Urology

Prostate cancers detected during screening are much more likely to be high risk when they affect black men and men aged 75 years or older.

Men over age 74 years were nine times more likely to have high-risk disease after a positive prostate-specific antigen test, and black men of all ages were twice as likely to have high-risk disease as were white men, based on a study of 4 years of data extracted from the Surveillance, Epidemiology and End Results (SEER) database.

The findings make the case for a more personalized approach to screening, Dr. Hong Zhang said at a press briefing during the 2013 Genitourinary Cancers Symposium.

Without prostate-specific antigen (PSA) screening, "we have no other way to detect prostate cancer sufficiently early to have the best chance of helping this group of high-risk patients," said Dr. Zhang of the University of Rochester (N.Y.).

The study brings a bit of context to current PSA screening guidelines, which are "all over the map," according to session moderator Dr. Bruce Roth of Washington University, St. Louis. In 2011, the United States Preventive Services Task Force determined that routine screening harms more men that it helps.

"The American Cancer Society recommends just screening older men and the USPTF recommends that nobody get screened," Dr. Roth said. Based on these results, the presumption that older men will die first of something other than their prostate cancer is not necessarily true. "In fact, a significant number of these men present with high-risk disease. Age is not the greatest determinant of who should and should not be screened."

During 2004-2008, 70,345 men were diagnosed with T1cN0M0 prostate cancer in SEER. Of these, 48% had low-risk disease (PSA less than 10 mg/L or Gleason score of 6 or less), 36% intermediate-risk disease (PSA between 10 mg/L and 20 mg/L or Gleason score 7), and 16% high-risk disease (PSA at least 20 mg/L, or Gleason score of 8 or higher).

The median age of patients with low-risk disease was 67 years; for those with intermediate-risk disease, median age was 70 years; and for high-risk disease, it was 72 years. Men 75 years or older accounted for 12% of the population, but for 24% of intermediate-risk and 26% of high-risk disease.

In a multivariate analysis, Dr. Zhang determined that, compared with younger men, those aged 75 years and older were almost five times more likely to have intermediate-risk disease and nine times more likely to have high-risk disease.

Blacks made up 13% of the low-risk category, 16% of the intermediate-risk category, and 18% of the high-risk category. Compared with whites, blacks were 1.5 times more likely to have intermediate-risk disease and twice as likely to have high-risk disease.

Dr. Zhang and Dr. Roth had no financial disclosures.

michele.sullivan@elsevier.com

Prostate cancers detected during screening are much more likely to be high risk when they affect black men and men aged 75 years or older.

Men over age 74 years were nine times more likely to have high-risk disease after a positive prostate-specific antigen test, and black men of all ages were twice as likely to have high-risk disease as were white men, based on a study of 4 years of data extracted from the Surveillance, Epidemiology and End Results (SEER) database.

The findings make the case for a more personalized approach to screening, Dr. Hong Zhang said at a press briefing during the 2013 Genitourinary Cancers Symposium.

Without prostate-specific antigen (PSA) screening, "we have no other way to detect prostate cancer sufficiently early to have the best chance of helping this group of high-risk patients," said Dr. Zhang of the University of Rochester (N.Y.).

The study brings a bit of context to current PSA screening guidelines, which are "all over the map," according to session moderator Dr. Bruce Roth of Washington University, St. Louis. In 2011, the United States Preventive Services Task Force determined that routine screening harms more men that it helps.

"The American Cancer Society recommends just screening older men and the USPTF recommends that nobody get screened," Dr. Roth said. Based on these results, the presumption that older men will die first of something other than their prostate cancer is not necessarily true. "In fact, a significant number of these men present with high-risk disease. Age is not the greatest determinant of who should and should not be screened."

During 2004-2008, 70,345 men were diagnosed with T1cN0M0 prostate cancer in SEER. Of these, 48% had low-risk disease (PSA less than 10 mg/L or Gleason score of 6 or less), 36% intermediate-risk disease (PSA between 10 mg/L and 20 mg/L or Gleason score 7), and 16% high-risk disease (PSA at least 20 mg/L, or Gleason score of 8 or higher).

The median age of patients with low-risk disease was 67 years; for those with intermediate-risk disease, median age was 70 years; and for high-risk disease, it was 72 years. Men 75 years or older accounted for 12% of the population, but for 24% of intermediate-risk and 26% of high-risk disease.

In a multivariate analysis, Dr. Zhang determined that, compared with younger men, those aged 75 years and older were almost five times more likely to have intermediate-risk disease and nine times more likely to have high-risk disease.

Blacks made up 13% of the low-risk category, 16% of the intermediate-risk category, and 18% of the high-risk category. Compared with whites, blacks were 1.5 times more likely to have intermediate-risk disease and twice as likely to have high-risk disease.

Dr. Zhang and Dr. Roth had no financial disclosures.

michele.sullivan@elsevier.com

Prostate cancers detected during screening are much more likely to be high risk when they affect black men and men aged 75 years or older.

Men over age 74 years were nine times more likely to have high-risk disease after a positive prostate-specific antigen test, and black men of all ages were twice as likely to have high-risk disease as were white men, based on a study of 4 years of data extracted from the Surveillance, Epidemiology and End Results (SEER) database.

The findings make the case for a more personalized approach to screening, Dr. Hong Zhang said at a press briefing during the 2013 Genitourinary Cancers Symposium.

Without prostate-specific antigen (PSA) screening, "we have no other way to detect prostate cancer sufficiently early to have the best chance of helping this group of high-risk patients," said Dr. Zhang of the University of Rochester (N.Y.).

The study brings a bit of context to current PSA screening guidelines, which are "all over the map," according to session moderator Dr. Bruce Roth of Washington University, St. Louis. In 2011, the United States Preventive Services Task Force determined that routine screening harms more men that it helps.

"The American Cancer Society recommends just screening older men and the USPTF recommends that nobody get screened," Dr. Roth said. Based on these results, the presumption that older men will die first of something other than their prostate cancer is not necessarily true. "In fact, a significant number of these men present with high-risk disease. Age is not the greatest determinant of who should and should not be screened."

During 2004-2008, 70,345 men were diagnosed with T1cN0M0 prostate cancer in SEER. Of these, 48% had low-risk disease (PSA less than 10 mg/L or Gleason score of 6 or less), 36% intermediate-risk disease (PSA between 10 mg/L and 20 mg/L or Gleason score 7), and 16% high-risk disease (PSA at least 20 mg/L, or Gleason score of 8 or higher).

The median age of patients with low-risk disease was 67 years; for those with intermediate-risk disease, median age was 70 years; and for high-risk disease, it was 72 years. Men 75 years or older accounted for 12% of the population, but for 24% of intermediate-risk and 26% of high-risk disease.

In a multivariate analysis, Dr. Zhang determined that, compared with younger men, those aged 75 years and older were almost five times more likely to have intermediate-risk disease and nine times more likely to have high-risk disease.

Blacks made up 13% of the low-risk category, 16% of the intermediate-risk category, and 18% of the high-risk category. Compared with whites, blacks were 1.5 times more likely to have intermediate-risk disease and twice as likely to have high-risk disease.

Dr. Zhang and Dr. Roth had no financial disclosures.

michele.sullivan@elsevier.com

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

Final results of the PIVOT trial offered no dramatic surprises, but reassuring confirmation of the increasingly accepted belief that watchful waiting is the best approach for low-risk prostate cancer. (N. Engl. J. Med. 2012; 367:203-213).

A thoughtful accompanying editorial offered perspective on this and other recent trials that suggest widespread use of aggressive treatments following detection of prostate cancer by PSA screening offer a "marginal benefit on the lifespan but at a considerable cost." Surgery and other radical procedures should be reserved for high grade "cancers that matter" – those most likely to be lethal, argue Dr. Ian M. Thompson Jr. of the University of Texas Health Science Center in San Antonio, and Catherine M. Tangen, Dr.P.H., of the Fred Hutchinson Cancer Research Center in Seattle.

Unfortunately, the findings will not put to rest the anxiety inherent in men who will be faced with decisions about whether to opt first for PSA screening, then for biopsies based on screening, and then for an array of possible treatments based on biopsy results. For many of those men, it will be hard to just say no.

Dr. Durado Brookes, director of prostate and colorectal cancer programs for the American Cancer Society, was quoted by the Los Angeles Times as saying, "When most men are told they have prostate cancer, their immediate thought is, ‘Oh my God, I’m going to die,’ and their immediate next step is, ‘Let’s do something about this.’ "

Action, rather than deliberation, is certainly the go-to position for most American men. For those who struggle with anxiety, knowledge that a cancer lies within their bodies may seem even more excruciating than going through with procedures that they might not actually need, and that may cause them harm.

In counseling anxious patients, psychologists focus on cultivating "distress tolerance." Patients learn to recognize physical and emotional signs of exaggerated panic, and to develop coping skills that essentially tell the brain’s deep fear center, the amygdala, to "chill out," as they logically contemplate the true scope of a perceived threat.

It takes practice, and patients often resist talking about or even thinking about the looming objects of their distress. But exposure to the threat, scientists have found, is key. And the good news is, cognitive and behavioral therapy for anxiety is quite successful for most patients, even using short-term interventions.

Talking to men with low-risk prostate cancer about the wise option of "watchful waiting" takes special skill, to convey the facts while competing with the hair-on-fire amygdala-fueled rants going on inside his head and the adamant opinions of his sister-in-law, neighbor, and the guy on his bowling team that he needs to get to surgery, and pronto, since "watchful waiting" is just part of the conspiracy to ration care.

What I think will help is to review with such patients the evolution of your own thinking about treatment of early-stage prostate cancer, explaining what research and clinical experiences led you to offer the advice you do.

Provide links to web sites or summaries that clearly summarize the latest research, and offer, if you can, a follow-up appointment to discuss what your patient has read.

Finally, tell the patient you care about him personally: his goals, his relationships and sexuality, and the quality of his life, as well as his lifespan. Let him know that you consider it a relief that he doesn’t require radical treatment because he doesn’t have what Dr. Thompson and Dr. Tangen would consider a "cancer that matters." Because he does matter, very much.

Your patients can tolerate the distress of "watchful waiting." It’ll get easier for them over time, as they live their lives well.

Dr. Freed is a psychologist in Santa Barbara, Calif., and a medical journalist.

Final results of the PIVOT trial offered no dramatic surprises, but reassuring confirmation of the increasingly accepted belief that watchful waiting is the best approach for low-risk prostate cancer. (N. Engl. J. Med. 2012; 367:203-213).

A thoughtful accompanying editorial offered perspective on this and other recent trials that suggest widespread use of aggressive treatments following detection of prostate cancer by PSA screening offer a "marginal benefit on the lifespan but at a considerable cost." Surgery and other radical procedures should be reserved for high grade "cancers that matter" – those most likely to be lethal, argue Dr. Ian M. Thompson Jr. of the University of Texas Health Science Center in San Antonio, and Catherine M. Tangen, Dr.P.H., of the Fred Hutchinson Cancer Research Center in Seattle.

Unfortunately, the findings will not put to rest the anxiety inherent in men who will be faced with decisions about whether to opt first for PSA screening, then for biopsies based on screening, and then for an array of possible treatments based on biopsy results. For many of those men, it will be hard to just say no.

Dr. Durado Brookes, director of prostate and colorectal cancer programs for the American Cancer Society, was quoted by the Los Angeles Times as saying, "When most men are told they have prostate cancer, their immediate thought is, ‘Oh my God, I’m going to die,’ and their immediate next step is, ‘Let’s do something about this.’ "

Action, rather than deliberation, is certainly the go-to position for most American men. For those who struggle with anxiety, knowledge that a cancer lies within their bodies may seem even more excruciating than going through with procedures that they might not actually need, and that may cause them harm.

In counseling anxious patients, psychologists focus on cultivating "distress tolerance." Patients learn to recognize physical and emotional signs of exaggerated panic, and to develop coping skills that essentially tell the brain’s deep fear center, the amygdala, to "chill out," as they logically contemplate the true scope of a perceived threat.

It takes practice, and patients often resist talking about or even thinking about the looming objects of their distress. But exposure to the threat, scientists have found, is key. And the good news is, cognitive and behavioral therapy for anxiety is quite successful for most patients, even using short-term interventions.

Talking to men with low-risk prostate cancer about the wise option of "watchful waiting" takes special skill, to convey the facts while competing with the hair-on-fire amygdala-fueled rants going on inside his head and the adamant opinions of his sister-in-law, neighbor, and the guy on his bowling team that he needs to get to surgery, and pronto, since "watchful waiting" is just part of the conspiracy to ration care.

What I think will help is to review with such patients the evolution of your own thinking about treatment of early-stage prostate cancer, explaining what research and clinical experiences led you to offer the advice you do.

Provide links to web sites or summaries that clearly summarize the latest research, and offer, if you can, a follow-up appointment to discuss what your patient has read.

Finally, tell the patient you care about him personally: his goals, his relationships and sexuality, and the quality of his life, as well as his lifespan. Let him know that you consider it a relief that he doesn’t require radical treatment because he doesn’t have what Dr. Thompson and Dr. Tangen would consider a "cancer that matters." Because he does matter, very much.

Your patients can tolerate the distress of "watchful waiting." It’ll get easier for them over time, as they live their lives well.

Dr. Freed is a psychologist in Santa Barbara, Calif., and a medical journalist.

Final results of the PIVOT trial offered no dramatic surprises, but reassuring confirmation of the increasingly accepted belief that watchful waiting is the best approach for low-risk prostate cancer. (N. Engl. J. Med. 2012; 367:203-213).

A thoughtful accompanying editorial offered perspective on this and other recent trials that suggest widespread use of aggressive treatments following detection of prostate cancer by PSA screening offer a "marginal benefit on the lifespan but at a considerable cost." Surgery and other radical procedures should be reserved for high grade "cancers that matter" – those most likely to be lethal, argue Dr. Ian M. Thompson Jr. of the University of Texas Health Science Center in San Antonio, and Catherine M. Tangen, Dr.P.H., of the Fred Hutchinson Cancer Research Center in Seattle.

Unfortunately, the findings will not put to rest the anxiety inherent in men who will be faced with decisions about whether to opt first for PSA screening, then for biopsies based on screening, and then for an array of possible treatments based on biopsy results. For many of those men, it will be hard to just say no.

Dr. Durado Brookes, director of prostate and colorectal cancer programs for the American Cancer Society, was quoted by the Los Angeles Times as saying, "When most men are told they have prostate cancer, their immediate thought is, ‘Oh my God, I’m going to die,’ and their immediate next step is, ‘Let’s do something about this.’ "

Action, rather than deliberation, is certainly the go-to position for most American men. For those who struggle with anxiety, knowledge that a cancer lies within their bodies may seem even more excruciating than going through with procedures that they might not actually need, and that may cause them harm.

In counseling anxious patients, psychologists focus on cultivating "distress tolerance." Patients learn to recognize physical and emotional signs of exaggerated panic, and to develop coping skills that essentially tell the brain’s deep fear center, the amygdala, to "chill out," as they logically contemplate the true scope of a perceived threat.

It takes practice, and patients often resist talking about or even thinking about the looming objects of their distress. But exposure to the threat, scientists have found, is key. And the good news is, cognitive and behavioral therapy for anxiety is quite successful for most patients, even using short-term interventions.

Talking to men with low-risk prostate cancer about the wise option of "watchful waiting" takes special skill, to convey the facts while competing with the hair-on-fire amygdala-fueled rants going on inside his head and the adamant opinions of his sister-in-law, neighbor, and the guy on his bowling team that he needs to get to surgery, and pronto, since "watchful waiting" is just part of the conspiracy to ration care.

What I think will help is to review with such patients the evolution of your own thinking about treatment of early-stage prostate cancer, explaining what research and clinical experiences led you to offer the advice you do.

Provide links to web sites or summaries that clearly summarize the latest research, and offer, if you can, a follow-up appointment to discuss what your patient has read.

Finally, tell the patient you care about him personally: his goals, his relationships and sexuality, and the quality of his life, as well as his lifespan. Let him know that you consider it a relief that he doesn’t require radical treatment because he doesn’t have what Dr. Thompson and Dr. Tangen would consider a "cancer that matters." Because he does matter, very much.

Your patients can tolerate the distress of "watchful waiting." It’ll get easier for them over time, as they live their lives well.

Dr. Freed is a psychologist in Santa Barbara, Calif., and a medical journalist.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Jehovah’s Witnesses, who do not accept transfusion of blood products, appear to fare at least as well as patients who do receive transfusions after undergoing similar cardiac surgery, according to a report published online July 2 in the Archives of Internal Medicine.

In a single-center study of more than 49,000 consecutive cardiac operations, Jehovah’s Witnesses who refused transfusions had fewer in-hospital complications, better early survival, and similar long-term survival as did transfusion recipients, said Dr. Gregory Pattakos of the Heart and Vascular Institute, Cleveland Clinic, and his associates.

The findings suggest that avoiding transfusions may be beneficial for other patients undergoing cardiac surgery, they noted.

Typically, physicians use a number of blood-conservation practices before, during, and after surgery in patients who are Witnesses, to avert the need for transfusions. These include preoperative erythropoietin, iron, and B-complex vitamins; hemoconcentration; minimal use of crystalloids; intraoperative antifibrinolytics; use of cell-saver and smaller cardiopulmonary bypass circuits; and postoperative tolerance of low hematocrit levels.

Dr. Pattakos and his colleagues assessed outcomes in 48,986 cardiac surgery patients who received red blood cell transfusions perioperatively in 1983-2011 and 322 Witnesses who did not. Since the study subjects could not be randomized for receiving transfusions, the investigators adjusted for baseline differences between the two study groups by using propensity matching.

Median follow-up was approximately 7-9 years.

Compared with transfusion recipients, Witnesses had similar rates of in-hospital mortality, stroke, atrial fibrillation, and renal failure. Witnesses had lower rates of postoperative MI, prolonged ventilation, and reoperation for bleeding complications, and they had shorter ICU stays and shorter hospitalizations than transfusion recipients, the researchers said (Arch. Intern. Med. 2012 [doi:10.1001/archinternmed.2012.2449]).

Witnesses’ survival rates were 86% at 5 years, 69% at 10 years, 51% at 15 years, and 34% at 20 years after surgery. These were not significantly different from the transfusion recipients\' survival rates of 74%, 53%, 35%, and 23%, respectively.

Some of the blood-conservation strategies adopted for Witnesses may benefit other patients as well. Unfortunately, the design of this study did not allow for determination of which strategies contributed most to the beneficial outcomes, they said.

One limitation of this study is that Jehovah’s Witnesses who presented to the Cleveland Clinic and were accepted there by surgeons "likely represent a select group who might have been expected by their physicians to have better outcomes," Dr. Pattakos and his associates added.

Jehovah’s Witnesses, who do not accept transfusion of blood products, appear to fare at least as well as patients who do receive transfusions after undergoing similar cardiac surgery, according to a report published online July 2 in the Archives of Internal Medicine.

In a single-center study of more than 49,000 consecutive cardiac operations, Jehovah’s Witnesses who refused transfusions had fewer in-hospital complications, better early survival, and similar long-term survival as did transfusion recipients, said Dr. Gregory Pattakos of the Heart and Vascular Institute, Cleveland Clinic, and his associates.

The findings suggest that avoiding transfusions may be beneficial for other patients undergoing cardiac surgery, they noted.

Typically, physicians use a number of blood-conservation practices before, during, and after surgery in patients who are Witnesses, to avert the need for transfusions. These include preoperative erythropoietin, iron, and B-complex vitamins; hemoconcentration; minimal use of crystalloids; intraoperative antifibrinolytics; use of cell-saver and smaller cardiopulmonary bypass circuits; and postoperative tolerance of low hematocrit levels.

Dr. Pattakos and his colleagues assessed outcomes in 48,986 cardiac surgery patients who received red blood cell transfusions perioperatively in 1983-2011 and 322 Witnesses who did not. Since the study subjects could not be randomized for receiving transfusions, the investigators adjusted for baseline differences between the two study groups by using propensity matching.

Median follow-up was approximately 7-9 years.

Compared with transfusion recipients, Witnesses had similar rates of in-hospital mortality, stroke, atrial fibrillation, and renal failure. Witnesses had lower rates of postoperative MI, prolonged ventilation, and reoperation for bleeding complications, and they had shorter ICU stays and shorter hospitalizations than transfusion recipients, the researchers said (Arch. Intern. Med. 2012 [doi:10.1001/archinternmed.2012.2449]).

Witnesses’ survival rates were 86% at 5 years, 69% at 10 years, 51% at 15 years, and 34% at 20 years after surgery. These were not significantly different from the transfusion recipients\' survival rates of 74%, 53%, 35%, and 23%, respectively.

Some of the blood-conservation strategies adopted for Witnesses may benefit other patients as well. Unfortunately, the design of this study did not allow for determination of which strategies contributed most to the beneficial outcomes, they said.

One limitation of this study is that Jehovah’s Witnesses who presented to the Cleveland Clinic and were accepted there by surgeons "likely represent a select group who might have been expected by their physicians to have better outcomes," Dr. Pattakos and his associates added.

Jehovah’s Witnesses, who do not accept transfusion of blood products, appear to fare at least as well as patients who do receive transfusions after undergoing similar cardiac surgery, according to a report published online July 2 in the Archives of Internal Medicine.

In a single-center study of more than 49,000 consecutive cardiac operations, Jehovah’s Witnesses who refused transfusions had fewer in-hospital complications, better early survival, and similar long-term survival as did transfusion recipients, said Dr. Gregory Pattakos of the Heart and Vascular Institute, Cleveland Clinic, and his associates.

The findings suggest that avoiding transfusions may be beneficial for other patients undergoing cardiac surgery, they noted.

Typically, physicians use a number of blood-conservation practices before, during, and after surgery in patients who are Witnesses, to avert the need for transfusions. These include preoperative erythropoietin, iron, and B-complex vitamins; hemoconcentration; minimal use of crystalloids; intraoperative antifibrinolytics; use of cell-saver and smaller cardiopulmonary bypass circuits; and postoperative tolerance of low hematocrit levels.

Dr. Pattakos and his colleagues assessed outcomes in 48,986 cardiac surgery patients who received red blood cell transfusions perioperatively in 1983-2011 and 322 Witnesses who did not. Since the study subjects could not be randomized for receiving transfusions, the investigators adjusted for baseline differences between the two study groups by using propensity matching.

Median follow-up was approximately 7-9 years.

Compared with transfusion recipients, Witnesses had similar rates of in-hospital mortality, stroke, atrial fibrillation, and renal failure. Witnesses had lower rates of postoperative MI, prolonged ventilation, and reoperation for bleeding complications, and they had shorter ICU stays and shorter hospitalizations than transfusion recipients, the researchers said (Arch. Intern. Med. 2012 [doi:10.1001/archinternmed.2012.2449]).

Witnesses’ survival rates were 86% at 5 years, 69% at 10 years, 51% at 15 years, and 34% at 20 years after surgery. These were not significantly different from the transfusion recipients\' survival rates of 74%, 53%, 35%, and 23%, respectively.

Some of the blood-conservation strategies adopted for Witnesses may benefit other patients as well. Unfortunately, the design of this study did not allow for determination of which strategies contributed most to the beneficial outcomes, they said.

One limitation of this study is that Jehovah’s Witnesses who presented to the Cleveland Clinic and were accepted there by surgeons "likely represent a select group who might have been expected by their physicians to have better outcomes," Dr. Pattakos and his associates added.

ATLANTA – Men with type 1 diabetes might not express an elevated level of prostate specific antigen, even if they have an early prostate cancer, suggest findings from a subanalysis of patients with type 1 diabetes.

In that prospective study, poor glycemic control was associated with decreased PSA levels, irrespective of age or body size, Dr. James Hotaling said during a poster session at the annual meeting of the American Urological Association.

"It’s well known that patients with type 2 diabetes have a decreased risk of prostate cancers as well as lower PSAs," said Dr. Hotaling of the University of Washington, Seattle.

"This lower PSA is thought to stem from a greater volume of distribution because many of these men are overweight or morbidly obese – and some hypothesize that they have lower testosterone because of the obesity and that this contributes to these findings."

Dr. Hotaling and his colleagues sought to determine whether men with type 1 diabetes showed a similar pattern. To do this, they examined data from year 17 of the Epidemiology of Diabetes Interventions and Complications (EDIC) study. EDIC began in 1994 and is the observational follow-up study of 1,441 participants in the earlier Diabetes Control and Complications Trial (DCCT).

PSA concentrations were measured in 627 men during year 17. The investigators stratified the subjects by both age (younger than 40 years, 41-59 years, and 60 years and older) and body mass index (normal, overweight, obese).

The subjects were a mean age of 52 years at the time of PSA measurement. Their mean HbA_1c was 8%, and the mean PSA 0.93 ng/mL.

PSA levels increased with age, from a low of 0.56 ng/mL in the youngest patients to a mean of 1.38 ng/mL in the oldest group.

PSA levels significantly decreased as HbA_1c increased. The mean PSA was 1.05 ng/mL when blood sugar was less than 7.5% and 0.76 ng/mL when blood sugar was above 8.5%.

"Each 10% increase in HbA_1c levels was associated with a PSA reduction of 1.37ng/mL," Dr. Hotaling said. "This association was independent of age and body size."

Our findings suggest that metabolic differences related to diabetes may affect the ability to detect early-stage prostate cancer. This finding also could represent a potentially modifiable risk factor that could be addressed.

The physiologic relationship between hyperglycemia and low PSA is not completely known, he added. "Proposed mechanisms are that hyperinsulinemia and insulin resistance lead to increased estradiol, which causes decreased testosterone and sex hormone–binding globulin, thus leading to a decreased PSA concentration."

EDIC is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hotaling reported having no financial disclosures.

ATLANTA – Men with type 1 diabetes might not express an elevated level of prostate specific antigen, even if they have an early prostate cancer, suggest findings from a subanalysis of patients with type 1 diabetes.

In that prospective study, poor glycemic control was associated with decreased PSA levels, irrespective of age or body size, Dr. James Hotaling said during a poster session at the annual meeting of the American Urological Association.

"It’s well known that patients with type 2 diabetes have a decreased risk of prostate cancers as well as lower PSAs," said Dr. Hotaling of the University of Washington, Seattle.

"This lower PSA is thought to stem from a greater volume of distribution because many of these men are overweight or morbidly obese – and some hypothesize that they have lower testosterone because of the obesity and that this contributes to these findings."

Dr. Hotaling and his colleagues sought to determine whether men with type 1 diabetes showed a similar pattern. To do this, they examined data from year 17 of the Epidemiology of Diabetes Interventions and Complications (EDIC) study. EDIC began in 1994 and is the observational follow-up study of 1,441 participants in the earlier Diabetes Control and Complications Trial (DCCT).

PSA concentrations were measured in 627 men during year 17. The investigators stratified the subjects by both age (younger than 40 years, 41-59 years, and 60 years and older) and body mass index (normal, overweight, obese).

The subjects were a mean age of 52 years at the time of PSA measurement. Their mean HbA_1c was 8%, and the mean PSA 0.93 ng/mL.

PSA levels increased with age, from a low of 0.56 ng/mL in the youngest patients to a mean of 1.38 ng/mL in the oldest group.

PSA levels significantly decreased as HbA_1c increased. The mean PSA was 1.05 ng/mL when blood sugar was less than 7.5% and 0.76 ng/mL when blood sugar was above 8.5%.

"Each 10% increase in HbA_1c levels was associated with a PSA reduction of 1.37ng/mL," Dr. Hotaling said. "This association was independent of age and body size."

Our findings suggest that metabolic differences related to diabetes may affect the ability to detect early-stage prostate cancer. This finding also could represent a potentially modifiable risk factor that could be addressed.

The physiologic relationship between hyperglycemia and low PSA is not completely known, he added. "Proposed mechanisms are that hyperinsulinemia and insulin resistance lead to increased estradiol, which causes decreased testosterone and sex hormone–binding globulin, thus leading to a decreased PSA concentration."

EDIC is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hotaling reported having no financial disclosures.

ATLANTA – Men with type 1 diabetes might not express an elevated level of prostate specific antigen, even if they have an early prostate cancer, suggest findings from a subanalysis of patients with type 1 diabetes.

In that prospective study, poor glycemic control was associated with decreased PSA levels, irrespective of age or body size, Dr. James Hotaling said during a poster session at the annual meeting of the American Urological Association.

"It’s well known that patients with type 2 diabetes have a decreased risk of prostate cancers as well as lower PSAs," said Dr. Hotaling of the University of Washington, Seattle.

"This lower PSA is thought to stem from a greater volume of distribution because many of these men are overweight or morbidly obese – and some hypothesize that they have lower testosterone because of the obesity and that this contributes to these findings."

Dr. Hotaling and his colleagues sought to determine whether men with type 1 diabetes showed a similar pattern. To do this, they examined data from year 17 of the Epidemiology of Diabetes Interventions and Complications (EDIC) study. EDIC began in 1994 and is the observational follow-up study of 1,441 participants in the earlier Diabetes Control and Complications Trial (DCCT).

PSA concentrations were measured in 627 men during year 17. The investigators stratified the subjects by both age (younger than 40 years, 41-59 years, and 60 years and older) and body mass index (normal, overweight, obese).

The subjects were a mean age of 52 years at the time of PSA measurement. Their mean HbA_1c was 8%, and the mean PSA 0.93 ng/mL.

PSA levels increased with age, from a low of 0.56 ng/mL in the youngest patients to a mean of 1.38 ng/mL in the oldest group.

PSA levels significantly decreased as HbA_1c increased. The mean PSA was 1.05 ng/mL when blood sugar was less than 7.5% and 0.76 ng/mL when blood sugar was above 8.5%.

"Each 10% increase in HbA_1c levels was associated with a PSA reduction of 1.37ng/mL," Dr. Hotaling said. "This association was independent of age and body size."

Our findings suggest that metabolic differences related to diabetes may affect the ability to detect early-stage prostate cancer. This finding also could represent a potentially modifiable risk factor that could be addressed.

The physiologic relationship between hyperglycemia and low PSA is not completely known, he added. "Proposed mechanisms are that hyperinsulinemia and insulin resistance lead to increased estradiol, which causes decreased testosterone and sex hormone–binding globulin, thus leading to a decreased PSA concentration."

EDIC is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hotaling reported having no financial disclosures.

CHICAGO – Updated and final analyses from four phase III prostate cancer trials offer continued support for radium-223, insights into denosumab and multimodal therapy, and an obituary for yet another drug in castration-resistant prostate cancer.

Radium-223 Boosts Overall Survival

Updated results from the phase III ALSYMPCA trial show that radium-223 chloride (Alpharadin) increased median overall survival by 3.6 months, from 11.3 months to 14.9 months (hazard ratio, 0.695; P = .00007), resulting in a 30.5% reduction in the risk of death, compared with placebo, in men with castration-resistant prostate cancer (CRPC) and bone metastases.

The experimental alpha-emitting particle also significantly prolonged the time to first skeletal-related event, from 6.7 months to 12.2 months (HR, 0.64; P less than .0001), said Dr. Chris Parker of the Royal Marsden Hospital, London, at the annual meeting of the American Society of Clinical Oncology.

The updated results surpass the overall survival benefit reported for radium-223 chloride in an interim analysis at the 2011 European Multidisciplinary Cancer Congress.

The Food and Drug Administration very quickly granted fast-track designation to radium-223 chloride, and earlier this year agreed that Bayer HealthCare could make the drug available to patients who had CRPC or hormone-refractory prostate cancer with symptomatic bone metastases at qualified clinical sites through its expanded-access program.

Based on the ALSYMPCA data, Bayer is expected to file radium-223 chloride for CRPC with regulatory authorities in the second half of 2012, and is planning trials in earlier-stage disease and other cancers. Recruitment is already underway for a trial of radium-223 in combination with docetaxel (Taxotere) in patients with bone metastasis from CRPC.

Denosumab Data Did Not Sway FDA

The shorter the prostate-specific antigen doubling time (PSADT), the greater the impact is of denosumab (Xgeva) in nonmetastatic CRPC, according to an exploratory, post hoc subset analysis of the denosumab 147 trial.

If the PSADT was 6 months or less, denosumab increased median bone metastasis-free survival by 7.2 months to 25.9 months, from a median of 18.7 months with placebo (HR, 0.77; P = .006), which translates into a 23% risk reduction.

If the PSADT was less than 4 months, the delay increased by 7.5 months, from a median of 18.3 months with placebo to 25.8 months with denosumab (HR, 0.71; P = .004), corresponding to a 29% risk reduction, reported Dr. Fred Saad, professor and chief of urology at the University of Montreal Hospital Centre.

Discussant Dr. Eric Small, codirector of urologic oncology at the University of California, San Francisco, said that the study validates PSADT as an important risk stratifier in this group of patients, but observed that denosumab is not approved for this indication, and it appears to have the greatest benefit in a diminishingly small group of patients with shorter and shorter PSA doubling times.

"This is wonderful hypothesis generation, but cannot be used for the basis of therapeutic decisions," he said.

Bone metastasis–free survival in the entire cohort was 25.2 months with placebo and 29.5 months with denosumab (HR, 0.85; P = .028).

In February, an FDA advisory panel voted that denosumab does not have a favorable risk-benefit profile as a treatment to reduce the risk of bone metastasis in high-risk men (defined as those with a PSA level of at least 8.0 ng/mL or a PSA that doubled within 10 months or less).

Multimodal Benefit Goes 10 Years

The survival benefit of adding radiotherapy (RT) to androgen deprivation therapy (ADT) was maintained at 10 years in men with locally advanced prostate cancer, according to the final analysis of a phase III intergroup trial carried out by the U.K. Medical Research Council, the National Cancer Institute of Canada, and the Southwest Oncology Group.

At 10 years, 55% of men who were treated with ADT plus RT were alive, compared with 49% given ADT alone (HR, 0.70; P = .0003). The difference in disease-specific survival was particularly striking at 15% vs. 26%, favoring the combination (HR, 0.46; P less than .0001).

"That’s more than halving the risk of death from prostate cancer," said Prof. Malcolm D. Mason, head of oncology and palliative medicine at Cardiff (Wales) University.

In an interim analysis reported at ASCO 2010, RT plus ADT provided significant improvements at 7 years in overall survival (HR, 0.77; P = .033) and disease-specific survival (DSS; HR, 0.54; P = .0001).

In the current analysis, bowel and urinary morbidity were transiently elevated with the addition of radiation, most often delivered at a dose of 65-69 Gy, but were no different after 3 years.

An exploratory analysis favored whole pelvic vs. prostate-only radiation for overall survival (HR, 0.90; P = .57) and DSS (HR, 0.65; P = .15), but Dr. Mason called this finding hypothesis generating.

He remarked that combined ADT plus RT is enshrined in the European Association of Urology and National Comprehensive Cancer Network guidelines, "but that uptake is uncertain, and we have concerns as to whether this has been taken up as much as it should have been."

Dr. Small agreed with the authors’ conclusion that ADT and RT should be offered to all men with locally advanced prostate cancer suitable for RT, but said the absolute difference in 10-year overall-survival is modest, at 6%. Because accrual took place 10 years ago, the results also cannot be fully extrapolated to the increasingly common high-risk patients seen in the United States, who tend to be at a high grade and lower stage.

He pointed out that the combination arm had a 5% absolute increase in deaths because of secondary malignancies, which warrants exploration. "It makes you wonder what the radiation is doing here," he added.

Still, Dr. Small commended the authors for persevering with what he described as a tough study to do with a nonradiation arm. "This study is a demonstration of the power of the cooperative groups, and in an era of shrinking resources, points out that undersourcing the cooperative groups – as has been advocated by some – is shortsighted," he said.

Atrasentan Flops Again

Dr. David I. Quinn had the unenviable task of delivering the final word on atrasentan (Xinlay) as a prostate cancer therapy. The selective endothelin blocker failed as monotherapy in two previous phase III trials, and was so ineffective in combination with docetaxel that the phase III Southwest Oncology Group S0421 trial in advanced castration-resistant disease was halted early last year.

A new post hoc analysis from S0421 identified an 8-month survival benefit with atrasentan in a distinct subset of poor-prognosis patients with skeletal metastases and four bone metabolism biomarkers (median, 13 months vs. 5 months; P = .02).

Still, the drug proved futile when compared with docetaxel plus placebo in the entire cohort for time to progression (median, 9 months for both; HR, 1.03; P = .71) and overall survival (median, 18 months for both; HR, 1.04; P = .61). The 2-year progression-free survival was 18% in both groups, and overall survival rates were 37% and 38%, respectively.

"Endothelin blockade with currently available drugs such as atrasentan and zibotentan, which has three negative studies, is now a failed experiment," said Dr. Quinn, coleader of genitourinary medical oncology at the University of Southern California, Los Angeles. "It has been superseded by osteoblast-targeted therapy that actually works, like radium-223."

Dr. Parker reported consulting or advising for Algeta and receiving honoraria from Bayer; his coauthors reported financial relationships including employment with Algeta, which initiated the ALSYMPCA trial. Dr. Saad reported consulting or advising for and receiving honorarium and research funding from Amgen. Dr. Mason reported no disclosures. Dr. Quinn reported financial relationships with several firms. SWOG S0421 was supported by the Eastern Cooperative Oncology Group and Cancer and Leukemia Group B. Dr. Small reported consulting or advising for Dendreon and receiving research funding from Genzyme and Sanofi.

CHICAGO – Updated and final analyses from four phase III prostate cancer trials offer continued support for radium-223, insights into denosumab and multimodal therapy, and an obituary for yet another drug in castration-resistant prostate cancer.

Radium-223 Boosts Overall Survival

Updated results from the phase III ALSYMPCA trial show that radium-223 chloride (Alpharadin) increased median overall survival by 3.6 months, from 11.3 months to 14.9 months (hazard ratio, 0.695; P = .00007), resulting in a 30.5% reduction in the risk of death, compared with placebo, in men with castration-resistant prostate cancer (CRPC) and bone metastases.

The experimental alpha-emitting particle also significantly prolonged the time to first skeletal-related event, from 6.7 months to 12.2 months (HR, 0.64; P less than .0001), said Dr. Chris Parker of the Royal Marsden Hospital, London, at the annual meeting of the American Society of Clinical Oncology.

The updated results surpass the overall survival benefit reported for radium-223 chloride in an interim analysis at the 2011 European Multidisciplinary Cancer Congress.

The Food and Drug Administration very quickly granted fast-track designation to radium-223 chloride, and earlier this year agreed that Bayer HealthCare could make the drug available to patients who had CRPC or hormone-refractory prostate cancer with symptomatic bone metastases at qualified clinical sites through its expanded-access program.

Based on the ALSYMPCA data, Bayer is expected to file radium-223 chloride for CRPC with regulatory authorities in the second half of 2012, and is planning trials in earlier-stage disease and other cancers. Recruitment is already underway for a trial of radium-223 in combination with docetaxel (Taxotere) in patients with bone metastasis from CRPC.

Denosumab Data Did Not Sway FDA

The shorter the prostate-specific antigen doubling time (PSADT), the greater the impact is of denosumab (Xgeva) in nonmetastatic CRPC, according to an exploratory, post hoc subset analysis of the denosumab 147 trial.

If the PSADT was 6 months or less, denosumab increased median bone metastasis-free survival by 7.2 months to 25.9 months, from a median of 18.7 months with placebo (HR, 0.77; P = .006), which translates into a 23% risk reduction.

If the PSADT was less than 4 months, the delay increased by 7.5 months, from a median of 18.3 months with placebo to 25.8 months with denosumab (HR, 0.71; P = .004), corresponding to a 29% risk reduction, reported Dr. Fred Saad, professor and chief of urology at the University of Montreal Hospital Centre.

Discussant Dr. Eric Small, codirector of urologic oncology at the University of California, San Francisco, said that the study validates PSADT as an important risk stratifier in this group of patients, but observed that denosumab is not approved for this indication, and it appears to have the greatest benefit in a diminishingly small group of patients with shorter and shorter PSA doubling times.

"This is wonderful hypothesis generation, but cannot be used for the basis of therapeutic decisions," he said.

Bone metastasis–free survival in the entire cohort was 25.2 months with placebo and 29.5 months with denosumab (HR, 0.85; P = .028).

In February, an FDA advisory panel voted that denosumab does not have a favorable risk-benefit profile as a treatment to reduce the risk of bone metastasis in high-risk men (defined as those with a PSA level of at least 8.0 ng/mL or a PSA that doubled within 10 months or less).

Multimodal Benefit Goes 10 Years

The survival benefit of adding radiotherapy (RT) to androgen deprivation therapy (ADT) was maintained at 10 years in men with locally advanced prostate cancer, according to the final analysis of a phase III intergroup trial carried out by the U.K. Medical Research Council, the National Cancer Institute of Canada, and the Southwest Oncology Group.

At 10 years, 55% of men who were treated with ADT plus RT were alive, compared with 49% given ADT alone (HR, 0.70; P = .0003). The difference in disease-specific survival was particularly striking at 15% vs. 26%, favoring the combination (HR, 0.46; P less than .0001).

"That’s more than halving the risk of death from prostate cancer," said Prof. Malcolm D. Mason, head of oncology and palliative medicine at Cardiff (Wales) University.

In an interim analysis reported at ASCO 2010, RT plus ADT provided significant improvements at 7 years in overall survival (HR, 0.77; P = .033) and disease-specific survival (DSS; HR, 0.54; P = .0001).

In the current analysis, bowel and urinary morbidity were transiently elevated with the addition of radiation, most often delivered at a dose of 65-69 Gy, but were no different after 3 years.

An exploratory analysis favored whole pelvic vs. prostate-only radiation for overall survival (HR, 0.90; P = .57) and DSS (HR, 0.65; P = .15), but Dr. Mason called this finding hypothesis generating.

He remarked that combined ADT plus RT is enshrined in the European Association of Urology and National Comprehensive Cancer Network guidelines, "but that uptake is uncertain, and we have concerns as to whether this has been taken up as much as it should have been."

Dr. Small agreed with the authors’ conclusion that ADT and RT should be offered to all men with locally advanced prostate cancer suitable for RT, but said the absolute difference in 10-year overall-survival is modest, at 6%. Because accrual took place 10 years ago, the results also cannot be fully extrapolated to the increasingly common high-risk patients seen in the United States, who tend to be at a high grade and lower stage.

He pointed out that the combination arm had a 5% absolute increase in deaths because of secondary malignancies, which warrants exploration. "It makes you wonder what the radiation is doing here," he added.

Still, Dr. Small commended the authors for persevering with what he described as a tough study to do with a nonradiation arm. "This study is a demonstration of the power of the cooperative groups, and in an era of shrinking resources, points out that undersourcing the cooperative groups – as has been advocated by some – is shortsighted," he said.

Atrasentan Flops Again

Dr. David I. Quinn had the unenviable task of delivering the final word on atrasentan (Xinlay) as a prostate cancer therapy. The selective endothelin blocker failed as monotherapy in two previous phase III trials, and was so ineffective in combination with docetaxel that the phase III Southwest Oncology Group S0421 trial in advanced castration-resistant disease was halted early last year.

A new post hoc analysis from S0421 identified an 8-month survival benefit with atrasentan in a distinct subset of poor-prognosis patients with skeletal metastases and four bone metabolism biomarkers (median, 13 months vs. 5 months; P = .02).

Still, the drug proved futile when compared with docetaxel plus placebo in the entire cohort for time to progression (median, 9 months for both; HR, 1.03; P = .71) and overall survival (median, 18 months for both; HR, 1.04; P = .61). The 2-year progression-free survival was 18% in both groups, and overall survival rates were 37% and 38%, respectively.

"Endothelin blockade with currently available drugs such as atrasentan and zibotentan, which has three negative studies, is now a failed experiment," said Dr. Quinn, coleader of genitourinary medical oncology at the University of Southern California, Los Angeles. "It has been superseded by osteoblast-targeted therapy that actually works, like radium-223."

Dr. Parker reported consulting or advising for Algeta and receiving honoraria from Bayer; his coauthors reported financial relationships including employment with Algeta, which initiated the ALSYMPCA trial. Dr. Saad reported consulting or advising for and receiving honorarium and research funding from Amgen. Dr. Mason reported no disclosures. Dr. Quinn reported financial relationships with several firms. SWOG S0421 was supported by the Eastern Cooperative Oncology Group and Cancer and Leukemia Group B. Dr. Small reported consulting or advising for Dendreon and receiving research funding from Genzyme and Sanofi.

CHICAGO – Updated and final analyses from four phase III prostate cancer trials offer continued support for radium-223, insights into denosumab and multimodal therapy, and an obituary for yet another drug in castration-resistant prostate cancer.

Radium-223 Boosts Overall Survival

Updated results from the phase III ALSYMPCA trial show that radium-223 chloride (Alpharadin) increased median overall survival by 3.6 months, from 11.3 months to 14.9 months (hazard ratio, 0.695; P = .00007), resulting in a 30.5% reduction in the risk of death, compared with placebo, in men with castration-resistant prostate cancer (CRPC) and bone metastases.

The experimental alpha-emitting particle also significantly prolonged the time to first skeletal-related event, from 6.7 months to 12.2 months (HR, 0.64; P less than .0001), said Dr. Chris Parker of the Royal Marsden Hospital, London, at the annual meeting of the American Society of Clinical Oncology.

The updated results surpass the overall survival benefit reported for radium-223 chloride in an interim analysis at the 2011 European Multidisciplinary Cancer Congress.

The Food and Drug Administration very quickly granted fast-track designation to radium-223 chloride, and earlier this year agreed that Bayer HealthCare could make the drug available to patients who had CRPC or hormone-refractory prostate cancer with symptomatic bone metastases at qualified clinical sites through its expanded-access program.

Based on the ALSYMPCA data, Bayer is expected to file radium-223 chloride for CRPC with regulatory authorities in the second half of 2012, and is planning trials in earlier-stage disease and other cancers. Recruitment is already underway for a trial of radium-223 in combination with docetaxel (Taxotere) in patients with bone metastasis from CRPC.

Denosumab Data Did Not Sway FDA

The shorter the prostate-specific antigen doubling time (PSADT), the greater the impact is of denosumab (Xgeva) in nonmetastatic CRPC, according to an exploratory, post hoc subset analysis of the denosumab 147 trial.

If the PSADT was 6 months or less, denosumab increased median bone metastasis-free survival by 7.2 months to 25.9 months, from a median of 18.7 months with placebo (HR, 0.77; P = .006), which translates into a 23% risk reduction.

If the PSADT was less than 4 months, the delay increased by 7.5 months, from a median of 18.3 months with placebo to 25.8 months with denosumab (HR, 0.71; P = .004), corresponding to a 29% risk reduction, reported Dr. Fred Saad, professor and chief of urology at the University of Montreal Hospital Centre.

Discussant Dr. Eric Small, codirector of urologic oncology at the University of California, San Francisco, said that the study validates PSADT as an important risk stratifier in this group of patients, but observed that denosumab is not approved for this indication, and it appears to have the greatest benefit in a diminishingly small group of patients with shorter and shorter PSA doubling times.

"This is wonderful hypothesis generation, but cannot be used for the basis of therapeutic decisions," he said.

Bone metastasis–free survival in the entire cohort was 25.2 months with placebo and 29.5 months with denosumab (HR, 0.85; P = .028).

In February, an FDA advisory panel voted that denosumab does not have a favorable risk-benefit profile as a treatment to reduce the risk of bone metastasis in high-risk men (defined as those with a PSA level of at least 8.0 ng/mL or a PSA that doubled within 10 months or less).

Multimodal Benefit Goes 10 Years

The survival benefit of adding radiotherapy (RT) to androgen deprivation therapy (ADT) was maintained at 10 years in men with locally advanced prostate cancer, according to the final analysis of a phase III intergroup trial carried out by the U.K. Medical Research Council, the National Cancer Institute of Canada, and the Southwest Oncology Group.

At 10 years, 55% of men who were treated with ADT plus RT were alive, compared with 49% given ADT alone (HR, 0.70; P = .0003). The difference in disease-specific survival was particularly striking at 15% vs. 26%, favoring the combination (HR, 0.46; P less than .0001).

"That’s more than halving the risk of death from prostate cancer," said Prof. Malcolm D. Mason, head of oncology and palliative medicine at Cardiff (Wales) University.

In an interim analysis reported at ASCO 2010, RT plus ADT provided significant improvements at 7 years in overall survival (HR, 0.77; P = .033) and disease-specific survival (DSS; HR, 0.54; P = .0001).

In the current analysis, bowel and urinary morbidity were transiently elevated with the addition of radiation, most often delivered at a dose of 65-69 Gy, but were no different after 3 years.

An exploratory analysis favored whole pelvic vs. prostate-only radiation for overall survival (HR, 0.90; P = .57) and DSS (HR, 0.65; P = .15), but Dr. Mason called this finding hypothesis generating.

He remarked that combined ADT plus RT is enshrined in the European Association of Urology and National Comprehensive Cancer Network guidelines, "but that uptake is uncertain, and we have concerns as to whether this has been taken up as much as it should have been."

Dr. Small agreed with the authors’ conclusion that ADT and RT should be offered to all men with locally advanced prostate cancer suitable for RT, but said the absolute difference in 10-year overall-survival is modest, at 6%. Because accrual took place 10 years ago, the results also cannot be fully extrapolated to the increasingly common high-risk patients seen in the United States, who tend to be at a high grade and lower stage.

He pointed out that the combination arm had a 5% absolute increase in deaths because of secondary malignancies, which warrants exploration. "It makes you wonder what the radiation is doing here," he added.

Still, Dr. Small commended the authors for persevering with what he described as a tough study to do with a nonradiation arm. "This study is a demonstration of the power of the cooperative groups, and in an era of shrinking resources, points out that undersourcing the cooperative groups – as has been advocated by some – is shortsighted," he said.

Atrasentan Flops Again

Dr. David I. Quinn had the unenviable task of delivering the final word on atrasentan (Xinlay) as a prostate cancer therapy. The selective endothelin blocker failed as monotherapy in two previous phase III trials, and was so ineffective in combination with docetaxel that the phase III Southwest Oncology Group S0421 trial in advanced castration-resistant disease was halted early last year.

A new post hoc analysis from S0421 identified an 8-month survival benefit with atrasentan in a distinct subset of poor-prognosis patients with skeletal metastases and four bone metabolism biomarkers (median, 13 months vs. 5 months; P = .02).

Still, the drug proved futile when compared with docetaxel plus placebo in the entire cohort for time to progression (median, 9 months for both; HR, 1.03; P = .71) and overall survival (median, 18 months for both; HR, 1.04; P = .61). The 2-year progression-free survival was 18% in both groups, and overall survival rates were 37% and 38%, respectively.

"Endothelin blockade with currently available drugs such as atrasentan and zibotentan, which has three negative studies, is now a failed experiment," said Dr. Quinn, coleader of genitourinary medical oncology at the University of Southern California, Los Angeles. "It has been superseded by osteoblast-targeted therapy that actually works, like radium-223."

Dr. Parker reported consulting or advising for Algeta and receiving honoraria from Bayer; his coauthors reported financial relationships including employment with Algeta, which initiated the ALSYMPCA trial. Dr. Saad reported consulting or advising for and receiving honorarium and research funding from Amgen. Dr. Mason reported no disclosures. Dr. Quinn reported financial relationships with several firms. SWOG S0421 was supported by the Eastern Cooperative Oncology Group and Cancer and Leukemia Group B. Dr. Small reported consulting or advising for Dendreon and receiving research funding from Genzyme and Sanofi.

CHICAGO – Delegates to the American Medical Association’s legislative body are not happy with the U.S. Preventive Services Task Force.

They voted overwhelmingly (322 to 93) to express "concern" over the task force’s recommendations on screening mammography and prostate-specific antigen screening. Both recommendations attracted a firestorm of criticism when they were issued – the mammography recommendation in 2009 and those on PSA testing in May.

Many delegates also said they thought that the USPSTF, a quasi-governmental group operating under the auspices of the Agency for Healthcare Research and Quality, had reached its decisions without proper input from specialty societies or experts in each field.

In a second resolution, the delegates voted to encourage the USPSTF to "implement procedures that allow for meaningful input on recommendation development from specialists and stakeholders in the topic area under study."

Alicia Ault/IMNG Medical Media

Dr. Arl Van Moore Jr., a delegate from the American College of Radiology, said that neither the ACR nor any prominent breast imaging or surgical societies were contacted by the USPSTF in creating the screening mammography recommendations.

"None of the recognized experts in the field were contacted, to the best of our knowledge," said Dr. Moore, an interventional radiologist in Charlotte, N.C.

The American Urological Association delegate, Dr. William Gee, did not mince words when it came to the PSA screening guidelines.

"The [USPSTF] did not use an open process and ignored the public in reaching their conclusions," he said.

But Dr. Sally J. Trippel, a preventive medicine specialist at the Mayo Clinic and delegate from Minnesota, defended the USPSTF and its process. The task force is "about as politically independent as any national organization can get," and "about as free of conflict of interest as is possible in any organization developing guidelines for American clinicians," she said.

She quoted from task force documents showing that urologists provided peer review of the PSA evidence review. "So there were experts from urology involved in the development of that guideline," and also for the one on screening mammography.

To further show its consternation with the task force, AMA delegates also approved a report that stated that starting at age 40, women should be "eligible for screening mammography," and encouraging physicians "to regularly discuss with their individual patients the benefits and risks of screening mammography, and whether screening is appropriate for each clinical situation given that the balance of benefits and risks will be viewed differently by each patient."

Primary care delegates from the American Academy of Family Physicians and the American College of Physicians opposed the resolutions of concern against the USPSTF and the mammography report.

The AAFP supported the task force when it issued its mammography recommendations "because it was the most comprehensive pattern and set of preventive guidelines using current methodology with what was available in science at that time," said Dr. Roland Goertz, AAFP delegate.

The task force basically recommends what the AMA report urged: that physicians have discussions with their patients about risks and benefits, he said. The problem is not the USPSTF recommendations, but that they are being used to deny payment, he added.

Alicia Ault/IMNG Medical Media

Dr. Richard Reiling, a delegate from the American College of Surgeons, said that the task force had confused patients with its mammography recommendation, and called for the AMA to convene all interested parties to craft a single guideline. The USPSTF was "wrong in presenting this report without listening to the stakeholders in the past," he said, adding, "let’s get one guideline out there."

Dr. Goertz agreed that there needed to be a common guideline.

ACP Delegate Dr. William Golden expressed the ACP’s view that the House of Delegates was not the appropriate venue for voting on particular guidelines. "The House should not be in the position of voting on what guideline is best," he said.

CHICAGO – Delegates to the American Medical Association’s legislative body are not happy with the U.S. Preventive Services Task Force.

They voted overwhelmingly (322 to 93) to express "concern" over the task force’s recommendations on screening mammography and prostate-specific antigen screening. Both recommendations attracted a firestorm of criticism when they were issued – the mammography recommendation in 2009 and those on PSA testing in May.

Many delegates also said they thought that the USPSTF, a quasi-governmental group operating under the auspices of the Agency for Healthcare Research and Quality, had reached its decisions without proper input from specialty societies or experts in each field.

In a second resolution, the delegates voted to encourage the USPSTF to "implement procedures that allow for meaningful input on recommendation development from specialists and stakeholders in the topic area under study."

Alicia Ault/IMNG Medical Media

Dr. Arl Van Moore Jr., a delegate from the American College of Radiology, said that neither the ACR nor any prominent breast imaging or surgical societies were contacted by the USPSTF in creating the screening mammography recommendations.

"None of the recognized experts in the field were contacted, to the best of our knowledge," said Dr. Moore, an interventional radiologist in Charlotte, N.C.

The American Urological Association delegate, Dr. William Gee, did not mince words when it came to the PSA screening guidelines.

"The [USPSTF] did not use an open process and ignored the public in reaching their conclusions," he said.

But Dr. Sally J. Trippel, a preventive medicine specialist at the Mayo Clinic and delegate from Minnesota, defended the USPSTF and its process. The task force is "about as politically independent as any national organization can get," and "about as free of conflict of interest as is possible in any organization developing guidelines for American clinicians," she said.

She quoted from task force documents showing that urologists provided peer review of the PSA evidence review. "So there were experts from urology involved in the development of that guideline," and also for the one on screening mammography.

To further show its consternation with the task force, AMA delegates also approved a report that stated that starting at age 40, women should be "eligible for screening mammography," and encouraging physicians "to regularly discuss with their individual patients the benefits and risks of screening mammography, and whether screening is appropriate for each clinical situation given that the balance of benefits and risks will be viewed differently by each patient."

Primary care delegates from the American Academy of Family Physicians and the American College of Physicians opposed the resolutions of concern against the USPSTF and the mammography report.

The AAFP supported the task force when it issued its mammography recommendations "because it was the most comprehensive pattern and set of preventive guidelines using current methodology with what was available in science at that time," said Dr. Roland Goertz, AAFP delegate.

The task force basically recommends what the AMA report urged: that physicians have discussions with their patients about risks and benefits, he said. The problem is not the USPSTF recommendations, but that they are being used to deny payment, he added.

Alicia Ault/IMNG Medical Media

Dr. Richard Reiling, a delegate from the American College of Surgeons, said that the task force had confused patients with its mammography recommendation, and called for the AMA to convene all interested parties to craft a single guideline. The USPSTF was "wrong in presenting this report without listening to the stakeholders in the past," he said, adding, "let’s get one guideline out there."

Dr. Goertz agreed that there needed to be a common guideline.

ACP Delegate Dr. William Golden expressed the ACP’s view that the House of Delegates was not the appropriate venue for voting on particular guidelines. "The House should not be in the position of voting on what guideline is best," he said.

CHICAGO – Delegates to the American Medical Association’s legislative body are not happy with the U.S. Preventive Services Task Force.

They voted overwhelmingly (322 to 93) to express "concern" over the task force’s recommendations on screening mammography and prostate-specific antigen screening. Both recommendations attracted a firestorm of criticism when they were issued – the mammography recommendation in 2009 and those on PSA testing in May.

Many delegates also said they thought that the USPSTF, a quasi-governmental group operating under the auspices of the Agency for Healthcare Research and Quality, had reached its decisions without proper input from specialty societies or experts in each field.

In a second resolution, the delegates voted to encourage the USPSTF to "implement procedures that allow for meaningful input on recommendation development from specialists and stakeholders in the topic area under study."

Alicia Ault/IMNG Medical Media

Dr. Arl Van Moore Jr., a delegate from the American College of Radiology, said that neither the ACR nor any prominent breast imaging or surgical societies were contacted by the USPSTF in creating the screening mammography recommendations.

"None of the recognized experts in the field were contacted, to the best of our knowledge," said Dr. Moore, an interventional radiologist in Charlotte, N.C.

The American Urological Association delegate, Dr. William Gee, did not mince words when it came to the PSA screening guidelines.

"The [USPSTF] did not use an open process and ignored the public in reaching their conclusions," he said.

But Dr. Sally J. Trippel, a preventive medicine specialist at the Mayo Clinic and delegate from Minnesota, defended the USPSTF and its process. The task force is "about as politically independent as any national organization can get," and "about as free of conflict of interest as is possible in any organization developing guidelines for American clinicians," she said.

She quoted from task force documents showing that urologists provided peer review of the PSA evidence review. "So there were experts from urology involved in the development of that guideline," and also for the one on screening mammography.

To further show its consternation with the task force, AMA delegates also approved a report that stated that starting at age 40, women should be "eligible for screening mammography," and encouraging physicians "to regularly discuss with their individual patients the benefits and risks of screening mammography, and whether screening is appropriate for each clinical situation given that the balance of benefits and risks will be viewed differently by each patient."

Primary care delegates from the American Academy of Family Physicians and the American College of Physicians opposed the resolutions of concern against the USPSTF and the mammography report.

The AAFP supported the task force when it issued its mammography recommendations "because it was the most comprehensive pattern and set of preventive guidelines using current methodology with what was available in science at that time," said Dr. Roland Goertz, AAFP delegate.

The task force basically recommends what the AMA report urged: that physicians have discussions with their patients about risks and benefits, he said. The problem is not the USPSTF recommendations, but that they are being used to deny payment, he added.

Alicia Ault/IMNG Medical Media

Dr. Richard Reiling, a delegate from the American College of Surgeons, said that the task force had confused patients with its mammography recommendation, and called for the AMA to convene all interested parties to craft a single guideline. The USPSTF was "wrong in presenting this report without listening to the stakeholders in the past," he said, adding, "let’s get one guideline out there."

Dr. Goertz agreed that there needed to be a common guideline.

ACP Delegate Dr. William Golden expressed the ACP’s view that the House of Delegates was not the appropriate venue for voting on particular guidelines. "The House should not be in the position of voting on what guideline is best," he said.

CHICAGO – An experimental therapy is closing in on a new target in metastatic castration-resistant prostate cancer: heat shock protein 27.

OGX-427 is a second-generation antisense oligonucleotide that is designed to reduce production of heat shock protein 27 (Hsp27), a cell-survival protein that is highly expressed in many cancers including prostate and associated with poorer prognosis. Hsp27 increases after castration therapy as a stress survival response and has been shown to be highly overexpressed in castration-resistant prostate cancer tissues, Dr. Kim N. Chi explained at the annual meeting of the American Society of Clinical Oncology.

In phase I studies, OGX-427 decreased tumor markers in patients with prostate and ovarian cancer and measurable disease by more than 15% in roughly one-third of patients. The drug has a prolonged half-life of about 10 days, but no dose-limiting toxicities were identified. Mostly the adverse events were dose-dependent, grade 1-2 infusion reactions, said Dr. Chi, chair of the genitourinary group and medical director of clinical trials at the Vancouver (British Columbia) Prostate Centre–BC Cancer Agency.

The goal of the current phase II trial was to improve the 12-week progression-free rate in chemotherapy naive men with metastatic castration-resistant prostate cancer. Patients were randomized to twice-daily prednisone 5 mg alone or with OGX-427 600 mg IV in three loading doses in the first week followed by 1,000 mg weekly for up to 24 weeks for patients with a best response of stable disease or continuously for responders.

The current analysis includes 42 of the 72 planned patients. Because of the frequent use of corticosteroids to manage infusion reactions, the control arm was added to isolate out the effect of OGX-427, he said.

The 22 patients in the OGX-427 arm were slightly younger than the 20 controls were (median 66 years vs. 72 years), but the OGX-427 arm had more patients with lung metastases (14% vs. 0%), elevated lactate dehydrogenase (36% vs. 15), elevated alkaline phosphatase (32% vs. 10%), prior prednisone therapy (23% vs. 15%) and 5 or more circulating tumor cells/7.5 mL of blood (96% vs. 90%), Dr. Chi pointed out.

Median treatment duration was 24 weeks with OGX-427 and 14 weeks with prednisone alone. In all, 93% of controls came off treatment because of disease progression vs. only 31% on OGX-427, although 25% also did so because of adverse events.

At 12 weeks, 71% of patients on OGX-427 were progression free, compared with 40% on prednisone alone, he said.

A prostate-specific antigen decline of 50% or more occurred in 50% and 20%, respectively.

The objective response rate was 44%, including one complete response and three partial responses, among nine evaluable OGX-427 patients vs. 0% among 12 evaluable controls.

Sixty percent of OGX-427 patients have had either a decrease of more than 5 circulating tumor cells/7.5 mL or maintained a less 5 cell/7.5 mL count, compared with 41% of controls having a similar decline.

Treatment-related events have been predominantly infusion related and were described as a flulike illness that occurs mainly in the first couple of infusions and includes grade 1/2 chills (55%), diarrhea (41%), nausea (32%), flushing (23%), vomiting (23%) and pyrexia (18%).

"Patients tend to build tolerance and they [events] are brief and self-limited," Dr. Chi said.

Grade 3/4 lymphopenia was more common with OGX-427 at 18% vs. 10% among controls but did not result in any infectious sequelae.

"These preliminary data identify Hsp27 as a novel therapeutic target and supports continued evaluation of OGX-427 for patients with castration-resistant prostate cancer," he concluded.

Discussant Dr. Karim Fizazi, with Institut Gustave Roussy, Villejuif, France, said he was surprised by the "quite-high" adverse event rates for chills, nausea, and diarrhea, but that fortunately they were mostly grade 1 and 2. He said the biological background for targeting Hsp27 is very strong and called the preliminary evidence of clinical activity exciting.

"If these data are confirmed, which I don’t really doubt they will, what will be the phase III development path for such IV [intravenous] weekly drug infusions in the context of all the drugs we now have in prostate cancer?" he asked.

The current trial is ongoing, with a phase II trial of OGX-427 plus abiraterone (Zytiga) in castration-resistant prostate cancer to be initiated later this year, according to OncoGenex Pharmaceuticals. The company is also developing the targeted anticlusterin molecule OGX-001 to be evaluated later this year in two phase III trials in castration-resistant disease.

Dr. Chi reports research funding from OncoGenex Pharmaceuticals, which is developing OGX-427. Dr. Fizazi reports a consultant or advisory role with OncoGenex and Exelixis.

CHICAGO – An experimental therapy is closing in on a new target in metastatic castration-resistant prostate cancer: heat shock protein 27.

OGX-427 is a second-generation antisense oligonucleotide that is designed to reduce production of heat shock protein 27 (Hsp27), a cell-survival protein that is highly expressed in many cancers including prostate and associated with poorer prognosis. Hsp27 increases after castration therapy as a stress survival response and has been shown to be highly overexpressed in castration-resistant prostate cancer tissues, Dr. Kim N. Chi explained at the annual meeting of the American Society of Clinical Oncology.

In phase I studies, OGX-427 decreased tumor markers in patients with prostate and ovarian cancer and measurable disease by more than 15% in roughly one-third of patients. The drug has a prolonged half-life of about 10 days, but no dose-limiting toxicities were identified. Mostly the adverse events were dose-dependent, grade 1-2 infusion reactions, said Dr. Chi, chair of the genitourinary group and medical director of clinical trials at the Vancouver (British Columbia) Prostate Centre–BC Cancer Agency.

The goal of the current phase II trial was to improve the 12-week progression-free rate in chemotherapy naive men with metastatic castration-resistant prostate cancer. Patients were randomized to twice-daily prednisone 5 mg alone or with OGX-427 600 mg IV in three loading doses in the first week followed by 1,000 mg weekly for up to 24 weeks for patients with a best response of stable disease or continuously for responders.

The current analysis includes 42 of the 72 planned patients. Because of the frequent use of corticosteroids to manage infusion reactions, the control arm was added to isolate out the effect of OGX-427, he said.

The 22 patients in the OGX-427 arm were slightly younger than the 20 controls were (median 66 years vs. 72 years), but the OGX-427 arm had more patients with lung metastases (14% vs. 0%), elevated lactate dehydrogenase (36% vs. 15), elevated alkaline phosphatase (32% vs. 10%), prior prednisone therapy (23% vs. 15%) and 5 or more circulating tumor cells/7.5 mL of blood (96% vs. 90%), Dr. Chi pointed out.

Median treatment duration was 24 weeks with OGX-427 and 14 weeks with prednisone alone. In all, 93% of controls came off treatment because of disease progression vs. only 31% on OGX-427, although 25% also did so because of adverse events.

At 12 weeks, 71% of patients on OGX-427 were progression free, compared with 40% on prednisone alone, he said.

A prostate-specific antigen decline of 50% or more occurred in 50% and 20%, respectively.

The objective response rate was 44%, including one complete response and three partial responses, among nine evaluable OGX-427 patients vs. 0% among 12 evaluable controls.

Sixty percent of OGX-427 patients have had either a decrease of more than 5 circulating tumor cells/7.5 mL or maintained a less 5 cell/7.5 mL count, compared with 41% of controls having a similar decline.

Treatment-related events have been predominantly infusion related and were described as a flulike illness that occurs mainly in the first couple of infusions and includes grade 1/2 chills (55%), diarrhea (41%), nausea (32%), flushing (23%), vomiting (23%) and pyrexia (18%).

"Patients tend to build tolerance and they [events] are brief and self-limited," Dr. Chi said.

Grade 3/4 lymphopenia was more common with OGX-427 at 18% vs. 10% among controls but did not result in any infectious sequelae.

"These preliminary data identify Hsp27 as a novel therapeutic target and supports continued evaluation of OGX-427 for patients with castration-resistant prostate cancer," he concluded.

Discussant Dr. Karim Fizazi, with Institut Gustave Roussy, Villejuif, France, said he was surprised by the "quite-high" adverse event rates for chills, nausea, and diarrhea, but that fortunately they were mostly grade 1 and 2. He said the biological background for targeting Hsp27 is very strong and called the preliminary evidence of clinical activity exciting.

"If these data are confirmed, which I don’t really doubt they will, what will be the phase III development path for such IV [intravenous] weekly drug infusions in the context of all the drugs we now have in prostate cancer?" he asked.

The current trial is ongoing, with a phase II trial of OGX-427 plus abiraterone (Zytiga) in castration-resistant prostate cancer to be initiated later this year, according to OncoGenex Pharmaceuticals. The company is also developing the targeted anticlusterin molecule OGX-001 to be evaluated later this year in two phase III trials in castration-resistant disease.

Dr. Chi reports research funding from OncoGenex Pharmaceuticals, which is developing OGX-427. Dr. Fizazi reports a consultant or advisory role with OncoGenex and Exelixis.

CHICAGO – An experimental therapy is closing in on a new target in metastatic castration-resistant prostate cancer: heat shock protein 27.

OGX-427 is a second-generation antisense oligonucleotide that is designed to reduce production of heat shock protein 27 (Hsp27), a cell-survival protein that is highly expressed in many cancers including prostate and associated with poorer prognosis. Hsp27 increases after castration therapy as a stress survival response and has been shown to be highly overexpressed in castration-resistant prostate cancer tissues, Dr. Kim N. Chi explained at the annual meeting of the American Society of Clinical Oncology.

In phase I studies, OGX-427 decreased tumor markers in patients with prostate and ovarian cancer and measurable disease by more than 15% in roughly one-third of patients. The drug has a prolonged half-life of about 10 days, but no dose-limiting toxicities were identified. Mostly the adverse events were dose-dependent, grade 1-2 infusion reactions, said Dr. Chi, chair of the genitourinary group and medical director of clinical trials at the Vancouver (British Columbia) Prostate Centre–BC Cancer Agency.

The goal of the current phase II trial was to improve the 12-week progression-free rate in chemotherapy naive men with metastatic castration-resistant prostate cancer. Patients were randomized to twice-daily prednisone 5 mg alone or with OGX-427 600 mg IV in three loading doses in the first week followed by 1,000 mg weekly for up to 24 weeks for patients with a best response of stable disease or continuously for responders.

The current analysis includes 42 of the 72 planned patients. Because of the frequent use of corticosteroids to manage infusion reactions, the control arm was added to isolate out the effect of OGX-427, he said.

The 22 patients in the OGX-427 arm were slightly younger than the 20 controls were (median 66 years vs. 72 years), but the OGX-427 arm had more patients with lung metastases (14% vs. 0%), elevated lactate dehydrogenase (36% vs. 15), elevated alkaline phosphatase (32% vs. 10%), prior prednisone therapy (23% vs. 15%) and 5 or more circulating tumor cells/7.5 mL of blood (96% vs. 90%), Dr. Chi pointed out.

Median treatment duration was 24 weeks with OGX-427 and 14 weeks with prednisone alone. In all, 93% of controls came off treatment because of disease progression vs. only 31% on OGX-427, although 25% also did so because of adverse events.

At 12 weeks, 71% of patients on OGX-427 were progression free, compared with 40% on prednisone alone, he said.

A prostate-specific antigen decline of 50% or more occurred in 50% and 20%, respectively.

The objective response rate was 44%, including one complete response and three partial responses, among nine evaluable OGX-427 patients vs. 0% among 12 evaluable controls.

Sixty percent of OGX-427 patients have had either a decrease of more than 5 circulating tumor cells/7.5 mL or maintained a less 5 cell/7.5 mL count, compared with 41% of controls having a similar decline.

Treatment-related events have been predominantly infusion related and were described as a flulike illness that occurs mainly in the first couple of infusions and includes grade 1/2 chills (55%), diarrhea (41%), nausea (32%), flushing (23%), vomiting (23%) and pyrexia (18%).

"Patients tend to build tolerance and they [events] are brief and self-limited," Dr. Chi said.

Grade 3/4 lymphopenia was more common with OGX-427 at 18% vs. 10% among controls but did not result in any infectious sequelae.

"These preliminary data identify Hsp27 as a novel therapeutic target and supports continued evaluation of OGX-427 for patients with castration-resistant prostate cancer," he concluded.

Discussant Dr. Karim Fizazi, with Institut Gustave Roussy, Villejuif, France, said he was surprised by the "quite-high" adverse event rates for chills, nausea, and diarrhea, but that fortunately they were mostly grade 1 and 2. He said the biological background for targeting Hsp27 is very strong and called the preliminary evidence of clinical activity exciting.

"If these data are confirmed, which I don’t really doubt they will, what will be the phase III development path for such IV [intravenous] weekly drug infusions in the context of all the drugs we now have in prostate cancer?" he asked.

The current trial is ongoing, with a phase II trial of OGX-427 plus abiraterone (Zytiga) in castration-resistant prostate cancer to be initiated later this year, according to OncoGenex Pharmaceuticals. The company is also developing the targeted anticlusterin molecule OGX-001 to be evaluated later this year in two phase III trials in castration-resistant disease.

Dr. Chi reports research funding from OncoGenex Pharmaceuticals, which is developing OGX-427. Dr. Fizazi reports a consultant or advisory role with OncoGenex and Exelixis.

Robert R. Bahnson, MD, FACS, chief of staff at The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and chairman of the Department of Urology at The Ohio State University in Columbus, was named chair of the ACSPA-SurgeonsPAC (the American College of Surgeons Professional Association’s political action committee). The announcement was made during the June 9 meeting of the ACS Board of Regents in Chicago, IL.

Dr. Bahnson has an expansive leadership record with the College. He currently serves as First Vice-President of the ACS and as a consultant to the 2012 Clinical Congress Program Planning Committee. In previous years, Dr. Bahnson served as Chair of the ACS Advisory Council for Urology and the Advisory Council Chairs. In addition, he served on the Board of Governors and the Postgraduate Education Committee. He also served as Vice-Chair of the Clinical Congress Program Planning Committee. A detailed article regarding Dr. Bahnson’s appointment will appear in the August issue the Bulletin of the American College of Surgeons. For more information, go to www.facs.org/acspa/index.html.☐

Robert R. Bahnson, MD, FACS, chief of staff at The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and chairman of the Department of Urology at The Ohio State University in Columbus, was named chair of the ACSPA-SurgeonsPAC (the American College of Surgeons Professional Association’s political action committee). The announcement was made during the June 9 meeting of the ACS Board of Regents in Chicago, IL.

Dr. Bahnson has an expansive leadership record with the College. He currently serves as First Vice-President of the ACS and as a consultant to the 2012 Clinical Congress Program Planning Committee. In previous years, Dr. Bahnson served as Chair of the ACS Advisory Council for Urology and the Advisory Council Chairs. In addition, he served on the Board of Governors and the Postgraduate Education Committee. He also served as Vice-Chair of the Clinical Congress Program Planning Committee. A detailed article regarding Dr. Bahnson’s appointment will appear in the August issue the Bulletin of the American College of Surgeons. For more information, go to www.facs.org/acspa/index.html.☐

Robert R. Bahnson, MD, FACS, chief of staff at The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and chairman of the Department of Urology at The Ohio State University in Columbus, was named chair of the ACSPA-SurgeonsPAC (the American College of Surgeons Professional Association’s political action committee). The announcement was made during the June 9 meeting of the ACS Board of Regents in Chicago, IL.

Dr. Bahnson has an expansive leadership record with the College. He currently serves as First Vice-President of the ACS and as a consultant to the 2012 Clinical Congress Program Planning Committee. In previous years, Dr. Bahnson served as Chair of the ACS Advisory Council for Urology and the Advisory Council Chairs. In addition, he served on the Board of Governors and the Postgraduate Education Committee. He also served as Vice-Chair of the Clinical Congress Program Planning Committee. A detailed article regarding Dr. Bahnson’s appointment will appear in the August issue the Bulletin of the American College of Surgeons. For more information, go to www.facs.org/acspa/index.html.☐