Genitourinary Cancer

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

Job stress was not directly associated with the risks of lung, breast, colorectal, or prostate cancer in a large retrospective study.

"Work-related psychosocial stress is unlikely to be an important risk factor for these cancers," wrote Katriina Heikkilä, Ph.D., and her coauthors in the Feb. 7 issue of the British Medical Journal (BMJ 2013;346b:f165 [doi: 10.1136/bmj.f165]).

"Thus, though reducing work stress would undoubtedly improve the psychological and physical well-being of the working individuals as well as the working population, it is unlikely to have an important impact on cancer burden at a population level."

The study does not completely exonerate the role of stress in predisposing to cancer, said Dr. Heikkilä of the Finnish Institute of Occupational Health, Helsinki.

"For example, in a meta-analysis of different types of stress and risk of breast cancer, stress from adverse life events was consistently associated with an increased risk (Breast Cancer Res. 2011;13:208). ... In a French study, people with brain cancer were more likely to report adverse life events than controls without cancer, but there was no clear evidence for a difference in terms of stress at work between these groups (J. Neurooncol. 2011;103:307-16)."

The review included 116,056 subjects who had participated in 10 different trials conducted in Denmark, Finland, and Sweden. The mean follow-up in these studies was 12 years, but follow-up ranged from 5-23 years.

This long span is a particular strength of the review, the authors noted, "because most cancers have a latent period of years or even decades. If a true association between job strain and incident cancer existed because the physiological stress response has a role in cancer promotion or progression (for example, via the regulation of the inflammatory pathways), the follow-up periods in our analyses should have been long enough to detect such an association."

At baseline, the subjects were a mean of 38 years old. Most (62%) were of normal weight. A quarter of the subjects smoked tobacco at baseline, while 10% were classified as heavy drinkers, defined as consuming at least 15 drinks per week for women and 22 drinks per week for men.

Psychological stress at work was defined as a combination of high work demand and low control at the workplace. The results were examined as stress or no stress, and in quartiles of high-stress job (high demand/low control); active job (high demand/high control); passive job (low demand/low control); and low-strain job (low demand/high control). This was measured with a Likert-type scale and ascertained by questions taken from two validated stress questionnaires. The investigators also controlled for age, gender, socioeconomic position, body mass index, smoking, and alcohol intake.

The overall rate of cancer was 5% (5,765). The largest proportion of these cancers was breast cancer (0.9% of the study cohort; 1,010), followed by prostate cancer (0.7%; 865), colorectal cancer (0.5%; 522), and lung cancer (0.3%; 374).

In the binary analysis of job stress/no job stress, there was no significant association with overall cancer risk (hazard ratio, 0.97).

Nor were there significant associations between job stress and colorectal cancer (HR, 1.16), breast cancer (HR, 0.97), lung cancer (HR, 1.17), or prostate cancer (HR, 0.86). "There was also no clear evidence for an association between the categories of job strain and the risk of cancer," the authors wrote.

The study "suggests that many of the previously reported associations ... between work-related stress and risk of cancer could have been influenced by chance, low power in some studies, different covariate adjustment, or residual confounding from possible unmeasured common causes of work stress and cancer. Such common causes could include shift work (for which there is some evidence of an association with risk of breast cancer) or other sources of stress, perhaps combined with one another."

The study was sponsored by several research consortiums and federal agencies in Scandinavia. None of the authors had any financial disclosures.

michele.sullivan@elsevier.com

Job stress was not directly associated with the risks of lung, breast, colorectal, or prostate cancer in a large retrospective study.

"Work-related psychosocial stress is unlikely to be an important risk factor for these cancers," wrote Katriina Heikkilä, Ph.D., and her coauthors in the Feb. 7 issue of the British Medical Journal (BMJ 2013;346b:f165 [doi: 10.1136/bmj.f165]).

"Thus, though reducing work stress would undoubtedly improve the psychological and physical well-being of the working individuals as well as the working population, it is unlikely to have an important impact on cancer burden at a population level."

The study does not completely exonerate the role of stress in predisposing to cancer, said Dr. Heikkilä of the Finnish Institute of Occupational Health, Helsinki.

"For example, in a meta-analysis of different types of stress and risk of breast cancer, stress from adverse life events was consistently associated with an increased risk (Breast Cancer Res. 2011;13:208). ... In a French study, people with brain cancer were more likely to report adverse life events than controls without cancer, but there was no clear evidence for a difference in terms of stress at work between these groups (J. Neurooncol. 2011;103:307-16)."

The review included 116,056 subjects who had participated in 10 different trials conducted in Denmark, Finland, and Sweden. The mean follow-up in these studies was 12 years, but follow-up ranged from 5-23 years.

This long span is a particular strength of the review, the authors noted, "because most cancers have a latent period of years or even decades. If a true association between job strain and incident cancer existed because the physiological stress response has a role in cancer promotion or progression (for example, via the regulation of the inflammatory pathways), the follow-up periods in our analyses should have been long enough to detect such an association."

At baseline, the subjects were a mean of 38 years old. Most (62%) were of normal weight. A quarter of the subjects smoked tobacco at baseline, while 10% were classified as heavy drinkers, defined as consuming at least 15 drinks per week for women and 22 drinks per week for men.

Psychological stress at work was defined as a combination of high work demand and low control at the workplace. The results were examined as stress or no stress, and in quartiles of high-stress job (high demand/low control); active job (high demand/high control); passive job (low demand/low control); and low-strain job (low demand/high control). This was measured with a Likert-type scale and ascertained by questions taken from two validated stress questionnaires. The investigators also controlled for age, gender, socioeconomic position, body mass index, smoking, and alcohol intake.

The overall rate of cancer was 5% (5,765). The largest proportion of these cancers was breast cancer (0.9% of the study cohort; 1,010), followed by prostate cancer (0.7%; 865), colorectal cancer (0.5%; 522), and lung cancer (0.3%; 374).

In the binary analysis of job stress/no job stress, there was no significant association with overall cancer risk (hazard ratio, 0.97).

Nor were there significant associations between job stress and colorectal cancer (HR, 1.16), breast cancer (HR, 0.97), lung cancer (HR, 1.17), or prostate cancer (HR, 0.86). "There was also no clear evidence for an association between the categories of job strain and the risk of cancer," the authors wrote.

The study "suggests that many of the previously reported associations ... between work-related stress and risk of cancer could have been influenced by chance, low power in some studies, different covariate adjustment, or residual confounding from possible unmeasured common causes of work stress and cancer. Such common causes could include shift work (for which there is some evidence of an association with risk of breast cancer) or other sources of stress, perhaps combined with one another."

The study was sponsored by several research consortiums and federal agencies in Scandinavia. None of the authors had any financial disclosures.

michele.sullivan@elsevier.com

Job stress was not directly associated with the risks of lung, breast, colorectal, or prostate cancer in a large retrospective study.

"Work-related psychosocial stress is unlikely to be an important risk factor for these cancers," wrote Katriina Heikkilä, Ph.D., and her coauthors in the Feb. 7 issue of the British Medical Journal (BMJ 2013;346b:f165 [doi: 10.1136/bmj.f165]).

"Thus, though reducing work stress would undoubtedly improve the psychological and physical well-being of the working individuals as well as the working population, it is unlikely to have an important impact on cancer burden at a population level."

The study does not completely exonerate the role of stress in predisposing to cancer, said Dr. Heikkilä of the Finnish Institute of Occupational Health, Helsinki.

"For example, in a meta-analysis of different types of stress and risk of breast cancer, stress from adverse life events was consistently associated with an increased risk (Breast Cancer Res. 2011;13:208). ... In a French study, people with brain cancer were more likely to report adverse life events than controls without cancer, but there was no clear evidence for a difference in terms of stress at work between these groups (J. Neurooncol. 2011;103:307-16)."

The review included 116,056 subjects who had participated in 10 different trials conducted in Denmark, Finland, and Sweden. The mean follow-up in these studies was 12 years, but follow-up ranged from 5-23 years.

This long span is a particular strength of the review, the authors noted, "because most cancers have a latent period of years or even decades. If a true association between job strain and incident cancer existed because the physiological stress response has a role in cancer promotion or progression (for example, via the regulation of the inflammatory pathways), the follow-up periods in our analyses should have been long enough to detect such an association."

At baseline, the subjects were a mean of 38 years old. Most (62%) were of normal weight. A quarter of the subjects smoked tobacco at baseline, while 10% were classified as heavy drinkers, defined as consuming at least 15 drinks per week for women and 22 drinks per week for men.

Psychological stress at work was defined as a combination of high work demand and low control at the workplace. The results were examined as stress or no stress, and in quartiles of high-stress job (high demand/low control); active job (high demand/high control); passive job (low demand/low control); and low-strain job (low demand/high control). This was measured with a Likert-type scale and ascertained by questions taken from two validated stress questionnaires. The investigators also controlled for age, gender, socioeconomic position, body mass index, smoking, and alcohol intake.

The overall rate of cancer was 5% (5,765). The largest proportion of these cancers was breast cancer (0.9% of the study cohort; 1,010), followed by prostate cancer (0.7%; 865), colorectal cancer (0.5%; 522), and lung cancer (0.3%; 374).

In the binary analysis of job stress/no job stress, there was no significant association with overall cancer risk (hazard ratio, 0.97).

Nor were there significant associations between job stress and colorectal cancer (HR, 1.16), breast cancer (HR, 0.97), lung cancer (HR, 1.17), or prostate cancer (HR, 0.86). "There was also no clear evidence for an association between the categories of job strain and the risk of cancer," the authors wrote.

The study "suggests that many of the previously reported associations ... between work-related stress and risk of cancer could have been influenced by chance, low power in some studies, different covariate adjustment, or residual confounding from possible unmeasured common causes of work stress and cancer. Such common causes could include shift work (for which there is some evidence of an association with risk of breast cancer) or other sources of stress, perhaps combined with one another."

The study was sponsored by several research consortiums and federal agencies in Scandinavia. None of the authors had any financial disclosures.

michele.sullivan@elsevier.com

Fifteen years after treatment for localized prostate cancer, men who underwent radical prostatectomy reported no differences in urinary, bowel, or sexual function compared with men who underwent external-beam radiation, according to a report published online Jan. 30 in the New England Journal of Medicine.

Using data from the Prostate Cancer Outcomes Study (PCOS), a population-based cohort of men across the United States diagnosed as having prostate cancer in the mid-1990s, researchers tracked the long-term disease-specific outcomes of 1,655 men who underwent radical prostatectomy (70.3% of patients) or radiotherapy (29.7%), with or without androgen-deprivation therapy.

Source: American Gastroenterological Association (www.youtube.com/AmerGastroAssn)

"Since the median life expectancy after treatment for prostate cancer is 13.8 years, a careful evaluation of long-term functional outcomes is critical to an understanding of the comprehensive experience of men living with a diagnosis of prostate cancer," said Dr. Matthew J. Resnick of the department of urologic surgery and the Center for Surgical Quality and Outcomes Research, Vanderbilt University, Nashville, Tenn., and his associates.

Even though men who had radical prostatectomy were more likely to be bothered by such difficulties as urinary incontinence, bowel urgency, and erectile dysfunction at 2 years and 5 years after treatment, those differences disappeared by the 15-year mark. At that time, the prevalence of ED was "nearly universal," affecting 87% of men in the prostatectomy group and 94% of those in the radiotherapy group; yet only 43% and 38%, respectively, reported that this bothered them.

"Long-term follow-up reveals consistent functional declines after 5 years. It remains unknown whether this continued decline is due to prostate cancer and its treatment, the normal aging process, or a combination of factors," the investigators said (N. Engl. J. Med. 2013 [doi10.1056/NEJMoa1209978]).

This study was funded by the National Cancer Institute. Dr. Resnick was supported by the VA National Quality Scholars Program and the T. J. Martell Foundation. Dr. Resnick reported ties to Dendreon and Bayer Healthcare, and his associates reported ties to Ferring and Johnson & Johnson.

Fifteen years after treatment for localized prostate cancer, men who underwent radical prostatectomy reported no differences in urinary, bowel, or sexual function compared with men who underwent external-beam radiation, according to a report published online Jan. 30 in the New England Journal of Medicine.

Using data from the Prostate Cancer Outcomes Study (PCOS), a population-based cohort of men across the United States diagnosed as having prostate cancer in the mid-1990s, researchers tracked the long-term disease-specific outcomes of 1,655 men who underwent radical prostatectomy (70.3% of patients) or radiotherapy (29.7%), with or without androgen-deprivation therapy.

Source: American Gastroenterological Association (www.youtube.com/AmerGastroAssn)

"Since the median life expectancy after treatment for prostate cancer is 13.8 years, a careful evaluation of long-term functional outcomes is critical to an understanding of the comprehensive experience of men living with a diagnosis of prostate cancer," said Dr. Matthew J. Resnick of the department of urologic surgery and the Center for Surgical Quality and Outcomes Research, Vanderbilt University, Nashville, Tenn., and his associates.

Even though men who had radical prostatectomy were more likely to be bothered by such difficulties as urinary incontinence, bowel urgency, and erectile dysfunction at 2 years and 5 years after treatment, those differences disappeared by the 15-year mark. At that time, the prevalence of ED was "nearly universal," affecting 87% of men in the prostatectomy group and 94% of those in the radiotherapy group; yet only 43% and 38%, respectively, reported that this bothered them.

"Long-term follow-up reveals consistent functional declines after 5 years. It remains unknown whether this continued decline is due to prostate cancer and its treatment, the normal aging process, or a combination of factors," the investigators said (N. Engl. J. Med. 2013 [doi10.1056/NEJMoa1209978]).

This study was funded by the National Cancer Institute. Dr. Resnick was supported by the VA National Quality Scholars Program and the T. J. Martell Foundation. Dr. Resnick reported ties to Dendreon and Bayer Healthcare, and his associates reported ties to Ferring and Johnson & Johnson.

Fifteen years after treatment for localized prostate cancer, men who underwent radical prostatectomy reported no differences in urinary, bowel, or sexual function compared with men who underwent external-beam radiation, according to a report published online Jan. 30 in the New England Journal of Medicine.

Using data from the Prostate Cancer Outcomes Study (PCOS), a population-based cohort of men across the United States diagnosed as having prostate cancer in the mid-1990s, researchers tracked the long-term disease-specific outcomes of 1,655 men who underwent radical prostatectomy (70.3% of patients) or radiotherapy (29.7%), with or without androgen-deprivation therapy.

Source: American Gastroenterological Association (www.youtube.com/AmerGastroAssn)

"Since the median life expectancy after treatment for prostate cancer is 13.8 years, a careful evaluation of long-term functional outcomes is critical to an understanding of the comprehensive experience of men living with a diagnosis of prostate cancer," said Dr. Matthew J. Resnick of the department of urologic surgery and the Center for Surgical Quality and Outcomes Research, Vanderbilt University, Nashville, Tenn., and his associates.

Even though men who had radical prostatectomy were more likely to be bothered by such difficulties as urinary incontinence, bowel urgency, and erectile dysfunction at 2 years and 5 years after treatment, those differences disappeared by the 15-year mark. At that time, the prevalence of ED was "nearly universal," affecting 87% of men in the prostatectomy group and 94% of those in the radiotherapy group; yet only 43% and 38%, respectively, reported that this bothered them.

"Long-term follow-up reveals consistent functional declines after 5 years. It remains unknown whether this continued decline is due to prostate cancer and its treatment, the normal aging process, or a combination of factors," the investigators said (N. Engl. J. Med. 2013 [doi10.1056/NEJMoa1209978]).

This study was funded by the National Cancer Institute. Dr. Resnick was supported by the VA National Quality Scholars Program and the T. J. Martell Foundation. Dr. Resnick reported ties to Dendreon and Bayer Healthcare, and his associates reported ties to Ferring and Johnson & Johnson.

At the risk of foolishly rushing into topics about which angels commonly fear discourse, we need to continue our journey this year through the clinical management of clinically localized prostate cancer. We – and I am including myself in this – should make a new year’s resolution to be self-reflective, explore our biases and preconceived notions, and observe and chart new and emerging data. Several trials are ongoing which may more brightly illuminate our path.

Dr. Jenny L. Donovan of the University of Bristol (England) recently published an article in the Journal of the National Cancer Institute Mongraphs brilliantly summarizing the current state of the debate (2012;45:191-6). She describes the maturation of our "group think" as we evolved from a strategy of watchful waiting only for those men with limited life expectancy to a deeper realization and appreciation for the downsides of radical intervention for nonaggressive disease.

Clinicians hold an enormous amount of sway in the decisions that patients make about clinical care, and personal and professional biases commonly take the helm. When it comes to complex clinical issues, most of us have neither a firm grasp on the data nor the time to explain it.

Decision aids are an effective clinical tool that can improve the quality of the decisions about screening and treatment. For prostate cancer screening, decision aids enhance patient knowledge, reduce decisional conflict, and reduce interest in prostate-specific antigen screening. Relatively less is known about how treatment should be presented to enhance decision making.

Dr. Donovan describes Prostate Testing for Cancer and Treatment (ProtecT), which has enrolled more than 3,000 men with clinically localized prostate cancer, and compares radical prostatectomy, radiotherapy, and active monitoring.

In the process of recruiting for the study, investigators learned that "watchful waiting" was frequently interpreted as "no treatment." As a result, the term was changed to "active monitoring." Decisions, in clinical medicine, as in business, are contingent upon the salesperson, and word choice is crucial. Data from this trial are expected in 2016.

In the meantime, we can facilitate our decision with the use of an amazingly helpful online decision aid produced by the federal Agency for Healthcare Research and Quality. This tool is designed for patients with clinically localized prostate cancer. This may serve as a useful homework assignment for our Internet-savvy patients.

Providing our patients with this degree of information will empower them and advance our clinical discussions about prostate cancer treatment.

This column, "What Matters," regularly appears in Internal Medicine News, a publication of Frontline Medical Communications. Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at imnews@elsevier.com.

At the risk of foolishly rushing into topics about which angels commonly fear discourse, we need to continue our journey this year through the clinical management of clinically localized prostate cancer. We – and I am including myself in this – should make a new year’s resolution to be self-reflective, explore our biases and preconceived notions, and observe and chart new and emerging data. Several trials are ongoing which may more brightly illuminate our path.

Dr. Jenny L. Donovan of the University of Bristol (England) recently published an article in the Journal of the National Cancer Institute Mongraphs brilliantly summarizing the current state of the debate (2012;45:191-6). She describes the maturation of our "group think" as we evolved from a strategy of watchful waiting only for those men with limited life expectancy to a deeper realization and appreciation for the downsides of radical intervention for nonaggressive disease.

Clinicians hold an enormous amount of sway in the decisions that patients make about clinical care, and personal and professional biases commonly take the helm. When it comes to complex clinical issues, most of us have neither a firm grasp on the data nor the time to explain it.

Decision aids are an effective clinical tool that can improve the quality of the decisions about screening and treatment. For prostate cancer screening, decision aids enhance patient knowledge, reduce decisional conflict, and reduce interest in prostate-specific antigen screening. Relatively less is known about how treatment should be presented to enhance decision making.

Dr. Donovan describes Prostate Testing for Cancer and Treatment (ProtecT), which has enrolled more than 3,000 men with clinically localized prostate cancer, and compares radical prostatectomy, radiotherapy, and active monitoring.

In the process of recruiting for the study, investigators learned that "watchful waiting" was frequently interpreted as "no treatment." As a result, the term was changed to "active monitoring." Decisions, in clinical medicine, as in business, are contingent upon the salesperson, and word choice is crucial. Data from this trial are expected in 2016.

In the meantime, we can facilitate our decision with the use of an amazingly helpful online decision aid produced by the federal Agency for Healthcare Research and Quality. This tool is designed for patients with clinically localized prostate cancer. This may serve as a useful homework assignment for our Internet-savvy patients.

Providing our patients with this degree of information will empower them and advance our clinical discussions about prostate cancer treatment.

This column, "What Matters," regularly appears in Internal Medicine News, a publication of Frontline Medical Communications. Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at imnews@elsevier.com.

At the risk of foolishly rushing into topics about which angels commonly fear discourse, we need to continue our journey this year through the clinical management of clinically localized prostate cancer. We – and I am including myself in this – should make a new year’s resolution to be self-reflective, explore our biases and preconceived notions, and observe and chart new and emerging data. Several trials are ongoing which may more brightly illuminate our path.

Dr. Jenny L. Donovan of the University of Bristol (England) recently published an article in the Journal of the National Cancer Institute Mongraphs brilliantly summarizing the current state of the debate (2012;45:191-6). She describes the maturation of our "group think" as we evolved from a strategy of watchful waiting only for those men with limited life expectancy to a deeper realization and appreciation for the downsides of radical intervention for nonaggressive disease.

Clinicians hold an enormous amount of sway in the decisions that patients make about clinical care, and personal and professional biases commonly take the helm. When it comes to complex clinical issues, most of us have neither a firm grasp on the data nor the time to explain it.

Decision aids are an effective clinical tool that can improve the quality of the decisions about screening and treatment. For prostate cancer screening, decision aids enhance patient knowledge, reduce decisional conflict, and reduce interest in prostate-specific antigen screening. Relatively less is known about how treatment should be presented to enhance decision making.

Dr. Donovan describes Prostate Testing for Cancer and Treatment (ProtecT), which has enrolled more than 3,000 men with clinically localized prostate cancer, and compares radical prostatectomy, radiotherapy, and active monitoring.

In the process of recruiting for the study, investigators learned that "watchful waiting" was frequently interpreted as "no treatment." As a result, the term was changed to "active monitoring." Decisions, in clinical medicine, as in business, are contingent upon the salesperson, and word choice is crucial. Data from this trial are expected in 2016.

In the meantime, we can facilitate our decision with the use of an amazingly helpful online decision aid produced by the federal Agency for Healthcare Research and Quality. This tool is designed for patients with clinically localized prostate cancer. This may serve as a useful homework assignment for our Internet-savvy patients.

Providing our patients with this degree of information will empower them and advance our clinical discussions about prostate cancer treatment.

This column, "What Matters," regularly appears in Internal Medicine News, a publication of Frontline Medical Communications. Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at imnews@elsevier.com.

Encouraging manufacturers to develop opioid products that are formulated to deter abuse is one of the main goals of a new draft guidance released Jan. 9 by the Food and Drug Administration.

"Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling" provides information for companies interested in developing formulations of opioids with potential abuse deterrent properties, Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said at a briefing.

The document explains the agency’s views on the types of studies that should be conducted to show that a product can deter abuse, how those studies will be evaluated by the agency, and what labeling claims would be allowed based on the results of the FDA’s evaluations of those data. The ability to add abuse deterrent claims to a product’s label is expected to encourage companies to develop these products, he said.

The technology of formulations that deter abuse and the clinical epidemiology and statistical methods used to evaluate the potential of such products for abuse deterrence is a relatively new area of research, and the FDA plans "to take a flexible approach" in evaluating these products as the science evolves, Dr. Throckmorton said.

During the briefing, he pointed out that the guidance is one of the components of the FDA’s effort to prevent prescription drug abuse and misuse, "while ensuring patients in pain continue to have access to these medicines." In 2009, almost 425,000 visits to emergency departments involving nonmedical or inappropriate use of opioids and an estimated 15,600 deaths in the United States were attributed to opioid products, he said.

This draft guidance fulfills mandates under the Food and Drug Administration Safety and Innovation Act and the Office of National Drug Control Policy’s Prescription Drug Abuse Prevention Plan.

The FDA statement announcing the guidance explains that abuse deterrent formulations "target the known or expected routes of abuse, such as crushing in order to snort or dissolving in order to inject, for the specific opioid drug substance in that formulation" and that the agency believes these formulations have "promise to help reduce prescription drug abuse."

Two opioid products with abuse deterrent formulations are currently available: Since 2010, OxyContin (controlled-release oxycodone) has been available in a formulation that prevents it from being chewed, crushed, or dissolved. A crush-resistant formulation of hydromorphone (Opana ER) was approved in September 2012. But the prescribing information for these products do not include claims regarding abuse deterrence properties.

The lack of abuse deterrent features was the main reason an FDA advisory panel recommended against approval of an extended-release, single-ingredient capsule formulation of hydrocodone at a meeting in December. Without such a feature, the product would quickly become widely abused once it was approved and marketed, some of the panelists predicted.

The FDA plans to hold a public meeting to discuss public feedback on the draft guidance.

During the briefing, Dr. Throckmorton said that the FDA had not yet decided what to do about generic formulations of opioids that have no abuse deterrent properties.

The guidance "is an important part of a larger effort by FDA aimed at preventing prescription drug abuse and misuse," and the agency is "extremely concerned about the inappropriate use of prescription opioids, which is a major public health challenge for our nation," FDA commissioner Dr. Margaret Hamburg said in the statement.

Comments and suggestions can be submitted to the FDA within 60 days of publication in the Federal Register, to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, Md., 20852 , with the docket number listed.

e.mechcatie@elsevier.com

Encouraging manufacturers to develop opioid products that are formulated to deter abuse is one of the main goals of a new draft guidance released Jan. 9 by the Food and Drug Administration.

"Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling" provides information for companies interested in developing formulations of opioids with potential abuse deterrent properties, Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said at a briefing.

The document explains the agency’s views on the types of studies that should be conducted to show that a product can deter abuse, how those studies will be evaluated by the agency, and what labeling claims would be allowed based on the results of the FDA’s evaluations of those data. The ability to add abuse deterrent claims to a product’s label is expected to encourage companies to develop these products, he said.

The technology of formulations that deter abuse and the clinical epidemiology and statistical methods used to evaluate the potential of such products for abuse deterrence is a relatively new area of research, and the FDA plans "to take a flexible approach" in evaluating these products as the science evolves, Dr. Throckmorton said.

During the briefing, he pointed out that the guidance is one of the components of the FDA’s effort to prevent prescription drug abuse and misuse, "while ensuring patients in pain continue to have access to these medicines." In 2009, almost 425,000 visits to emergency departments involving nonmedical or inappropriate use of opioids and an estimated 15,600 deaths in the United States were attributed to opioid products, he said.

This draft guidance fulfills mandates under the Food and Drug Administration Safety and Innovation Act and the Office of National Drug Control Policy’s Prescription Drug Abuse Prevention Plan.

The FDA statement announcing the guidance explains that abuse deterrent formulations "target the known or expected routes of abuse, such as crushing in order to snort or dissolving in order to inject, for the specific opioid drug substance in that formulation" and that the agency believes these formulations have "promise to help reduce prescription drug abuse."

Two opioid products with abuse deterrent formulations are currently available: Since 2010, OxyContin (controlled-release oxycodone) has been available in a formulation that prevents it from being chewed, crushed, or dissolved. A crush-resistant formulation of hydromorphone (Opana ER) was approved in September 2012. But the prescribing information for these products do not include claims regarding abuse deterrence properties.

The lack of abuse deterrent features was the main reason an FDA advisory panel recommended against approval of an extended-release, single-ingredient capsule formulation of hydrocodone at a meeting in December. Without such a feature, the product would quickly become widely abused once it was approved and marketed, some of the panelists predicted.

The FDA plans to hold a public meeting to discuss public feedback on the draft guidance.

During the briefing, Dr. Throckmorton said that the FDA had not yet decided what to do about generic formulations of opioids that have no abuse deterrent properties.

The guidance "is an important part of a larger effort by FDA aimed at preventing prescription drug abuse and misuse," and the agency is "extremely concerned about the inappropriate use of prescription opioids, which is a major public health challenge for our nation," FDA commissioner Dr. Margaret Hamburg said in the statement.

Comments and suggestions can be submitted to the FDA within 60 days of publication in the Federal Register, to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, Md., 20852 , with the docket number listed.

e.mechcatie@elsevier.com

Encouraging manufacturers to develop opioid products that are formulated to deter abuse is one of the main goals of a new draft guidance released Jan. 9 by the Food and Drug Administration.

"Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling" provides information for companies interested in developing formulations of opioids with potential abuse deterrent properties, Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said at a briefing.

The document explains the agency’s views on the types of studies that should be conducted to show that a product can deter abuse, how those studies will be evaluated by the agency, and what labeling claims would be allowed based on the results of the FDA’s evaluations of those data. The ability to add abuse deterrent claims to a product’s label is expected to encourage companies to develop these products, he said.

The technology of formulations that deter abuse and the clinical epidemiology and statistical methods used to evaluate the potential of such products for abuse deterrence is a relatively new area of research, and the FDA plans "to take a flexible approach" in evaluating these products as the science evolves, Dr. Throckmorton said.

During the briefing, he pointed out that the guidance is one of the components of the FDA’s effort to prevent prescription drug abuse and misuse, "while ensuring patients in pain continue to have access to these medicines." In 2009, almost 425,000 visits to emergency departments involving nonmedical or inappropriate use of opioids and an estimated 15,600 deaths in the United States were attributed to opioid products, he said.

This draft guidance fulfills mandates under the Food and Drug Administration Safety and Innovation Act and the Office of National Drug Control Policy’s Prescription Drug Abuse Prevention Plan.

The FDA statement announcing the guidance explains that abuse deterrent formulations "target the known or expected routes of abuse, such as crushing in order to snort or dissolving in order to inject, for the specific opioid drug substance in that formulation" and that the agency believes these formulations have "promise to help reduce prescription drug abuse."

Two opioid products with abuse deterrent formulations are currently available: Since 2010, OxyContin (controlled-release oxycodone) has been available in a formulation that prevents it from being chewed, crushed, or dissolved. A crush-resistant formulation of hydromorphone (Opana ER) was approved in September 2012. But the prescribing information for these products do not include claims regarding abuse deterrence properties.

The lack of abuse deterrent features was the main reason an FDA advisory panel recommended against approval of an extended-release, single-ingredient capsule formulation of hydrocodone at a meeting in December. Without such a feature, the product would quickly become widely abused once it was approved and marketed, some of the panelists predicted.

The FDA plans to hold a public meeting to discuss public feedback on the draft guidance.

During the briefing, Dr. Throckmorton said that the FDA had not yet decided what to do about generic formulations of opioids that have no abuse deterrent properties.

The guidance "is an important part of a larger effort by FDA aimed at preventing prescription drug abuse and misuse," and the agency is "extremely concerned about the inappropriate use of prescription opioids, which is a major public health challenge for our nation," FDA commissioner Dr. Margaret Hamburg said in the statement.

Comments and suggestions can be submitted to the FDA within 60 days of publication in the Federal Register, to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, Md., 20852 , with the docket number listed.

e.mechcatie@elsevier.com

Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.

The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.

The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.

European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.

Opens Door for Broader Use

Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.

The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.

Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.

The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.

The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.

Expanded Indication Followed Priority Review

The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.

Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.

The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).

Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.

Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.

Overall survival and radiographic progression-free survival were the coprimary end points of the trial.

Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.

Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.

The most common laboratory abnormalities included anemia; elevations in alkaline phosphatase, triglycerides, and cholesterol; hyperglycemia; lymphopenia; hypophosphatemia; and hypokalemia.

The expanded approval "demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement announcing the approval.

First-Line Use Possible in Future

In the interview, Dr. Moul predicted that abiraterone may have a role as a first-line treatment in the future, referring to a clinical study of abiraterone combined with traditional androgen deprivation prior to radical prostatectomy "that showed a fairly dramatic shrinkage of the tumor."

The new options for treating advanced prostate cancer that have become available since the spring of 2010 have generated questions over the use and sequencing of these agents, he said.

"For example, should doctors use Provenge before or after Zytiga? Should doctors use Provenge and Zytiga together since they are now both FDA approved in the same setting, prechemotherapy? Should some patients still start with chemotherapy first?" he asked.

Dr. Moul described enzalutamide as another "very promising" oral cancer therapy, which also may eventually be approved in the prechemotherapy setting for castration-resistant prostate cancer. "Then doctors and patients will have three choices in Provenge, Zytiga, and Xtandi, and they will have to figure out how to sequence this new feast of agents," he said.

Dr. Moul is a paid consultant to Janssen; he was not an investigator in the study that was the basis of the expanded approval. One of the study investigators, Dr. Daniel George, is the director of the section of genitourinary medical oncology at Duke University Medical Center.

Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.

The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.

The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.

European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.

Opens Door for Broader Use

Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.

The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.

Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.

The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.

The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.

Expanded Indication Followed Priority Review

The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.

Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.

The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).

Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.

Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.

Overall survival and radiographic progression-free survival were the coprimary end points of the trial.

Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.

Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.

The most common laboratory abnormalities included anemia; elevations in alkaline phosphatase, triglycerides, and cholesterol; hyperglycemia; lymphopenia; hypophosphatemia; and hypokalemia.

The expanded approval "demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement announcing the approval.

First-Line Use Possible in Future

In the interview, Dr. Moul predicted that abiraterone may have a role as a first-line treatment in the future, referring to a clinical study of abiraterone combined with traditional androgen deprivation prior to radical prostatectomy "that showed a fairly dramatic shrinkage of the tumor."

The new options for treating advanced prostate cancer that have become available since the spring of 2010 have generated questions over the use and sequencing of these agents, he said.

"For example, should doctors use Provenge before or after Zytiga? Should doctors use Provenge and Zytiga together since they are now both FDA approved in the same setting, prechemotherapy? Should some patients still start with chemotherapy first?" he asked.

Dr. Moul described enzalutamide as another "very promising" oral cancer therapy, which also may eventually be approved in the prechemotherapy setting for castration-resistant prostate cancer. "Then doctors and patients will have three choices in Provenge, Zytiga, and Xtandi, and they will have to figure out how to sequence this new feast of agents," he said.

Dr. Moul is a paid consultant to Janssen; he was not an investigator in the study that was the basis of the expanded approval. One of the study investigators, Dr. Daniel George, is the director of the section of genitourinary medical oncology at Duke University Medical Center.

Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.

The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.

The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.

European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.

Opens Door for Broader Use

Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.

The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.

Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.

The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.

The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.

Expanded Indication Followed Priority Review

The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.

Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.

The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).

Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.

Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.

Overall survival and radiographic progression-free survival were the coprimary end points of the trial.

Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.

Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.

The most common laboratory abnormalities included anemia; elevations in alkaline phosphatase, triglycerides, and cholesterol; hyperglycemia; lymphopenia; hypophosphatemia; and hypokalemia.

The expanded approval "demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement announcing the approval.

First-Line Use Possible in Future

In the interview, Dr. Moul predicted that abiraterone may have a role as a first-line treatment in the future, referring to a clinical study of abiraterone combined with traditional androgen deprivation prior to radical prostatectomy "that showed a fairly dramatic shrinkage of the tumor."

The new options for treating advanced prostate cancer that have become available since the spring of 2010 have generated questions over the use and sequencing of these agents, he said.

"For example, should doctors use Provenge before or after Zytiga? Should doctors use Provenge and Zytiga together since they are now both FDA approved in the same setting, prechemotherapy? Should some patients still start with chemotherapy first?" he asked.

Dr. Moul described enzalutamide as another "very promising" oral cancer therapy, which also may eventually be approved in the prechemotherapy setting for castration-resistant prostate cancer. "Then doctors and patients will have three choices in Provenge, Zytiga, and Xtandi, and they will have to figure out how to sequence this new feast of agents," he said.

Dr. Moul is a paid consultant to Janssen; he was not an investigator in the study that was the basis of the expanded approval. One of the study investigators, Dr. Daniel George, is the director of the section of genitourinary medical oncology at Duke University Medical Center.

Medicare could save about $33 million a year on certain prostate cancer drugs if it reinstated policies that pay only the price of the least costly treatment among a group of clinically comparable drugs.

Limiting the payments for clinically comparable luteinizing hormone-releasing hormone (LHRH) agonists would bring down the cost of these prostate cancer treatments from $264.6 million to $231.3 million a year, or about 13%, according to a report from the Health and Human Services department’s Office of Inspector General (OIG). About 20% of the savings would go to patients, who would save $6.7 million in reduced coinsurance.

From 1995 until April 2010, the Centers for Medicare and Medicaid Services (CMS) imposed "least costly alternative" policies for many physician-administered drugs covered under Medicare Part B. If the patient or physician wanted to use a more expensive drug, one of them would have to pay the difference.

CMS rescinded the policies in April 2010 after a court ruled that the agency did not have the legal authority to set payments in this way.

The OIG began investigating the impact of the least costly alternative policies at the request of Rep. Ken Calvert (R-Calif.), who wanted to know if eliminating the policy had created an incentive for physicians to administer higher-priced treatments.

Based on the OIG report, that appears to have happened.

Looking at the use of triptorelin pamoate (Trelstar), goserelin acetate implant (Zoladex), and leuprolide acetate suspension (Lupron, Eligard), the OIG found that physicians favored use of the more expensive drugs while the least costly alternative policies were in place but that their use was slowly declining. At the same time, the use of the least expensive drug was slowing rising.

After the payment policies were rescinded, use of the more expensive treatments increased significantly.

In 2010, Lupron and Eligard, the most expensive drugs, were administered about twice as often as the least expensive drug, Trelstar. In the year after payment restrictions were removed, the use of Lupron and Eligard rose 31% while Trelstar use fell 74%, according to the OIG report.

Dr. Walter Stadler, professor of medicine and surgery at the University of Chicago, said that the spike in utilization of the more expensive agents is probably the result of marketing, not any clinical differences in the medications. "They are completely and totally equivalent in terms of their efficacy and how they work," he said.

Physicians may be basing their choice on which manufacturers offer them the best deal on the bulk purchase of the drugs, he said, even if that’s not the best deal for Medicare or the insurer.

The OIG report also noted another trend in the utilization of the LHRH agonists: their overall use in prostate cancer is declining. The decrease in utilization began more a year before the least costly alternative policies were rescinded and has continued, according to the OIG, making it likely that it is unrelated to the policy.

Dr. Stadler said that the overall decline is probably caused by a combination of decreasing payments to physicians for the drugs and increasing medical evidence that the LHRH agonists are not always the best treatment option.

Medicare could save about $33 million a year on certain prostate cancer drugs if it reinstated policies that pay only the price of the least costly treatment among a group of clinically comparable drugs.

Limiting the payments for clinically comparable luteinizing hormone-releasing hormone (LHRH) agonists would bring down the cost of these prostate cancer treatments from $264.6 million to $231.3 million a year, or about 13%, according to a report from the Health and Human Services department’s Office of Inspector General (OIG). About 20% of the savings would go to patients, who would save $6.7 million in reduced coinsurance.

From 1995 until April 2010, the Centers for Medicare and Medicaid Services (CMS) imposed "least costly alternative" policies for many physician-administered drugs covered under Medicare Part B. If the patient or physician wanted to use a more expensive drug, one of them would have to pay the difference.

CMS rescinded the policies in April 2010 after a court ruled that the agency did not have the legal authority to set payments in this way.

The OIG began investigating the impact of the least costly alternative policies at the request of Rep. Ken Calvert (R-Calif.), who wanted to know if eliminating the policy had created an incentive for physicians to administer higher-priced treatments.

Based on the OIG report, that appears to have happened.

Looking at the use of triptorelin pamoate (Trelstar), goserelin acetate implant (Zoladex), and leuprolide acetate suspension (Lupron, Eligard), the OIG found that physicians favored use of the more expensive drugs while the least costly alternative policies were in place but that their use was slowly declining. At the same time, the use of the least expensive drug was slowing rising.

After the payment policies were rescinded, use of the more expensive treatments increased significantly.

In 2010, Lupron and Eligard, the most expensive drugs, were administered about twice as often as the least expensive drug, Trelstar. In the year after payment restrictions were removed, the use of Lupron and Eligard rose 31% while Trelstar use fell 74%, according to the OIG report.

Dr. Walter Stadler, professor of medicine and surgery at the University of Chicago, said that the spike in utilization of the more expensive agents is probably the result of marketing, not any clinical differences in the medications. "They are completely and totally equivalent in terms of their efficacy and how they work," he said.

Physicians may be basing their choice on which manufacturers offer them the best deal on the bulk purchase of the drugs, he said, even if that’s not the best deal for Medicare or the insurer.

The OIG report also noted another trend in the utilization of the LHRH agonists: their overall use in prostate cancer is declining. The decrease in utilization began more a year before the least costly alternative policies were rescinded and has continued, according to the OIG, making it likely that it is unrelated to the policy.

Dr. Stadler said that the overall decline is probably caused by a combination of decreasing payments to physicians for the drugs and increasing medical evidence that the LHRH agonists are not always the best treatment option.

Medicare could save about $33 million a year on certain prostate cancer drugs if it reinstated policies that pay only the price of the least costly treatment among a group of clinically comparable drugs.

Limiting the payments for clinically comparable luteinizing hormone-releasing hormone (LHRH) agonists would bring down the cost of these prostate cancer treatments from $264.6 million to $231.3 million a year, or about 13%, according to a report from the Health and Human Services department’s Office of Inspector General (OIG). About 20% of the savings would go to patients, who would save $6.7 million in reduced coinsurance.

From 1995 until April 2010, the Centers for Medicare and Medicaid Services (CMS) imposed "least costly alternative" policies for many physician-administered drugs covered under Medicare Part B. If the patient or physician wanted to use a more expensive drug, one of them would have to pay the difference.

CMS rescinded the policies in April 2010 after a court ruled that the agency did not have the legal authority to set payments in this way.

The OIG began investigating the impact of the least costly alternative policies at the request of Rep. Ken Calvert (R-Calif.), who wanted to know if eliminating the policy had created an incentive for physicians to administer higher-priced treatments.

Based on the OIG report, that appears to have happened.

Looking at the use of triptorelin pamoate (Trelstar), goserelin acetate implant (Zoladex), and leuprolide acetate suspension (Lupron, Eligard), the OIG found that physicians favored use of the more expensive drugs while the least costly alternative policies were in place but that their use was slowly declining. At the same time, the use of the least expensive drug was slowing rising.

After the payment policies were rescinded, use of the more expensive treatments increased significantly.

In 2010, Lupron and Eligard, the most expensive drugs, were administered about twice as often as the least expensive drug, Trelstar. In the year after payment restrictions were removed, the use of Lupron and Eligard rose 31% while Trelstar use fell 74%, according to the OIG report.

Dr. Walter Stadler, professor of medicine and surgery at the University of Chicago, said that the spike in utilization of the more expensive agents is probably the result of marketing, not any clinical differences in the medications. "They are completely and totally equivalent in terms of their efficacy and how they work," he said.

Physicians may be basing their choice on which manufacturers offer them the best deal on the bulk purchase of the drugs, he said, even if that’s not the best deal for Medicare or the insurer.

The OIG report also noted another trend in the utilization of the LHRH agonists: their overall use in prostate cancer is declining. The decrease in utilization began more a year before the least costly alternative policies were rescinded and has continued, according to the OIG, making it likely that it is unrelated to the policy.

Dr. Stadler said that the overall decline is probably caused by a combination of decreasing payments to physicians for the drugs and increasing medical evidence that the LHRH agonists are not always the best treatment option.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

Is your patient with bladder cancer blessed with long telomeres? If so, you can expect him to live many years with the disease – as long as he is not depressed, that is.

An intriguing observational study from the department of epidemiology at the University of Texas M.D. Anderson Cancer Center in Houston found that a magic combination of euthymia and telomere length translated into a staggering sixfold increase in survival in 464 patients with bladder cancer.

To put actual numbers to that, it means that depressed patients with short telomeres lived an average of 31.3 months – about 2.5 years – while those with no depression and long telomeres lived an astonishing 199.8 months, or 16.6 years.

Patients with short telomeres and high levels of depression had a threefold risk of mortality.

"This is the first study of its kind that analyzes bladder cancer outcomes," said Meng Chen, Ph.D., a coinvestigator on the study presented during the annual American Association for Cancer Research international conference on frontiers in cancer prevention research.

She continued, "Psychological factors are not usually included in epidemiologic studies," which, given the study results, begs the question, "Why not?"

Short telomeres have been previously identified as likely suspects in several biomarker studies of aging and diseases, including cancer. A press release from M.D. Anderson explained, "As people grow older, telomeres on the tips of chromosomes, which protect chromosomes from unraveling as cells replicate, shorten, and eventually fail, leading to cell death."

Are short telomeres the egg, presaging a bad outcome in bladder cancer patients, or the chicken, telegraphing damage already done? No one knows for sure. The jury isn’t in on the precise role telomeres play in disease progression, much less on how to alter the picture.

Stress has also been associated with shortened telomeres, prompting coauthor Jie Lin, Ph.D., to recommend that enhanced stress management be incorporated into cancer treatment.

It certainly makes sense.

Until telomere enhancement procedures become the rage, it seems prudent to me to identify the risk we now know exists – depression – and treat it well, in patients with bladder cancer and other forms of the disease.

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

Is your patient with bladder cancer blessed with long telomeres? If so, you can expect him to live many years with the disease – as long as he is not depressed, that is.

An intriguing observational study from the department of epidemiology at the University of Texas M.D. Anderson Cancer Center in Houston found that a magic combination of euthymia and telomere length translated into a staggering sixfold increase in survival in 464 patients with bladder cancer.

To put actual numbers to that, it means that depressed patients with short telomeres lived an average of 31.3 months – about 2.5 years – while those with no depression and long telomeres lived an astonishing 199.8 months, or 16.6 years.

Patients with short telomeres and high levels of depression had a threefold risk of mortality.

"This is the first study of its kind that analyzes bladder cancer outcomes," said Meng Chen, Ph.D., a coinvestigator on the study presented during the annual American Association for Cancer Research international conference on frontiers in cancer prevention research.

She continued, "Psychological factors are not usually included in epidemiologic studies," which, given the study results, begs the question, "Why not?"

Short telomeres have been previously identified as likely suspects in several biomarker studies of aging and diseases, including cancer. A press release from M.D. Anderson explained, "As people grow older, telomeres on the tips of chromosomes, which protect chromosomes from unraveling as cells replicate, shorten, and eventually fail, leading to cell death."

Are short telomeres the egg, presaging a bad outcome in bladder cancer patients, or the chicken, telegraphing damage already done? No one knows for sure. The jury isn’t in on the precise role telomeres play in disease progression, much less on how to alter the picture.

Stress has also been associated with shortened telomeres, prompting coauthor Jie Lin, Ph.D., to recommend that enhanced stress management be incorporated into cancer treatment.

It certainly makes sense.

Until telomere enhancement procedures become the rage, it seems prudent to me to identify the risk we now know exists – depression – and treat it well, in patients with bladder cancer and other forms of the disease.

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

Is your patient with bladder cancer blessed with long telomeres? If so, you can expect him to live many years with the disease – as long as he is not depressed, that is.

An intriguing observational study from the department of epidemiology at the University of Texas M.D. Anderson Cancer Center in Houston found that a magic combination of euthymia and telomere length translated into a staggering sixfold increase in survival in 464 patients with bladder cancer.

To put actual numbers to that, it means that depressed patients with short telomeres lived an average of 31.3 months – about 2.5 years – while those with no depression and long telomeres lived an astonishing 199.8 months, or 16.6 years.

Patients with short telomeres and high levels of depression had a threefold risk of mortality.

"This is the first study of its kind that analyzes bladder cancer outcomes," said Meng Chen, Ph.D., a coinvestigator on the study presented during the annual American Association for Cancer Research international conference on frontiers in cancer prevention research.

She continued, "Psychological factors are not usually included in epidemiologic studies," which, given the study results, begs the question, "Why not?"

Short telomeres have been previously identified as likely suspects in several biomarker studies of aging and diseases, including cancer. A press release from M.D. Anderson explained, "As people grow older, telomeres on the tips of chromosomes, which protect chromosomes from unraveling as cells replicate, shorten, and eventually fail, leading to cell death."

Are short telomeres the egg, presaging a bad outcome in bladder cancer patients, or the chicken, telegraphing damage already done? No one knows for sure. The jury isn’t in on the precise role telomeres play in disease progression, much less on how to alter the picture.

Stress has also been associated with shortened telomeres, prompting coauthor Jie Lin, Ph.D., to recommend that enhanced stress management be incorporated into cancer treatment.

It certainly makes sense.

Until telomere enhancement procedures become the rage, it seems prudent to me to identify the risk we now know exists – depression – and treat it well, in patients with bladder cancer and other forms of the disease.

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

BOSTON – The drugs that have revitalized the love lives of millions of aging men may also help preserve sexual function in men undergoing radiation therapy for prostate cancer, investigators reported at the annual meeting of the American Society for Radiation Oncology.

Men who took sildenafil citrate (Viagra) before, during, and for 6 months after radiotherapy for prostate cancer had better sexual function and reported better overall satisfaction than did men who took placebo in a randomized double-blind trial, said Dr. Michael J. Zelefsky, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York City.

Men who were also treated with androgen deprivation, however, did not appear to experience a benefit from sildenafil and were excluded from the analysis.

"We believe our study is a very important one, for it demonstrates proof of principle that penile rehabilitation is important in the population of radiotherapy patients treated for prostate cancer, and demonstrates a significant benefit for improved sexual function outcomes," Dr. Zelefsky said at a plenary session.

Studies in animal models have suggested that phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, vardenafil (Levitra), and tadalafil (Cialis) could help to preserve or rehabilitate penile function by protecting the vascular endothelium of the corpus cavernosum of the penis and smooth muscle tissue involved in erections.

Dr. Zelefsky pointed to a European randomized trial showing that patients who had undergone bilateral nerve-sparing prostatectomy and were randomized to vardenafil had improved spontaneous erections compared with placebo-taking controls (Eur. Urol. 2008;54:924-31).

Pretreatment Potency Assessed

The current study enrolled 295 men who had excellent sexual function (defined as a score of 17 or greater on the International Index of Erectile Function 5 [IIEF-5]) and were scheduled to undergo radiotherapy to the prostate with either external-beam radiation (EBRT) or brachytherapy. They were randomly assigned on a 2:1 basis to sildenafil or placebo, respectively.

Sildenafil was given in a 50-mg dose starting 3 days before therapy and continuing out to 6 months. Patients were followed with the patient-derived IIEF-5 (including domains of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction), International Prostate Symptom Score (IPSS), and a quality of life questionnaire every 3 months for the first year, and then every 6 months up to 2 years.

"Thirty one patients were treated with androgen-deprivation therapy, and when we looked at erectile function scores over time, there were no significant differences or improvements noted with the use of daily sildenafil compared to the placebo group, suggesting that there was no apparent benefit among this cohort of patients. For this reason, we excluded this cohort and turned our attention to a group of patients who did not receive androgen deprivation therapy, leaving us with an evaluable cohort of 142 patients," Dr. Zelefsky said. The analysis included patients who completed surveys before treatment and at least one additional time period.

There were no significant between-group differences at baseline in factors that might affect erectile function, such as smoking history, diabetes, or hypertension.

Overall total IEFF-5 scores were significantly higher among patients in the sildenafil arm at 6 (P = .006), 12 (P=.02) and 24 months (P = .04) after therapy. However, at 24 months, there were significant differences in favor of sildenafil only in the IEFF-5 domains of sexual desire (P = .001) and overall satisfaction (P = .04).

The investigators also noted that the differences between the treatment groups became less apparent beyond 12 months.

Does This Set a New Standard?

The study had a few minor limitations, including variations in treatment, once-daily rather than more frequent dosing, and the lack of information on a relationship or partner effect, but these do not detract from the conclusion, said invited discussant Dr. Thomas M. Pisansky, professor of radiation oncology at Mayo Clinic, Rochester, Minn.

"Nonetheless, this does serve as an additional test of proof of principle of early PDE5 inhibitor use. Does this represent a new standard? I believe that for the time being it certainly does, but additional study is warranted, and that is ongoing," he said.

Dr. Pisansky added that it is incumbent upon radiation oncologists, when evaluating patients for radiotherapy to the prostate, to incorporate a validated instrument of sexual function such as the IIEF-5.

Dr. Zelefsky and a coauthor disclosed receiving grants from Pfizer, maker of Viagra. Dr. Pisansky reported no conflicts of interest.

BOSTON – The drugs that have revitalized the love lives of millions of aging men may also help preserve sexual function in men undergoing radiation therapy for prostate cancer, investigators reported at the annual meeting of the American Society for Radiation Oncology.

Men who took sildenafil citrate (Viagra) before, during, and for 6 months after radiotherapy for prostate cancer had better sexual function and reported better overall satisfaction than did men who took placebo in a randomized double-blind trial, said Dr. Michael J. Zelefsky, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York City.

Men who were also treated with androgen deprivation, however, did not appear to experience a benefit from sildenafil and were excluded from the analysis.

"We believe our study is a very important one, for it demonstrates proof of principle that penile rehabilitation is important in the population of radiotherapy patients treated for prostate cancer, and demonstrates a significant benefit for improved sexual function outcomes," Dr. Zelefsky said at a plenary session.

Studies in animal models have suggested that phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, vardenafil (Levitra), and tadalafil (Cialis) could help to preserve or rehabilitate penile function by protecting the vascular endothelium of the corpus cavernosum of the penis and smooth muscle tissue involved in erections.

Dr. Zelefsky pointed to a European randomized trial showing that patients who had undergone bilateral nerve-sparing prostatectomy and were randomized to vardenafil had improved spontaneous erections compared with placebo-taking controls (Eur. Urol. 2008;54:924-31).

Pretreatment Potency Assessed

The current study enrolled 295 men who had excellent sexual function (defined as a score of 17 or greater on the International Index of Erectile Function 5 [IIEF-5]) and were scheduled to undergo radiotherapy to the prostate with either external-beam radiation (EBRT) or brachytherapy. They were randomly assigned on a 2:1 basis to sildenafil or placebo, respectively.

Sildenafil was given in a 50-mg dose starting 3 days before therapy and continuing out to 6 months. Patients were followed with the patient-derived IIEF-5 (including domains of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction), International Prostate Symptom Score (IPSS), and a quality of life questionnaire every 3 months for the first year, and then every 6 months up to 2 years.

"Thirty one patients were treated with androgen-deprivation therapy, and when we looked at erectile function scores over time, there were no significant differences or improvements noted with the use of daily sildenafil compared to the placebo group, suggesting that there was no apparent benefit among this cohort of patients. For this reason, we excluded this cohort and turned our attention to a group of patients who did not receive androgen deprivation therapy, leaving us with an evaluable cohort of 142 patients," Dr. Zelefsky said. The analysis included patients who completed surveys before treatment and at least one additional time period.

There were no significant between-group differences at baseline in factors that might affect erectile function, such as smoking history, diabetes, or hypertension.

Overall total IEFF-5 scores were significantly higher among patients in the sildenafil arm at 6 (P = .006), 12 (P=.02) and 24 months (P = .04) after therapy. However, at 24 months, there were significant differences in favor of sildenafil only in the IEFF-5 domains of sexual desire (P = .001) and overall satisfaction (P = .04).

The investigators also noted that the differences between the treatment groups became less apparent beyond 12 months.

Does This Set a New Standard?

The study had a few minor limitations, including variations in treatment, once-daily rather than more frequent dosing, and the lack of information on a relationship or partner effect, but these do not detract from the conclusion, said invited discussant Dr. Thomas M. Pisansky, professor of radiation oncology at Mayo Clinic, Rochester, Minn.

"Nonetheless, this does serve as an additional test of proof of principle of early PDE5 inhibitor use. Does this represent a new standard? I believe that for the time being it certainly does, but additional study is warranted, and that is ongoing," he said.

Dr. Pisansky added that it is incumbent upon radiation oncologists, when evaluating patients for radiotherapy to the prostate, to incorporate a validated instrument of sexual function such as the IIEF-5.

Dr. Zelefsky and a coauthor disclosed receiving grants from Pfizer, maker of Viagra. Dr. Pisansky reported no conflicts of interest.

BOSTON – The drugs that have revitalized the love lives of millions of aging men may also help preserve sexual function in men undergoing radiation therapy for prostate cancer, investigators reported at the annual meeting of the American Society for Radiation Oncology.

Men who took sildenafil citrate (Viagra) before, during, and for 6 months after radiotherapy for prostate cancer had better sexual function and reported better overall satisfaction than did men who took placebo in a randomized double-blind trial, said Dr. Michael J. Zelefsky, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York City.

Men who were also treated with androgen deprivation, however, did not appear to experience a benefit from sildenafil and were excluded from the analysis.

"We believe our study is a very important one, for it demonstrates proof of principle that penile rehabilitation is important in the population of radiotherapy patients treated for prostate cancer, and demonstrates a significant benefit for improved sexual function outcomes," Dr. Zelefsky said at a plenary session.

Studies in animal models have suggested that phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, vardenafil (Levitra), and tadalafil (Cialis) could help to preserve or rehabilitate penile function by protecting the vascular endothelium of the corpus cavernosum of the penis and smooth muscle tissue involved in erections.

Dr. Zelefsky pointed to a European randomized trial showing that patients who had undergone bilateral nerve-sparing prostatectomy and were randomized to vardenafil had improved spontaneous erections compared with placebo-taking controls (Eur. Urol. 2008;54:924-31).

Pretreatment Potency Assessed

The current study enrolled 295 men who had excellent sexual function (defined as a score of 17 or greater on the International Index of Erectile Function 5 [IIEF-5]) and were scheduled to undergo radiotherapy to the prostate with either external-beam radiation (EBRT) or brachytherapy. They were randomly assigned on a 2:1 basis to sildenafil or placebo, respectively.

Sildenafil was given in a 50-mg dose starting 3 days before therapy and continuing out to 6 months. Patients were followed with the patient-derived IIEF-5 (including domains of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction), International Prostate Symptom Score (IPSS), and a quality of life questionnaire every 3 months for the first year, and then every 6 months up to 2 years.

"Thirty one patients were treated with androgen-deprivation therapy, and when we looked at erectile function scores over time, there were no significant differences or improvements noted with the use of daily sildenafil compared to the placebo group, suggesting that there was no apparent benefit among this cohort of patients. For this reason, we excluded this cohort and turned our attention to a group of patients who did not receive androgen deprivation therapy, leaving us with an evaluable cohort of 142 patients," Dr. Zelefsky said. The analysis included patients who completed surveys before treatment and at least one additional time period.

There were no significant between-group differences at baseline in factors that might affect erectile function, such as smoking history, diabetes, or hypertension.

Overall total IEFF-5 scores were significantly higher among patients in the sildenafil arm at 6 (P = .006), 12 (P=.02) and 24 months (P = .04) after therapy. However, at 24 months, there were significant differences in favor of sildenafil only in the IEFF-5 domains of sexual desire (P = .001) and overall satisfaction (P = .04).

The investigators also noted that the differences between the treatment groups became less apparent beyond 12 months.

Does This Set a New Standard?

The study had a few minor limitations, including variations in treatment, once-daily rather than more frequent dosing, and the lack of information on a relationship or partner effect, but these do not detract from the conclusion, said invited discussant Dr. Thomas M. Pisansky, professor of radiation oncology at Mayo Clinic, Rochester, Minn.

"Nonetheless, this does serve as an additional test of proof of principle of early PDE5 inhibitor use. Does this represent a new standard? I believe that for the time being it certainly does, but additional study is warranted, and that is ongoing," he said.

Dr. Pisansky added that it is incumbent upon radiation oncologists, when evaluating patients for radiotherapy to the prostate, to incorporate a validated instrument of sexual function such as the IIEF-5.

Dr. Zelefsky and a coauthor disclosed receiving grants from Pfizer, maker of Viagra. Dr. Pisansky reported no conflicts of interest.