News

TOPLINE:

Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.

METHODOLOGY:

• This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
• The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
• More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
• The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.

TAKEAWAY:

• At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
• Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
• KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
• Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.

IN PRACTICE:

“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”

SOURCE:

Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.

DISCLOSURES:

This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.

METHODOLOGY:

• This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
• The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
• More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
• The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.

TAKEAWAY:

• At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
• Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
• KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
• Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.

IN PRACTICE:

“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”

SOURCE:

Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.

DISCLOSURES:

This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.

METHODOLOGY:

• This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
• The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
• More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
• The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.

TAKEAWAY:

• At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
• Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
• KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
• Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.

IN PRACTICE:

“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”

SOURCE:

Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.

DISCLOSURES:

This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.

For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.

Why have CAR T-cell therapies been less effective against solid tumors?

Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.

CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.

“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.

Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.

Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.

A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.

In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.

Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.

Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.

Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.

“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.

Several cell-based agents are in early trials to treat a range of solid tumors.

Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.

Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.

Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.

“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.

Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.

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

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.

For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.

Why have CAR T-cell therapies been less effective against solid tumors?

Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.

CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.

“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.

Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.

Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.

A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.

In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.

Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.

Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.

Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.

“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.

Several cell-based agents are in early trials to treat a range of solid tumors.

Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.

Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.

Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.

“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.

Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.

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

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.

For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.

Why have CAR T-cell therapies been less effective against solid tumors?

Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.

CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.

“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.

Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.

Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.

A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.

In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.

Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.

Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.

Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.

“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.

Several cell-based agents are in early trials to treat a range of solid tumors.

Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.

Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.

Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.

“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.

Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.

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

Only about 5% of hereditary prostate cancer (HPC) cases can be explained by known genetic variants, but a groundbreaking US Department of Veterans Affairs (VA) study could revolutionize the diagnosis, prevention, and treatment of HPC in a similar fashion that the discovery of the BRAC2 gene did in breast cancer.

The study, conducted at the VA Tennessee Valley Healthcare System in accordance with Vanderbilt University Medical Center and the VA Million Veteran Program (MVP), linked variants of the WNT9B gene with a greater risk of prostate cancer.

About 15,000 veterans are diagnosed with prostate cancer and treated at the VA annually, and > 200,000 veterans are prostate cancer survivors. According to Bruce Montgomery, MD, an oncologist with VA Puget Sound Health Care System, “Veterans are unique in that those men exposed to Agent Orange during the Vietnam War are at elevated risk for prostate cancer.” Montgomery added that germline pathogenic variants in genes such as BRCA2 and HOXB13 are other risk factors.

This genome-wide study searched for recurrently observed variants that carried the most risk. The study gathered data from a familial case-control population in the Nashville Familial Prostate Cancer Study (NFPCS) and International Consortium for Prostate Cancer Genetics (ICPCG). For evidence of replication, the study turned to 4 biobanks: the MVP, All of Us, the UK Biobank, and FinnGen.

The NFPCS is a case-control study based on family history. Patients included those undergoing treatment for prostate cancer and controls undergoing routine screening at Vanderbilt University Medical Center and the Nashville VA Medical Center between 2003 and 2009. Patients were included in the analysis if they had also had a first- or second-degree relative with prostate cancer. 

The ICPCG dataset encompasses unrelated HPC cases aggregated from 12 study sites across Finland, France, Germany, the UK, and the US. The MVP is the nation’s largest biorepository of veteran data and has one of the world’s most diverse cohorts of any genetic research program. More than 1 million veterans are enrolled, and 800-plus researchers are working on > 100 projects.

Pathogenic variants of only 2 genes met the replication requirement with genome-wide significance: HOXB13 and WNT9B. HOXB13 has been reported on in the literature, but this is the first study to investigate WNT9B.

Researchers identified 2 variants of the WNT9B gene: WNT9B E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing one-half million patients. The association of WNT9B E152K with prostate cancer was supported by the familial study populations and each biobank, with genome-wide significance. Variant WNT9B Q47R reached genome-wide significance in the Finnish study. The Q47R founder haplotype was also carried by familial prostate cancer cases in the US and UK.

Autosomal dominant WNT9B pathogenic variants are already known to cause embryonic developmental sequence defects, leading later to prostatic cysts, enlarged prostate, and seminal vesicle cysts. Seminal vesicle adenocarcinoma (or squamous cell carcinoma) and clear cell carcinoma of the prostate have also been reported. 

The study found that HOXB13 and WNT9B “share an unexpected commonality.” Both genes function in embryonic genitourinary development. WNT9B pathogenic variants cause the autosomal dominant Mayer-Rokitansky-Küster-Hauser syndrome, featuring genitourinary developmental defects. The study concluded: “Collectively, our observations implicate inherited variation in pathways guiding embryonic genitourinary development in the development of prostate cancer.”

“Significant investments” in VA-specific clinical trials recently have been pursued through a joint agreement between the VA and the Prostate Cancer Foundation, Montgomery said: “The Prostate Cancer Foundation is supporting tumor and germline sequencing of prostate cancer for veterans with advanced disease and providing resources to set up research infrastructure at 10 centers nationwide.” 

The VA has also published a prostate cancer clinical pathway and is in the process of creating a national prostate cancer registry. Such a database, as well as the MVP are both unique to the VA and key to research such as the Predicting Metastatic Progression of High Risk Localized Prostate Cancer study, which began in 2023. Five VA medical centers are collaborating on an artificial intelligence algorithm that will detect patterns indicative of aggressive prostate cancer. 

“A digital repository for data will allow for development, testing, and validation of prognostic classifiers that could positively impact clinical management of veterans with high-risk prostate cancer,” said Matthew Rettig, MD, chief of oncology and hematology at the Greater Los Angeles VA Medical Center who was coprincipal investigator for the study. “The infrastructure developed by this research will serve as a valuable hub for future discovery.”

About 12% of men with metastatic prostate cancer carry a pathogenic germline alteration that could warrant the use of PARP (poly [ADP-ribose] polymerase) inhibitors or platinum chemotherapy, neither of which is part of standard care. National Comprehensive Cancer Network guidelines recommend germline testing in men with metastatic prostate cancer. In addition, “the family members of veterans who carry these alterations could benefit from undergoing testing and taking advantage of potentially life-saving interventions and surveillance strategies if they are also carriers,” Montgomery wrote.

The VA is committed to improving access to germline testing for men with metastatic prostate cancer in several ways. Montgomery pointed to the system-wide VA genetic counseling and testing resource, the Genomic Medicine Service, and said somatic testing is available across the VA through the National Precision Oncology Program. Both programs can be extremely important to veterans because they provide access to precision oncology studies, along with off-label use of effective treatments. 

Precision oncology is the most rapidly moving area in prostate cancer, according to Montgomery. “In the VA, this has been embraced as a very specific need to find these therapeutic options for all veterans as quickly as possible. I am most excited by how the enthusiasm for these approaches is supported at all levels, both nationally and locally, because it makes implementing very significant changes to research and treatment possible.”

Only about 5% of hereditary prostate cancer (HPC) cases can be explained by known genetic variants, but a groundbreaking US Department of Veterans Affairs (VA) study could revolutionize the diagnosis, prevention, and treatment of HPC in a similar fashion that the discovery of the BRAC2 gene did in breast cancer.

The study, conducted at the VA Tennessee Valley Healthcare System in accordance with Vanderbilt University Medical Center and the VA Million Veteran Program (MVP), linked variants of the WNT9B gene with a greater risk of prostate cancer.

About 15,000 veterans are diagnosed with prostate cancer and treated at the VA annually, and > 200,000 veterans are prostate cancer survivors. According to Bruce Montgomery, MD, an oncologist with VA Puget Sound Health Care System, “Veterans are unique in that those men exposed to Agent Orange during the Vietnam War are at elevated risk for prostate cancer.” Montgomery added that germline pathogenic variants in genes such as BRCA2 and HOXB13 are other risk factors.

This genome-wide study searched for recurrently observed variants that carried the most risk. The study gathered data from a familial case-control population in the Nashville Familial Prostate Cancer Study (NFPCS) and International Consortium for Prostate Cancer Genetics (ICPCG). For evidence of replication, the study turned to 4 biobanks: the MVP, All of Us, the UK Biobank, and FinnGen.

The NFPCS is a case-control study based on family history. Patients included those undergoing treatment for prostate cancer and controls undergoing routine screening at Vanderbilt University Medical Center and the Nashville VA Medical Center between 2003 and 2009. Patients were included in the analysis if they had also had a first- or second-degree relative with prostate cancer. 

The ICPCG dataset encompasses unrelated HPC cases aggregated from 12 study sites across Finland, France, Germany, the UK, and the US. The MVP is the nation’s largest biorepository of veteran data and has one of the world’s most diverse cohorts of any genetic research program. More than 1 million veterans are enrolled, and 800-plus researchers are working on > 100 projects.

Pathogenic variants of only 2 genes met the replication requirement with genome-wide significance: HOXB13 and WNT9B. HOXB13 has been reported on in the literature, but this is the first study to investigate WNT9B.

Researchers identified 2 variants of the WNT9B gene: WNT9B E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing one-half million patients. The association of WNT9B E152K with prostate cancer was supported by the familial study populations and each biobank, with genome-wide significance. Variant WNT9B Q47R reached genome-wide significance in the Finnish study. The Q47R founder haplotype was also carried by familial prostate cancer cases in the US and UK.

Autosomal dominant WNT9B pathogenic variants are already known to cause embryonic developmental sequence defects, leading later to prostatic cysts, enlarged prostate, and seminal vesicle cysts. Seminal vesicle adenocarcinoma (or squamous cell carcinoma) and clear cell carcinoma of the prostate have also been reported. 

The study found that HOXB13 and WNT9B “share an unexpected commonality.” Both genes function in embryonic genitourinary development. WNT9B pathogenic variants cause the autosomal dominant Mayer-Rokitansky-Küster-Hauser syndrome, featuring genitourinary developmental defects. The study concluded: “Collectively, our observations implicate inherited variation in pathways guiding embryonic genitourinary development in the development of prostate cancer.”

“Significant investments” in VA-specific clinical trials recently have been pursued through a joint agreement between the VA and the Prostate Cancer Foundation, Montgomery said: “The Prostate Cancer Foundation is supporting tumor and germline sequencing of prostate cancer for veterans with advanced disease and providing resources to set up research infrastructure at 10 centers nationwide.” 

The VA has also published a prostate cancer clinical pathway and is in the process of creating a national prostate cancer registry. Such a database, as well as the MVP are both unique to the VA and key to research such as the Predicting Metastatic Progression of High Risk Localized Prostate Cancer study, which began in 2023. Five VA medical centers are collaborating on an artificial intelligence algorithm that will detect patterns indicative of aggressive prostate cancer. 

“A digital repository for data will allow for development, testing, and validation of prognostic classifiers that could positively impact clinical management of veterans with high-risk prostate cancer,” said Matthew Rettig, MD, chief of oncology and hematology at the Greater Los Angeles VA Medical Center who was coprincipal investigator for the study. “The infrastructure developed by this research will serve as a valuable hub for future discovery.”

About 12% of men with metastatic prostate cancer carry a pathogenic germline alteration that could warrant the use of PARP (poly [ADP-ribose] polymerase) inhibitors or platinum chemotherapy, neither of which is part of standard care. National Comprehensive Cancer Network guidelines recommend germline testing in men with metastatic prostate cancer. In addition, “the family members of veterans who carry these alterations could benefit from undergoing testing and taking advantage of potentially life-saving interventions and surveillance strategies if they are also carriers,” Montgomery wrote.

The VA is committed to improving access to germline testing for men with metastatic prostate cancer in several ways. Montgomery pointed to the system-wide VA genetic counseling and testing resource, the Genomic Medicine Service, and said somatic testing is available across the VA through the National Precision Oncology Program. Both programs can be extremely important to veterans because they provide access to precision oncology studies, along with off-label use of effective treatments. 

Precision oncology is the most rapidly moving area in prostate cancer, according to Montgomery. “In the VA, this has been embraced as a very specific need to find these therapeutic options for all veterans as quickly as possible. I am most excited by how the enthusiasm for these approaches is supported at all levels, both nationally and locally, because it makes implementing very significant changes to research and treatment possible.”

Only about 5% of hereditary prostate cancer (HPC) cases can be explained by known genetic variants, but a groundbreaking US Department of Veterans Affairs (VA) study could revolutionize the diagnosis, prevention, and treatment of HPC in a similar fashion that the discovery of the BRAC2 gene did in breast cancer.

The study, conducted at the VA Tennessee Valley Healthcare System in accordance with Vanderbilt University Medical Center and the VA Million Veteran Program (MVP), linked variants of the WNT9B gene with a greater risk of prostate cancer.

About 15,000 veterans are diagnosed with prostate cancer and treated at the VA annually, and > 200,000 veterans are prostate cancer survivors. According to Bruce Montgomery, MD, an oncologist with VA Puget Sound Health Care System, “Veterans are unique in that those men exposed to Agent Orange during the Vietnam War are at elevated risk for prostate cancer.” Montgomery added that germline pathogenic variants in genes such as BRCA2 and HOXB13 are other risk factors.

This genome-wide study searched for recurrently observed variants that carried the most risk. The study gathered data from a familial case-control population in the Nashville Familial Prostate Cancer Study (NFPCS) and International Consortium for Prostate Cancer Genetics (ICPCG). For evidence of replication, the study turned to 4 biobanks: the MVP, All of Us, the UK Biobank, and FinnGen.

The NFPCS is a case-control study based on family history. Patients included those undergoing treatment for prostate cancer and controls undergoing routine screening at Vanderbilt University Medical Center and the Nashville VA Medical Center between 2003 and 2009. Patients were included in the analysis if they had also had a first- or second-degree relative with prostate cancer. 

The ICPCG dataset encompasses unrelated HPC cases aggregated from 12 study sites across Finland, France, Germany, the UK, and the US. The MVP is the nation’s largest biorepository of veteran data and has one of the world’s most diverse cohorts of any genetic research program. More than 1 million veterans are enrolled, and 800-plus researchers are working on > 100 projects.

Pathogenic variants of only 2 genes met the replication requirement with genome-wide significance: HOXB13 and WNT9B. HOXB13 has been reported on in the literature, but this is the first study to investigate WNT9B.

Researchers identified 2 variants of the WNT9B gene: WNT9B E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing one-half million patients. The association of WNT9B E152K with prostate cancer was supported by the familial study populations and each biobank, with genome-wide significance. Variant WNT9B Q47R reached genome-wide significance in the Finnish study. The Q47R founder haplotype was also carried by familial prostate cancer cases in the US and UK.

Autosomal dominant WNT9B pathogenic variants are already known to cause embryonic developmental sequence defects, leading later to prostatic cysts, enlarged prostate, and seminal vesicle cysts. Seminal vesicle adenocarcinoma (or squamous cell carcinoma) and clear cell carcinoma of the prostate have also been reported. 

The study found that HOXB13 and WNT9B “share an unexpected commonality.” Both genes function in embryonic genitourinary development. WNT9B pathogenic variants cause the autosomal dominant Mayer-Rokitansky-Küster-Hauser syndrome, featuring genitourinary developmental defects. The study concluded: “Collectively, our observations implicate inherited variation in pathways guiding embryonic genitourinary development in the development of prostate cancer.”

“Significant investments” in VA-specific clinical trials recently have been pursued through a joint agreement between the VA and the Prostate Cancer Foundation, Montgomery said: “The Prostate Cancer Foundation is supporting tumor and germline sequencing of prostate cancer for veterans with advanced disease and providing resources to set up research infrastructure at 10 centers nationwide.” 

The VA has also published a prostate cancer clinical pathway and is in the process of creating a national prostate cancer registry. Such a database, as well as the MVP are both unique to the VA and key to research such as the Predicting Metastatic Progression of High Risk Localized Prostate Cancer study, which began in 2023. Five VA medical centers are collaborating on an artificial intelligence algorithm that will detect patterns indicative of aggressive prostate cancer. 

“A digital repository for data will allow for development, testing, and validation of prognostic classifiers that could positively impact clinical management of veterans with high-risk prostate cancer,” said Matthew Rettig, MD, chief of oncology and hematology at the Greater Los Angeles VA Medical Center who was coprincipal investigator for the study. “The infrastructure developed by this research will serve as a valuable hub for future discovery.”

About 12% of men with metastatic prostate cancer carry a pathogenic germline alteration that could warrant the use of PARP (poly [ADP-ribose] polymerase) inhibitors or platinum chemotherapy, neither of which is part of standard care. National Comprehensive Cancer Network guidelines recommend germline testing in men with metastatic prostate cancer. In addition, “the family members of veterans who carry these alterations could benefit from undergoing testing and taking advantage of potentially life-saving interventions and surveillance strategies if they are also carriers,” Montgomery wrote.

The VA is committed to improving access to germline testing for men with metastatic prostate cancer in several ways. Montgomery pointed to the system-wide VA genetic counseling and testing resource, the Genomic Medicine Service, and said somatic testing is available across the VA through the National Precision Oncology Program. Both programs can be extremely important to veterans because they provide access to precision oncology studies, along with off-label use of effective treatments. 

Precision oncology is the most rapidly moving area in prostate cancer, according to Montgomery. “In the VA, this has been embraced as a very specific need to find these therapeutic options for all veterans as quickly as possible. I am most excited by how the enthusiasm for these approaches is supported at all levels, both nationally and locally, because it makes implementing very significant changes to research and treatment possible.”

TOPLINE: Chronic obstructive pulmonary disease (COPD) guidelines are significantly underutilized in clinical practice, with studies attempting to improve implementation yielding inconsistent results. A team of US Department of Veterans Affairs (VA) researchers developed a pilot program and surveyed both patients and primary care practitioners (PCPs) to better understand the barriers to guideline-based COPD care primary care settings.

METHODOLOGY: 

•      Researchers conducted a pilot study using an implementation design at the Central Arkansas Veterans Healthcare System (CAVHS) to explore implementation gaps in a primary care setting
•      Analysis included semi-structured interviews with 17 respondents, comprising both patients and PCPs, to explore barriers and facilitators to 4 COPD clinical practice guidelines
•      The Consolidated Framework of Implementation Science was used to design interview guides focusing on inhaler education, spirometry, pulmonary rehabilitation, and COPD-specific patient education
•      Primary care teams followed a collaborative model including physicians, advanced practice nurses, nurses, social workers, pharmacists, and administrative staff working together with patients

TAKEAWAY:

•      A total of 17 respondents, including patients and PCPs participated in the study, with the patient sample reflecting the general COPD population at CAVHS
•      Both PCPs and patients consistently rated all assessed COPD clinical practice guidelines as highly important, despite significant practice gaps in implementation
•      PCPs reported very low rates of providing education on inhaler use, citing time constraints, lack of educational resources, and low familiarity as primary barriers
•      The main PCP-related barriers to pulmonary rehabilitation included limited knowledge about the program, unfamiliarity with CAVHS resources, and challenges with the referral process

IN PRACTICE: "Reasons behind this insufficient uptake of COPD guidelines include providers' low familiarity with guidelines, perception of minimal value of guidelines, and time constraints. Studies attempting to improve COPD-CPG uptake have shown mixed results and the best practice to bridge this implementation gap remains unknown," wrote the authors of the study.[Note To Staff: This quote was picked by Plume]

SOURCE: The study was led by Deepa Raghavan, Karen L Drummond, Sonya Sanders, and JoAnn Kirchner at Central Arkansas Veterans Healthcare System. It was published online in Chronic Respiratory Disease.

TOPLINE: Chronic obstructive pulmonary disease (COPD) guidelines are significantly underutilized in clinical practice, with studies attempting to improve implementation yielding inconsistent results. A team of US Department of Veterans Affairs (VA) researchers developed a pilot program and surveyed both patients and primary care practitioners (PCPs) to better understand the barriers to guideline-based COPD care primary care settings.

METHODOLOGY: 

•      Researchers conducted a pilot study using an implementation design at the Central Arkansas Veterans Healthcare System (CAVHS) to explore implementation gaps in a primary care setting
•      Analysis included semi-structured interviews with 17 respondents, comprising both patients and PCPs, to explore barriers and facilitators to 4 COPD clinical practice guidelines
•      The Consolidated Framework of Implementation Science was used to design interview guides focusing on inhaler education, spirometry, pulmonary rehabilitation, and COPD-specific patient education
•      Primary care teams followed a collaborative model including physicians, advanced practice nurses, nurses, social workers, pharmacists, and administrative staff working together with patients

TAKEAWAY:

•      A total of 17 respondents, including patients and PCPs participated in the study, with the patient sample reflecting the general COPD population at CAVHS
•      Both PCPs and patients consistently rated all assessed COPD clinical practice guidelines as highly important, despite significant practice gaps in implementation
•      PCPs reported very low rates of providing education on inhaler use, citing time constraints, lack of educational resources, and low familiarity as primary barriers
•      The main PCP-related barriers to pulmonary rehabilitation included limited knowledge about the program, unfamiliarity with CAVHS resources, and challenges with the referral process

IN PRACTICE: "Reasons behind this insufficient uptake of COPD guidelines include providers' low familiarity with guidelines, perception of minimal value of guidelines, and time constraints. Studies attempting to improve COPD-CPG uptake have shown mixed results and the best practice to bridge this implementation gap remains unknown," wrote the authors of the study.[Note To Staff: This quote was picked by Plume]

SOURCE: The study was led by Deepa Raghavan, Karen L Drummond, Sonya Sanders, and JoAnn Kirchner at Central Arkansas Veterans Healthcare System. It was published online in Chronic Respiratory Disease.

TOPLINE: Chronic obstructive pulmonary disease (COPD) guidelines are significantly underutilized in clinical practice, with studies attempting to improve implementation yielding inconsistent results. A team of US Department of Veterans Affairs (VA) researchers developed a pilot program and surveyed both patients and primary care practitioners (PCPs) to better understand the barriers to guideline-based COPD care primary care settings.

METHODOLOGY: 

•      Researchers conducted a pilot study using an implementation design at the Central Arkansas Veterans Healthcare System (CAVHS) to explore implementation gaps in a primary care setting
•      Analysis included semi-structured interviews with 17 respondents, comprising both patients and PCPs, to explore barriers and facilitators to 4 COPD clinical practice guidelines
•      The Consolidated Framework of Implementation Science was used to design interview guides focusing on inhaler education, spirometry, pulmonary rehabilitation, and COPD-specific patient education
•      Primary care teams followed a collaborative model including physicians, advanced practice nurses, nurses, social workers, pharmacists, and administrative staff working together with patients

TAKEAWAY:

•      A total of 17 respondents, including patients and PCPs participated in the study, with the patient sample reflecting the general COPD population at CAVHS
•      Both PCPs and patients consistently rated all assessed COPD clinical practice guidelines as highly important, despite significant practice gaps in implementation
•      PCPs reported very low rates of providing education on inhaler use, citing time constraints, lack of educational resources, and low familiarity as primary barriers
•      The main PCP-related barriers to pulmonary rehabilitation included limited knowledge about the program, unfamiliarity with CAVHS resources, and challenges with the referral process

IN PRACTICE: "Reasons behind this insufficient uptake of COPD guidelines include providers' low familiarity with guidelines, perception of minimal value of guidelines, and time constraints. Studies attempting to improve COPD-CPG uptake have shown mixed results and the best practice to bridge this implementation gap remains unknown," wrote the authors of the study.[Note To Staff: This quote was picked by Plume]

SOURCE: The study was led by Deepa Raghavan, Karen L Drummond, Sonya Sanders, and JoAnn Kirchner at Central Arkansas Veterans Healthcare System. It was published online in Chronic Respiratory Disease.

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Better lung function, expressed as higher forced vital capacity (FVC), is associated with a reduced risk for the onset of heart disease, diabetes, and stroke over a follow-up period of approximately 10 years, according to a cross-sectional analysis of a population-based study.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of a population-based study (the BOLD study) between 2003 and 2016 to investigate the association between lung function and the onset of cardiometabolic diseases by using data from participants across 15 countries.
• Overall, 5916 participants (mean age, 54 years; 55% women) were included, and the mean follow-up duration was 9.5 years.
• Lung function was evaluated as forced expiratory volume in 1 second (FEV1), FVC, and FEV1/FVC ratio, measured using spirometry at baseline, and postbronchodilator values of these measures were expressed as the percent of the predicted values at baseline.
• The onset of cardiometabolic diseases was identified through participant-reported doctor diagnoses of hypertension, heart disease, diabetes, and stroke at follow-up but not at baseline.

TAKEAWAY:

• Each 10% predicted FVC was associated with a 9% reduced risk for the onset of diabetes (adjusted odds ratio [aOR], 0.91; 95% CI, 0.84-0.99), a 14% reduced risk for the onset of heart disease (aOR, 0.86; 95% CI, 0.80-0.92), and a 19% reduced risk for the onset of stroke (aOR, 0.81; 95% CI, 0.73-0.89).
• Each 10% predicted FEV1 was associated with a reduced risk for the onset of heart disease (aOR, 0.88; 95% CI, 0.83-0.94) and stroke (aOR, 0.83; 95% CI, 0.76-0.90).
• A high FEV1/FVC ratio was associated with an increased risk for the onset of diabetes (aOR per 10%, 1.21; 95% CI, 1.08-1.35) but not associated with other cardiometabolic diseases.
• Moderate heterogeneity was observed across study sites regarding the association between high lung function and the risk for the onset of diabetes and stroke.

IN PRACTICE:

“FVC is not included in any risk score for predicting the risk of cardiometabolic events, although data also suggests that FVC predicted mortality more strongly than systolic blood pressure or BMI [body mass index]. Our results and several previous studies suggest that including FVC will improve the precision of risk scores used to predict the onset of diabetes and cardiovascular diseases,” the authors wrote.

SOURCE:

This study was led by Christer Janson, Department of Medical Sciences Respiratory Medicine, Uppsala Universitet, Uppsala, Sweden. It was published online on January 19, 2025, in BMJ Open Respiratory Research.

LIMITATIONS:

The primary limitation of this study was the reliance on the self-reported onset of cardiometabolic diseases, which is particularly challenging in low- and middle-income countries with underdeveloped healthcare systems. The observed outcomes could be the result of an undiagnosed condition. The data did not allow differentiation between various types of heart diseases or strokes.

DISCLOSURES:

The BOLD study received support through grants from the Wellcome Trust and Medical Research Council, and the follow-up study at some centers was supported by an unrestricted grant from AstraZeneca. Four authors reported receiving support from various sources related or unrelated to this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Better lung function, expressed as higher forced vital capacity (FVC), is associated with a reduced risk for the onset of heart disease, diabetes, and stroke over a follow-up period of approximately 10 years, according to a cross-sectional analysis of a population-based study.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of a population-based study (the BOLD study) between 2003 and 2016 to investigate the association between lung function and the onset of cardiometabolic diseases by using data from participants across 15 countries.
• Overall, 5916 participants (mean age, 54 years; 55% women) were included, and the mean follow-up duration was 9.5 years.
• Lung function was evaluated as forced expiratory volume in 1 second (FEV1), FVC, and FEV1/FVC ratio, measured using spirometry at baseline, and postbronchodilator values of these measures were expressed as the percent of the predicted values at baseline.
• The onset of cardiometabolic diseases was identified through participant-reported doctor diagnoses of hypertension, heart disease, diabetes, and stroke at follow-up but not at baseline.

TAKEAWAY:

• Each 10% predicted FVC was associated with a 9% reduced risk for the onset of diabetes (adjusted odds ratio [aOR], 0.91; 95% CI, 0.84-0.99), a 14% reduced risk for the onset of heart disease (aOR, 0.86; 95% CI, 0.80-0.92), and a 19% reduced risk for the onset of stroke (aOR, 0.81; 95% CI, 0.73-0.89).
• Each 10% predicted FEV1 was associated with a reduced risk for the onset of heart disease (aOR, 0.88; 95% CI, 0.83-0.94) and stroke (aOR, 0.83; 95% CI, 0.76-0.90).
• A high FEV1/FVC ratio was associated with an increased risk for the onset of diabetes (aOR per 10%, 1.21; 95% CI, 1.08-1.35) but not associated with other cardiometabolic diseases.
• Moderate heterogeneity was observed across study sites regarding the association between high lung function and the risk for the onset of diabetes and stroke.

IN PRACTICE:

“FVC is not included in any risk score for predicting the risk of cardiometabolic events, although data also suggests that FVC predicted mortality more strongly than systolic blood pressure or BMI [body mass index]. Our results and several previous studies suggest that including FVC will improve the precision of risk scores used to predict the onset of diabetes and cardiovascular diseases,” the authors wrote.

SOURCE:

This study was led by Christer Janson, Department of Medical Sciences Respiratory Medicine, Uppsala Universitet, Uppsala, Sweden. It was published online on January 19, 2025, in BMJ Open Respiratory Research.

LIMITATIONS:

The primary limitation of this study was the reliance on the self-reported onset of cardiometabolic diseases, which is particularly challenging in low- and middle-income countries with underdeveloped healthcare systems. The observed outcomes could be the result of an undiagnosed condition. The data did not allow differentiation between various types of heart diseases or strokes.

DISCLOSURES:

The BOLD study received support through grants from the Wellcome Trust and Medical Research Council, and the follow-up study at some centers was supported by an unrestricted grant from AstraZeneca. Four authors reported receiving support from various sources related or unrelated to this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Better lung function, expressed as higher forced vital capacity (FVC), is associated with a reduced risk for the onset of heart disease, diabetes, and stroke over a follow-up period of approximately 10 years, according to a cross-sectional analysis of a population-based study.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of a population-based study (the BOLD study) between 2003 and 2016 to investigate the association between lung function and the onset of cardiometabolic diseases by using data from participants across 15 countries.
• Overall, 5916 participants (mean age, 54 years; 55% women) were included, and the mean follow-up duration was 9.5 years.
• Lung function was evaluated as forced expiratory volume in 1 second (FEV1), FVC, and FEV1/FVC ratio, measured using spirometry at baseline, and postbronchodilator values of these measures were expressed as the percent of the predicted values at baseline.
• The onset of cardiometabolic diseases was identified through participant-reported doctor diagnoses of hypertension, heart disease, diabetes, and stroke at follow-up but not at baseline.

TAKEAWAY:

• Each 10% predicted FVC was associated with a 9% reduced risk for the onset of diabetes (adjusted odds ratio [aOR], 0.91; 95% CI, 0.84-0.99), a 14% reduced risk for the onset of heart disease (aOR, 0.86; 95% CI, 0.80-0.92), and a 19% reduced risk for the onset of stroke (aOR, 0.81; 95% CI, 0.73-0.89).
• Each 10% predicted FEV1 was associated with a reduced risk for the onset of heart disease (aOR, 0.88; 95% CI, 0.83-0.94) and stroke (aOR, 0.83; 95% CI, 0.76-0.90).
• A high FEV1/FVC ratio was associated with an increased risk for the onset of diabetes (aOR per 10%, 1.21; 95% CI, 1.08-1.35) but not associated with other cardiometabolic diseases.
• Moderate heterogeneity was observed across study sites regarding the association between high lung function and the risk for the onset of diabetes and stroke.

IN PRACTICE:

“FVC is not included in any risk score for predicting the risk of cardiometabolic events, although data also suggests that FVC predicted mortality more strongly than systolic blood pressure or BMI [body mass index]. Our results and several previous studies suggest that including FVC will improve the precision of risk scores used to predict the onset of diabetes and cardiovascular diseases,” the authors wrote.

SOURCE:

This study was led by Christer Janson, Department of Medical Sciences Respiratory Medicine, Uppsala Universitet, Uppsala, Sweden. It was published online on January 19, 2025, in BMJ Open Respiratory Research.

LIMITATIONS:

The primary limitation of this study was the reliance on the self-reported onset of cardiometabolic diseases, which is particularly challenging in low- and middle-income countries with underdeveloped healthcare systems. The observed outcomes could be the result of an undiagnosed condition. The data did not allow differentiation between various types of heart diseases or strokes.

DISCLOSURES:

The BOLD study received support through grants from the Wellcome Trust and Medical Research Council, and the follow-up study at some centers was supported by an unrestricted grant from AstraZeneca. Four authors reported receiving support from various sources related or unrelated to this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Dear colleagues,

 

We now have the ability to remove almost any large colon polyp endoscopically using a variety of techniques — from the widely used endoscopic mucosal resection to the increasingly prevalent endoscopic submucosal dissection. Yet, in this new era, are there specific polyps for which we should exercise caution and consult a surgeon first?

In this issue of Perspectives, Dr. Jeffrey Mosko and Dr. Moamen Gabr discuss the importance of careful polyp selection and argue that almost all polyps can be safely removed endoscopically, with low recurrence rates. In contrast, Dr. Ira Leeds from colorectal surgery offers a counterpoint, urging caution when managing polyps in the cecum and rectum while highlighting the role of minimally invasive surgical approaches. We hope these discussions provide valuable insights to support your approach to managing large colorectal polyps, especially in an era of increasing colon cancer screening. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Advantages of Endoscopic Resection for Large Colon Polyps

BY MOAMEN GABR, MD, MSC, AND JEFFREY D. MOSKO MD, MSC

General Advantages

Endoscopy has revolutionized the management of large colorectal polyps, offering a minimally invasive alternative to surgical resection. The dawn of endoscopic resection in the late 20th century, particularly the evolution of endoscopic mucosal resection (EMR) in Japan, marked a paradigm shift in the treatment of colonic lesions by enabling the removal of lesions that would otherwise necessitate surgery.

Endoscopic resection of colorectal polyps is generally performed in an outpatient setting, allowing patients to recover at home the same day. This not only minimizes disruption to daily life but also significantly enhances patient satisfaction.

Most procedures are performed under moderate or deep sedation eliminating the need for general anesthesia. This represents a critical benefit, particularly for older or medically frail patients who are at higher risk of anesthesia-related complications.

From an economic perspective, endoscopic resection reduces healthcare costs by eliminating prolonged hospital stays and complex perioperative care. Additionally, preserving the colon’s structure and function avoids long-term consequences such as altered bowel habits or ostomy dependence, common with surgical interventions.

The advantages of endoscopic intervention are clear: safety, cost-effectiveness, organ preservation, and convenience for patients.

 

Lesion Selection

The superiority of endoscopic resection relies on selecting lesions appropriately, specifically those with a low risk of lymph node metastases. This meticulous process should include assessing a lesion’s size, location, morphology, granularity, microvascular and surface pit pattern using a combination of high-definition white light endoscopy, virtual chromoendoscopy and image magnification (when available).

Gross morphologic assessment utilizes the Paris and LST classifications. Combining the Paris classification, lesion granularity and location is both straightforward and revealing. Ulcerated/excavated lesions (0-III) are concerning for deep invasion. Depressed (0-IIc) morphologies are strongly associated with T1 CRC. Nodular lesions (0-Is or IIa + Is) have a higher risk of T1 colorectal cancer (CRC), compared with flat lesions (0-IIa or 0-IIb). Non-granular lesions (0-Is and 0-IIa + Is) have a higher risk of covert cancer. Finally, the rectosigmoid location is associated with an increased risk of T1 CRC (vs. proximal locations).

Endoscopic surface pattern assessment increases one’s diagnostic accuracy. There are three primary endoscopic surface pattern classifications: NBI International Colorectal Endoscopic (NICE), Japanese NBI expert team (JNET), and Kudo pit pattern classifications. Colonic lesions that have a NICE Type 3, JNET 3, or Kudo type Vn pattern should be referred promptly for surgical resection. Lesions with a JNET 2B or Kudo type VI carry a higher risk of superficial T1 CRC but can still be removed endoscopically (see below) in expert centers. All other lesions should undergo endoscopic resection. 

 

Endoscopic Resection Techniques

Endoscopic resection of large colorectal polyps encompasses two primary techniques: EMR and endoscopic submucosal dissection (ESD), each tailored to specific lesion characteristics and operator expertise.

EMR, the technique of choice for the vast majority of lesions, relies on injecting a submucosal cushion to lift the lesion before excision. Recent advances, including enhanced snare designs and underwater EMR, have improved en-bloc resection rates, significantly reducing recurrence and enhancing the efficacy of this technique.

ESD offers unparalleled precision for en-bloc resection of complex lesions, particularly those with fibrosis or high-risk features. Cutting-edge innovations, such as traction devices, have streamlined the procedure, addressing the traditional challenges of ESD. Despite being more time intensive, ESD minimizes recurrence and provides complete histopathological evaluation, critical for the management of malignant or pre-malignant lesions.

For non-lifting polyps, newer techniques such as endoscopic full-thickness resection (eFTR), using tools like the Full-Thickness Resection Device (FTRD), enable resection of up to 2-3 cm of the colonic or rectal wall. This ensures complete removal of any lesion and its underlying tissue, effectively preventing recurrence.

These advancements demonstrate how endoscopy can tackle even the most challenging colorectal polyps, reinforcing its position as the preferred treatment modality.

 

Perceived Limitations 

With ongoing refinement over the last 2 decades, many of the perceived limitations (below) of endoscopic resection have now been overcome.

• Difficult locations/access: Historically lesions at the anorectal junction, ileocecal valve, appendiceal orifice and anastomoses were preferentially sent for surgery. In spite of unique technical challenges at each of these locations, there is now compelling data supporting EMR for these scenarios. We now also have techniques aimed at enabling the resection of lesions with poor access including patient repositioning, distal attachments, variable endoscope diameter/flexibility, traction and overtube devices.
• Recurrence: In the past, recurrence after endoscopic resection of lesions > 20 mm has been reported to be as high as 20%. With our current systematic approach to complete resection, meticulous examination of the post-resection defect for residual polyp tissue, adjunctive techniques to address submucosal fibrosis (hot avulsion, CAST, submucosal release) and thermal ablation to the resection margin (EMR-T), the risk of recurrence for piecemeal resections can be decreased to < 5%. In fact, some groups argue for the en-bloc resection of all large colorectal lesions based on the extremely low (< 1%) recurrence rates and potential for decreased follow-up.
• Post-resection bleeding: Post-resection bleeding is no longer a major limitation of any endoscopic approach because of the combination of improved intra-procedural hemostatic and resection techniques, optimized electrosurgical technology, and enhanced defect closure capabilities and devices (with prophylactic defect closure now supported by randomized control trial level data).
• Perforation: Deep mural injury, once an endoscopists’ worst fear during resection, is no longer a surgical emergency. It can now be predicted, identified (Sydney classification) and successfully managed. In spite of more widespread aggressive resection strategies, the risk of emergency surgery in patients undergoing EMR and even ESD (where the risk of DMI is significantly higher) is extremely low.

Endoscopic resection for large colorectal polyps is effective, available, minimally invasive and organ sparing making it the standard of care for the management of colonic polyps. With ongoing iteration in techniques, more invasive surgical approaches can be avoided in almost all patients with benign and low-risk T1 colorectal cancers.

Dr. Gabr is associate GI division director at the University of Cincinnati, Ohio. Dr. Mosko is based in the division of gastroenterology at St. Michael’s Hospital, Toronto, Ontario, Canada. The authors declare no conflicts of interest.

Blurred Lines: Polyp Needing Surgical versus Endoscopic Excision

BY IRA LEEDS, MD

I am grateful for the invitation to join in discussion with Dr. Gabr and Dr. Mosko on the ever-increasing role of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, as a surgeon, I do carry at least mild trepidation entering one of the literary “safe spaces” of my gastroenterology colleagues.

With the increasing evidentiary support of EMR approaches and the increasing experience of those performing ESD, these two techniques are quickly becoming the options of choice. As these practices become ubiquitous, it is important to recognize both their advantages and limitations, compared with available surgical options. The decision to proceed with EMR and ESD is essentially a turning point away from early surgical referral for a complex lesion. In this discussion, I intend to highlight when EMR and ESD have a clear advantage to early surgical referral, why I believe that early surgical referral is still superior to advanced endoscopic techniques in the rectum, and why the approach for right-sided lesions should hinge on careful shared decision-making. 

 

Endoscopic approaches nearly always beat surgical approaches when considering short-term risks. Even in the best surgical series, colorectal surgery typically leads to complications in 10%-15% of patients, 1%-5% being serious. Moreover, transabdominal surgical interventions (ie, colectomy) require considerable recovery involving at least a few days in the inpatient setting and over a month of activity restrictions. Finally, there is a minority of chronically unwell patients who cannot tolerate surgical intervention but may be fortunate enough to have a lesion that with enhanced attention can be endoscopically resectioned. While EMR and ESD also contribute a disproportionate burden of complications to endoscopy practice, overall complication rates are still favorable when compared with surgical resection.

Moreover, the most feared short-term complication of EMR and ESD, perforation, has the added benefit of a “controlled failure” to colectomy. Advanced endoscopic approaches already require a prepared colon, and patients are given strict return instructions. Hence, the yearly handful of postprocedural perforations that I get called upon to assist with typically tolerate a routine surgical exploration, repair or resection, and recover at rates equal to or better than elective colon resections. For these reasons, lesions that can be endoscopically removed within appropriate risk tolerances, can and should be considered for EMR or ESD at time of diagnosis.

There are two clinical scenarios where this consideration for up-front EMR or ESD requires further caution. First, any rectal lesion considered for advanced endoscopic techniques really needs to be done in multidisciplinary conference with a colorectal surgeon. In the modern era of colorectal surgery, surgeons now have numerous approaches to reach the rectum that bridge the gap between traditional endoscopy and transabdominal resection. For many rectal lesions, transanal laparoscopic and robotic approaches offer the opportunity for local excision. The most commonly practiced approach, transanal minimally invasive microsurgery (TAMIS), provides many of the benefits of endoscopy (eg, same-day discharge, no activity restrictions, limited periprocedural physiologic stress, low complication rates) while providing the surgical precision, repair strategies, and specimen orientation of conventional surgery. Anecdotally, the time it takes to do a high-quality TAMIS excision in the rectum can be substantially less than that required for a comparable ESD.

For rectal lesions in particular, specimen quality is paramount for oncologic prognosis. Regardless of any intrinsic favorable histopathology or deft hand of the endoscopist, a TAMIS approach will typically provide for a deeper partial thickness or even full thickness excision. More times each year than I would like, I find myself at a multidisciplinary tumor board discussing an endoscopically removed rectal lesion done in a piecemeal fashion or insufficient deep ESD where appropriate risk stratification is impossible and we end up offering patients a likely overly aggressive proctectomy or a potentially oncologically unsound re-excision. Consideration of EMR/ESD vs TAMIS up front would allow better sorting of which technique is most suited to which lesion and avoid these diagnostic dilemmas that only seem to be more common as EMR and ESD practices proliferate.

For a different set of reasons, an advanced cecal adenoma may also be more suited to upfront surgical considerations. Right colon lesions can be more challenging for surveillance for a host of reasons. Procedurally, right colon lesions are undeniably more difficult. The thin-walled cecum can be unforgiving for repeated polypectomies. Despite it being an uncomfortable subject for colonoscopists, the evidence suggests that getting to the cecum is not consistent or 100% expected. Finally, patients can be unwilling to undergo serial bowel preparation and endoscopic examination. In contrast, a laparoscopic right colectomy avoids these issues while also attributing little additional risk. Laparoscopic right-colon operations have overall complication rates of less than 10% and major complications of less than 1%. Hospital stays for laparoscopic right colectomy are typically 3 days or less. Finally, surgery reduces both the frequency of surveillance, and a shortened colon makes surveillance easier.

Advanced polypectomy techniques broaden our ability to address even difficult lesions under the ideally aligned degree of invasive procedure. However, like any procedure, these techniques have their own advantages and limitations. There will always be a minority of premalignant colon lesions that are best suited to surgery-first approaches to treatment. In my practice, maintaining open lines of communication and regular interaction with my endoscopy colleagues naturally leads to polyps being addressed in their most suitable fashion.

Dr. Leeds is assistant professor of surgery at the Yale School of Medicine and a staff surgeon at the VA Connecticut Healthcare System. He declares no conflicts of interest.

Dear colleagues,

 

We now have the ability to remove almost any large colon polyp endoscopically using a variety of techniques — from the widely used endoscopic mucosal resection to the increasingly prevalent endoscopic submucosal dissection. Yet, in this new era, are there specific polyps for which we should exercise caution and consult a surgeon first?

In this issue of Perspectives, Dr. Jeffrey Mosko and Dr. Moamen Gabr discuss the importance of careful polyp selection and argue that almost all polyps can be safely removed endoscopically, with low recurrence rates. In contrast, Dr. Ira Leeds from colorectal surgery offers a counterpoint, urging caution when managing polyps in the cecum and rectum while highlighting the role of minimally invasive surgical approaches. We hope these discussions provide valuable insights to support your approach to managing large colorectal polyps, especially in an era of increasing colon cancer screening. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Advantages of Endoscopic Resection for Large Colon Polyps

BY MOAMEN GABR, MD, MSC, AND JEFFREY D. MOSKO MD, MSC

General Advantages

Endoscopy has revolutionized the management of large colorectal polyps, offering a minimally invasive alternative to surgical resection. The dawn of endoscopic resection in the late 20th century, particularly the evolution of endoscopic mucosal resection (EMR) in Japan, marked a paradigm shift in the treatment of colonic lesions by enabling the removal of lesions that would otherwise necessitate surgery.

Endoscopic resection of colorectal polyps is generally performed in an outpatient setting, allowing patients to recover at home the same day. This not only minimizes disruption to daily life but also significantly enhances patient satisfaction.

Most procedures are performed under moderate or deep sedation eliminating the need for general anesthesia. This represents a critical benefit, particularly for older or medically frail patients who are at higher risk of anesthesia-related complications.

From an economic perspective, endoscopic resection reduces healthcare costs by eliminating prolonged hospital stays and complex perioperative care. Additionally, preserving the colon’s structure and function avoids long-term consequences such as altered bowel habits or ostomy dependence, common with surgical interventions.

The advantages of endoscopic intervention are clear: safety, cost-effectiveness, organ preservation, and convenience for patients.

 

Lesion Selection

The superiority of endoscopic resection relies on selecting lesions appropriately, specifically those with a low risk of lymph node metastases. This meticulous process should include assessing a lesion’s size, location, morphology, granularity, microvascular and surface pit pattern using a combination of high-definition white light endoscopy, virtual chromoendoscopy and image magnification (when available).

Gross morphologic assessment utilizes the Paris and LST classifications. Combining the Paris classification, lesion granularity and location is both straightforward and revealing. Ulcerated/excavated lesions (0-III) are concerning for deep invasion. Depressed (0-IIc) morphologies are strongly associated with T1 CRC. Nodular lesions (0-Is or IIa + Is) have a higher risk of T1 colorectal cancer (CRC), compared with flat lesions (0-IIa or 0-IIb). Non-granular lesions (0-Is and 0-IIa + Is) have a higher risk of covert cancer. Finally, the rectosigmoid location is associated with an increased risk of T1 CRC (vs. proximal locations).

Endoscopic surface pattern assessment increases one’s diagnostic accuracy. There are three primary endoscopic surface pattern classifications: NBI International Colorectal Endoscopic (NICE), Japanese NBI expert team (JNET), and Kudo pit pattern classifications. Colonic lesions that have a NICE Type 3, JNET 3, or Kudo type Vn pattern should be referred promptly for surgical resection. Lesions with a JNET 2B or Kudo type VI carry a higher risk of superficial T1 CRC but can still be removed endoscopically (see below) in expert centers. All other lesions should undergo endoscopic resection. 

 

Endoscopic Resection Techniques

Endoscopic resection of large colorectal polyps encompasses two primary techniques: EMR and endoscopic submucosal dissection (ESD), each tailored to specific lesion characteristics and operator expertise.

EMR, the technique of choice for the vast majority of lesions, relies on injecting a submucosal cushion to lift the lesion before excision. Recent advances, including enhanced snare designs and underwater EMR, have improved en-bloc resection rates, significantly reducing recurrence and enhancing the efficacy of this technique.

ESD offers unparalleled precision for en-bloc resection of complex lesions, particularly those with fibrosis or high-risk features. Cutting-edge innovations, such as traction devices, have streamlined the procedure, addressing the traditional challenges of ESD. Despite being more time intensive, ESD minimizes recurrence and provides complete histopathological evaluation, critical for the management of malignant or pre-malignant lesions.

For non-lifting polyps, newer techniques such as endoscopic full-thickness resection (eFTR), using tools like the Full-Thickness Resection Device (FTRD), enable resection of up to 2-3 cm of the colonic or rectal wall. This ensures complete removal of any lesion and its underlying tissue, effectively preventing recurrence.

These advancements demonstrate how endoscopy can tackle even the most challenging colorectal polyps, reinforcing its position as the preferred treatment modality.

 

Perceived Limitations 

With ongoing refinement over the last 2 decades, many of the perceived limitations (below) of endoscopic resection have now been overcome.

• Difficult locations/access: Historically lesions at the anorectal junction, ileocecal valve, appendiceal orifice and anastomoses were preferentially sent for surgery. In spite of unique technical challenges at each of these locations, there is now compelling data supporting EMR for these scenarios. We now also have techniques aimed at enabling the resection of lesions with poor access including patient repositioning, distal attachments, variable endoscope diameter/flexibility, traction and overtube devices.
• Recurrence: In the past, recurrence after endoscopic resection of lesions > 20 mm has been reported to be as high as 20%. With our current systematic approach to complete resection, meticulous examination of the post-resection defect for residual polyp tissue, adjunctive techniques to address submucosal fibrosis (hot avulsion, CAST, submucosal release) and thermal ablation to the resection margin (EMR-T), the risk of recurrence for piecemeal resections can be decreased to < 5%. In fact, some groups argue for the en-bloc resection of all large colorectal lesions based on the extremely low (< 1%) recurrence rates and potential for decreased follow-up.
• Post-resection bleeding: Post-resection bleeding is no longer a major limitation of any endoscopic approach because of the combination of improved intra-procedural hemostatic and resection techniques, optimized electrosurgical technology, and enhanced defect closure capabilities and devices (with prophylactic defect closure now supported by randomized control trial level data).
• Perforation: Deep mural injury, once an endoscopists’ worst fear during resection, is no longer a surgical emergency. It can now be predicted, identified (Sydney classification) and successfully managed. In spite of more widespread aggressive resection strategies, the risk of emergency surgery in patients undergoing EMR and even ESD (where the risk of DMI is significantly higher) is extremely low.

Endoscopic resection for large colorectal polyps is effective, available, minimally invasive and organ sparing making it the standard of care for the management of colonic polyps. With ongoing iteration in techniques, more invasive surgical approaches can be avoided in almost all patients with benign and low-risk T1 colorectal cancers.

Dr. Gabr is associate GI division director at the University of Cincinnati, Ohio. Dr. Mosko is based in the division of gastroenterology at St. Michael’s Hospital, Toronto, Ontario, Canada. The authors declare no conflicts of interest.

Blurred Lines: Polyp Needing Surgical versus Endoscopic Excision

BY IRA LEEDS, MD

I am grateful for the invitation to join in discussion with Dr. Gabr and Dr. Mosko on the ever-increasing role of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, as a surgeon, I do carry at least mild trepidation entering one of the literary “safe spaces” of my gastroenterology colleagues.

With the increasing evidentiary support of EMR approaches and the increasing experience of those performing ESD, these two techniques are quickly becoming the options of choice. As these practices become ubiquitous, it is important to recognize both their advantages and limitations, compared with available surgical options. The decision to proceed with EMR and ESD is essentially a turning point away from early surgical referral for a complex lesion. In this discussion, I intend to highlight when EMR and ESD have a clear advantage to early surgical referral, why I believe that early surgical referral is still superior to advanced endoscopic techniques in the rectum, and why the approach for right-sided lesions should hinge on careful shared decision-making. 

 

Endoscopic approaches nearly always beat surgical approaches when considering short-term risks. Even in the best surgical series, colorectal surgery typically leads to complications in 10%-15% of patients, 1%-5% being serious. Moreover, transabdominal surgical interventions (ie, colectomy) require considerable recovery involving at least a few days in the inpatient setting and over a month of activity restrictions. Finally, there is a minority of chronically unwell patients who cannot tolerate surgical intervention but may be fortunate enough to have a lesion that with enhanced attention can be endoscopically resectioned. While EMR and ESD also contribute a disproportionate burden of complications to endoscopy practice, overall complication rates are still favorable when compared with surgical resection.

Moreover, the most feared short-term complication of EMR and ESD, perforation, has the added benefit of a “controlled failure” to colectomy. Advanced endoscopic approaches already require a prepared colon, and patients are given strict return instructions. Hence, the yearly handful of postprocedural perforations that I get called upon to assist with typically tolerate a routine surgical exploration, repair or resection, and recover at rates equal to or better than elective colon resections. For these reasons, lesions that can be endoscopically removed within appropriate risk tolerances, can and should be considered for EMR or ESD at time of diagnosis.

There are two clinical scenarios where this consideration for up-front EMR or ESD requires further caution. First, any rectal lesion considered for advanced endoscopic techniques really needs to be done in multidisciplinary conference with a colorectal surgeon. In the modern era of colorectal surgery, surgeons now have numerous approaches to reach the rectum that bridge the gap between traditional endoscopy and transabdominal resection. For many rectal lesions, transanal laparoscopic and robotic approaches offer the opportunity for local excision. The most commonly practiced approach, transanal minimally invasive microsurgery (TAMIS), provides many of the benefits of endoscopy (eg, same-day discharge, no activity restrictions, limited periprocedural physiologic stress, low complication rates) while providing the surgical precision, repair strategies, and specimen orientation of conventional surgery. Anecdotally, the time it takes to do a high-quality TAMIS excision in the rectum can be substantially less than that required for a comparable ESD.

For rectal lesions in particular, specimen quality is paramount for oncologic prognosis. Regardless of any intrinsic favorable histopathology or deft hand of the endoscopist, a TAMIS approach will typically provide for a deeper partial thickness or even full thickness excision. More times each year than I would like, I find myself at a multidisciplinary tumor board discussing an endoscopically removed rectal lesion done in a piecemeal fashion or insufficient deep ESD where appropriate risk stratification is impossible and we end up offering patients a likely overly aggressive proctectomy or a potentially oncologically unsound re-excision. Consideration of EMR/ESD vs TAMIS up front would allow better sorting of which technique is most suited to which lesion and avoid these diagnostic dilemmas that only seem to be more common as EMR and ESD practices proliferate.

For a different set of reasons, an advanced cecal adenoma may also be more suited to upfront surgical considerations. Right colon lesions can be more challenging for surveillance for a host of reasons. Procedurally, right colon lesions are undeniably more difficult. The thin-walled cecum can be unforgiving for repeated polypectomies. Despite it being an uncomfortable subject for colonoscopists, the evidence suggests that getting to the cecum is not consistent or 100% expected. Finally, patients can be unwilling to undergo serial bowel preparation and endoscopic examination. In contrast, a laparoscopic right colectomy avoids these issues while also attributing little additional risk. Laparoscopic right-colon operations have overall complication rates of less than 10% and major complications of less than 1%. Hospital stays for laparoscopic right colectomy are typically 3 days or less. Finally, surgery reduces both the frequency of surveillance, and a shortened colon makes surveillance easier.

Advanced polypectomy techniques broaden our ability to address even difficult lesions under the ideally aligned degree of invasive procedure. However, like any procedure, these techniques have their own advantages and limitations. There will always be a minority of premalignant colon lesions that are best suited to surgery-first approaches to treatment. In my practice, maintaining open lines of communication and regular interaction with my endoscopy colleagues naturally leads to polyps being addressed in their most suitable fashion.

Dr. Leeds is assistant professor of surgery at the Yale School of Medicine and a staff surgeon at the VA Connecticut Healthcare System. He declares no conflicts of interest.

Dear colleagues,

 

We now have the ability to remove almost any large colon polyp endoscopically using a variety of techniques — from the widely used endoscopic mucosal resection to the increasingly prevalent endoscopic submucosal dissection. Yet, in this new era, are there specific polyps for which we should exercise caution and consult a surgeon first?

In this issue of Perspectives, Dr. Jeffrey Mosko and Dr. Moamen Gabr discuss the importance of careful polyp selection and argue that almost all polyps can be safely removed endoscopically, with low recurrence rates. In contrast, Dr. Ira Leeds from colorectal surgery offers a counterpoint, urging caution when managing polyps in the cecum and rectum while highlighting the role of minimally invasive surgical approaches. We hope these discussions provide valuable insights to support your approach to managing large colorectal polyps, especially in an era of increasing colon cancer screening. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Advantages of Endoscopic Resection for Large Colon Polyps

BY MOAMEN GABR, MD, MSC, AND JEFFREY D. MOSKO MD, MSC

General Advantages

Endoscopy has revolutionized the management of large colorectal polyps, offering a minimally invasive alternative to surgical resection. The dawn of endoscopic resection in the late 20th century, particularly the evolution of endoscopic mucosal resection (EMR) in Japan, marked a paradigm shift in the treatment of colonic lesions by enabling the removal of lesions that would otherwise necessitate surgery.

Endoscopic resection of colorectal polyps is generally performed in an outpatient setting, allowing patients to recover at home the same day. This not only minimizes disruption to daily life but also significantly enhances patient satisfaction.

Most procedures are performed under moderate or deep sedation eliminating the need for general anesthesia. This represents a critical benefit, particularly for older or medically frail patients who are at higher risk of anesthesia-related complications.

From an economic perspective, endoscopic resection reduces healthcare costs by eliminating prolonged hospital stays and complex perioperative care. Additionally, preserving the colon’s structure and function avoids long-term consequences such as altered bowel habits or ostomy dependence, common with surgical interventions.

The advantages of endoscopic intervention are clear: safety, cost-effectiveness, organ preservation, and convenience for patients.

 

Lesion Selection

The superiority of endoscopic resection relies on selecting lesions appropriately, specifically those with a low risk of lymph node metastases. This meticulous process should include assessing a lesion’s size, location, morphology, granularity, microvascular and surface pit pattern using a combination of high-definition white light endoscopy, virtual chromoendoscopy and image magnification (when available).

Gross morphologic assessment utilizes the Paris and LST classifications. Combining the Paris classification, lesion granularity and location is both straightforward and revealing. Ulcerated/excavated lesions (0-III) are concerning for deep invasion. Depressed (0-IIc) morphologies are strongly associated with T1 CRC. Nodular lesions (0-Is or IIa + Is) have a higher risk of T1 colorectal cancer (CRC), compared with flat lesions (0-IIa or 0-IIb). Non-granular lesions (0-Is and 0-IIa + Is) have a higher risk of covert cancer. Finally, the rectosigmoid location is associated with an increased risk of T1 CRC (vs. proximal locations).

Endoscopic surface pattern assessment increases one’s diagnostic accuracy. There are three primary endoscopic surface pattern classifications: NBI International Colorectal Endoscopic (NICE), Japanese NBI expert team (JNET), and Kudo pit pattern classifications. Colonic lesions that have a NICE Type 3, JNET 3, or Kudo type Vn pattern should be referred promptly for surgical resection. Lesions with a JNET 2B or Kudo type VI carry a higher risk of superficial T1 CRC but can still be removed endoscopically (see below) in expert centers. All other lesions should undergo endoscopic resection. 

 

Endoscopic Resection Techniques

Endoscopic resection of large colorectal polyps encompasses two primary techniques: EMR and endoscopic submucosal dissection (ESD), each tailored to specific lesion characteristics and operator expertise.

EMR, the technique of choice for the vast majority of lesions, relies on injecting a submucosal cushion to lift the lesion before excision. Recent advances, including enhanced snare designs and underwater EMR, have improved en-bloc resection rates, significantly reducing recurrence and enhancing the efficacy of this technique.

ESD offers unparalleled precision for en-bloc resection of complex lesions, particularly those with fibrosis or high-risk features. Cutting-edge innovations, such as traction devices, have streamlined the procedure, addressing the traditional challenges of ESD. Despite being more time intensive, ESD minimizes recurrence and provides complete histopathological evaluation, critical for the management of malignant or pre-malignant lesions.

For non-lifting polyps, newer techniques such as endoscopic full-thickness resection (eFTR), using tools like the Full-Thickness Resection Device (FTRD), enable resection of up to 2-3 cm of the colonic or rectal wall. This ensures complete removal of any lesion and its underlying tissue, effectively preventing recurrence.

These advancements demonstrate how endoscopy can tackle even the most challenging colorectal polyps, reinforcing its position as the preferred treatment modality.

 

Perceived Limitations 

With ongoing refinement over the last 2 decades, many of the perceived limitations (below) of endoscopic resection have now been overcome.

• Difficult locations/access: Historically lesions at the anorectal junction, ileocecal valve, appendiceal orifice and anastomoses were preferentially sent for surgery. In spite of unique technical challenges at each of these locations, there is now compelling data supporting EMR for these scenarios. We now also have techniques aimed at enabling the resection of lesions with poor access including patient repositioning, distal attachments, variable endoscope diameter/flexibility, traction and overtube devices.
• Recurrence: In the past, recurrence after endoscopic resection of lesions > 20 mm has been reported to be as high as 20%. With our current systematic approach to complete resection, meticulous examination of the post-resection defect for residual polyp tissue, adjunctive techniques to address submucosal fibrosis (hot avulsion, CAST, submucosal release) and thermal ablation to the resection margin (EMR-T), the risk of recurrence for piecemeal resections can be decreased to < 5%. In fact, some groups argue for the en-bloc resection of all large colorectal lesions based on the extremely low (< 1%) recurrence rates and potential for decreased follow-up.
• Post-resection bleeding: Post-resection bleeding is no longer a major limitation of any endoscopic approach because of the combination of improved intra-procedural hemostatic and resection techniques, optimized electrosurgical technology, and enhanced defect closure capabilities and devices (with prophylactic defect closure now supported by randomized control trial level data).
• Perforation: Deep mural injury, once an endoscopists’ worst fear during resection, is no longer a surgical emergency. It can now be predicted, identified (Sydney classification) and successfully managed. In spite of more widespread aggressive resection strategies, the risk of emergency surgery in patients undergoing EMR and even ESD (where the risk of DMI is significantly higher) is extremely low.

Endoscopic resection for large colorectal polyps is effective, available, minimally invasive and organ sparing making it the standard of care for the management of colonic polyps. With ongoing iteration in techniques, more invasive surgical approaches can be avoided in almost all patients with benign and low-risk T1 colorectal cancers.

Dr. Gabr is associate GI division director at the University of Cincinnati, Ohio. Dr. Mosko is based in the division of gastroenterology at St. Michael’s Hospital, Toronto, Ontario, Canada. The authors declare no conflicts of interest.

Blurred Lines: Polyp Needing Surgical versus Endoscopic Excision

BY IRA LEEDS, MD

I am grateful for the invitation to join in discussion with Dr. Gabr and Dr. Mosko on the ever-increasing role of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, as a surgeon, I do carry at least mild trepidation entering one of the literary “safe spaces” of my gastroenterology colleagues.

With the increasing evidentiary support of EMR approaches and the increasing experience of those performing ESD, these two techniques are quickly becoming the options of choice. As these practices become ubiquitous, it is important to recognize both their advantages and limitations, compared with available surgical options. The decision to proceed with EMR and ESD is essentially a turning point away from early surgical referral for a complex lesion. In this discussion, I intend to highlight when EMR and ESD have a clear advantage to early surgical referral, why I believe that early surgical referral is still superior to advanced endoscopic techniques in the rectum, and why the approach for right-sided lesions should hinge on careful shared decision-making. 

 

Endoscopic approaches nearly always beat surgical approaches when considering short-term risks. Even in the best surgical series, colorectal surgery typically leads to complications in 10%-15% of patients, 1%-5% being serious. Moreover, transabdominal surgical interventions (ie, colectomy) require considerable recovery involving at least a few days in the inpatient setting and over a month of activity restrictions. Finally, there is a minority of chronically unwell patients who cannot tolerate surgical intervention but may be fortunate enough to have a lesion that with enhanced attention can be endoscopically resectioned. While EMR and ESD also contribute a disproportionate burden of complications to endoscopy practice, overall complication rates are still favorable when compared with surgical resection.

Moreover, the most feared short-term complication of EMR and ESD, perforation, has the added benefit of a “controlled failure” to colectomy. Advanced endoscopic approaches already require a prepared colon, and patients are given strict return instructions. Hence, the yearly handful of postprocedural perforations that I get called upon to assist with typically tolerate a routine surgical exploration, repair or resection, and recover at rates equal to or better than elective colon resections. For these reasons, lesions that can be endoscopically removed within appropriate risk tolerances, can and should be considered for EMR or ESD at time of diagnosis.

There are two clinical scenarios where this consideration for up-front EMR or ESD requires further caution. First, any rectal lesion considered for advanced endoscopic techniques really needs to be done in multidisciplinary conference with a colorectal surgeon. In the modern era of colorectal surgery, surgeons now have numerous approaches to reach the rectum that bridge the gap between traditional endoscopy and transabdominal resection. For many rectal lesions, transanal laparoscopic and robotic approaches offer the opportunity for local excision. The most commonly practiced approach, transanal minimally invasive microsurgery (TAMIS), provides many of the benefits of endoscopy (eg, same-day discharge, no activity restrictions, limited periprocedural physiologic stress, low complication rates) while providing the surgical precision, repair strategies, and specimen orientation of conventional surgery. Anecdotally, the time it takes to do a high-quality TAMIS excision in the rectum can be substantially less than that required for a comparable ESD.

For rectal lesions in particular, specimen quality is paramount for oncologic prognosis. Regardless of any intrinsic favorable histopathology or deft hand of the endoscopist, a TAMIS approach will typically provide for a deeper partial thickness or even full thickness excision. More times each year than I would like, I find myself at a multidisciplinary tumor board discussing an endoscopically removed rectal lesion done in a piecemeal fashion or insufficient deep ESD where appropriate risk stratification is impossible and we end up offering patients a likely overly aggressive proctectomy or a potentially oncologically unsound re-excision. Consideration of EMR/ESD vs TAMIS up front would allow better sorting of which technique is most suited to which lesion and avoid these diagnostic dilemmas that only seem to be more common as EMR and ESD practices proliferate.

For a different set of reasons, an advanced cecal adenoma may also be more suited to upfront surgical considerations. Right colon lesions can be more challenging for surveillance for a host of reasons. Procedurally, right colon lesions are undeniably more difficult. The thin-walled cecum can be unforgiving for repeated polypectomies. Despite it being an uncomfortable subject for colonoscopists, the evidence suggests that getting to the cecum is not consistent or 100% expected. Finally, patients can be unwilling to undergo serial bowel preparation and endoscopic examination. In contrast, a laparoscopic right colectomy avoids these issues while also attributing little additional risk. Laparoscopic right-colon operations have overall complication rates of less than 10% and major complications of less than 1%. Hospital stays for laparoscopic right colectomy are typically 3 days or less. Finally, surgery reduces both the frequency of surveillance, and a shortened colon makes surveillance easier.

Advanced polypectomy techniques broaden our ability to address even difficult lesions under the ideally aligned degree of invasive procedure. However, like any procedure, these techniques have their own advantages and limitations. There will always be a minority of premalignant colon lesions that are best suited to surgery-first approaches to treatment. In my practice, maintaining open lines of communication and regular interaction with my endoscopy colleagues naturally leads to polyps being addressed in their most suitable fashion.

Dr. Leeds is assistant professor of surgery at the Yale School of Medicine and a staff surgeon at the VA Connecticut Healthcare System. He declares no conflicts of interest.

The US Department of Veterans Affairs (VA) announced on Feb. 7, 2025, that 116 Veterans Health Administration job classifications will not be eligible for the deferred resignation plan emailed by the Office of Personnel Management (OPM). The exemptions include Title 38 and Hybrid Title 38 positions, including doctors, nurses, and most medical staff.

The original OPM email offer had a Feb. 6, 2025, deadline for accepting the offer and a resignation date of no later than Sept. 30, 2025. However, the offer has been put on hold following a limited temporary restraining order from a Federal District Court in Massachusetts. Judge George O’Toole enjoined the OPM from “taking any further action to implement the so-called Fork Directive.” Arguments on the program’s legal merits began at a separate hearing on Monday.

The 116 roles exempted include physicians, nurses, pharmacists and pharmacy technicians, therapists, data scientists, dieticians, health and medical instrument technicians, among other roles.

OPM also included Voluntary Early Retirement Authority (VERA) in the deferred resignation offer. In a Feb. 6 email, the VA’s Office of the Chief Human Capital Officer (OCHCO) said: “The Department of Veterans Affairs established a list of occupations that are excluded from participating in DRP and VERA. If your occupation is on this list, you are not eligible to participate in the DRP.”

The US Department of Veterans Affairs (VA) announced on Feb. 7, 2025, that 116 Veterans Health Administration job classifications will not be eligible for the deferred resignation plan emailed by the Office of Personnel Management (OPM). The exemptions include Title 38 and Hybrid Title 38 positions, including doctors, nurses, and most medical staff.

The original OPM email offer had a Feb. 6, 2025, deadline for accepting the offer and a resignation date of no later than Sept. 30, 2025. However, the offer has been put on hold following a limited temporary restraining order from a Federal District Court in Massachusetts. Judge George O’Toole enjoined the OPM from “taking any further action to implement the so-called Fork Directive.” Arguments on the program’s legal merits began at a separate hearing on Monday.

The 116 roles exempted include physicians, nurses, pharmacists and pharmacy technicians, therapists, data scientists, dieticians, health and medical instrument technicians, among other roles.

OPM also included Voluntary Early Retirement Authority (VERA) in the deferred resignation offer. In a Feb. 6 email, the VA’s Office of the Chief Human Capital Officer (OCHCO) said: “The Department of Veterans Affairs established a list of occupations that are excluded from participating in DRP and VERA. If your occupation is on this list, you are not eligible to participate in the DRP.”

The US Department of Veterans Affairs (VA) announced on Feb. 7, 2025, that 116 Veterans Health Administration job classifications will not be eligible for the deferred resignation plan emailed by the Office of Personnel Management (OPM). The exemptions include Title 38 and Hybrid Title 38 positions, including doctors, nurses, and most medical staff.

The original OPM email offer had a Feb. 6, 2025, deadline for accepting the offer and a resignation date of no later than Sept. 30, 2025. However, the offer has been put on hold following a limited temporary restraining order from a Federal District Court in Massachusetts. Judge George O’Toole enjoined the OPM from “taking any further action to implement the so-called Fork Directive.” Arguments on the program’s legal merits began at a separate hearing on Monday.

The 116 roles exempted include physicians, nurses, pharmacists and pharmacy technicians, therapists, data scientists, dieticians, health and medical instrument technicians, among other roles.

OPM also included Voluntary Early Retirement Authority (VERA) in the deferred resignation offer. In a Feb. 6 email, the VA’s Office of the Chief Human Capital Officer (OCHCO) said: “The Department of Veterans Affairs established a list of occupations that are excluded from participating in DRP and VERA. If your occupation is on this list, you are not eligible to participate in the DRP.”

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

 

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

 

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

 

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

 

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

 

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

 

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.

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

It is the best possible news after an advanced melanoma diagnosis: A clean 10-year scan. This, in all likelihood, means the patient is cured and can leave the office free from their annual ‘scanxiety.’ 

But even in the best-case scenarios, oncologists may dodge the word cure, searching for others such as “remission,” “no evidence of disease,” and “most likely cured” to communicate the good news. Using these more open-ended terms can give patients reassurance without providing false hope that the cancer won’t ever return.

The “risk of future recurrence — even when very small — makes oncologists reluctant to use the word cure, fearing it will be interpreted as a promise, and particularly one that might be broken,” Belinda E. Kiely, MD, and Martin R. Stockler, MD, medical oncologists from the University of Sydney in Australia, wrote in a recent editorial.

Is it ever safe for oncologists to use the word cure? Might doing so backfire? Or does a patient’s underlying fear of recurrence transcend the word?

 

A Word’s Heavy Impact

Part of clinicians’ hesitance to use the word cure may stem from a lack of accepted definition for the term in oncology.

For some experts, a cure means patients will have a normal life expectancy not affected by cancer. Being able to confidently tell a patient that “requires very long-term follow-up,” said James Larkin, PhD, a medical oncologist at The Royal Marsden Hospital, London, England.

The National Cancer Institute (NCI) has a similar definition: “Cure means that there are no traces of your cancer after treatment and the cancer will never come back,” the NCI website says.

The American Society of Clinical Oncology, however, defines cure much more narrowly, as “when a person’s cancer has not returned for at least 5 years after treatment.” 

Not having a standard definition of cure in oncology makes it even more challenging for an oncologist to know how to communicate that a cancer very likely won’t return, without overpromising.

Some of the hesitance in framing good news comes from nuances in prognoses that depend on the type and stage of cancer, explained Marleen Kok, MD, PhD, a breast cancer specialist from the Netherlands Cancer Institute in Amsterdam.

Patients with localized early-stage breast cancer, for instance, have a 5-year survival rate of nearly 100%, and most live 2 decades or longer but, for some, the cancer will return.

“If you talk about early disease, indeed, we cure 80% of breast cancer patients,” Kok said during a press conference at the annual 2024 European Society of Medical Oncology meeting. But sub-dividing breast cancer into tumor type adds complexity. “With triple negative breast cancer, if they relapse, they relapse during the first 2 or 3 years so, at 5 years, the majority are disease free. But that’s different for estrogen receptor positive breast cancer,” in which recurrences can come much later.

In advanced cancers, oncologists may, understandably, be more hesitant to use the word cure. However, ongoing progress in cancer treatments is making the prospect of a cure more likely for some patients.

Take recent findings in melanoma. The landmark CheckMate 067 study in advanced disease revealed that patients receiving the immunotherapy combination of nivolumab plus ipilimumab had a median melanoma-specific survival > 10 years and a median overall survival of about 6 years.

The findings from the trial suggest that “many patients may die from causes unrelated to melanoma — or, in essence, they are cured,” outside expert Elisa Funck-Brentano, MD, PhD, from Ambroise-Paré Hospital in Paris, France, explained to Medscape Medical News.

With CheckMate 067, “what we’re talking about here is potential cure of metastatic solid tumors, which in general is something that’s new,” said senior author Larkin. In fact, late relapses after the 2- to 3-year mark in immunotherapy-treated melanoma are extremely rare.

CheckMate 067 “really made people tempted to use the word cure, and I will say some people in our field do,” said Pauline Funchain, MD, a medical oncologist at Stanford Cancer Institute, and associate professor at Stanford University, Palo Alto, California. “The rest of us really, really want to, but are hesitant because of what we know about melanoma.”

Because the reality is late relapse is still possible.

The cancer can show up decades later and I think, as oncologists, that experience has sort of shaken us,” Funchain told this news organization.

“Oncologists are scarred by those examples,” agreed Evan Hall, MD, a medical oncologist at Fred Hutch Cancer Center and assistant professor at the University of Washington School of Medicine, both in Seattle.

Clinical trials also don’t typically frame patient outcomes in terms of being cured. A recent analysis, which examined the use of “cure” and “hope” in 13,363 oncology articles published between 2000 and 2019 in JAMA Oncology and the Journal of Clinical Oncology, found that both words were used infrequently, especially in primary research articles, and their use decreased significantly over time, even as survival rates in oncology improved. The word cure, for instance, appeared in about 0.1% of sentences in primary research papers published in either journal, though the context of its use was not identified.

Outcomes in cancer clinical trials, which may assess hundreds even thousands of patients, are largely framed in terms of risks and rates of survival — 85% of patients who received treatment X are alive at 5 years or patients receiving treatment Y have a 20% risk for recurrence, for instance.

These risks and rates can’t tell an oncologist whether the patient sitting in front of them can close the cancer chapter of their lives for good.

“I just saw a patient the other day who was 30 years out from their melanoma diagnosis, and they had a recurrence,” Hall recalled. That’s why, “ultimately, it’s a hard thing to tell somebody they’re cured,” he said. “I personally don’t really like using that term.”

While the literature on using the word cure in oncology is limited, one older survey of oncology clinicians supports this view that many feel reluctant to use the term. Of 117 oncology clinicians who responded, 81% said they were “hesitant to tell a patient that they are cured,” and 63% said that they “would never tell a patient that they are cured,” while just 36% said they were comfortable saying the word, with most respondents waiting at least 6-10 years before doing so.

A more recent Italian survey, however, revealed a more favorable view of the word cure in oncology. The survey, which included 224 clinicians and 249 patients, reported that > 90% of cancer physicians, which included surgeons, radiotherapists, and medical oncologists, agreed that it’s possible for a patient to be cured, while about 84% of patients believed this. And > 80% of respondents said using the word cure would be “beneficial” to patients.

Still, even for those hearing the word cure and feeling comforted by an oncologist’s reassurance, it may only provide short-term relief. Fear that the cancer will come slinking, even roaring, back eventually may loom. And this lingering worry can haunt cancer survivors for years.

In a recent cross-sectional study of 229 adults who survived childhood cancer and had lived cancer-free for decades, researchers found that one third reported experiencing clinically significant elevated fear that their primary cancer would recur or a subsequent malignant neoplasm would develop. Similar anxiety has been documented in long-term survivors of adult-onset cancers.

To some degree, every survivor will experience fear and anxiety that their cancer will come back and, at a certain level, that is normal, the study’s senior author Nicole Alberts, PhD, a psychologist, associate professor, and Canada research chair in Behavioural Health Intervention at Concordia University, Montréal, Quebec, Canada, told this news organization.

Although an oncologist’s words do matter and clinicians may wrestle with the right words for patients in the moment, it can take more than words to quell patients’ fear, she said.

“What we know about that kind of anxiety is that there’s this cycle where reassurance doesn’t really help in the long-term,” Alberts said. In other words, hearing the word cure from their oncologist initially makes people feel better, but the anxiety may eventually come back.

Alberts tries to help patients acknowledge and accept uncertainty while also calming residual or lingering anxiety about a cancer recurrence. Ultimately, Alberts’ goal is to help cancer survivors “find the sweet spot to live again.”

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

It is the best possible news after an advanced melanoma diagnosis: A clean 10-year scan. This, in all likelihood, means the patient is cured and can leave the office free from their annual ‘scanxiety.’ 

But even in the best-case scenarios, oncologists may dodge the word cure, searching for others such as “remission,” “no evidence of disease,” and “most likely cured” to communicate the good news. Using these more open-ended terms can give patients reassurance without providing false hope that the cancer won’t ever return.

The “risk of future recurrence — even when very small — makes oncologists reluctant to use the word cure, fearing it will be interpreted as a promise, and particularly one that might be broken,” Belinda E. Kiely, MD, and Martin R. Stockler, MD, medical oncologists from the University of Sydney in Australia, wrote in a recent editorial.

Is it ever safe for oncologists to use the word cure? Might doing so backfire? Or does a patient’s underlying fear of recurrence transcend the word?

 

A Word’s Heavy Impact

Part of clinicians’ hesitance to use the word cure may stem from a lack of accepted definition for the term in oncology.

For some experts, a cure means patients will have a normal life expectancy not affected by cancer. Being able to confidently tell a patient that “requires very long-term follow-up,” said James Larkin, PhD, a medical oncologist at The Royal Marsden Hospital, London, England.

The National Cancer Institute (NCI) has a similar definition: “Cure means that there are no traces of your cancer after treatment and the cancer will never come back,” the NCI website says.

The American Society of Clinical Oncology, however, defines cure much more narrowly, as “when a person’s cancer has not returned for at least 5 years after treatment.” 

Not having a standard definition of cure in oncology makes it even more challenging for an oncologist to know how to communicate that a cancer very likely won’t return, without overpromising.

Some of the hesitance in framing good news comes from nuances in prognoses that depend on the type and stage of cancer, explained Marleen Kok, MD, PhD, a breast cancer specialist from the Netherlands Cancer Institute in Amsterdam.

Patients with localized early-stage breast cancer, for instance, have a 5-year survival rate of nearly 100%, and most live 2 decades or longer but, for some, the cancer will return.

“If you talk about early disease, indeed, we cure 80% of breast cancer patients,” Kok said during a press conference at the annual 2024 European Society of Medical Oncology meeting. But sub-dividing breast cancer into tumor type adds complexity. “With triple negative breast cancer, if they relapse, they relapse during the first 2 or 3 years so, at 5 years, the majority are disease free. But that’s different for estrogen receptor positive breast cancer,” in which recurrences can come much later.

In advanced cancers, oncologists may, understandably, be more hesitant to use the word cure. However, ongoing progress in cancer treatments is making the prospect of a cure more likely for some patients.

Take recent findings in melanoma. The landmark CheckMate 067 study in advanced disease revealed that patients receiving the immunotherapy combination of nivolumab plus ipilimumab had a median melanoma-specific survival > 10 years and a median overall survival of about 6 years.

The findings from the trial suggest that “many patients may die from causes unrelated to melanoma — or, in essence, they are cured,” outside expert Elisa Funck-Brentano, MD, PhD, from Ambroise-Paré Hospital in Paris, France, explained to Medscape Medical News.

With CheckMate 067, “what we’re talking about here is potential cure of metastatic solid tumors, which in general is something that’s new,” said senior author Larkin. In fact, late relapses after the 2- to 3-year mark in immunotherapy-treated melanoma are extremely rare.

CheckMate 067 “really made people tempted to use the word cure, and I will say some people in our field do,” said Pauline Funchain, MD, a medical oncologist at Stanford Cancer Institute, and associate professor at Stanford University, Palo Alto, California. “The rest of us really, really want to, but are hesitant because of what we know about melanoma.”

Because the reality is late relapse is still possible.

The cancer can show up decades later and I think, as oncologists, that experience has sort of shaken us,” Funchain told this news organization.

“Oncologists are scarred by those examples,” agreed Evan Hall, MD, a medical oncologist at Fred Hutch Cancer Center and assistant professor at the University of Washington School of Medicine, both in Seattle.

Clinical trials also don’t typically frame patient outcomes in terms of being cured. A recent analysis, which examined the use of “cure” and “hope” in 13,363 oncology articles published between 2000 and 2019 in JAMA Oncology and the Journal of Clinical Oncology, found that both words were used infrequently, especially in primary research articles, and their use decreased significantly over time, even as survival rates in oncology improved. The word cure, for instance, appeared in about 0.1% of sentences in primary research papers published in either journal, though the context of its use was not identified.

Outcomes in cancer clinical trials, which may assess hundreds even thousands of patients, are largely framed in terms of risks and rates of survival — 85% of patients who received treatment X are alive at 5 years or patients receiving treatment Y have a 20% risk for recurrence, for instance.

These risks and rates can’t tell an oncologist whether the patient sitting in front of them can close the cancer chapter of their lives for good.

“I just saw a patient the other day who was 30 years out from their melanoma diagnosis, and they had a recurrence,” Hall recalled. That’s why, “ultimately, it’s a hard thing to tell somebody they’re cured,” he said. “I personally don’t really like using that term.”

While the literature on using the word cure in oncology is limited, one older survey of oncology clinicians supports this view that many feel reluctant to use the term. Of 117 oncology clinicians who responded, 81% said they were “hesitant to tell a patient that they are cured,” and 63% said that they “would never tell a patient that they are cured,” while just 36% said they were comfortable saying the word, with most respondents waiting at least 6-10 years before doing so.

A more recent Italian survey, however, revealed a more favorable view of the word cure in oncology. The survey, which included 224 clinicians and 249 patients, reported that > 90% of cancer physicians, which included surgeons, radiotherapists, and medical oncologists, agreed that it’s possible for a patient to be cured, while about 84% of patients believed this. And > 80% of respondents said using the word cure would be “beneficial” to patients.

Still, even for those hearing the word cure and feeling comforted by an oncologist’s reassurance, it may only provide short-term relief. Fear that the cancer will come slinking, even roaring, back eventually may loom. And this lingering worry can haunt cancer survivors for years.

In a recent cross-sectional study of 229 adults who survived childhood cancer and had lived cancer-free for decades, researchers found that one third reported experiencing clinically significant elevated fear that their primary cancer would recur or a subsequent malignant neoplasm would develop. Similar anxiety has been documented in long-term survivors of adult-onset cancers.

To some degree, every survivor will experience fear and anxiety that their cancer will come back and, at a certain level, that is normal, the study’s senior author Nicole Alberts, PhD, a psychologist, associate professor, and Canada research chair in Behavioural Health Intervention at Concordia University, Montréal, Quebec, Canada, told this news organization.

Although an oncologist’s words do matter and clinicians may wrestle with the right words for patients in the moment, it can take more than words to quell patients’ fear, she said.

“What we know about that kind of anxiety is that there’s this cycle where reassurance doesn’t really help in the long-term,” Alberts said. In other words, hearing the word cure from their oncologist initially makes people feel better, but the anxiety may eventually come back.

Alberts tries to help patients acknowledge and accept uncertainty while also calming residual or lingering anxiety about a cancer recurrence. Ultimately, Alberts’ goal is to help cancer survivors “find the sweet spot to live again.”

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

It is the best possible news after an advanced melanoma diagnosis: A clean 10-year scan. This, in all likelihood, means the patient is cured and can leave the office free from their annual ‘scanxiety.’ 

But even in the best-case scenarios, oncologists may dodge the word cure, searching for others such as “remission,” “no evidence of disease,” and “most likely cured” to communicate the good news. Using these more open-ended terms can give patients reassurance without providing false hope that the cancer won’t ever return.

The “risk of future recurrence — even when very small — makes oncologists reluctant to use the word cure, fearing it will be interpreted as a promise, and particularly one that might be broken,” Belinda E. Kiely, MD, and Martin R. Stockler, MD, medical oncologists from the University of Sydney in Australia, wrote in a recent editorial.

Is it ever safe for oncologists to use the word cure? Might doing so backfire? Or does a patient’s underlying fear of recurrence transcend the word?

 

A Word’s Heavy Impact

Part of clinicians’ hesitance to use the word cure may stem from a lack of accepted definition for the term in oncology.

For some experts, a cure means patients will have a normal life expectancy not affected by cancer. Being able to confidently tell a patient that “requires very long-term follow-up,” said James Larkin, PhD, a medical oncologist at The Royal Marsden Hospital, London, England.

The National Cancer Institute (NCI) has a similar definition: “Cure means that there are no traces of your cancer after treatment and the cancer will never come back,” the NCI website says.

The American Society of Clinical Oncology, however, defines cure much more narrowly, as “when a person’s cancer has not returned for at least 5 years after treatment.” 

Not having a standard definition of cure in oncology makes it even more challenging for an oncologist to know how to communicate that a cancer very likely won’t return, without overpromising.

Some of the hesitance in framing good news comes from nuances in prognoses that depend on the type and stage of cancer, explained Marleen Kok, MD, PhD, a breast cancer specialist from the Netherlands Cancer Institute in Amsterdam.

Patients with localized early-stage breast cancer, for instance, have a 5-year survival rate of nearly 100%, and most live 2 decades or longer but, for some, the cancer will return.

“If you talk about early disease, indeed, we cure 80% of breast cancer patients,” Kok said during a press conference at the annual 2024 European Society of Medical Oncology meeting. But sub-dividing breast cancer into tumor type adds complexity. “With triple negative breast cancer, if they relapse, they relapse during the first 2 or 3 years so, at 5 years, the majority are disease free. But that’s different for estrogen receptor positive breast cancer,” in which recurrences can come much later.

In advanced cancers, oncologists may, understandably, be more hesitant to use the word cure. However, ongoing progress in cancer treatments is making the prospect of a cure more likely for some patients.

Take recent findings in melanoma. The landmark CheckMate 067 study in advanced disease revealed that patients receiving the immunotherapy combination of nivolumab plus ipilimumab had a median melanoma-specific survival > 10 years and a median overall survival of about 6 years.

The findings from the trial suggest that “many patients may die from causes unrelated to melanoma — or, in essence, they are cured,” outside expert Elisa Funck-Brentano, MD, PhD, from Ambroise-Paré Hospital in Paris, France, explained to Medscape Medical News.

With CheckMate 067, “what we’re talking about here is potential cure of metastatic solid tumors, which in general is something that’s new,” said senior author Larkin. In fact, late relapses after the 2- to 3-year mark in immunotherapy-treated melanoma are extremely rare.

CheckMate 067 “really made people tempted to use the word cure, and I will say some people in our field do,” said Pauline Funchain, MD, a medical oncologist at Stanford Cancer Institute, and associate professor at Stanford University, Palo Alto, California. “The rest of us really, really want to, but are hesitant because of what we know about melanoma.”

Because the reality is late relapse is still possible.

The cancer can show up decades later and I think, as oncologists, that experience has sort of shaken us,” Funchain told this news organization.

“Oncologists are scarred by those examples,” agreed Evan Hall, MD, a medical oncologist at Fred Hutch Cancer Center and assistant professor at the University of Washington School of Medicine, both in Seattle.

Clinical trials also don’t typically frame patient outcomes in terms of being cured. A recent analysis, which examined the use of “cure” and “hope” in 13,363 oncology articles published between 2000 and 2019 in JAMA Oncology and the Journal of Clinical Oncology, found that both words were used infrequently, especially in primary research articles, and their use decreased significantly over time, even as survival rates in oncology improved. The word cure, for instance, appeared in about 0.1% of sentences in primary research papers published in either journal, though the context of its use was not identified.

Outcomes in cancer clinical trials, which may assess hundreds even thousands of patients, are largely framed in terms of risks and rates of survival — 85% of patients who received treatment X are alive at 5 years or patients receiving treatment Y have a 20% risk for recurrence, for instance.

These risks and rates can’t tell an oncologist whether the patient sitting in front of them can close the cancer chapter of their lives for good.

“I just saw a patient the other day who was 30 years out from their melanoma diagnosis, and they had a recurrence,” Hall recalled. That’s why, “ultimately, it’s a hard thing to tell somebody they’re cured,” he said. “I personally don’t really like using that term.”

While the literature on using the word cure in oncology is limited, one older survey of oncology clinicians supports this view that many feel reluctant to use the term. Of 117 oncology clinicians who responded, 81% said they were “hesitant to tell a patient that they are cured,” and 63% said that they “would never tell a patient that they are cured,” while just 36% said they were comfortable saying the word, with most respondents waiting at least 6-10 years before doing so.

A more recent Italian survey, however, revealed a more favorable view of the word cure in oncology. The survey, which included 224 clinicians and 249 patients, reported that > 90% of cancer physicians, which included surgeons, radiotherapists, and medical oncologists, agreed that it’s possible for a patient to be cured, while about 84% of patients believed this. And > 80% of respondents said using the word cure would be “beneficial” to patients.

Still, even for those hearing the word cure and feeling comforted by an oncologist’s reassurance, it may only provide short-term relief. Fear that the cancer will come slinking, even roaring, back eventually may loom. And this lingering worry can haunt cancer survivors for years.

In a recent cross-sectional study of 229 adults who survived childhood cancer and had lived cancer-free for decades, researchers found that one third reported experiencing clinically significant elevated fear that their primary cancer would recur or a subsequent malignant neoplasm would develop. Similar anxiety has been documented in long-term survivors of adult-onset cancers.

To some degree, every survivor will experience fear and anxiety that their cancer will come back and, at a certain level, that is normal, the study’s senior author Nicole Alberts, PhD, a psychologist, associate professor, and Canada research chair in Behavioural Health Intervention at Concordia University, Montréal, Quebec, Canada, told this news organization.

Although an oncologist’s words do matter and clinicians may wrestle with the right words for patients in the moment, it can take more than words to quell patients’ fear, she said.

“What we know about that kind of anxiety is that there’s this cycle where reassurance doesn’t really help in the long-term,” Alberts said. In other words, hearing the word cure from their oncologist initially makes people feel better, but the anxiety may eventually come back.

Alberts tries to help patients acknowledge and accept uncertainty while also calming residual or lingering anxiety about a cancer recurrence. Ultimately, Alberts’ goal is to help cancer survivors “find the sweet spot to live again.”

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