nerve stimulation unit, moist heat, celiac plexus block, and emotional support.

Psychosocial Issues/Substance Use

Psychosocial support for the patient was provided by the interdisciplinary palliative care team and the ORC team in both the inpatient and outpatient settings. Despite efforts from case management to get the veteran home services once discharged from the CLC, he declined repeatedly. Thus, the CLC social worker obtained a guardian alert for the veteran on discharge.

Close outpatient follow-up for medical and psychosocial support was very critical. When an outpatient, the veteran was scheduled for biweekly appointments with palliative care or ORC. When admitted to the hospital, the palliative care team medical director and psychologist conducted joint visits with him. Although he denied depressed mood and anxiety throughout his treatment, he often reflected on regrets that he had as he faced the end of his life. Specifically, he shared thoughts about being estranged from his surviving brother given his long struggle with substance use. Although he did not think a relationship was possible with his brother at the end of life, he still cared deeply for him and wanted to make him aware of his pancreatic cancer diagnosis. This was particularly important to him because their late brother had also died of pancreatic cancer. It was the patient’s wish at the end of his life to alert his surviving brother of his diagnosis so he and his children could get adequate screening throughout their lives. Although he had spoken of this desire often, it wasn’t until his disease progressed and he elected to transition to hospice that he felt ready to write the letter. The palliative care team assisted the veteran in writing and mailing a letter to his brother informing him of his diagnosis and transition to hospice as well as communicating that his brother and his family had been in his thoughts at the end of his life. The patient’s brother received this letter and with assistance from the CLC social worker made arrangements to visit the veteran at bedside at the inpatient CLC hospice unit the final days of his life.

Discussion

There are very little data on the safety of cancer-directed therapy in patients with active SUD. The limited studies that have been done showed conflicting results.

A retrospective study among women with co-occurring SUD and locally advanced cervical cancer who were undergoing primary radiation therapy found that SUD was not associated with a difference in toxicity or survival outcomes.⁷ However, other research suggests that SUD may be associated with an increase in all-cause mortality as well as other adverse outcomes for patients and health care systems (eg, emergency department visits, hospitalizations).⁸ A retrospective study of patients with a history of SUD and nonsmall cell lung cancer showed that these patients had higher rates of depression, less family support, increased rates of missed appointments, more emergency department visits and more hospitalizations.⁹ Patients with chronic myeloid leukemia or myelodysplastic syndromes who had long-term cocaine use had a 6-fold increased risk of death, which was not found in patients who had long-term alcohol or marijuana use.²

The limited data highlight the need for careful consideration of ways to mitigate potentially adverse outcomes in this population while still providing clinically indicated cancer treatment. Integrated VA health care systems provide unique resources that can maximize veteran safety during cancer treatment. Utilization of VA resources and close interdisciplinary collaboration across VA HCPs can help to ensure equitable access to state-of-the-art cancer therapies for veterans with comorbid SUD.

VA Services for Patients With Comorbidities

This case highlights several distinct aspects of VA health care that make it possible to safely treat individuals with complex comorbidities. One important aspect of this was collaboration with the CLC to admit the veteran for his initial treatment after a positive cocaine test. CLC admission was nonpunitive and allowed ongoing involvement in the VA community. This provided an essential, safe, and structured environment in which 6 cycles of chemotherapy could be delivered.

Although the patient left the CLC after 2 months due to floor restrictions negatively impacting his quality of life and ability to spend time with close friends, several important events occurred during this stay. First, the patient established close relationships with the CLC staff and the palliative care team; both groups followed him throughout his inpatient and outpatient care. These relationships proved essential throughout his care as they were the foundation of difficult conversations about substance use, treatment adherence, and eventually, transition to hospice.

In addition, the opportunity to administer 6 cycles of chemotherapy at the CLC was enough to lead to clinical benefit and radiographic response to treatment. Clinical benefits while in the CLC included maintenance of a good appetite, 15-lb weight gain and preserved performance status (ECOG [Eastern Cooperative Group]-1), which allowed him to actively participate in multiple social and recreational activities while in the CLC. From early conversations, this patient was clear that he wanted treatment as long as his life could be prolonged with good quality of life. Having evidence of the benefit of treatment, at least initially, increased the patient’s confidence in treatment. There were a few conversations when the challenges of treatment mounted (eg, pain, needs for abstinence from cocaine prior to admission for chemotherapy, frequent doctor appointments), and the patient would remind himself of these data to recommit himself to treatment. The opportunity to admit him to the inpatient VA facility, including bed availability for 3 days during his treatment once he left the CLC was important. This plan to admit the patient following a negative urine toxicology test for cocaine was made collaboratively with the veteran and the oncology and palliative care teams. The plan allowed the patient to achieve his treatment goals while maintaining his safety and reducing theoretical cardiac toxicities with his cancer treatment.

Finally, the availability of a multidisciplinary team approach including palliative care, oncology, psychology, addiction medicine and addiction psychiatry, was critical for addressing the veteran’s malignant pain. Palliative care worked in close collaboration with the ORC to prescribe and renew pain medications. ORC offered ongoing consultation on pain management in the context of OUD. As the veteran’s cancer progressed and functional decline prohibited his daily attendance at the community methadone clinic, palliative care and ORC met with the methadone clinic to arrange a less frequent methadone pickup schedule (the patient previously needed daily pickup). Non-VA settings may not have access to these resources to safely treat the biopsychosocial issues that arise in complex cases.

Substance Use and Cancer Treatments

This case raises several critical questions for oncologic care. Cocaine and fluorouracil are both associated with cardiotoxicity, and many oncologists would not feel it is safe to administer a regimen containing fluorouracil to a patient with active cocaine use. The National Comprehensive Cancer Network (NCCN) panel recommends FOLFIRINOX as a preferred category 1 recommendation for first-line treatment of patients with advanced pancreas cancer with good performance status.¹⁰ This recommendation is based on the PRODIGE trial, which has shown improved overall survival (OS): 11.1 vs 6.8 months for patients who received single-agent gemcitabine.¹¹ If patients are not candidates for FOLFIRINOX and have good performance status, the NCCN recommends gemcitabine plus albumin-bound paclitaxel with category 1 level of evidence based on the IMPACT trial, which showed improvement in OS (8.7 vs 6.6 months compared with single-agent gemcitabine).¹²

Some oncologists may have additional concerns administering fluorouracil treatment alternatives (such as gemcitabine and albumin-bound paclitaxel) to individuals with active SUD because of concerns about altered mental status impacting the ability to report important adverse effects. In the absence of sufficient data, HCPs must determine whether they feel it is safe to administer these agents in individuals with active cocaine use. However, denying these patients the possible benefits of standard-of-care life-prolonging therapies without established data raises concerns regarding the ethics of such practices. There is concern that the stigma surrounding cocaine use might contribute to withholding treatment, while treatment is continued for individuals taking prescribed stimulant medications that also have cardiotoxicity risks. VA health care facilities are uniquely situated to use all available resources to address these issues using interprofessional patient-centered care and determine the most optimal treatment based on a risk/benefit discussion between the patient and the HCP.

SUD Screening

This case begs the question of whether oncologists are adequately screening for a range of SUDs, and when they encounter an issue, how they are addressing it. Many oncologists do not receive adequate training on assessment of current or recent substance use. There are health care and systems-level practices that may increase patient safety for individuals with ongoing substance use who are undergoing cancer treatment. Training on obtaining appropriate substance use histories, motivational interviewing to resolve ambivalence about substance use in the direction of change, and shared decision making about treatment options could increase confidence in understanding and addressing substance use issues. It is also important to educate oncologists on how to address patients who return to or continued substance use during treatment. In this case the collaboration from palliative care, psychology, addiction medicine, and addiction psychiatry through the ORC was essential in assisting with ongoing assessment of substance use, guiding difficult conversations about the impact of substance use on the treatment plan, and identifying risk-mitigation strategies. Close collaboration and full utilization of all VA resources allowed this patient to receive first-line treatment for pancreatic cancer in order to reach his goal of prolonging his life while maintaining acceptable quality of life. Table 2 provides best practices for management of patients with comorbid SUD and cancer.

More research is needed into cancer treatment for patients with SUD, especially in the current era of cancer care using novel cancer treatments leading to significantly improved survival in many cancer types. Ideally, oncologists should be routinely or consistently screening patients for substance use, including alcohol. The patient should participate in this decision-making process after being educated about the risks and benefits. These patients can be followed using a multimodal approach to increase their rates of success and improve their quality of life. Although the literature is limited and no formal guidelines are available, VA oncologists are fortunate to have a range of resources available to them to navigate these difficult cases. Veterans have elevated rates of SUD, making this a critical issue to consider in the VA.¹³ It is the hope that this case can highlight how to take advantage of the many VA resources in order to ensure equitable cancer care for all veterans.

Conclusions

This case demonstrates that cancer-directed treatment is safe and feasible in a patient with advanced pancreatic cancer and coexisting active SUD by using a multidisciplinary approach. The multidisciplinary team included palliative care, oncology, psychology, addiction medicine, and addiction psychiatry. Critical steps for a successful outcome include gathering history about SUD; motivational interviewing to resolve ambivalence about treatment for SUD; shared decision making about cancer treatment; and risk-reduction strategies in pain and SUD management.

Treatment advancements in many cancer types have led to significantly longer survival, and it is critical to develop safe protocols to treat patients with active SUD so they also can derive benefit from these very significant medical advancements.

Acknowledgments

Michal Rose, MD, Director of VACHS Cancer Center, and Chandrika Kumar, MD, Director of VACHS Community Living Center, for their collaboration in care for this veteran.

Substance use disorders (SUDs) are an important but understudied aspect of treating patients diagnosed with cancer. Substance use can affect cancer treatment outcomes, including morbidity and mortality.^1,2 Additionally, patients with cancer and SUD may have unique psychosocial needs that require close attention and management. There is a paucity of data regarding the best approach to treating such patients. For example, cocaine use may increase the cardiovascular and hematologic risk of some traditional chemotherapy agents.^3,4 Newer targeted agents and immunotherapies remain understudied with respect to SUD risk.

Although the US Department of Veterans Affairs (VA) has established helpful clinical practice guidelines for the treatment of SUD, there are no guidelines for treating patients with SUD and cancer.⁵ Clinicians have limited confidence in treatment approach, and treatment is inconsistent among oncologists nationwide even within the same practice. Furthermore, it can be challenging to safely prescribe opioids for cancer-related pain in individuals with SUD. There is a high risk of SUD and mental health disorders in veterans, making this population particularly vulnerable. We report a case of a male with metastatic pancreatic cancer, severe opioid use disorder (OUD) and moderate cocaine use disorder (CUD) who received pain management and cancer treatment under the direction of a multidisciplinary team approach.

Case Report

A 63-year-old male with a medical history of HIV treated with highly active antiretroviral therapy (HAART), compensated cirrhosis, severe OUD, moderate CUD, and sedative use disorder in sustained remission was admitted to the West Haven campus of the VA Connecticut Healthcare System (VACHS) with abdominal pain, weight loss and fatigue. He used heroin 1 month prior to his admission and reported regular cocaine and marijuana use (Table 1). He was diagnosed with HIV in 1989, and his medical history included herpes zoster and oral candidiasis but no other opportunistic infections. Several months prior to this admission, he had an undetectable viral load and CD4 count of 688.

At the time of this admission, the patient was adherent to methadone treatment. He reported increased abdominal pain. Computed tomography (CT) showed a 2.4-cm mass in the pancreatic uncinate process, multiple liver metastases, retroperitoneal lymphadenopathy, and small lung nodules. A CT-guided liver biopsy showed adenocarcinoma consistent with a primary cancer of the pancreas. Given the complexity of the case, a multidisciplinary team approach was used to treat his cancer and the sequelae safely, including the oncology team, community living center team, palliative care team, and interprofessional opioid reassessment clinic team (ORC).

Cancer Treatment

Chemotherapy with FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) was recommended. The first cycle of treatment originally was planned for the outpatient setting, and a peripherally inserted central catheter (PICC) line was placed. However, after a urine toxicology test was positive for cocaine, the PICC line was removed due to concern for possible use of PICC line for nonprescribed substance use. The patient expressed suicidal ideation at the time and was admitted for psychiatric consult and pain control. Cycle 1 FOLFIRINOX was started during this admission. A PICC line was again put in place and then removed before discharge. A celiac plexus block was performed several days after this admission for pain control.

Given concern about cocaine use increasing the risk of cardiac toxicity with FOLFIRINOX treatment, treating providers sconsulted with the community living center (CLC) about possible admission for future chemotherapy administration and pain management. The CLC at VACHS has 38 beds for rehabilitation, long-term care, and hospice with the mission to restore each veteran to his or her highest level of well-being. After discussion with this patient and CLC staff, he agreed to a CLC admission. The patient agreed to remain in the facility, wear a secure care device, and not leave without staff accompaniment. He was able to obtain a 2-hour pass to pay bills and rent. During the 2 months he was admitted to the CLC he would present to the VACHS Cancer Center for chemotherapy every 2 weeks. He completed 6 cycles of chemotherapy while admitted. During the admission, he was transferred to active medical service for 2 days for fever and malaise, and then returned to the CLC. The patient elected to leave the CLC after 2 months as the inability to see close friends was interfering with his quality of life.

Upon being discharged from the CLC, shared decision making took place with the patient to establish a new treatment plan. In collaboration with the patient, a plan was made to admit him every 2 weeks for continued chemotherapy. A PICC line was placed on each day of admission and removed prior to discharge. It was also agreed that treatment would be delayed if a urine drug test was positive for cocaine on the morning of admission. The patient was also seen by ORC every 2 weeks after being discharged from the CLC.

Imaging after cycle 6 showed decreased size of liver metastases, retroperitoneal lymph nodes, and pancreas mass. Cancer antigen 19-9 (CA19-9) tumor marker was reduced from 3513 U/mL pretreatment to 50 U/mL after cycle 7. Chemotherapy cycle 7 was delayed 6 days due to active cocaine and heroin use. A repeat urine was obtained several days later, which was negative for cocaine, and he was admitted for cycle 7 chemotherapy. Using this treatment approach of admissions for every cycle, the patient was able to receive 11 cycles of FOLFIRINOX with clinical benefit.

Palliative Care/Pain Management

Safely treating the patient’s malignant pain in the context of his OUD was critically important. In order to do this the palliative care team worked closely alongside ORC, is a multidisciplinary team consisting of health care providers (HCPs) from addiction psychiatry, internal medicine, health psychology and pharmacy who are consulted to evaluate veterans’ current opioid regimens and make recommendations to optimize both safety and efficacy. ORC followed this particular veteran as an outpatient and consulted on pain issues during his admission. They recommended the continuation of methadone at 120 mg daily and increased oral oxycodone to 30 mg every 6 hours, and then further increased to 45 mg every 6 hours. He continued to have increased pain despite higher doses of oxycodone, and pain medication was changed to oral hydromorphone 28 mg every 6 hours with the continuation of methadone. ORC and the palliative care team obtained consent from the veteran and a release of Information form signed by the patient to contact his community methadone clinic for further collaboration around pain management throughout the time caring for the veteran.

Even with improvement in disease based on imaging and tumor markers, opioid medications could not be decreased in this case. This is likely in part due to the multidimensional nature of pain. Careful assessment of the biologic, emotional, social, and spiritual contributors to pain is needed in the management of pain, especially at end of life.⁶ Nonpharmacologic pain management strategies used in this case included a transcutaneous electrical nerve stimulation unit, moist heat, celiac plexus block, and emotional support.

Psychosocial Issues/Substance Use

Psychosocial support for the patient was provided by the interdisciplinary palliative care team and the ORC team in both the inpatient and outpatient settings. Despite efforts from case management to get the veteran home services once discharged from the CLC, he declined repeatedly. Thus, the CLC social worker obtained a guardian alert for the veteran on discharge.

Close outpatient follow-up for medical and psychosocial support was very critical. When an outpatient, the veteran was scheduled for biweekly appointments with palliative care or ORC. When admitted to the hospital, the palliative care team medical director and psychologist conducted joint visits with him. Although he denied depressed mood and anxiety throughout his treatment, he often reflected on regrets that he had as he faced the end of his life. Specifically, he shared thoughts about being estranged from his surviving brother given his long struggle with substance use. Although he did not think a relationship was possible with his brother at the end of life, he still cared deeply for him and wanted to make him aware of his pancreatic cancer diagnosis. This was particularly important to him because their late brother had also died of pancreatic cancer. It was the patient’s wish at the end of his life to alert his surviving brother of his diagnosis so he and his children could get adequate screening throughout their lives. Although he had spoken of this desire often, it wasn’t until his disease progressed and he elected to transition to hospice that he felt ready to write the letter. The palliative care team assisted the veteran in writing and mailing a letter to his brother informing him of his diagnosis and transition to hospice as well as communicating that his brother and his family had been in his thoughts at the end of his life. The patient’s brother received this letter and with assistance from the CLC social worker made arrangements to visit the veteran at bedside at the inpatient CLC hospice unit the final days of his life.

Discussion

There are very little data on the safety of cancer-directed therapy in patients with active SUD. The limited studies that have been done showed conflicting results.

A retrospective study among women with co-occurring SUD and locally advanced cervical cancer who were undergoing primary radiation therapy found that SUD was not associated with a difference in toxicity or survival outcomes.⁷ However, other research suggests that SUD may be associated with an increase in all-cause mortality as well as other adverse outcomes for patients and health care systems (eg, emergency department visits, hospitalizations).⁸ A retrospective study of patients with a history of SUD and nonsmall cell lung cancer showed that these patients had higher rates of depression, less family support, increased rates of missed appointments, more emergency department visits and more hospitalizations.⁹ Patients with chronic myeloid leukemia or myelodysplastic syndromes who had long-term cocaine use had a 6-fold increased risk of death, which was not found in patients who had long-term alcohol or marijuana use.²

The limited data highlight the need for careful consideration of ways to mitigate potentially adverse outcomes in this population while still providing clinically indicated cancer treatment. Integrated VA health care systems provide unique resources that can maximize veteran safety during cancer treatment. Utilization of VA resources and close interdisciplinary collaboration across VA HCPs can help to ensure equitable access to state-of-the-art cancer therapies for veterans with comorbid SUD.

VA Services for Patients With Comorbidities

This case highlights several distinct aspects of VA health care that make it possible to safely treat individuals with complex comorbidities. One important aspect of this was collaboration with the CLC to admit the veteran for his initial treatment after a positive cocaine test. CLC admission was nonpunitive and allowed ongoing involvement in the VA community. This provided an essential, safe, and structured environment in which 6 cycles of chemotherapy could be delivered.

Although the patient left the CLC after 2 months due to floor restrictions negatively impacting his quality of life and ability to spend time with close friends, several important events occurred during this stay. First, the patient established close relationships with the CLC staff and the palliative care team; both groups followed him throughout his inpatient and outpatient care. These relationships proved essential throughout his care as they were the foundation of difficult conversations about substance use, treatment adherence, and eventually, transition to hospice.

In addition, the opportunity to administer 6 cycles of chemotherapy at the CLC was enough to lead to clinical benefit and radiographic response to treatment. Clinical benefits while in the CLC included maintenance of a good appetite, 15-lb weight gain and preserved performance status (ECOG [Eastern Cooperative Group]-1), which allowed him to actively participate in multiple social and recreational activities while in the CLC. From early conversations, this patient was clear that he wanted treatment as long as his life could be prolonged with good quality of life. Having evidence of the benefit of treatment, at least initially, increased the patient’s confidence in treatment. There were a few conversations when the challenges of treatment mounted (eg, pain, needs for abstinence from cocaine prior to admission for chemotherapy, frequent doctor appointments), and the patient would remind himself of these data to recommit himself to treatment. The opportunity to admit him to the inpatient VA facility, including bed availability for 3 days during his treatment once he left the CLC was important. This plan to admit the patient following a negative urine toxicology test for cocaine was made collaboratively with the veteran and the oncology and palliative care teams. The plan allowed the patient to achieve his treatment goals while maintaining his safety and reducing theoretical cardiac toxicities with his cancer treatment.

Finally, the availability of a multidisciplinary team approach including palliative care, oncology, psychology, addiction medicine and addiction psychiatry, was critical for addressing the veteran’s malignant pain. Palliative care worked in close collaboration with the ORC to prescribe and renew pain medications. ORC offered ongoing consultation on pain management in the context of OUD. As the veteran’s cancer progressed and functional decline prohibited his daily attendance at the community methadone clinic, palliative care and ORC met with the methadone clinic to arrange a less frequent methadone pickup schedule (the patient previously needed daily pickup). Non-VA settings may not have access to these resources to safely treat the biopsychosocial issues that arise in complex cases.

Substance Use and Cancer Treatments

This case raises several critical questions for oncologic care. Cocaine and fluorouracil are both associated with cardiotoxicity, and many oncologists would not feel it is safe to administer a regimen containing fluorouracil to a patient with active cocaine use. The National Comprehensive Cancer Network (NCCN) panel recommends FOLFIRINOX as a preferred category 1 recommendation for first-line treatment of patients with advanced pancreas cancer with good performance status.¹⁰ This recommendation is based on the PRODIGE trial, which has shown improved overall survival (OS): 11.1 vs 6.8 months for patients who received single-agent gemcitabine.¹¹ If patients are not candidates for FOLFIRINOX and have good performance status, the NCCN recommends gemcitabine plus albumin-bound paclitaxel with category 1 level of evidence based on the IMPACT trial, which showed improvement in OS (8.7 vs 6.6 months compared with single-agent gemcitabine).¹²

Some oncologists may have additional concerns administering fluorouracil treatment alternatives (such as gemcitabine and albumin-bound paclitaxel) to individuals with active SUD because of concerns about altered mental status impacting the ability to report important adverse effects. In the absence of sufficient data, HCPs must determine whether they feel it is safe to administer these agents in individuals with active cocaine use. However, denying these patients the possible benefits of standard-of-care life-prolonging therapies without established data raises concerns regarding the ethics of such practices. There is concern that the stigma surrounding cocaine use might contribute to withholding treatment, while treatment is continued for individuals taking prescribed stimulant medications that also have cardiotoxicity risks. VA health care facilities are uniquely situated to use all available resources to address these issues using interprofessional patient-centered care and determine the most optimal treatment based on a risk/benefit discussion between the patient and the HCP.

SUD Screening

This case begs the question of whether oncologists are adequately screening for a range of SUDs, and when they encounter an issue, how they are addressing it. Many oncologists do not receive adequate training on assessment of current or recent substance use. There are health care and systems-level practices that may increase patient safety for individuals with ongoing substance use who are undergoing cancer treatment. Training on obtaining appropriate substance use histories, motivational interviewing to resolve ambivalence about substance use in the direction of change, and shared decision making about treatment options could increase confidence in understanding and addressing substance use issues. It is also important to educate oncologists on how to address patients who return to or continued substance use during treatment. In this case the collaboration from palliative care, psychology, addiction medicine, and addiction psychiatry through the ORC was essential in assisting with ongoing assessment of substance use, guiding difficult conversations about the impact of substance use on the treatment plan, and identifying risk-mitigation strategies. Close collaboration and full utilization of all VA resources allowed this patient to receive first-line treatment for pancreatic cancer in order to reach his goal of prolonging his life while maintaining acceptable quality of life. Table 2 provides best practices for management of patients with comorbid SUD and cancer.

More research is needed into cancer treatment for patients with SUD, especially in the current era of cancer care using novel cancer treatments leading to significantly improved survival in many cancer types. Ideally, oncologists should be routinely or consistently screening patients for substance use, including alcohol. The patient should participate in this decision-making process after being educated about the risks and benefits. These patients can be followed using a multimodal approach to increase their rates of success and improve their quality of life. Although the literature is limited and no formal guidelines are available, VA oncologists are fortunate to have a range of resources available to them to navigate these difficult cases. Veterans have elevated rates of SUD, making this a critical issue to consider in the VA.¹³ It is the hope that this case can highlight how to take advantage of the many VA resources in order to ensure equitable cancer care for all veterans.

Conclusions

This case demonstrates that cancer-directed treatment is safe and feasible in a patient with advanced pancreatic cancer and coexisting active SUD by using a multidisciplinary approach. The multidisciplinary team included palliative care, oncology, psychology, addiction medicine, and addiction psychiatry. Critical steps for a successful outcome include gathering history about SUD; motivational interviewing to resolve ambivalence about treatment for SUD; shared decision making about cancer treatment; and risk-reduction strategies in pain and SUD management.

Treatment advancements in many cancer types have led to significantly longer survival, and it is critical to develop safe protocols to treat patients with active SUD so they also can derive benefit from these very significant medical advancements.

Acknowledgments

Michal Rose, MD, Director of VACHS Cancer Center, and Chandrika Kumar, MD, Director of VACHS Community Living Center, for their collaboration in care for this veteran.

Substance use disorders (SUDs) are an important but understudied aspect of treating patients diagnosed with cancer. Substance use can affect cancer treatment outcomes, including morbidity and mortality.^1,2 Additionally, patients with cancer and SUD may have unique psychosocial needs that require close attention and management. There is a paucity of data regarding the best approach to treating such patients. For example, cocaine use may increase the cardiovascular and hematologic risk of some traditional chemotherapy agents.^3,4 Newer targeted agents and immunotherapies remain understudied with respect to SUD risk.

Although the US Department of Veterans Affairs (VA) has established helpful clinical practice guidelines for the treatment of SUD, there are no guidelines for treating patients with SUD and cancer.⁵ Clinicians have limited confidence in treatment approach, and treatment is inconsistent among oncologists nationwide even within the same practice. Furthermore, it can be challenging to safely prescribe opioids for cancer-related pain in individuals with SUD. There is a high risk of SUD and mental health disorders in veterans, making this population particularly vulnerable. We report a case of a male with metastatic pancreatic cancer, severe opioid use disorder (OUD) and moderate cocaine use disorder (CUD) who received pain management and cancer treatment under the direction of a multidisciplinary team approach.

Case Report

A 63-year-old male with a medical history of HIV treated with highly active antiretroviral therapy (HAART), compensated cirrhosis, severe OUD, moderate CUD, and sedative use disorder in sustained remission was admitted to the West Haven campus of the VA Connecticut Healthcare System (VACHS) with abdominal pain, weight loss and fatigue. He used heroin 1 month prior to his admission and reported regular cocaine and marijuana use (Table 1). He was diagnosed with HIV in 1989, and his medical history included herpes zoster and oral candidiasis but no other opportunistic infections. Several months prior to this admission, he had an undetectable viral load and CD4 count of 688.

At the time of this admission, the patient was adherent to methadone treatment. He reported increased abdominal pain. Computed tomography (CT) showed a 2.4-cm mass in the pancreatic uncinate process, multiple liver metastases, retroperitoneal lymphadenopathy, and small lung nodules. A CT-guided liver biopsy showed adenocarcinoma consistent with a primary cancer of the pancreas. Given the complexity of the case, a multidisciplinary team approach was used to treat his cancer and the sequelae safely, including the oncology team, community living center team, palliative care team, and interprofessional opioid reassessment clinic team (ORC).

Cancer Treatment

Chemotherapy with FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) was recommended. The first cycle of treatment originally was planned for the outpatient setting, and a peripherally inserted central catheter (PICC) line was placed. However, after a urine toxicology test was positive for cocaine, the PICC line was removed due to concern for possible use of PICC line for nonprescribed substance use. The patient expressed suicidal ideation at the time and was admitted for psychiatric consult and pain control. Cycle 1 FOLFIRINOX was started during this admission. A PICC line was again put in place and then removed before discharge. A celiac plexus block was performed several days after this admission for pain control.

Given concern about cocaine use increasing the risk of cardiac toxicity with FOLFIRINOX treatment, treating providers sconsulted with the community living center (CLC) about possible admission for future chemotherapy administration and pain management. The CLC at VACHS has 38 beds for rehabilitation, long-term care, and hospice with the mission to restore each veteran to his or her highest level of well-being. After discussion with this patient and CLC staff, he agreed to a CLC admission. The patient agreed to remain in the facility, wear a secure care device, and not leave without staff accompaniment. He was able to obtain a 2-hour pass to pay bills and rent. During the 2 months he was admitted to the CLC he would present to the VACHS Cancer Center for chemotherapy every 2 weeks. He completed 6 cycles of chemotherapy while admitted. During the admission, he was transferred to active medical service for 2 days for fever and malaise, and then returned to the CLC. The patient elected to leave the CLC after 2 months as the inability to see close friends was interfering with his quality of life.

Upon being discharged from the CLC, shared decision making took place with the patient to establish a new treatment plan. In collaboration with the patient, a plan was made to admit him every 2 weeks for continued chemotherapy. A PICC line was placed on each day of admission and removed prior to discharge. It was also agreed that treatment would be delayed if a urine drug test was positive for cocaine on the morning of admission. The patient was also seen by ORC every 2 weeks after being discharged from the CLC.

Imaging after cycle 6 showed decreased size of liver metastases, retroperitoneal lymph nodes, and pancreas mass. Cancer antigen 19-9 (CA19-9) tumor marker was reduced from 3513 U/mL pretreatment to 50 U/mL after cycle 7. Chemotherapy cycle 7 was delayed 6 days due to active cocaine and heroin use. A repeat urine was obtained several days later, which was negative for cocaine, and he was admitted for cycle 7 chemotherapy. Using this treatment approach of admissions for every cycle, the patient was able to receive 11 cycles of FOLFIRINOX with clinical benefit.

Palliative Care/Pain Management

Safely treating the patient’s malignant pain in the context of his OUD was critically important. In order to do this the palliative care team worked closely alongside ORC, is a multidisciplinary team consisting of health care providers (HCPs) from addiction psychiatry, internal medicine, health psychology and pharmacy who are consulted to evaluate veterans’ current opioid regimens and make recommendations to optimize both safety and efficacy. ORC followed this particular veteran as an outpatient and consulted on pain issues during his admission. They recommended the continuation of methadone at 120 mg daily and increased oral oxycodone to 30 mg every 6 hours, and then further increased to 45 mg every 6 hours. He continued to have increased pain despite higher doses of oxycodone, and pain medication was changed to oral hydromorphone 28 mg every 6 hours with the continuation of methadone. ORC and the palliative care team obtained consent from the veteran and a release of Information form signed by the patient to contact his community methadone clinic for further collaboration around pain management throughout the time caring for the veteran.

Even with improvement in disease based on imaging and tumor markers, opioid medications could not be decreased in this case. This is likely in part due to the multidimensional nature of pain. Careful assessment of the biologic, emotional, social, and spiritual contributors to pain is needed in the management of pain, especially at end of life.⁶ Nonpharmacologic pain management strategies used in this case included a transcutaneous electrical nerve stimulation unit, moist heat, celiac plexus block, and emotional support.

Psychosocial Issues/Substance Use

Psychosocial support for the patient was provided by the interdisciplinary palliative care team and the ORC team in both the inpatient and outpatient settings. Despite efforts from case management to get the veteran home services once discharged from the CLC, he declined repeatedly. Thus, the CLC social worker obtained a guardian alert for the veteran on discharge.

Close outpatient follow-up for medical and psychosocial support was very critical. When an outpatient, the veteran was scheduled for biweekly appointments with palliative care or ORC. When admitted to the hospital, the palliative care team medical director and psychologist conducted joint visits with him. Although he denied depressed mood and anxiety throughout his treatment, he often reflected on regrets that he had as he faced the end of his life. Specifically, he shared thoughts about being estranged from his surviving brother given his long struggle with substance use. Although he did not think a relationship was possible with his brother at the end of life, he still cared deeply for him and wanted to make him aware of his pancreatic cancer diagnosis. This was particularly important to him because their late brother had also died of pancreatic cancer. It was the patient’s wish at the end of his life to alert his surviving brother of his diagnosis so he and his children could get adequate screening throughout their lives. Although he had spoken of this desire often, it wasn’t until his disease progressed and he elected to transition to hospice that he felt ready to write the letter. The palliative care team assisted the veteran in writing and mailing a letter to his brother informing him of his diagnosis and transition to hospice as well as communicating that his brother and his family had been in his thoughts at the end of his life. The patient’s brother received this letter and with assistance from the CLC social worker made arrangements to visit the veteran at bedside at the inpatient CLC hospice unit the final days of his life.

Discussion

There are very little data on the safety of cancer-directed therapy in patients with active SUD. The limited studies that have been done showed conflicting results.

A retrospective study among women with co-occurring SUD and locally advanced cervical cancer who were undergoing primary radiation therapy found that SUD was not associated with a difference in toxicity or survival outcomes.⁷ However, other research suggests that SUD may be associated with an increase in all-cause mortality as well as other adverse outcomes for patients and health care systems (eg, emergency department visits, hospitalizations).⁸ A retrospective study of patients with a history of SUD and nonsmall cell lung cancer showed that these patients had higher rates of depression, less family support, increased rates of missed appointments, more emergency department visits and more hospitalizations.⁹ Patients with chronic myeloid leukemia or myelodysplastic syndromes who had long-term cocaine use had a 6-fold increased risk of death, which was not found in patients who had long-term alcohol or marijuana use.²

The limited data highlight the need for careful consideration of ways to mitigate potentially adverse outcomes in this population while still providing clinically indicated cancer treatment. Integrated VA health care systems provide unique resources that can maximize veteran safety during cancer treatment. Utilization of VA resources and close interdisciplinary collaboration across VA HCPs can help to ensure equitable access to state-of-the-art cancer therapies for veterans with comorbid SUD.

VA Services for Patients With Comorbidities

This case highlights several distinct aspects of VA health care that make it possible to safely treat individuals with complex comorbidities. One important aspect of this was collaboration with the CLC to admit the veteran for his initial treatment after a positive cocaine test. CLC admission was nonpunitive and allowed ongoing involvement in the VA community. This provided an essential, safe, and structured environment in which 6 cycles of chemotherapy could be delivered.

Although the patient left the CLC after 2 months due to floor restrictions negatively impacting his quality of life and ability to spend time with close friends, several important events occurred during this stay. First, the patient established close relationships with the CLC staff and the palliative care team; both groups followed him throughout his inpatient and outpatient care. These relationships proved essential throughout his care as they were the foundation of difficult conversations about substance use, treatment adherence, and eventually, transition to hospice.

In addition, the opportunity to administer 6 cycles of chemotherapy at the CLC was enough to lead to clinical benefit and radiographic response to treatment. Clinical benefits while in the CLC included maintenance of a good appetite, 15-lb weight gain and preserved performance status (ECOG [Eastern Cooperative Group]-1), which allowed him to actively participate in multiple social and recreational activities while in the CLC. From early conversations, this patient was clear that he wanted treatment as long as his life could be prolonged with good quality of life. Having evidence of the benefit of treatment, at least initially, increased the patient’s confidence in treatment. There were a few conversations when the challenges of treatment mounted (eg, pain, needs for abstinence from cocaine prior to admission for chemotherapy, frequent doctor appointments), and the patient would remind himself of these data to recommit himself to treatment. The opportunity to admit him to the inpatient VA facility, including bed availability for 3 days during his treatment once he left the CLC was important. This plan to admit the patient following a negative urine toxicology test for cocaine was made collaboratively with the veteran and the oncology and palliative care teams. The plan allowed the patient to achieve his treatment goals while maintaining his safety and reducing theoretical cardiac toxicities with his cancer treatment.

Finally, the availability of a multidisciplinary team approach including palliative care, oncology, psychology, addiction medicine and addiction psychiatry, was critical for addressing the veteran’s malignant pain. Palliative care worked in close collaboration with the ORC to prescribe and renew pain medications. ORC offered ongoing consultation on pain management in the context of OUD. As the veteran’s cancer progressed and functional decline prohibited his daily attendance at the community methadone clinic, palliative care and ORC met with the methadone clinic to arrange a less frequent methadone pickup schedule (the patient previously needed daily pickup). Non-VA settings may not have access to these resources to safely treat the biopsychosocial issues that arise in complex cases.

Substance Use and Cancer Treatments

This case raises several critical questions for oncologic care. Cocaine and fluorouracil are both associated with cardiotoxicity, and many oncologists would not feel it is safe to administer a regimen containing fluorouracil to a patient with active cocaine use. The National Comprehensive Cancer Network (NCCN) panel recommends FOLFIRINOX as a preferred category 1 recommendation for first-line treatment of patients with advanced pancreas cancer with good performance status.¹⁰ This recommendation is based on the PRODIGE trial, which has shown improved overall survival (OS): 11.1 vs 6.8 months for patients who received single-agent gemcitabine.¹¹ If patients are not candidates for FOLFIRINOX and have good performance status, the NCCN recommends gemcitabine plus albumin-bound paclitaxel with category 1 level of evidence based on the IMPACT trial, which showed improvement in OS (8.7 vs 6.6 months compared with single-agent gemcitabine).¹²

Some oncologists may have additional concerns administering fluorouracil treatment alternatives (such as gemcitabine and albumin-bound paclitaxel) to individuals with active SUD because of concerns about altered mental status impacting the ability to report important adverse effects. In the absence of sufficient data, HCPs must determine whether they feel it is safe to administer these agents in individuals with active cocaine use. However, denying these patients the possible benefits of standard-of-care life-prolonging therapies without established data raises concerns regarding the ethics of such practices. There is concern that the stigma surrounding cocaine use might contribute to withholding treatment, while treatment is continued for individuals taking prescribed stimulant medications that also have cardiotoxicity risks. VA health care facilities are uniquely situated to use all available resources to address these issues using interprofessional patient-centered care and determine the most optimal treatment based on a risk/benefit discussion between the patient and the HCP.

SUD Screening

This case begs the question of whether oncologists are adequately screening for a range of SUDs, and when they encounter an issue, how they are addressing it. Many oncologists do not receive adequate training on assessment of current or recent substance use. There are health care and systems-level practices that may increase patient safety for individuals with ongoing substance use who are undergoing cancer treatment. Training on obtaining appropriate substance use histories, motivational interviewing to resolve ambivalence about substance use in the direction of change, and shared decision making about treatment options could increase confidence in understanding and addressing substance use issues. It is also important to educate oncologists on how to address patients who return to or continued substance use during treatment. In this case the collaboration from palliative care, psychology, addiction medicine, and addiction psychiatry through the ORC was essential in assisting with ongoing assessment of substance use, guiding difficult conversations about the impact of substance use on the treatment plan, and identifying risk-mitigation strategies. Close collaboration and full utilization of all VA resources allowed this patient to receive first-line treatment for pancreatic cancer in order to reach his goal of prolonging his life while maintaining acceptable quality of life. Table 2 provides best practices for management of patients with comorbid SUD and cancer.

More research is needed into cancer treatment for patients with SUD, especially in the current era of cancer care using novel cancer treatments leading to significantly improved survival in many cancer types. Ideally, oncologists should be routinely or consistently screening patients for substance use, including alcohol. The patient should participate in this decision-making process after being educated about the risks and benefits. These patients can be followed using a multimodal approach to increase their rates of success and improve their quality of life. Although the literature is limited and no formal guidelines are available, VA oncologists are fortunate to have a range of resources available to them to navigate these difficult cases. Veterans have elevated rates of SUD, making this a critical issue to consider in the VA.¹³ It is the hope that this case can highlight how to take advantage of the many VA resources in order to ensure equitable cancer care for all veterans.

Conclusions

This case demonstrates that cancer-directed treatment is safe and feasible in a patient with advanced pancreatic cancer and coexisting active SUD by using a multidisciplinary approach. The multidisciplinary team included palliative care, oncology, psychology, addiction medicine, and addiction psychiatry. Critical steps for a successful outcome include gathering history about SUD; motivational interviewing to resolve ambivalence about treatment for SUD; shared decision making about cancer treatment; and risk-reduction strategies in pain and SUD management.

Treatment advancements in many cancer types have led to significantly longer survival, and it is critical to develop safe protocols to treat patients with active SUD so they also can derive benefit from these very significant medical advancements.

Acknowledgments

Michal Rose, MD, Director of VACHS Cancer Center, and Chandrika Kumar, MD, Director of VACHS Community Living Center, for their collaboration in care for this veteran.

A 62-year-old male veteran with a history of pulmonary embolism (PE) and prostate cancer status after brachytherapy presented to the emergency department with new onset shortness of breath and left-sided chest pain after prolonged car travel. He underwent a chest computed tomography (CT) angiogram that showed no PE recurrence; however, the scan revealed an incidental transverse colon mass that appeared well circumscribed, homogeneous, and radiolucent with no enhancement, septations, or hypervascularity but no evidence of colonic distension or obstruction (Figure 1). 

• What is your diagnosis?
• How would you treat this patient?
   

   

The patient reported having chronic constipation and a dull, left-sided abdominal discomfort for the past year. He noted that his abdominal pain worsened after eating and mildly improved after taking castor oil. He had no surgical history and no family history of cancer. The patient reported no fever, fatigue, weight loss, chills, nausea, vomiting, diarrhea, hematochezia, dysuria, hematuria, or melena. Vital signs, physical examination, and initial routine laboratory work were all within appropriate ranges, and a fecal occult blood test was negative.

A colonoscopy was performed, revealing a near-obstructing submucosal mass in the transverse colon near the splenic flexure with a smooth surface and a positive Cushion (Pillow) sign (Figure 2). The patient underwent surgical exploration that resulted in finding a soft, 11-cm lesion arising from the mesenteric side of the transverse colon (Figure 3). Hematoxylin and eosin (H&E) stains were used on a sample from the mass (Figure 4).

The tumor was enucleated via a colotomy over the mass, and the colotomy repaired primarily. Gross examination revealed homogenous yellow fatty tissue, and the H&E stains showed mature, well-differentiated adipocytes with uniform nuclei surrounded by a fibrous capsule. Based on this pathologic examination, this patient was diagnosed with a lipoma of the transverse colon. The resected tissue showed negative margins, indicating full removal of the lipoma.

The patient stabilized well after surgery and remained under inpatient care for observation; due to lack of appetite following the surgery, the patient did not start eating solids again until 2 days after the lipoma removal. By postoperative day 4, the patient had return of bowel function and was tolerating a regular diet with no recurrence of his prandial pain, shortness of breath, or left-sided chest pain. While the precise cause of the patient’s initial presentation of shortness of breath and left-sided chest pain was not ascertained, it is likely that the lipoma, near completely obstructed his bowel, caused abdominal contents and distended intestines to push against his diaphragm, leading to pain and dyspnea. This was likely exacerbated by sensitization to these symptoms from his prior PE. He was discharged home on postoperative day 4 with outpatient follow-up with general surgery.

Discussion

Lipomas are common benign tumors arising from aberrantly multiplying adipocytes. Although lipomas are most commonly found subcutaneously, the lesions can occur anywhere along the gastrointestinal (GI) tract, most often in the colon.¹ The incidence rate of colon lipomas ranges from 0.2 to 4.4% among patients in their fifth to sixth decades of life, more commonly found in females.² These lesions are the most common submucosal mesenchymal lesions of the colon, with a predilection for the right ascending colon.¹ The etiology of colon lipomas is largely unknown; one known cause is trauma, thought to induce cytokine release or HMGA2-LPP fusion gene arrangements leading to adipocyte proliferation.³

Most colon lipomas are asymptomatic and discovered incidentally; symptoms typically arise when the lesions are > 2 cm in diameter and include abdominal pain, changes in bowel habits, rectal bleeding, and in extreme cases, obstruction and perforation.⁴ On CT imaging, colon lipomas will appear radiolucent, homogenous, and well circumscribed. The lesions usually do not warrant intervention unless they are symptomatic. If symptomatic, resection of the lesion is the first-line treatment and usually results in complete resolution of symptoms with no recurrence.²

While either a surgical or endoscopic approach may be used for resection, an increased risk of perforation of the colon with larger lipomas has been shown with endoscopic excision.⁵ With surgical resection, an open or minimally invasive approach may be offered, based on surgeon comfort with minimally invasive colon procedures. Minimally invasive colonic surgeries may be associated with a shorter length of stay, decreased postoperative pain, and faster return of bowel function. In this case, the surgeon chose an open approach due to the large size of the mass (11 cm) as well as location of the mass in the transverse colon, which made it easy to access directly through a small laparotomy incision made in the superior midline over the transverse colon.

When a colonic mesenchymal mass is seen on colonoscopy, it is important to consider other, nonbenign lesions that present this way. The most common malignant mesenchymal tumor of the GI tract is a gastrointestinal stromal tumor (GIST), a soft-tissue sarcoma that occurs predominantly in the stomach and small intestine.⁶ These tumors arise from the interstitial cells of Cajal (ICC) and are associated with mutations of KIT and PDGFR-α genes.⁷ The incidence in the United States is approximately 0.70 per 100,000 people per year, predominantly found in adults in their fifth or sixth decade of life.⁸ While this tumor typically occurs in the upper GI tract, very rarely, GISTs can be found in the colon.⁶ Common constitutional symptoms of colon GIST are similar to those of colon lipomas and include abdominal pain, changes in bowel habits, nausea, vomiting, and in some cases, weight loss.

CT imaging is often enough to differentiate a colon lipoma from a colon GIST. On CT, large GIST tumors tend to show irregular, lobulated margins, mucosal ulceration, central necrosis, cavitation, hemorrhage, and hypervascularity—vastly different from the CT findings of colon lipomas. If imaging is equivocal, an ultrasound-guided fine needle aspiration biopsy may be performed, differentiating GIST through the presence of ICC tumor cells as well as KIT and PDGFR-α proteins.

In our patient, colonoscopy showed a positive Cushion sign (tumor indented on depression with biopsy forceps), pathognomonic for a colon lipoma, and CT imaging showed a radiolucent, well-circumscribed lesion.⁹ This was more consistent with a colon lipoma than a GIST. Because the patient was symptomatic with a near obstructing lesion, the appropriate next step was removal of the lesion. Had this instead been a GIST tumor, a more extensive oncologic surgical resection would have been warranted, with adequate mesentery and lymph nodes collected.

This case is notable because colon lipomas exceeding 2 cm are rare and are usually an incidental finding on CT. However, larger lipomas can lead to symptoms, including obstruction if not removed in a timely manner.

A 62-year-old male veteran with a history of pulmonary embolism (PE) and prostate cancer status after brachytherapy presented to the emergency department with new onset shortness of breath and left-sided chest pain after prolonged car travel. He underwent a chest computed tomography (CT) angiogram that showed no PE recurrence; however, the scan revealed an incidental transverse colon mass that appeared well circumscribed, homogeneous, and radiolucent with no enhancement, septations, or hypervascularity but no evidence of colonic distension or obstruction (Figure 1). 

• What is your diagnosis?
• How would you treat this patient?
   

   

The patient reported having chronic constipation and a dull, left-sided abdominal discomfort for the past year. He noted that his abdominal pain worsened after eating and mildly improved after taking castor oil. He had no surgical history and no family history of cancer. The patient reported no fever, fatigue, weight loss, chills, nausea, vomiting, diarrhea, hematochezia, dysuria, hematuria, or melena. Vital signs, physical examination, and initial routine laboratory work were all within appropriate ranges, and a fecal occult blood test was negative.

A colonoscopy was performed, revealing a near-obstructing submucosal mass in the transverse colon near the splenic flexure with a smooth surface and a positive Cushion (Pillow) sign (Figure 2). The patient underwent surgical exploration that resulted in finding a soft, 11-cm lesion arising from the mesenteric side of the transverse colon (Figure 3). Hematoxylin and eosin (H&E) stains were used on a sample from the mass (Figure 4).

The tumor was enucleated via a colotomy over the mass, and the colotomy repaired primarily. Gross examination revealed homogenous yellow fatty tissue, and the H&E stains showed mature, well-differentiated adipocytes with uniform nuclei surrounded by a fibrous capsule. Based on this pathologic examination, this patient was diagnosed with a lipoma of the transverse colon. The resected tissue showed negative margins, indicating full removal of the lipoma.

The patient stabilized well after surgery and remained under inpatient care for observation; due to lack of appetite following the surgery, the patient did not start eating solids again until 2 days after the lipoma removal. By postoperative day 4, the patient had return of bowel function and was tolerating a regular diet with no recurrence of his prandial pain, shortness of breath, or left-sided chest pain. While the precise cause of the patient’s initial presentation of shortness of breath and left-sided chest pain was not ascertained, it is likely that the lipoma, near completely obstructed his bowel, caused abdominal contents and distended intestines to push against his diaphragm, leading to pain and dyspnea. This was likely exacerbated by sensitization to these symptoms from his prior PE. He was discharged home on postoperative day 4 with outpatient follow-up with general surgery.

Discussion

Lipomas are common benign tumors arising from aberrantly multiplying adipocytes. Although lipomas are most commonly found subcutaneously, the lesions can occur anywhere along the gastrointestinal (GI) tract, most often in the colon.¹ The incidence rate of colon lipomas ranges from 0.2 to 4.4% among patients in their fifth to sixth decades of life, more commonly found in females.² These lesions are the most common submucosal mesenchymal lesions of the colon, with a predilection for the right ascending colon.¹ The etiology of colon lipomas is largely unknown; one known cause is trauma, thought to induce cytokine release or HMGA2-LPP fusion gene arrangements leading to adipocyte proliferation.³

Most colon lipomas are asymptomatic and discovered incidentally; symptoms typically arise when the lesions are > 2 cm in diameter and include abdominal pain, changes in bowel habits, rectal bleeding, and in extreme cases, obstruction and perforation.⁴ On CT imaging, colon lipomas will appear radiolucent, homogenous, and well circumscribed. The lesions usually do not warrant intervention unless they are symptomatic. If symptomatic, resection of the lesion is the first-line treatment and usually results in complete resolution of symptoms with no recurrence.²

While either a surgical or endoscopic approach may be used for resection, an increased risk of perforation of the colon with larger lipomas has been shown with endoscopic excision.⁵ With surgical resection, an open or minimally invasive approach may be offered, based on surgeon comfort with minimally invasive colon procedures. Minimally invasive colonic surgeries may be associated with a shorter length of stay, decreased postoperative pain, and faster return of bowel function. In this case, the surgeon chose an open approach due to the large size of the mass (11 cm) as well as location of the mass in the transverse colon, which made it easy to access directly through a small laparotomy incision made in the superior midline over the transverse colon.

When a colonic mesenchymal mass is seen on colonoscopy, it is important to consider other, nonbenign lesions that present this way. The most common malignant mesenchymal tumor of the GI tract is a gastrointestinal stromal tumor (GIST), a soft-tissue sarcoma that occurs predominantly in the stomach and small intestine.⁶ These tumors arise from the interstitial cells of Cajal (ICC) and are associated with mutations of KIT and PDGFR-α genes.⁷ The incidence in the United States is approximately 0.70 per 100,000 people per year, predominantly found in adults in their fifth or sixth decade of life.⁸ While this tumor typically occurs in the upper GI tract, very rarely, GISTs can be found in the colon.⁶ Common constitutional symptoms of colon GIST are similar to those of colon lipomas and include abdominal pain, changes in bowel habits, nausea, vomiting, and in some cases, weight loss.

CT imaging is often enough to differentiate a colon lipoma from a colon GIST. On CT, large GIST tumors tend to show irregular, lobulated margins, mucosal ulceration, central necrosis, cavitation, hemorrhage, and hypervascularity—vastly different from the CT findings of colon lipomas. If imaging is equivocal, an ultrasound-guided fine needle aspiration biopsy may be performed, differentiating GIST through the presence of ICC tumor cells as well as KIT and PDGFR-α proteins.

In our patient, colonoscopy showed a positive Cushion sign (tumor indented on depression with biopsy forceps), pathognomonic for a colon lipoma, and CT imaging showed a radiolucent, well-circumscribed lesion.⁹ This was more consistent with a colon lipoma than a GIST. Because the patient was symptomatic with a near obstructing lesion, the appropriate next step was removal of the lesion. Had this instead been a GIST tumor, a more extensive oncologic surgical resection would have been warranted, with adequate mesentery and lymph nodes collected.

This case is notable because colon lipomas exceeding 2 cm are rare and are usually an incidental finding on CT. However, larger lipomas can lead to symptoms, including obstruction if not removed in a timely manner.

A 62-year-old male veteran with a history of pulmonary embolism (PE) and prostate cancer status after brachytherapy presented to the emergency department with new onset shortness of breath and left-sided chest pain after prolonged car travel. He underwent a chest computed tomography (CT) angiogram that showed no PE recurrence; however, the scan revealed an incidental transverse colon mass that appeared well circumscribed, homogeneous, and radiolucent with no enhancement, septations, or hypervascularity but no evidence of colonic distension or obstruction (Figure 1). 

• What is your diagnosis?
• How would you treat this patient?
   

   

The patient reported having chronic constipation and a dull, left-sided abdominal discomfort for the past year. He noted that his abdominal pain worsened after eating and mildly improved after taking castor oil. He had no surgical history and no family history of cancer. The patient reported no fever, fatigue, weight loss, chills, nausea, vomiting, diarrhea, hematochezia, dysuria, hematuria, or melena. Vital signs, physical examination, and initial routine laboratory work were all within appropriate ranges, and a fecal occult blood test was negative.

A colonoscopy was performed, revealing a near-obstructing submucosal mass in the transverse colon near the splenic flexure with a smooth surface and a positive Cushion (Pillow) sign (Figure 2). The patient underwent surgical exploration that resulted in finding a soft, 11-cm lesion arising from the mesenteric side of the transverse colon (Figure 3). Hematoxylin and eosin (H&E) stains were used on a sample from the mass (Figure 4).

The tumor was enucleated via a colotomy over the mass, and the colotomy repaired primarily. Gross examination revealed homogenous yellow fatty tissue, and the H&E stains showed mature, well-differentiated adipocytes with uniform nuclei surrounded by a fibrous capsule. Based on this pathologic examination, this patient was diagnosed with a lipoma of the transverse colon. The resected tissue showed negative margins, indicating full removal of the lipoma.

The patient stabilized well after surgery and remained under inpatient care for observation; due to lack of appetite following the surgery, the patient did not start eating solids again until 2 days after the lipoma removal. By postoperative day 4, the patient had return of bowel function and was tolerating a regular diet with no recurrence of his prandial pain, shortness of breath, or left-sided chest pain. While the precise cause of the patient’s initial presentation of shortness of breath and left-sided chest pain was not ascertained, it is likely that the lipoma, near completely obstructed his bowel, caused abdominal contents and distended intestines to push against his diaphragm, leading to pain and dyspnea. This was likely exacerbated by sensitization to these symptoms from his prior PE. He was discharged home on postoperative day 4 with outpatient follow-up with general surgery.

Discussion

Lipomas are common benign tumors arising from aberrantly multiplying adipocytes. Although lipomas are most commonly found subcutaneously, the lesions can occur anywhere along the gastrointestinal (GI) tract, most often in the colon.¹ The incidence rate of colon lipomas ranges from 0.2 to 4.4% among patients in their fifth to sixth decades of life, more commonly found in females.² These lesions are the most common submucosal mesenchymal lesions of the colon, with a predilection for the right ascending colon.¹ The etiology of colon lipomas is largely unknown; one known cause is trauma, thought to induce cytokine release or HMGA2-LPP fusion gene arrangements leading to adipocyte proliferation.³

Most colon lipomas are asymptomatic and discovered incidentally; symptoms typically arise when the lesions are > 2 cm in diameter and include abdominal pain, changes in bowel habits, rectal bleeding, and in extreme cases, obstruction and perforation.⁴ On CT imaging, colon lipomas will appear radiolucent, homogenous, and well circumscribed. The lesions usually do not warrant intervention unless they are symptomatic. If symptomatic, resection of the lesion is the first-line treatment and usually results in complete resolution of symptoms with no recurrence.²

While either a surgical or endoscopic approach may be used for resection, an increased risk of perforation of the colon with larger lipomas has been shown with endoscopic excision.⁵ With surgical resection, an open or minimally invasive approach may be offered, based on surgeon comfort with minimally invasive colon procedures. Minimally invasive colonic surgeries may be associated with a shorter length of stay, decreased postoperative pain, and faster return of bowel function. In this case, the surgeon chose an open approach due to the large size of the mass (11 cm) as well as location of the mass in the transverse colon, which made it easy to access directly through a small laparotomy incision made in the superior midline over the transverse colon.

When a colonic mesenchymal mass is seen on colonoscopy, it is important to consider other, nonbenign lesions that present this way. The most common malignant mesenchymal tumor of the GI tract is a gastrointestinal stromal tumor (GIST), a soft-tissue sarcoma that occurs predominantly in the stomach and small intestine.⁶ These tumors arise from the interstitial cells of Cajal (ICC) and are associated with mutations of KIT and PDGFR-α genes.⁷ The incidence in the United States is approximately 0.70 per 100,000 people per year, predominantly found in adults in their fifth or sixth decade of life.⁸ While this tumor typically occurs in the upper GI tract, very rarely, GISTs can be found in the colon.⁶ Common constitutional symptoms of colon GIST are similar to those of colon lipomas and include abdominal pain, changes in bowel habits, nausea, vomiting, and in some cases, weight loss.

CT imaging is often enough to differentiate a colon lipoma from a colon GIST. On CT, large GIST tumors tend to show irregular, lobulated margins, mucosal ulceration, central necrosis, cavitation, hemorrhage, and hypervascularity—vastly different from the CT findings of colon lipomas. If imaging is equivocal, an ultrasound-guided fine needle aspiration biopsy may be performed, differentiating GIST through the presence of ICC tumor cells as well as KIT and PDGFR-α proteins.

In our patient, colonoscopy showed a positive Cushion sign (tumor indented on depression with biopsy forceps), pathognomonic for a colon lipoma, and CT imaging showed a radiolucent, well-circumscribed lesion.⁹ This was more consistent with a colon lipoma than a GIST. Because the patient was symptomatic with a near obstructing lesion, the appropriate next step was removal of the lesion. Had this instead been a GIST tumor, a more extensive oncologic surgical resection would have been warranted, with adequate mesentery and lymph nodes collected.

This case is notable because colon lipomas exceeding 2 cm are rare and are usually an incidental finding on CT. However, larger lipomas can lead to symptoms, including obstruction if not removed in a timely manner.

Colorectal cancer is the second most common cause of death in the United States. ¹ A colonoscopy is the current gold standard for prevention and early detection of colorectal cancers. During a colonoscopy procedure, polyps and lesions are biopsied and removed. The most effective method of colon cleansing for the procedure is achieved by using one of several commercially available colon lavage preparations. Before the colonoscopy, patients are prescribed and instructed to take one of these bowel preparations.

Background

Adequate bowel preparation is defined as sufficient for identification of polyps > 5 mm.² The impact of inadequate bowel preparation extends beyond the need for additional or repeat procedure(s) and includes potentially missed polyps and cancers. Inferior bowel preparation quality is associated with a significant decrease in the detection of flat or sessile serrated polyps.³ Missed polyps increase the risk of interval colorectal cancers. A high-quality bowel preparation together with the individual skill and experience of the endoscopist are crucial for adequate polyp detection. In addition, other risks of inadequate bowel preparation and repeated colonoscopies reduce adenoma detection rates, undetected carcinomas, and increase the risk of complications, possibly resulting in lawsuits.³

A major difficulty facing the Veterans Health Administration (VHA) medical center gastroenterologists is what to do when a patient is not properly prepared after standard prescreening education and the bowel preparation regimen. Traditionally, the patient is given additional medication and asked to return the next day for a repeat colonoscopy. Alternatively, the patient is given a 2-day bowel preparation to be used prior to a new appointment.

The choice of bowel preparation has been standardized within the US Department of Veterans Affairs (VA) Connecticut Healthcare System in West Haven (VACHS); therefore, it is out of the scope of this article to discuss regimens that we do not use. However, several other bowel preparation regimens are available and effective when all the directions are properly followed. The VACHS follows a standard 1-day colonoscopy preparation that excludes solid foods the entire day before the colonoscopy and drinking a split-dosing of 1-gallon colon electrolyte lavage (ie, one-half gallon on both the evening before and the morning of colonoscopy). The endoscopists use the 10-point Boston Bowel Preparation Scale to maintain a standardized manner of rating the quality of the bowel cleanout. One of 10 registered nurses (RNs) provides a colonoscopy preparation education class with a standardized slideshow and matching 1-day preparation instruction.

Questionnaire

A gastroenterology (GI) advance practice registered nurse (APRN) developed a patient questionnaire after reviewing patient records from 2016 through 2018 and noting information gaps in patient re-education. The information was not clearly and completely documented relating to frequency of bowel movements, constipation, and daily hydration/fluid intake. Several questions were consistently asked of patients who had previously failed 2 bowel preparations to determine the issues preventing a successful bowel cleansing. Notes from the GI and nutrition clinics and the primary care provider (PCP) were reviewed for information on constipation, frequency and quality of bowel movements, average beverage consumption, and hydration status.

The GI APRN conducted the review and used notes from the past year as well as the notes for prior colon preparations documenting bowel preparations and their resulting quality. A review was conducted on each patient who failed the standard 2-day bowel preparation before the GI APRN bowel preparation education session. The review revealed that no single note provided all necessary information. All colonoscopy prescreening education notes contained information from the standard prescreening preparation education class presentation, and any individual patient issues related to preparation consumption. GI and PCP notes included constipation information; however, frequency of bowel movements was seldom mentioned; and no fluid consumption information was provided except for alcohol related to abuse/addiction issues. Of the patients that had been seen by the Nutrition Department staff, their notes included caloric intake, appropriate food/dietary choices, and soda consumption; alcohol use was documented but related only to caloric intake; again, no other fluid intake amounts were documented.

Design

The questionnaire consists of 5 closed-ended, patient-centered questions aimed at accomplishing patient education in a time-efficient manner. It also is a tool to achieve consistency among staff in determining barriers and issues, improve documentation, and then assist the patient in achieving a good-to-excellent quality bowel preparation. The questions elicit information that allow an RN or PCP determine the factors that contributed to bowel preparation failure and allow for a tailored patient-education session. With a clear picture of the patient’s issues and obstacles, the patient-centered prescreening preparation education could focus on solutions to specific barriers, increase patient comprehension and adherence to the instructions, and identify complicating behavioral factors of the prior bowel preparation. For example, question 1 was designed to discover whether the patient failed to consume the preparation and why, such as volume, timing, or taste; question 4 was designed to assist in figuring out whether constipation for any reason may be present, whether currently diagnosed or not; and question 5 determined the risk of dehydration with or without constipation as a key cleansing issue.

The answers to these few questions determined whether the inadequate bowel preparation quality was due to issues of poor understanding, poor following of the directions, or to other complicating factors.

The prescreening bowel preparation education classes are delivered in groups classes, telehealth group classes, and by phone.

Discussion

Following implementation of the questionnaire from 2018 to 2019, a clinical chart review was conducted in 2019 of the first 100 patients who failed the standardized 2-day preparation from 2018 to 2019. These patients were selected by the GI attending physicians based on their multiple prior research studies and the total number of veterans served within VACHS to reflect an adequate test of change. Twenty patients canceled their appointments or refused to obtain an additional colonoscopy. Of the remaining 80 patients, 68 (85%) improved on the bowel preparation screening to an adequate rating.

Within the VACHS, the result of inadequate colon preparation leads to either an aborted colonoscopy or a longer examination duration due to time spent washing the colon mucosa and then suctioning the liquified stool. Using newchoicehealth.com 2021 national data, the colonoscopy average price range was $1800 to $12,500; the national average amount paid is $2750.⁷ The average screening or diagnostic colonoscopy cost was $4469.⁸

Using the Colonoscopy Patient-Education Bowel Prep Questionnaire resulted in increased patient satisfaction, better use of current patient appointment slots, increased unique encounters, and direct and indirect fiscal savings. Patient satisfaction resulted from no additional repeat colonoscopies per patient’s statements. The other findings resulted from the reduction in repeat appointments: The appointment slots that would have been taken by repeat colonoscopies were available for new patients, resulting in an increase in unique encounters.

Fiscal savings resulted from avoiding the need for additional bowel preparations for those patients or using the GI staff time (nurses and clerks) to reschedule and educate patients. Prior to the use of the questionnaire, patients who failed preparations would be re-educated, given a new preparation prescription or mailed a new preparation, scheduled, and then mailed the appropriate paperwork, thus, increasing the workload for nurses and clerks.

Conclusions

Use of the questionnaire resulted in increased high-quality bowel preparation, an increase in the number of unique patients served, and improved efficiency. In addition, recovered appointment slots and modest reductions in additional purchases of preparation kits resulted in a potential cost savings for VACHS. Proper cleansing instructions as well as identifying and overcoming barriers to achieving adequate preparation for colonoscopy resulted in improved patient satisfaction, quality care, and cost savings.

Regardless of the type of colon preparation, addressing patient barriers to bowel preparation is translatable to other endoscopy facilities and practices that provide patient education within the VA.

Colorectal cancer is the second most common cause of death in the United States. ¹ A colonoscopy is the current gold standard for prevention and early detection of colorectal cancers. During a colonoscopy procedure, polyps and lesions are biopsied and removed. The most effective method of colon cleansing for the procedure is achieved by using one of several commercially available colon lavage preparations. Before the colonoscopy, patients are prescribed and instructed to take one of these bowel preparations.

Background

Adequate bowel preparation is defined as sufficient for identification of polyps > 5 mm.² The impact of inadequate bowel preparation extends beyond the need for additional or repeat procedure(s) and includes potentially missed polyps and cancers. Inferior bowel preparation quality is associated with a significant decrease in the detection of flat or sessile serrated polyps.³ Missed polyps increase the risk of interval colorectal cancers. A high-quality bowel preparation together with the individual skill and experience of the endoscopist are crucial for adequate polyp detection. In addition, other risks of inadequate bowel preparation and repeated colonoscopies reduce adenoma detection rates, undetected carcinomas, and increase the risk of complications, possibly resulting in lawsuits.³

A major difficulty facing the Veterans Health Administration (VHA) medical center gastroenterologists is what to do when a patient is not properly prepared after standard prescreening education and the bowel preparation regimen. Traditionally, the patient is given additional medication and asked to return the next day for a repeat colonoscopy. Alternatively, the patient is given a 2-day bowel preparation to be used prior to a new appointment.

The choice of bowel preparation has been standardized within the US Department of Veterans Affairs (VA) Connecticut Healthcare System in West Haven (VACHS); therefore, it is out of the scope of this article to discuss regimens that we do not use. However, several other bowel preparation regimens are available and effective when all the directions are properly followed. The VACHS follows a standard 1-day colonoscopy preparation that excludes solid foods the entire day before the colonoscopy and drinking a split-dosing of 1-gallon colon electrolyte lavage (ie, one-half gallon on both the evening before and the morning of colonoscopy). The endoscopists use the 10-point Boston Bowel Preparation Scale to maintain a standardized manner of rating the quality of the bowel cleanout. One of 10 registered nurses (RNs) provides a colonoscopy preparation education class with a standardized slideshow and matching 1-day preparation instruction.

Questionnaire

A gastroenterology (GI) advance practice registered nurse (APRN) developed a patient questionnaire after reviewing patient records from 2016 through 2018 and noting information gaps in patient re-education. The information was not clearly and completely documented relating to frequency of bowel movements, constipation, and daily hydration/fluid intake. Several questions were consistently asked of patients who had previously failed 2 bowel preparations to determine the issues preventing a successful bowel cleansing. Notes from the GI and nutrition clinics and the primary care provider (PCP) were reviewed for information on constipation, frequency and quality of bowel movements, average beverage consumption, and hydration status.

The GI APRN conducted the review and used notes from the past year as well as the notes for prior colon preparations documenting bowel preparations and their resulting quality. A review was conducted on each patient who failed the standard 2-day bowel preparation before the GI APRN bowel preparation education session. The review revealed that no single note provided all necessary information. All colonoscopy prescreening education notes contained information from the standard prescreening preparation education class presentation, and any individual patient issues related to preparation consumption. GI and PCP notes included constipation information; however, frequency of bowel movements was seldom mentioned; and no fluid consumption information was provided except for alcohol related to abuse/addiction issues. Of the patients that had been seen by the Nutrition Department staff, their notes included caloric intake, appropriate food/dietary choices, and soda consumption; alcohol use was documented but related only to caloric intake; again, no other fluid intake amounts were documented.

Design

The questionnaire consists of 5 closed-ended, patient-centered questions aimed at accomplishing patient education in a time-efficient manner. It also is a tool to achieve consistency among staff in determining barriers and issues, improve documentation, and then assist the patient in achieving a good-to-excellent quality bowel preparation. The questions elicit information that allow an RN or PCP determine the factors that contributed to bowel preparation failure and allow for a tailored patient-education session. With a clear picture of the patient’s issues and obstacles, the patient-centered prescreening preparation education could focus on solutions to specific barriers, increase patient comprehension and adherence to the instructions, and identify complicating behavioral factors of the prior bowel preparation. For example, question 1 was designed to discover whether the patient failed to consume the preparation and why, such as volume, timing, or taste; question 4 was designed to assist in figuring out whether constipation for any reason may be present, whether currently diagnosed or not; and question 5 determined the risk of dehydration with or without constipation as a key cleansing issue.

The answers to these few questions determined whether the inadequate bowel preparation quality was due to issues of poor understanding, poor following of the directions, or to other complicating factors.

The prescreening bowel preparation education classes are delivered in groups classes, telehealth group classes, and by phone.

Discussion

Following implementation of the questionnaire from 2018 to 2019, a clinical chart review was conducted in 2019 of the first 100 patients who failed the standardized 2-day preparation from 2018 to 2019. These patients were selected by the GI attending physicians based on their multiple prior research studies and the total number of veterans served within VACHS to reflect an adequate test of change. Twenty patients canceled their appointments or refused to obtain an additional colonoscopy. Of the remaining 80 patients, 68 (85%) improved on the bowel preparation screening to an adequate rating.

Within the VACHS, the result of inadequate colon preparation leads to either an aborted colonoscopy or a longer examination duration due to time spent washing the colon mucosa and then suctioning the liquified stool. Using newchoicehealth.com 2021 national data, the colonoscopy average price range was $1800 to $12,500; the national average amount paid is $2750.⁷ The average screening or diagnostic colonoscopy cost was $4469.⁸

Using the Colonoscopy Patient-Education Bowel Prep Questionnaire resulted in increased patient satisfaction, better use of current patient appointment slots, increased unique encounters, and direct and indirect fiscal savings. Patient satisfaction resulted from no additional repeat colonoscopies per patient’s statements. The other findings resulted from the reduction in repeat appointments: The appointment slots that would have been taken by repeat colonoscopies were available for new patients, resulting in an increase in unique encounters.

Fiscal savings resulted from avoiding the need for additional bowel preparations for those patients or using the GI staff time (nurses and clerks) to reschedule and educate patients. Prior to the use of the questionnaire, patients who failed preparations would be re-educated, given a new preparation prescription or mailed a new preparation, scheduled, and then mailed the appropriate paperwork, thus, increasing the workload for nurses and clerks.

Conclusions

Use of the questionnaire resulted in increased high-quality bowel preparation, an increase in the number of unique patients served, and improved efficiency. In addition, recovered appointment slots and modest reductions in additional purchases of preparation kits resulted in a potential cost savings for VACHS. Proper cleansing instructions as well as identifying and overcoming barriers to achieving adequate preparation for colonoscopy resulted in improved patient satisfaction, quality care, and cost savings.

Regardless of the type of colon preparation, addressing patient barriers to bowel preparation is translatable to other endoscopy facilities and practices that provide patient education within the VA.

Colorectal cancer is the second most common cause of death in the United States. ¹ A colonoscopy is the current gold standard for prevention and early detection of colorectal cancers. During a colonoscopy procedure, polyps and lesions are biopsied and removed. The most effective method of colon cleansing for the procedure is achieved by using one of several commercially available colon lavage preparations. Before the colonoscopy, patients are prescribed and instructed to take one of these bowel preparations.

Background

Adequate bowel preparation is defined as sufficient for identification of polyps > 5 mm.² The impact of inadequate bowel preparation extends beyond the need for additional or repeat procedure(s) and includes potentially missed polyps and cancers. Inferior bowel preparation quality is associated with a significant decrease in the detection of flat or sessile serrated polyps.³ Missed polyps increase the risk of interval colorectal cancers. A high-quality bowel preparation together with the individual skill and experience of the endoscopist are crucial for adequate polyp detection. In addition, other risks of inadequate bowel preparation and repeated colonoscopies reduce adenoma detection rates, undetected carcinomas, and increase the risk of complications, possibly resulting in lawsuits.³

A major difficulty facing the Veterans Health Administration (VHA) medical center gastroenterologists is what to do when a patient is not properly prepared after standard prescreening education and the bowel preparation regimen. Traditionally, the patient is given additional medication and asked to return the next day for a repeat colonoscopy. Alternatively, the patient is given a 2-day bowel preparation to be used prior to a new appointment.

The choice of bowel preparation has been standardized within the US Department of Veterans Affairs (VA) Connecticut Healthcare System in West Haven (VACHS); therefore, it is out of the scope of this article to discuss regimens that we do not use. However, several other bowel preparation regimens are available and effective when all the directions are properly followed. The VACHS follows a standard 1-day colonoscopy preparation that excludes solid foods the entire day before the colonoscopy and drinking a split-dosing of 1-gallon colon electrolyte lavage (ie, one-half gallon on both the evening before and the morning of colonoscopy). The endoscopists use the 10-point Boston Bowel Preparation Scale to maintain a standardized manner of rating the quality of the bowel cleanout. One of 10 registered nurses (RNs) provides a colonoscopy preparation education class with a standardized slideshow and matching 1-day preparation instruction.

Questionnaire

A gastroenterology (GI) advance practice registered nurse (APRN) developed a patient questionnaire after reviewing patient records from 2016 through 2018 and noting information gaps in patient re-education. The information was not clearly and completely documented relating to frequency of bowel movements, constipation, and daily hydration/fluid intake. Several questions were consistently asked of patients who had previously failed 2 bowel preparations to determine the issues preventing a successful bowel cleansing. Notes from the GI and nutrition clinics and the primary care provider (PCP) were reviewed for information on constipation, frequency and quality of bowel movements, average beverage consumption, and hydration status.

The GI APRN conducted the review and used notes from the past year as well as the notes for prior colon preparations documenting bowel preparations and their resulting quality. A review was conducted on each patient who failed the standard 2-day bowel preparation before the GI APRN bowel preparation education session. The review revealed that no single note provided all necessary information. All colonoscopy prescreening education notes contained information from the standard prescreening preparation education class presentation, and any individual patient issues related to preparation consumption. GI and PCP notes included constipation information; however, frequency of bowel movements was seldom mentioned; and no fluid consumption information was provided except for alcohol related to abuse/addiction issues. Of the patients that had been seen by the Nutrition Department staff, their notes included caloric intake, appropriate food/dietary choices, and soda consumption; alcohol use was documented but related only to caloric intake; again, no other fluid intake amounts were documented.

Design

The questionnaire consists of 5 closed-ended, patient-centered questions aimed at accomplishing patient education in a time-efficient manner. It also is a tool to achieve consistency among staff in determining barriers and issues, improve documentation, and then assist the patient in achieving a good-to-excellent quality bowel preparation. The questions elicit information that allow an RN or PCP determine the factors that contributed to bowel preparation failure and allow for a tailored patient-education session. With a clear picture of the patient’s issues and obstacles, the patient-centered prescreening preparation education could focus on solutions to specific barriers, increase patient comprehension and adherence to the instructions, and identify complicating behavioral factors of the prior bowel preparation. For example, question 1 was designed to discover whether the patient failed to consume the preparation and why, such as volume, timing, or taste; question 4 was designed to assist in figuring out whether constipation for any reason may be present, whether currently diagnosed or not; and question 5 determined the risk of dehydration with or without constipation as a key cleansing issue.

The answers to these few questions determined whether the inadequate bowel preparation quality was due to issues of poor understanding, poor following of the directions, or to other complicating factors.

The prescreening bowel preparation education classes are delivered in groups classes, telehealth group classes, and by phone.

Discussion

Following implementation of the questionnaire from 2018 to 2019, a clinical chart review was conducted in 2019 of the first 100 patients who failed the standardized 2-day preparation from 2018 to 2019. These patients were selected by the GI attending physicians based on their multiple prior research studies and the total number of veterans served within VACHS to reflect an adequate test of change. Twenty patients canceled their appointments or refused to obtain an additional colonoscopy. Of the remaining 80 patients, 68 (85%) improved on the bowel preparation screening to an adequate rating.

Within the VACHS, the result of inadequate colon preparation leads to either an aborted colonoscopy or a longer examination duration due to time spent washing the colon mucosa and then suctioning the liquified stool. Using newchoicehealth.com 2021 national data, the colonoscopy average price range was $1800 to $12,500; the national average amount paid is $2750.⁷ The average screening or diagnostic colonoscopy cost was $4469.⁸

Using the Colonoscopy Patient-Education Bowel Prep Questionnaire resulted in increased patient satisfaction, better use of current patient appointment slots, increased unique encounters, and direct and indirect fiscal savings. Patient satisfaction resulted from no additional repeat colonoscopies per patient’s statements. The other findings resulted from the reduction in repeat appointments: The appointment slots that would have been taken by repeat colonoscopies were available for new patients, resulting in an increase in unique encounters.

Fiscal savings resulted from avoiding the need for additional bowel preparations for those patients or using the GI staff time (nurses and clerks) to reschedule and educate patients. Prior to the use of the questionnaire, patients who failed preparations would be re-educated, given a new preparation prescription or mailed a new preparation, scheduled, and then mailed the appropriate paperwork, thus, increasing the workload for nurses and clerks.

Conclusions

Use of the questionnaire resulted in increased high-quality bowel preparation, an increase in the number of unique patients served, and improved efficiency. In addition, recovered appointment slots and modest reductions in additional purchases of preparation kits resulted in a potential cost savings for VACHS. Proper cleansing instructions as well as identifying and overcoming barriers to achieving adequate preparation for colonoscopy resulted in improved patient satisfaction, quality care, and cost savings.

Regardless of the type of colon preparation, addressing patient barriers to bowel preparation is translatable to other endoscopy facilities and practices that provide patient education within the VA.

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Upfront resection of an asymptomatic primary tumor does not improve survival over chemotherapy alone in stage IV colorectal cancer with unresectable synchronous metastases, according to a randomized trial in Japan with 165 patients.

Median overall survival was slightly more than 2 years with or without primary resection, plus upfront surgery delayed systemic treatment and had a 4% risk of fatal complications. The trial was terminated early because of futility.

“PTR [primary tumor resection] should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” said investigators led by Yukihide Kanemitsu, MD, a colorectal surgeon at National Cancer Center Hospital in Tokyo.

“This paper is important for establishing solid evidence-based decisions. Why perform an invasive procedure on a patient that introduces additional risks if it won’t change their disease course?” said colorectal surgeon Deborah Keller, MD, clinical assistant professor of surgery at the University of California at Davis Medical Center, when asked for comment.

She explained that, in general, when the primary tumor is not obstructing, the standard of care is upfront chemotherapy, as supported by National Comprehensive Cancer Network guidelines.

“However, there was a change in practice over the last few years” after several retrospective studies reported better overall survival with surgery before chemotherapy, but “the studies were not the highest quality of evidence,” she said.

To bring better data to bear, the Japanese team randomized 84 patients to chemotherapy alone and 81 to PTR followed by chemotherapy. Primary tumors were asymptomatic, and patients had no more than three unresectable metastases in the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy was either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab at investigator discretion.

The trial was halted at interim analysis in September 2019. With a median follow-up of 22 months, median overall survival – the primary endpoint – was 25.9 months in the surgery-first arm and 26.7 months in the chemotherapy-alone group (P = .69). Subgroup analysis found no populations that benefited from PTR. Median progression free survival was 10.4 months with PTR first and 12.1 months with chemotherapy alone (P = .48)

Twenty-seven patients in the PTR arm had grade 3 or worse surgery-related adverse events, including anastomotic leakage in 3 and increased aspartate aminotransferase in 13. Three patients (4%) died within 30 days of surgery. Chemotherapy-related grade 3 or worse adverse events were more frequent and severe in the PTR arm (48% PTR versus 34% chemotherapy alone).

“For those who had been performing resections, this could push the paradigm back to chemotherapy alone,” Dr. Keller said.

Eleven patients (13%) in the chemotherapy-alone arm required surgery for intestinal obstruction or other primary tumor symptoms that developed after randomization, which means that 87% avoided surgery entirely, the investigators noted.

In the PTR group, surgery was performed within 21 days of enrollment, and chemotherapy started a median of 34 days after PTR. Chemotherapy was started within 14 days of enrollment in the chemotherapy-alone arm.

The groups were well balanced, including colon and rectosigmoid tumor locations in 93% of both arms and liver metastases in 73% of both. A bit over half the subjects were men and the median age was 65 years.

The team noted that early termination meant that the planned sample size was not achieved, which in turn limited the statistical power of the conclusions. “It is hoped that the comprehensive results of [ongoing trials] will clearly demonstrate the role of PTR for these patients,” they said.

The study was conducted by the Japan Clinical Oncology Group at 38 cancer centers in Japan. The work was funded by the Ministry of Health of Japan. The investigators had numerous industry ties, including Dr. Kanemitsu, who reported honoraria from Chugai Pharma, Ethicon, Covidien, and Intuitive Surgical, and being a Covidien adviser.

aotto@mdedge.com

Upfront resection of an asymptomatic primary tumor does not improve survival over chemotherapy alone in stage IV colorectal cancer with unresectable synchronous metastases, according to a randomized trial in Japan with 165 patients.

Median overall survival was slightly more than 2 years with or without primary resection, plus upfront surgery delayed systemic treatment and had a 4% risk of fatal complications. The trial was terminated early because of futility.

“PTR [primary tumor resection] should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” said investigators led by Yukihide Kanemitsu, MD, a colorectal surgeon at National Cancer Center Hospital in Tokyo.

“This paper is important for establishing solid evidence-based decisions. Why perform an invasive procedure on a patient that introduces additional risks if it won’t change their disease course?” said colorectal surgeon Deborah Keller, MD, clinical assistant professor of surgery at the University of California at Davis Medical Center, when asked for comment.

She explained that, in general, when the primary tumor is not obstructing, the standard of care is upfront chemotherapy, as supported by National Comprehensive Cancer Network guidelines.

“However, there was a change in practice over the last few years” after several retrospective studies reported better overall survival with surgery before chemotherapy, but “the studies were not the highest quality of evidence,” she said.

To bring better data to bear, the Japanese team randomized 84 patients to chemotherapy alone and 81 to PTR followed by chemotherapy. Primary tumors were asymptomatic, and patients had no more than three unresectable metastases in the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy was either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab at investigator discretion.

The trial was halted at interim analysis in September 2019. With a median follow-up of 22 months, median overall survival – the primary endpoint – was 25.9 months in the surgery-first arm and 26.7 months in the chemotherapy-alone group (P = .69). Subgroup analysis found no populations that benefited from PTR. Median progression free survival was 10.4 months with PTR first and 12.1 months with chemotherapy alone (P = .48)

Twenty-seven patients in the PTR arm had grade 3 or worse surgery-related adverse events, including anastomotic leakage in 3 and increased aspartate aminotransferase in 13. Three patients (4%) died within 30 days of surgery. Chemotherapy-related grade 3 or worse adverse events were more frequent and severe in the PTR arm (48% PTR versus 34% chemotherapy alone).

“For those who had been performing resections, this could push the paradigm back to chemotherapy alone,” Dr. Keller said.

Eleven patients (13%) in the chemotherapy-alone arm required surgery for intestinal obstruction or other primary tumor symptoms that developed after randomization, which means that 87% avoided surgery entirely, the investigators noted.

In the PTR group, surgery was performed within 21 days of enrollment, and chemotherapy started a median of 34 days after PTR. Chemotherapy was started within 14 days of enrollment in the chemotherapy-alone arm.

The groups were well balanced, including colon and rectosigmoid tumor locations in 93% of both arms and liver metastases in 73% of both. A bit over half the subjects were men and the median age was 65 years.

The team noted that early termination meant that the planned sample size was not achieved, which in turn limited the statistical power of the conclusions. “It is hoped that the comprehensive results of [ongoing trials] will clearly demonstrate the role of PTR for these patients,” they said.

The study was conducted by the Japan Clinical Oncology Group at 38 cancer centers in Japan. The work was funded by the Ministry of Health of Japan. The investigators had numerous industry ties, including Dr. Kanemitsu, who reported honoraria from Chugai Pharma, Ethicon, Covidien, and Intuitive Surgical, and being a Covidien adviser.

aotto@mdedge.com

Upfront resection of an asymptomatic primary tumor does not improve survival over chemotherapy alone in stage IV colorectal cancer with unresectable synchronous metastases, according to a randomized trial in Japan with 165 patients.

Median overall survival was slightly more than 2 years with or without primary resection, plus upfront surgery delayed systemic treatment and had a 4% risk of fatal complications. The trial was terminated early because of futility.

“PTR [primary tumor resection] should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” said investigators led by Yukihide Kanemitsu, MD, a colorectal surgeon at National Cancer Center Hospital in Tokyo.

“This paper is important for establishing solid evidence-based decisions. Why perform an invasive procedure on a patient that introduces additional risks if it won’t change their disease course?” said colorectal surgeon Deborah Keller, MD, clinical assistant professor of surgery at the University of California at Davis Medical Center, when asked for comment.

She explained that, in general, when the primary tumor is not obstructing, the standard of care is upfront chemotherapy, as supported by National Comprehensive Cancer Network guidelines.

“However, there was a change in practice over the last few years” after several retrospective studies reported better overall survival with surgery before chemotherapy, but “the studies were not the highest quality of evidence,” she said.

To bring better data to bear, the Japanese team randomized 84 patients to chemotherapy alone and 81 to PTR followed by chemotherapy. Primary tumors were asymptomatic, and patients had no more than three unresectable metastases in the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy was either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab at investigator discretion.

The trial was halted at interim analysis in September 2019. With a median follow-up of 22 months, median overall survival – the primary endpoint – was 25.9 months in the surgery-first arm and 26.7 months in the chemotherapy-alone group (P = .69). Subgroup analysis found no populations that benefited from PTR. Median progression free survival was 10.4 months with PTR first and 12.1 months with chemotherapy alone (P = .48)

Twenty-seven patients in the PTR arm had grade 3 or worse surgery-related adverse events, including anastomotic leakage in 3 and increased aspartate aminotransferase in 13. Three patients (4%) died within 30 days of surgery. Chemotherapy-related grade 3 or worse adverse events were more frequent and severe in the PTR arm (48% PTR versus 34% chemotherapy alone).

“For those who had been performing resections, this could push the paradigm back to chemotherapy alone,” Dr. Keller said.

Eleven patients (13%) in the chemotherapy-alone arm required surgery for intestinal obstruction or other primary tumor symptoms that developed after randomization, which means that 87% avoided surgery entirely, the investigators noted.

In the PTR group, surgery was performed within 21 days of enrollment, and chemotherapy started a median of 34 days after PTR. Chemotherapy was started within 14 days of enrollment in the chemotherapy-alone arm.

The groups were well balanced, including colon and rectosigmoid tumor locations in 93% of both arms and liver metastases in 73% of both. A bit over half the subjects were men and the median age was 65 years.

The team noted that early termination meant that the planned sample size was not achieved, which in turn limited the statistical power of the conclusions. “It is hoped that the comprehensive results of [ongoing trials] will clearly demonstrate the role of PTR for these patients,” they said.

The study was conducted by the Japan Clinical Oncology Group at 38 cancer centers in Japan. The work was funded by the Ministry of Health of Japan. The investigators had numerous industry ties, including Dr. Kanemitsu, who reported honoraria from Chugai Pharma, Ethicon, Covidien, and Intuitive Surgical, and being a Covidien adviser.

aotto@mdedge.com

The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online Dec. 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explained.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” wrote the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggested.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,”  Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard Medical School, Boston, wrote in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock ... directly translates to a higher risk of colorectal cancer,” they noted.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they pointed out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m² vs 28.29 kg/m²).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists wrote.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators said.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online Dec. 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explained.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” wrote the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggested.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,”  Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard Medical School, Boston, wrote in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock ... directly translates to a higher risk of colorectal cancer,” they noted.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they pointed out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m² vs 28.29 kg/m²).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists wrote.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators said.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online Dec. 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explained.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” wrote the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggested.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,”  Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard Medical School, Boston, wrote in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock ... directly translates to a higher risk of colorectal cancer,” they noted.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they pointed out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m² vs 28.29 kg/m²).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists wrote.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators said.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A cute colonic pseudo-obstruction, or Ogilvie syndrome, is dilatation of the colon without mechanical obstruction. It is often seen postoperatively after cesarean section , pelvic , spinal, or other orthopedic surgery, such as knee arthroplasty. ¹ One study demonstrated an incidence of acute colonic pseudo-obstruction of 1.3% following hip replacement surgery. ²

The most common symptoms are abdominal distension, pain, nausea, vomiting, constipation, or diarrhea. Bowel sounds are present in the majority of cases.³ It is important to recognize the varied presentations of ileus in the postoperative setting. The most serious complications of acute colonic pseudo-obstruction are colonic ischemia and bowel perforation.

Case Presentation

An 84-year-old man underwent a total left hip arthroplasty revision. The evening after his surgery, his blood pressure (BP) decreased from 93/54 to 71/47 mm Hg, and his heart rate was 73 beats per minute. He was awake, in no acute distress, but reported loose stools. Results of cardiac and pulmonary examinations were normal, showing a regular rate and rhythm with no murmurs and clear lungs. There was normal jugular venous pressure and chronic pitting edema of the lower extremities bilaterally.

An abdominal examination revealed positive bowel sounds, a large ventral hernia, which was easily reducible, and a distended abdomen. His BP remained unchanged after IV normal saline 4 L, and urine output was 200 cc over 4 hours, which the care team determined represented adequate resuscitation. An infection workup, including chest X-ray, urinalysis, and blood and urine cultures, was unrevealing. Hemoglobin was stable at 8.5 g/dL (normal range 14-18), and creatinine level 0.66 mg/dL (normal range 0.7-1.2) at baseline. A transthoracic echocardiogram showed impaired diastolic filling suggestive of extrinsic compression of the left ventricle by mediastinal contents (Figure 1). An abdominal X-ray revealed diffuse dilatation of large bowel loops up to 10 cm, causing elevation and rightward shift of the heart (Figure 2A). A computed tomography scan of the abdomen showed total colonic dilatation without obstruction (Figure 2B).

Discussion

We present an unusual case of left ventricular compression leading to hypotension due to acute colonic pseudo-obstruction. Our patient presented with the rare complication of hypotension due to cardiac compression, which we have not previously seen reported in the literature. Analogous instance of cardiac compression may arise from hiatal hernias and diaphragmatic paralysis. ^4-6

Management of acute colonic pseudo-obstruction is through nothing by mouth status and abdominal decompression. For more severe cases, neostigmine, colonoscopic decompression, and surgery can be considered.

This surgical complication was diagnosed by internal medicine hospitalist consultants on a surgical comanagement service. In the comanagement model, the surgical specialties of orthopedic surgery, neurosurgery, and podiatry at San Francisco Veterans Affairs Medical Center in California have hospitalists who work with the team as active consultants for the medical care of the patients. Hospitalists develop a unique skill set in which they can anticipate new diagnoses, prevent or identify early complications, and individualize a patient’s postoperative care.⁷ One study found that a surgical comanagement service was associated with a decrease in the number of patients with at least 1 surgical complication, decrease in length of stay and 30-day readmissions for a medical cause, decreased consultant use, and an average cost savings per patient of about $2,600 to $4,300.⁸

Conclusions

With the increasing prevalence of hospitalist comanagement services, it is important for surgeons and nonsurgeons alike to recognize acute colonic pseudo-obstruction as a possible surgical complication.

A cute colonic pseudo-obstruction, or Ogilvie syndrome, is dilatation of the colon without mechanical obstruction. It is often seen postoperatively after cesarean section , pelvic , spinal, or other orthopedic surgery, such as knee arthroplasty. ¹ One study demonstrated an incidence of acute colonic pseudo-obstruction of 1.3% following hip replacement surgery. ²

The most common symptoms are abdominal distension, pain, nausea, vomiting, constipation, or diarrhea. Bowel sounds are present in the majority of cases.³ It is important to recognize the varied presentations of ileus in the postoperative setting. The most serious complications of acute colonic pseudo-obstruction are colonic ischemia and bowel perforation.

Case Presentation

An 84-year-old man underwent a total left hip arthroplasty revision. The evening after his surgery, his blood pressure (BP) decreased from 93/54 to 71/47 mm Hg, and his heart rate was 73 beats per minute. He was awake, in no acute distress, but reported loose stools. Results of cardiac and pulmonary examinations were normal, showing a regular rate and rhythm with no murmurs and clear lungs. There was normal jugular venous pressure and chronic pitting edema of the lower extremities bilaterally.

An abdominal examination revealed positive bowel sounds, a large ventral hernia, which was easily reducible, and a distended abdomen. His BP remained unchanged after IV normal saline 4 L, and urine output was 200 cc over 4 hours, which the care team determined represented adequate resuscitation. An infection workup, including chest X-ray, urinalysis, and blood and urine cultures, was unrevealing. Hemoglobin was stable at 8.5 g/dL (normal range 14-18), and creatinine level 0.66 mg/dL (normal range 0.7-1.2) at baseline. A transthoracic echocardiogram showed impaired diastolic filling suggestive of extrinsic compression of the left ventricle by mediastinal contents (Figure 1). An abdominal X-ray revealed diffuse dilatation of large bowel loops up to 10 cm, causing elevation and rightward shift of the heart (Figure 2A). A computed tomography scan of the abdomen showed total colonic dilatation without obstruction (Figure 2B).

Discussion

We present an unusual case of left ventricular compression leading to hypotension due to acute colonic pseudo-obstruction. Our patient presented with the rare complication of hypotension due to cardiac compression, which we have not previously seen reported in the literature. Analogous instance of cardiac compression may arise from hiatal hernias and diaphragmatic paralysis. ^4-6

Management of acute colonic pseudo-obstruction is through nothing by mouth status and abdominal decompression. For more severe cases, neostigmine, colonoscopic decompression, and surgery can be considered.

This surgical complication was diagnosed by internal medicine hospitalist consultants on a surgical comanagement service. In the comanagement model, the surgical specialties of orthopedic surgery, neurosurgery, and podiatry at San Francisco Veterans Affairs Medical Center in California have hospitalists who work with the team as active consultants for the medical care of the patients. Hospitalists develop a unique skill set in which they can anticipate new diagnoses, prevent or identify early complications, and individualize a patient’s postoperative care.⁷ One study found that a surgical comanagement service was associated with a decrease in the number of patients with at least 1 surgical complication, decrease in length of stay and 30-day readmissions for a medical cause, decreased consultant use, and an average cost savings per patient of about $2,600 to $4,300.⁸

Conclusions

With the increasing prevalence of hospitalist comanagement services, it is important for surgeons and nonsurgeons alike to recognize acute colonic pseudo-obstruction as a possible surgical complication.

A cute colonic pseudo-obstruction, or Ogilvie syndrome, is dilatation of the colon without mechanical obstruction. It is often seen postoperatively after cesarean section , pelvic , spinal, or other orthopedic surgery, such as knee arthroplasty. ¹ One study demonstrated an incidence of acute colonic pseudo-obstruction of 1.3% following hip replacement surgery. ²

The most common symptoms are abdominal distension, pain, nausea, vomiting, constipation, or diarrhea. Bowel sounds are present in the majority of cases.³ It is important to recognize the varied presentations of ileus in the postoperative setting. The most serious complications of acute colonic pseudo-obstruction are colonic ischemia and bowel perforation.

Case Presentation

An 84-year-old man underwent a total left hip arthroplasty revision. The evening after his surgery, his blood pressure (BP) decreased from 93/54 to 71/47 mm Hg, and his heart rate was 73 beats per minute. He was awake, in no acute distress, but reported loose stools. Results of cardiac and pulmonary examinations were normal, showing a regular rate and rhythm with no murmurs and clear lungs. There was normal jugular venous pressure and chronic pitting edema of the lower extremities bilaterally.

An abdominal examination revealed positive bowel sounds, a large ventral hernia, which was easily reducible, and a distended abdomen. His BP remained unchanged after IV normal saline 4 L, and urine output was 200 cc over 4 hours, which the care team determined represented adequate resuscitation. An infection workup, including chest X-ray, urinalysis, and blood and urine cultures, was unrevealing. Hemoglobin was stable at 8.5 g/dL (normal range 14-18), and creatinine level 0.66 mg/dL (normal range 0.7-1.2) at baseline. A transthoracic echocardiogram showed impaired diastolic filling suggestive of extrinsic compression of the left ventricle by mediastinal contents (Figure 1). An abdominal X-ray revealed diffuse dilatation of large bowel loops up to 10 cm, causing elevation and rightward shift of the heart (Figure 2A). A computed tomography scan of the abdomen showed total colonic dilatation without obstruction (Figure 2B).

Discussion

We present an unusual case of left ventricular compression leading to hypotension due to acute colonic pseudo-obstruction. Our patient presented with the rare complication of hypotension due to cardiac compression, which we have not previously seen reported in the literature. Analogous instance of cardiac compression may arise from hiatal hernias and diaphragmatic paralysis. ^4-6

Management of acute colonic pseudo-obstruction is through nothing by mouth status and abdominal decompression. For more severe cases, neostigmine, colonoscopic decompression, and surgery can be considered.

This surgical complication was diagnosed by internal medicine hospitalist consultants on a surgical comanagement service. In the comanagement model, the surgical specialties of orthopedic surgery, neurosurgery, and podiatry at San Francisco Veterans Affairs Medical Center in California have hospitalists who work with the team as active consultants for the medical care of the patients. Hospitalists develop a unique skill set in which they can anticipate new diagnoses, prevent or identify early complications, and individualize a patient’s postoperative care.⁷ One study found that a surgical comanagement service was associated with a decrease in the number of patients with at least 1 surgical complication, decrease in length of stay and 30-day readmissions for a medical cause, decreased consultant use, and an average cost savings per patient of about $2,600 to $4,300.⁸

Conclusions

With the increasing prevalence of hospitalist comanagement services, it is important for surgeons and nonsurgeons alike to recognize acute colonic pseudo-obstruction as a possible surgical complication.

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR rate was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I Chin, MD, of Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly, longer follow-up will be needed in this study, but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that, despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long-course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long-course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”
 

Seven local failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short-course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease. Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months, while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX – consisting of leucovorin, fluorouracil (5-FU), and oxaliplatin – or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent on treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51%, and, for patients with locally advanced disease, the clinical CR rate was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 of the 5 achieved a pCR, and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm, and one patient had progressive disease. All underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy, and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas, for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities, and no grade 3 or 4 toxicities were observed. “Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function, so our goal is to treat patients without surgery and maintain good bowel function,” Chin noted.

“For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology,” she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.
 

This article first appeared on Medscape.com.

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR rate was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I Chin, MD, of Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly, longer follow-up will be needed in this study, but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that, despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long-course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long-course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”
 

Seven local failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short-course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease. Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months, while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX – consisting of leucovorin, fluorouracil (5-FU), and oxaliplatin – or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent on treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51%, and, for patients with locally advanced disease, the clinical CR rate was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 of the 5 achieved a pCR, and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm, and one patient had progressive disease. All underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy, and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas, for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities, and no grade 3 or 4 toxicities were observed. “Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function, so our goal is to treat patients without surgery and maintain good bowel function,” Chin noted.

“For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology,” she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.
 

This article first appeared on Medscape.com.

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR rate was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I Chin, MD, of Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly, longer follow-up will be needed in this study, but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that, despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long-course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long-course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”
 

Seven local failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short-course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease. Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months, while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX – consisting of leucovorin, fluorouracil (5-FU), and oxaliplatin – or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent on treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51%, and, for patients with locally advanced disease, the clinical CR rate was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 of the 5 achieved a pCR, and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm, and one patient had progressive disease. All underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy, and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas, for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities, and no grade 3 or 4 toxicities were observed. “Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function, so our goal is to treat patients without surgery and maintain good bowel function,” Chin noted.

“For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology,” she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.
 

This article first appeared on Medscape.com.

Screening for colorectal cancer (CRC) should begin at age 45 years instead of 50 years, as recommended in the current guideline, the US Preventive Services Task Force (USPSTF) said in a draft recommendation that is open for public comment.

“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.

The recommendation is that all adults aged 45-75 years be screened for CRC.

This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.

For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.

Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
 

Mounting pressure

The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.

Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).

The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.

“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”

Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.

The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.

The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.

“The right test is the one a patient will do,” Dr. Barry commented.

Defining populations

CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.

“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”

Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
 

Limit screening to those at higher risk

In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.

As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.

The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”

Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
 

A version of this article originally appeared on Medscape.com.

Screening for colorectal cancer (CRC) should begin at age 45 years instead of 50 years, as recommended in the current guideline, the US Preventive Services Task Force (USPSTF) said in a draft recommendation that is open for public comment.

“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.

The recommendation is that all adults aged 45-75 years be screened for CRC.

This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.

For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.

Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
 

Mounting pressure

The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.

Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).

The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.

“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”

Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.

The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.

The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.

“The right test is the one a patient will do,” Dr. Barry commented.

Defining populations

CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.

“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”

Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
 

Limit screening to those at higher risk

In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.

As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.

The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”

Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
 

A version of this article originally appeared on Medscape.com.

Screening for colorectal cancer (CRC) should begin at age 45 years instead of 50 years, as recommended in the current guideline, the US Preventive Services Task Force (USPSTF) said in a draft recommendation that is open for public comment.

“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.

The recommendation is that all adults aged 45-75 years be screened for CRC.

This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.

For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.

Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
 

Mounting pressure

The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.

Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).

The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.

“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”

Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.

The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.

The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.

“The right test is the one a patient will do,” Dr. Barry commented.

Defining populations

CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.

“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”

Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
 

Limit screening to those at higher risk

In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.

As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.

The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”

Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
 

A version of this article originally appeared on Medscape.com.