Genitourinary Cancer

ORLANDO – The variant, labeled AR-47, is a truncated form of the androgen receptor that is missing the ligand-binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone (Zytiga) and enzalutamide (Xtandi) normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC).

But a study of circulating tumor cells (CTCs) from 37 men with mCRPC shows that patients whose tumor cells are positive for AR-V7 retain their sensitivity to taxanes.

“In this particular study, there was a 41% response rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or enzalutamide in this setting,” said Dr. Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore,

Dr. Antonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

Testing for the presence of AR-V7 could in the future help guide clinicians when choosing therapies for men with mCRPC, Dr. Antonarakis said.

The investigators used a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana).

For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) of men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -negative men was not significant.

When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = .003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide.

“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, before the data become clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial,” Dr. Antonarakis said.

He noted that there is currently no commercial assay for AR-V7.

ORLANDO – The variant, labeled AR-47, is a truncated form of the androgen receptor that is missing the ligand-binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone (Zytiga) and enzalutamide (Xtandi) normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC).

But a study of circulating tumor cells (CTCs) from 37 men with mCRPC shows that patients whose tumor cells are positive for AR-V7 retain their sensitivity to taxanes.

“In this particular study, there was a 41% response rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or enzalutamide in this setting,” said Dr. Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore,

Dr. Antonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

Testing for the presence of AR-V7 could in the future help guide clinicians when choosing therapies for men with mCRPC, Dr. Antonarakis said.

The investigators used a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana).

For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) of men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -negative men was not significant.

When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = .003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide.

“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, before the data become clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial,” Dr. Antonarakis said.

He noted that there is currently no commercial assay for AR-V7.

ORLANDO – The variant, labeled AR-47, is a truncated form of the androgen receptor that is missing the ligand-binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone (Zytiga) and enzalutamide (Xtandi) normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC).

But a study of circulating tumor cells (CTCs) from 37 men with mCRPC shows that patients whose tumor cells are positive for AR-V7 retain their sensitivity to taxanes.

“In this particular study, there was a 41% response rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or enzalutamide in this setting,” said Dr. Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore,

Dr. Antonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

Testing for the presence of AR-V7 could in the future help guide clinicians when choosing therapies for men with mCRPC, Dr. Antonarakis said.

The investigators used a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana).

For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) of men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -negative men was not significant.

When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = .003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide.

“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, before the data become clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial,” Dr. Antonarakis said.

He noted that there is currently no commercial assay for AR-V7.

ORLANDO – Men with a history of testicular cancer are at higher risk for prostate cancer than men with a history of melanoma, and testicular cancer survivors also tend to have a higher incidence of higher-grade disease, investigators report.

A study of data on more than 32,000 men with a history of testicular cancer showed a cumulative incidence of prostate cancer by age 80 years of 12.6%, compared with 2.8% among more than 147,000 controls – men with a history of melanoma (P < .0001).

The incidence of intermediate- to high-risk prostate cancers was also higher among testicular cancer survivors, with a cumulative incidence by age 80 years of 5.8%, compared with 1.1% for controls (P < .0001), reported Dr. Mohummad Minhaj Siddiqui, director of urologic robotic surgery at the University of Maryland Medical Center, Baltimore.

“Based on these findings, we believe that men with history of testicular cancer should consider discussing the risks and benefits of prostate cancer screening with their physicians,” he said at a briefing prior to his presentation of the data in a scientific poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

“Further validation studies are needed to confirm these results, we believe, based on other cohorts, and to determine if men with a history of testicular cancer should have closer screening for prostate cancer in some other way,” he added.

Dr. Charles J. Ryan, who moderated the briefing but was not involved in the study, commented that the investigators corrected for prior radiation therapy in men with testicular cancer, suggesting that the data provide a good estimation of the actual risk.

Dr. Ryan is an ASCO Expert and is with the departments of medicine and urology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Dr. Siddiqui and his colleagues combed through Surveillance, Epidemiology and End Results (SEER) data to identify 32,435 men with a history of testicular cancer, including all subtypes.

They chose 147,044 men with a history of melanoma for the control group, because there is no known association between melanoma and prostate cancer risk.

They looked at data on men aged 40 years and older to allow for sufficient age at which prostate cancer might be diagnosed, and looked at the rate of all prostate cancer as well as intermediate-risk (Gleason score of 7), and high-risk cancers (Gleason score 8 or higher).

“We looked at alternate risk factors, such as age, race, and radiation history, and found that even when controlling for the influence of these risk factors, there was still an increased risk of developing intermediate- to high-risk prostate cancer in men with a history of testicular cancer as opposed to the control population,” Dr. Siddiqui said.

He emphasized, however, that despite the elevated risk for intermediate- to high-grade prostate cancer among testicular cancer survivors, the overall risk is relatively low; 95% of men with a history of testicular cancer will never get prostate cancer, he said.

ORLANDO – Men with a history of testicular cancer are at higher risk for prostate cancer than men with a history of melanoma, and testicular cancer survivors also tend to have a higher incidence of higher-grade disease, investigators report.

A study of data on more than 32,000 men with a history of testicular cancer showed a cumulative incidence of prostate cancer by age 80 years of 12.6%, compared with 2.8% among more than 147,000 controls – men with a history of melanoma (P < .0001).

The incidence of intermediate- to high-risk prostate cancers was also higher among testicular cancer survivors, with a cumulative incidence by age 80 years of 5.8%, compared with 1.1% for controls (P < .0001), reported Dr. Mohummad Minhaj Siddiqui, director of urologic robotic surgery at the University of Maryland Medical Center, Baltimore.

“Based on these findings, we believe that men with history of testicular cancer should consider discussing the risks and benefits of prostate cancer screening with their physicians,” he said at a briefing prior to his presentation of the data in a scientific poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

“Further validation studies are needed to confirm these results, we believe, based on other cohorts, and to determine if men with a history of testicular cancer should have closer screening for prostate cancer in some other way,” he added.

Dr. Charles J. Ryan, who moderated the briefing but was not involved in the study, commented that the investigators corrected for prior radiation therapy in men with testicular cancer, suggesting that the data provide a good estimation of the actual risk.

Dr. Ryan is an ASCO Expert and is with the departments of medicine and urology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Dr. Siddiqui and his colleagues combed through Surveillance, Epidemiology and End Results (SEER) data to identify 32,435 men with a history of testicular cancer, including all subtypes.

They chose 147,044 men with a history of melanoma for the control group, because there is no known association between melanoma and prostate cancer risk.

They looked at data on men aged 40 years and older to allow for sufficient age at which prostate cancer might be diagnosed, and looked at the rate of all prostate cancer as well as intermediate-risk (Gleason score of 7), and high-risk cancers (Gleason score 8 or higher).

“We looked at alternate risk factors, such as age, race, and radiation history, and found that even when controlling for the influence of these risk factors, there was still an increased risk of developing intermediate- to high-risk prostate cancer in men with a history of testicular cancer as opposed to the control population,” Dr. Siddiqui said.

He emphasized, however, that despite the elevated risk for intermediate- to high-grade prostate cancer among testicular cancer survivors, the overall risk is relatively low; 95% of men with a history of testicular cancer will never get prostate cancer, he said.

ORLANDO – Men with a history of testicular cancer are at higher risk for prostate cancer than men with a history of melanoma, and testicular cancer survivors also tend to have a higher incidence of higher-grade disease, investigators report.

A study of data on more than 32,000 men with a history of testicular cancer showed a cumulative incidence of prostate cancer by age 80 years of 12.6%, compared with 2.8% among more than 147,000 controls – men with a history of melanoma (P < .0001).

The incidence of intermediate- to high-risk prostate cancers was also higher among testicular cancer survivors, with a cumulative incidence by age 80 years of 5.8%, compared with 1.1% for controls (P < .0001), reported Dr. Mohummad Minhaj Siddiqui, director of urologic robotic surgery at the University of Maryland Medical Center, Baltimore.

“Based on these findings, we believe that men with history of testicular cancer should consider discussing the risks and benefits of prostate cancer screening with their physicians,” he said at a briefing prior to his presentation of the data in a scientific poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

“Further validation studies are needed to confirm these results, we believe, based on other cohorts, and to determine if men with a history of testicular cancer should have closer screening for prostate cancer in some other way,” he added.

Dr. Charles J. Ryan, who moderated the briefing but was not involved in the study, commented that the investigators corrected for prior radiation therapy in men with testicular cancer, suggesting that the data provide a good estimation of the actual risk.

Dr. Ryan is an ASCO Expert and is with the departments of medicine and urology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Dr. Siddiqui and his colleagues combed through Surveillance, Epidemiology and End Results (SEER) data to identify 32,435 men with a history of testicular cancer, including all subtypes.

They chose 147,044 men with a history of melanoma for the control group, because there is no known association between melanoma and prostate cancer risk.

They looked at data on men aged 40 years and older to allow for sufficient age at which prostate cancer might be diagnosed, and looked at the rate of all prostate cancer as well as intermediate-risk (Gleason score of 7), and high-risk cancers (Gleason score 8 or higher).

“We looked at alternate risk factors, such as age, race, and radiation history, and found that even when controlling for the influence of these risk factors, there was still an increased risk of developing intermediate- to high-risk prostate cancer in men with a history of testicular cancer as opposed to the control population,” Dr. Siddiqui said.

He emphasized, however, that despite the elevated risk for intermediate- to high-grade prostate cancer among testicular cancer survivors, the overall risk is relatively low; 95% of men with a history of testicular cancer will never get prostate cancer, he said.

ORLANDO – Bicalutamide significantly improved overall survival of men with locally advanced, nonmetastatic prostate cancer, but offered no additional benefit for men with localized disease, investigators reported.

Long-term follow-up results from the randomized controlled Scandinavian Prostate Cancer Group 6 study show that after a median follow-up of 14.6 years, men with locally advanced disease who received 150 mg bicalutamide (Casodex) daily in addition to standard care had significantly better overall survival (OS) than did men with locally advanced disease who received a placebo (hazard ratio 0.77, P =. 01), reported Dr. Frederic Birkabaek Thomsen of Rigshopitalet at the University of Copenhagen, Denmark.

In contrast, men with localized disease had no benefit from bicalutamide (HR 1.19, P = .056).

“There was an even distribution between prostate cancer–specific mortality in both patients with localized and locally advanced disease. However, in patients with localized disease, there was an increase in other-cause mortality of patients randomized to bicalutamide. In contrast, in locally advanced disease, there was a slight increase in other-cause mortality in patients randomized to placebo, Dr. Thomsen said at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

The current analysis builds on earlier findings from the study. In 2006, the investigators reported that after a median 7.1 years of follow-up, bicalutamide in patients with locally advanced disease significantly improved both progression-free survival (HR 0.47; P < .001) and overall survival (HR 0.65, P = .001).

The study enrolled 1,218 patients; 607 were assigned to bicalutamide, 611 to placebo. The groups were well matched by median age (70 years in each group), median prostate-specific antigen (PSA; 13.8 and 12.6 ng/mL, respectively), and tumor grade and disease stage.

In each treatment arm, at least 89% of patients were managed with watchful waiting, about 12% had radical prostatectomy, and 4%-6% had radiation with external beam or brachytherapy.

In the cohort as a whole, there was no difference between treatment arms in overall survival at 14.6 years’ median follow-up. But when the results were stratified by clinical tumor stage, there was, as noted above, a significant survival advantage from bicalutamide among patients with locally advanced disease.

An analysis stratifying survival by tumor stage and baseline PSA suggested that bicalutamide was most effective in men with locally advanced cancer and more extensive disease at baseline, with a nonsignificant hazard ratio of 0.87 for those with a baseline PSA around 10 ng/mL, compared with 0.76 (P = .015) for men with a baseline PSA hovering around 30 ng/mL.

Dr. Thomsen noted that although other studies from the United States and Europe have failed to show a benefit of bicalutamide in patients with locally advanced prostate cancer, patients in other trials received bicalutamide as an adjuvant to radical prostatectomy or radiation, whereas the majority of patients in the Scandinavian trial were managed with observation alone. Patients in the trial were also younger and tended to have more advanced disease than patients in other trials, which may explain the bicalutamide benefit they saw, he added.

Dr. Thomsen presented the findings in an oral abstract session and scientific poster session.

ORLANDO – Bicalutamide significantly improved overall survival of men with locally advanced, nonmetastatic prostate cancer, but offered no additional benefit for men with localized disease, investigators reported.

Long-term follow-up results from the randomized controlled Scandinavian Prostate Cancer Group 6 study show that after a median follow-up of 14.6 years, men with locally advanced disease who received 150 mg bicalutamide (Casodex) daily in addition to standard care had significantly better overall survival (OS) than did men with locally advanced disease who received a placebo (hazard ratio 0.77, P =. 01), reported Dr. Frederic Birkabaek Thomsen of Rigshopitalet at the University of Copenhagen, Denmark.

In contrast, men with localized disease had no benefit from bicalutamide (HR 1.19, P = .056).

“There was an even distribution between prostate cancer–specific mortality in both patients with localized and locally advanced disease. However, in patients with localized disease, there was an increase in other-cause mortality of patients randomized to bicalutamide. In contrast, in locally advanced disease, there was a slight increase in other-cause mortality in patients randomized to placebo, Dr. Thomsen said at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

The current analysis builds on earlier findings from the study. In 2006, the investigators reported that after a median 7.1 years of follow-up, bicalutamide in patients with locally advanced disease significantly improved both progression-free survival (HR 0.47; P < .001) and overall survival (HR 0.65, P = .001).

The study enrolled 1,218 patients; 607 were assigned to bicalutamide, 611 to placebo. The groups were well matched by median age (70 years in each group), median prostate-specific antigen (PSA; 13.8 and 12.6 ng/mL, respectively), and tumor grade and disease stage.

In each treatment arm, at least 89% of patients were managed with watchful waiting, about 12% had radical prostatectomy, and 4%-6% had radiation with external beam or brachytherapy.

In the cohort as a whole, there was no difference between treatment arms in overall survival at 14.6 years’ median follow-up. But when the results were stratified by clinical tumor stage, there was, as noted above, a significant survival advantage from bicalutamide among patients with locally advanced disease.

An analysis stratifying survival by tumor stage and baseline PSA suggested that bicalutamide was most effective in men with locally advanced cancer and more extensive disease at baseline, with a nonsignificant hazard ratio of 0.87 for those with a baseline PSA around 10 ng/mL, compared with 0.76 (P = .015) for men with a baseline PSA hovering around 30 ng/mL.

Dr. Thomsen noted that although other studies from the United States and Europe have failed to show a benefit of bicalutamide in patients with locally advanced prostate cancer, patients in other trials received bicalutamide as an adjuvant to radical prostatectomy or radiation, whereas the majority of patients in the Scandinavian trial were managed with observation alone. Patients in the trial were also younger and tended to have more advanced disease than patients in other trials, which may explain the bicalutamide benefit they saw, he added.

Dr. Thomsen presented the findings in an oral abstract session and scientific poster session.

ORLANDO – Bicalutamide significantly improved overall survival of men with locally advanced, nonmetastatic prostate cancer, but offered no additional benefit for men with localized disease, investigators reported.

Long-term follow-up results from the randomized controlled Scandinavian Prostate Cancer Group 6 study show that after a median follow-up of 14.6 years, men with locally advanced disease who received 150 mg bicalutamide (Casodex) daily in addition to standard care had significantly better overall survival (OS) than did men with locally advanced disease who received a placebo (hazard ratio 0.77, P =. 01), reported Dr. Frederic Birkabaek Thomsen of Rigshopitalet at the University of Copenhagen, Denmark.

In contrast, men with localized disease had no benefit from bicalutamide (HR 1.19, P = .056).

“There was an even distribution between prostate cancer–specific mortality in both patients with localized and locally advanced disease. However, in patients with localized disease, there was an increase in other-cause mortality of patients randomized to bicalutamide. In contrast, in locally advanced disease, there was a slight increase in other-cause mortality in patients randomized to placebo, Dr. Thomsen said at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

The current analysis builds on earlier findings from the study. In 2006, the investigators reported that after a median 7.1 years of follow-up, bicalutamide in patients with locally advanced disease significantly improved both progression-free survival (HR 0.47; P < .001) and overall survival (HR 0.65, P = .001).

The study enrolled 1,218 patients; 607 were assigned to bicalutamide, 611 to placebo. The groups were well matched by median age (70 years in each group), median prostate-specific antigen (PSA; 13.8 and 12.6 ng/mL, respectively), and tumor grade and disease stage.

In each treatment arm, at least 89% of patients were managed with watchful waiting, about 12% had radical prostatectomy, and 4%-6% had radiation with external beam or brachytherapy.

In the cohort as a whole, there was no difference between treatment arms in overall survival at 14.6 years’ median follow-up. But when the results were stratified by clinical tumor stage, there was, as noted above, a significant survival advantage from bicalutamide among patients with locally advanced disease.

An analysis stratifying survival by tumor stage and baseline PSA suggested that bicalutamide was most effective in men with locally advanced cancer and more extensive disease at baseline, with a nonsignificant hazard ratio of 0.87 for those with a baseline PSA around 10 ng/mL, compared with 0.76 (P = .015) for men with a baseline PSA hovering around 30 ng/mL.

Dr. Thomsen noted that although other studies from the United States and Europe have failed to show a benefit of bicalutamide in patients with locally advanced prostate cancer, patients in other trials received bicalutamide as an adjuvant to radical prostatectomy or radiation, whereas the majority of patients in the Scandinavian trial were managed with observation alone. Patients in the trial were also younger and tended to have more advanced disease than patients in other trials, which may explain the bicalutamide benefit they saw, he added.

Dr. Thomsen presented the findings in an oral abstract session and scientific poster session.

Active surveillance may not be the best option for patients diagnosed with intermediate-risk prostate cancer, results of a prospective study suggest.

Among 945 men managed with active surveillance, the risk of dying from prostate cancer within 15 years of diagnosis was nearly fourfold higher for those with an initial diagnosis of intermediate-risk disease than for those with low-risk disease.

“What surprised us was that their actually seemed to be a greater risk of dying of prostate cancer for patients diagnosed with intermediate risk disease and placed on surveillance,” said Dr. Andrew Loblaw, a radiation oncologist at Sunnybrook Health Sciences Centre in Toronto.

“When we actually stratify it by patients in the low-risk category, we see that [active surveillance] is a very safe and reasonable approach, and appropriate in our minds for low-risk patients, in line with the guideline recommendations. But despite the selection factors that we use in our clinic for intermediate-risk patients, we’re still seeing, at least in this analysis, greater risk of dying from prostate cancer, and we think that more research is needed to better identify the group of patients that may be watched conservatively,” he said in a media briefing held covering studies to be presented later at the 2015 Genitourinary Cancers Symposium, jointly sponsored by the American Society of Clinical Oncology (ASCO), American Society of Clinical Radiology (ASTRO), and Society of Urologic Oncology (SUO).

Dr. Charles J. Ryan, who moderated the briefing but was not involved in the study said that the findings are provocative.

“There are a number of things that we don’t know from these data. For example, did some of these patients who were on active surveillance go on to receive local therapy later, what were the subsequent therapies they received for metastatic disease, et cetera. But it is an important point to state the fact that some patients with intermediate risk do in fact die of prostate cancer,” said Dr. Ryan, an ASCO Expert with the departments of medicine and urology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Ontario guidelines: ‘Preferred strategy’

Cancer Care Ontario guidelines for the management of low-risk prostate cancer state that “for patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the preferred disease management strategy.”

In the United States, the National Comprehensive Cancer Network (NCCN) recommends active surveillance as an alternative to radiation or surgery in the management of men with low-risk prostate cancer and a life expectancy of 10 years or more. Active surveillance is not, however, recommended for men with intermediate-risk disease.

To see whether there were significant differences in outcomes between patients with conservatively managed low- or intermediate-risk disease, the investigators looked at prospectively collected data on 945 men managed with active surveillance at their center from 1995 through 2013. Of this group, 237 had been diagnosed with intermediate-risk disease, defined as a prostate-specific androgen (PSA) level greater than 10, Gleason score of 7, or clinical stage T2b/2c.

Patients were offered intervention if they had a PSA doubling time of less than 3 years, a change in Gleason score, or clinical disease progression.

The authors found that 10-year overall survival (OS) was 67.3% for patients with intermediate risk, compared with 84.2% for those with low-risk disease, and the respective 15-year OS rates were 50.8% vs. 66.7% (hazard ratio, 2.13; P < .0001).

When they looked at cause-specific survival (CSS) rates, they also found significant differences, with a 10-year CSS for intermediate-risk patients of 97.2%, compared with 98.3% for low-risk patients, and 15-year CSS rates of 88.5% vs. 96.7% (HR, 3.74; P = .01).

The investigators concluded that “active surveillance for intermediate-risk prostate cancer has significantly lower overall survival and cause-specific survival, compared with low-risk patients, and therefore extreme caution should be exercised if it were to be implemented in intermediate-risk patients.”

The data are scheduled for presentation in a poster session at the symposium.

Active surveillance may not be the best option for patients diagnosed with intermediate-risk prostate cancer, results of a prospective study suggest.

Among 945 men managed with active surveillance, the risk of dying from prostate cancer within 15 years of diagnosis was nearly fourfold higher for those with an initial diagnosis of intermediate-risk disease than for those with low-risk disease.

“What surprised us was that their actually seemed to be a greater risk of dying of prostate cancer for patients diagnosed with intermediate risk disease and placed on surveillance,” said Dr. Andrew Loblaw, a radiation oncologist at Sunnybrook Health Sciences Centre in Toronto.

“When we actually stratify it by patients in the low-risk category, we see that [active surveillance] is a very safe and reasonable approach, and appropriate in our minds for low-risk patients, in line with the guideline recommendations. But despite the selection factors that we use in our clinic for intermediate-risk patients, we’re still seeing, at least in this analysis, greater risk of dying from prostate cancer, and we think that more research is needed to better identify the group of patients that may be watched conservatively,” he said in a media briefing held covering studies to be presented later at the 2015 Genitourinary Cancers Symposium, jointly sponsored by the American Society of Clinical Oncology (ASCO), American Society of Clinical Radiology (ASTRO), and Society of Urologic Oncology (SUO).

Dr. Charles J. Ryan, who moderated the briefing but was not involved in the study said that the findings are provocative.

“There are a number of things that we don’t know from these data. For example, did some of these patients who were on active surveillance go on to receive local therapy later, what were the subsequent therapies they received for metastatic disease, et cetera. But it is an important point to state the fact that some patients with intermediate risk do in fact die of prostate cancer,” said Dr. Ryan, an ASCO Expert with the departments of medicine and urology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Ontario guidelines: ‘Preferred strategy’

Cancer Care Ontario guidelines for the management of low-risk prostate cancer state that “for patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the preferred disease management strategy.”

In the United States, the National Comprehensive Cancer Network (NCCN) recommends active surveillance as an alternative to radiation or surgery in the management of men with low-risk prostate cancer and a life expectancy of 10 years or more. Active surveillance is not, however, recommended for men with intermediate-risk disease.

To see whether there were significant differences in outcomes between patients with conservatively managed low- or intermediate-risk disease, the investigators looked at prospectively collected data on 945 men managed with active surveillance at their center from 1995 through 2013. Of this group, 237 had been diagnosed with intermediate-risk disease, defined as a prostate-specific androgen (PSA) level greater than 10, Gleason score of 7, or clinical stage T2b/2c.

Patients were offered intervention if they had a PSA doubling time of less than 3 years, a change in Gleason score, or clinical disease progression.

The authors found that 10-year overall survival (OS) was 67.3% for patients with intermediate risk, compared with 84.2% for those with low-risk disease, and the respective 15-year OS rates were 50.8% vs. 66.7% (hazard ratio, 2.13; P < .0001).

When they looked at cause-specific survival (CSS) rates, they also found significant differences, with a 10-year CSS for intermediate-risk patients of 97.2%, compared with 98.3% for low-risk patients, and 15-year CSS rates of 88.5% vs. 96.7% (HR, 3.74; P = .01).

The investigators concluded that “active surveillance for intermediate-risk prostate cancer has significantly lower overall survival and cause-specific survival, compared with low-risk patients, and therefore extreme caution should be exercised if it were to be implemented in intermediate-risk patients.”

The data are scheduled for presentation in a poster session at the symposium.

Active surveillance may not be the best option for patients diagnosed with intermediate-risk prostate cancer, results of a prospective study suggest.

Among 945 men managed with active surveillance, the risk of dying from prostate cancer within 15 years of diagnosis was nearly fourfold higher for those with an initial diagnosis of intermediate-risk disease than for those with low-risk disease.

“What surprised us was that their actually seemed to be a greater risk of dying of prostate cancer for patients diagnosed with intermediate risk disease and placed on surveillance,” said Dr. Andrew Loblaw, a radiation oncologist at Sunnybrook Health Sciences Centre in Toronto.

“When we actually stratify it by patients in the low-risk category, we see that [active surveillance] is a very safe and reasonable approach, and appropriate in our minds for low-risk patients, in line with the guideline recommendations. But despite the selection factors that we use in our clinic for intermediate-risk patients, we’re still seeing, at least in this analysis, greater risk of dying from prostate cancer, and we think that more research is needed to better identify the group of patients that may be watched conservatively,” he said in a media briefing held covering studies to be presented later at the 2015 Genitourinary Cancers Symposium, jointly sponsored by the American Society of Clinical Oncology (ASCO), American Society of Clinical Radiology (ASTRO), and Society of Urologic Oncology (SUO).

Dr. Charles J. Ryan, who moderated the briefing but was not involved in the study said that the findings are provocative.

“There are a number of things that we don’t know from these data. For example, did some of these patients who were on active surveillance go on to receive local therapy later, what were the subsequent therapies they received for metastatic disease, et cetera. But it is an important point to state the fact that some patients with intermediate risk do in fact die of prostate cancer,” said Dr. Ryan, an ASCO Expert with the departments of medicine and urology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Ontario guidelines: ‘Preferred strategy’

Cancer Care Ontario guidelines for the management of low-risk prostate cancer state that “for patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the preferred disease management strategy.”

In the United States, the National Comprehensive Cancer Network (NCCN) recommends active surveillance as an alternative to radiation or surgery in the management of men with low-risk prostate cancer and a life expectancy of 10 years or more. Active surveillance is not, however, recommended for men with intermediate-risk disease.

To see whether there were significant differences in outcomes between patients with conservatively managed low- or intermediate-risk disease, the investigators looked at prospectively collected data on 945 men managed with active surveillance at their center from 1995 through 2013. Of this group, 237 had been diagnosed with intermediate-risk disease, defined as a prostate-specific androgen (PSA) level greater than 10, Gleason score of 7, or clinical stage T2b/2c.

Patients were offered intervention if they had a PSA doubling time of less than 3 years, a change in Gleason score, or clinical disease progression.

The authors found that 10-year overall survival (OS) was 67.3% for patients with intermediate risk, compared with 84.2% for those with low-risk disease, and the respective 15-year OS rates were 50.8% vs. 66.7% (hazard ratio, 2.13; P < .0001).

When they looked at cause-specific survival (CSS) rates, they also found significant differences, with a 10-year CSS for intermediate-risk patients of 97.2%, compared with 98.3% for low-risk patients, and 15-year CSS rates of 88.5% vs. 96.7% (HR, 3.74; P = .01).

The investigators concluded that “active surveillance for intermediate-risk prostate cancer has significantly lower overall survival and cause-specific survival, compared with low-risk patients, and therefore extreme caution should be exercised if it were to be implemented in intermediate-risk patients.”

The data are scheduled for presentation in a poster session at the symposium.

PARIS – Health status should be evaluated when determining how best to treat an older man with prostate cancer, attendees at an international congress on anticancer treatment were told.

According to recently updated guidelines issued by the International Society of Geriatric Oncology (SIOG), patient preferences should also be a priority when deciding upon prostate cancer treatment, but not their chronological age.

“In the first SIOG guidelines [Crit. Rev. Oncol. Hematol. 2010;731:68-91], we introduced an approach for assessing health status that was somewhat difficult to use by urologists or medical oncologists who had no training in geriatric oncology,” Dr. John-Pierre Droz, professor emeritus of medical oncology at Université Claude Bernard in Lyon, France, said in an interview.

In the updated guidelines (Lancet Oncol. 2014;15:e404-14), however, the use of the G-8 simplified health assessment tool is recommended that takes just 4 minutes to compete and can be used to determine if further health status assessments are necessary.

“This assessment can be performed by a trained nurse,” Dr. Droz said, making the assessment much easier to integrate into clinician’s daily practice.

The G-8 screening tool (Ann. Oncol. 2012;23:2166-72) consists of eight items that take into account patients’ food intake and weight loss in the past 3 months, their body mass index, mobility, prescription drug use, and neuropsychological status. Their age and assessment of their perceived health status in comparison to people of the same age are also included.

A score above 14 is favorable on the G-8 and patients can be categorized as being “fit” and no further geriatric assessment is suggested. But the guidelines recommend a more comprehensive geriatric assessment if a score below this threshold is obtained, which includes comorbidities measured via the Cumulative Illness Rating Scale-Geriatric, evaluation of nutritional status, and patients’ cognitive and physical functions. The latter includes using the familiar concepts of activities of daily living and independent activities of daily living.

Based on these further assessments elderly patients can be categorized as vulnerable, where the health status parameters are potentially improved with appropriate measures; or frail,when changes to health status are deemed permanent or irreversible.

In general, elderly men with prostate cancer who fall into the “fit” health assessment category should have the same treatment options as younger patients. Patients who fall into the “vulnerable” category should be able to receive standard treatment after measures are taken to address any reversible impairments such as malnutrition. Adapted treatment might be more appropriate in senior men who fall into the “frail” category, and palliative care is recommended for those identified with terminal illness.

The potential for side effects to occur and patients’ willingness to accept these is vital to consider when selecting treatments, perhaps more so in elderly individuals who may be more prone to experience adverse events, particularly if they have comorbid disease. Age marginally influences genitourinary and gastrointestinal toxicity seen with external beam radiation therapy, for example, but increases the risk for erectile dysfunction in older men.

Considering first-line treatment for metastatic castrate-resistant prostate cancer disease, “This is exactly the same as in younger patients,” Dr. Droz said. So, docetaxel at the usual dose of 75 mg/m² given three times a week should be suitable for the treatment of both fit and vulnerable patients. A reduced frequency docetaxel regimen, such as weekly or twice weekly, may be more suitable in a frail patient.

Abiraterone acetate is also suitable in the first-line setting in asymptomatic or mildly symptomatic patients who do not have liver metastases. Bone-targeted drugs can also be used to prevent bone loss and for the treatment of bone metastases.

As for second-line treatment, cabazitaxel, abiraterone, and enzalutamide are available, but careful monitoring is needed in older patients, advised Dr. Droz. As in younger men, the optimal sequence of these therapies needs further research.

Dr. Droz commented that the efficacy of treatments for both localized and advanced prostate cancer in older men is similar to that in younger men. However, “the critical issue in the decision-making process is the competition between the risk of death due to prostate cancer and the risk of death due to health status,” he observed.

Dr. Droz has received honoraria from Sanofi.

PARIS – Health status should be evaluated when determining how best to treat an older man with prostate cancer, attendees at an international congress on anticancer treatment were told.

According to recently updated guidelines issued by the International Society of Geriatric Oncology (SIOG), patient preferences should also be a priority when deciding upon prostate cancer treatment, but not their chronological age.

“In the first SIOG guidelines [Crit. Rev. Oncol. Hematol. 2010;731:68-91], we introduced an approach for assessing health status that was somewhat difficult to use by urologists or medical oncologists who had no training in geriatric oncology,” Dr. John-Pierre Droz, professor emeritus of medical oncology at Université Claude Bernard in Lyon, France, said in an interview.

In the updated guidelines (Lancet Oncol. 2014;15:e404-14), however, the use of the G-8 simplified health assessment tool is recommended that takes just 4 minutes to compete and can be used to determine if further health status assessments are necessary.

“This assessment can be performed by a trained nurse,” Dr. Droz said, making the assessment much easier to integrate into clinician’s daily practice.

The G-8 screening tool (Ann. Oncol. 2012;23:2166-72) consists of eight items that take into account patients’ food intake and weight loss in the past 3 months, their body mass index, mobility, prescription drug use, and neuropsychological status. Their age and assessment of their perceived health status in comparison to people of the same age are also included.

A score above 14 is favorable on the G-8 and patients can be categorized as being “fit” and no further geriatric assessment is suggested. But the guidelines recommend a more comprehensive geriatric assessment if a score below this threshold is obtained, which includes comorbidities measured via the Cumulative Illness Rating Scale-Geriatric, evaluation of nutritional status, and patients’ cognitive and physical functions. The latter includes using the familiar concepts of activities of daily living and independent activities of daily living.

Based on these further assessments elderly patients can be categorized as vulnerable, where the health status parameters are potentially improved with appropriate measures; or frail,when changes to health status are deemed permanent or irreversible.

In general, elderly men with prostate cancer who fall into the “fit” health assessment category should have the same treatment options as younger patients. Patients who fall into the “vulnerable” category should be able to receive standard treatment after measures are taken to address any reversible impairments such as malnutrition. Adapted treatment might be more appropriate in senior men who fall into the “frail” category, and palliative care is recommended for those identified with terminal illness.

The potential for side effects to occur and patients’ willingness to accept these is vital to consider when selecting treatments, perhaps more so in elderly individuals who may be more prone to experience adverse events, particularly if they have comorbid disease. Age marginally influences genitourinary and gastrointestinal toxicity seen with external beam radiation therapy, for example, but increases the risk for erectile dysfunction in older men.

Considering first-line treatment for metastatic castrate-resistant prostate cancer disease, “This is exactly the same as in younger patients,” Dr. Droz said. So, docetaxel at the usual dose of 75 mg/m² given three times a week should be suitable for the treatment of both fit and vulnerable patients. A reduced frequency docetaxel regimen, such as weekly or twice weekly, may be more suitable in a frail patient.

Abiraterone acetate is also suitable in the first-line setting in asymptomatic or mildly symptomatic patients who do not have liver metastases. Bone-targeted drugs can also be used to prevent bone loss and for the treatment of bone metastases.

As for second-line treatment, cabazitaxel, abiraterone, and enzalutamide are available, but careful monitoring is needed in older patients, advised Dr. Droz. As in younger men, the optimal sequence of these therapies needs further research.

Dr. Droz commented that the efficacy of treatments for both localized and advanced prostate cancer in older men is similar to that in younger men. However, “the critical issue in the decision-making process is the competition between the risk of death due to prostate cancer and the risk of death due to health status,” he observed.

Dr. Droz has received honoraria from Sanofi.

PARIS – Health status should be evaluated when determining how best to treat an older man with prostate cancer, attendees at an international congress on anticancer treatment were told.

According to recently updated guidelines issued by the International Society of Geriatric Oncology (SIOG), patient preferences should also be a priority when deciding upon prostate cancer treatment, but not their chronological age.

“In the first SIOG guidelines [Crit. Rev. Oncol. Hematol. 2010;731:68-91], we introduced an approach for assessing health status that was somewhat difficult to use by urologists or medical oncologists who had no training in geriatric oncology,” Dr. John-Pierre Droz, professor emeritus of medical oncology at Université Claude Bernard in Lyon, France, said in an interview.

In the updated guidelines (Lancet Oncol. 2014;15:e404-14), however, the use of the G-8 simplified health assessment tool is recommended that takes just 4 minutes to compete and can be used to determine if further health status assessments are necessary.

“This assessment can be performed by a trained nurse,” Dr. Droz said, making the assessment much easier to integrate into clinician’s daily practice.

The G-8 screening tool (Ann. Oncol. 2012;23:2166-72) consists of eight items that take into account patients’ food intake and weight loss in the past 3 months, their body mass index, mobility, prescription drug use, and neuropsychological status. Their age and assessment of their perceived health status in comparison to people of the same age are also included.

A score above 14 is favorable on the G-8 and patients can be categorized as being “fit” and no further geriatric assessment is suggested. But the guidelines recommend a more comprehensive geriatric assessment if a score below this threshold is obtained, which includes comorbidities measured via the Cumulative Illness Rating Scale-Geriatric, evaluation of nutritional status, and patients’ cognitive and physical functions. The latter includes using the familiar concepts of activities of daily living and independent activities of daily living.

Based on these further assessments elderly patients can be categorized as vulnerable, where the health status parameters are potentially improved with appropriate measures; or frail,when changes to health status are deemed permanent or irreversible.

In general, elderly men with prostate cancer who fall into the “fit” health assessment category should have the same treatment options as younger patients. Patients who fall into the “vulnerable” category should be able to receive standard treatment after measures are taken to address any reversible impairments such as malnutrition. Adapted treatment might be more appropriate in senior men who fall into the “frail” category, and palliative care is recommended for those identified with terminal illness.

The potential for side effects to occur and patients’ willingness to accept these is vital to consider when selecting treatments, perhaps more so in elderly individuals who may be more prone to experience adverse events, particularly if they have comorbid disease. Age marginally influences genitourinary and gastrointestinal toxicity seen with external beam radiation therapy, for example, but increases the risk for erectile dysfunction in older men.

Considering first-line treatment for metastatic castrate-resistant prostate cancer disease, “This is exactly the same as in younger patients,” Dr. Droz said. So, docetaxel at the usual dose of 75 mg/m² given three times a week should be suitable for the treatment of both fit and vulnerable patients. A reduced frequency docetaxel regimen, such as weekly or twice weekly, may be more suitable in a frail patient.

Abiraterone acetate is also suitable in the first-line setting in asymptomatic or mildly symptomatic patients who do not have liver metastases. Bone-targeted drugs can also be used to prevent bone loss and for the treatment of bone metastases.

As for second-line treatment, cabazitaxel, abiraterone, and enzalutamide are available, but careful monitoring is needed in older patients, advised Dr. Droz. As in younger men, the optimal sequence of these therapies needs further research.

Dr. Droz commented that the efficacy of treatments for both localized and advanced prostate cancer in older men is similar to that in younger men. However, “the critical issue in the decision-making process is the competition between the risk of death due to prostate cancer and the risk of death due to health status,” he observed.

Dr. Droz has received honoraria from Sanofi.

Men with favorable intermediate-risk prostate cancer could be considered for active surveillance, say the authors of a study, published in JAMA Oncology, showing no significant increase in prostate cancer–specific mortality in this group, compared with those with low-risk disease.

The prospective cohort study in 5,580 men with brachytherapy-treated localized adenocarcinoma of the prostate defined favorable intermediate-risk disease as a Gleason score of 3 + 4 or less, below 50% positive biopsy scores, and one or fewer National Comprehensive Cancer Network determinants of intermediate-risk prostate cancer.

Researchers found no significant increases in prostate cancer–specific or all-cause mortality in the favorable intermediate-risk group, compared with the low-risk group (JAMA Oncology 2015 Feb. 19 [doi:10.1001/jamaoncol.2014.284]).

“This lack of a significant difference in the risk of PCSM [prostate cancer–specific mortality] was evident even though men with low-risk PC had lower median PSA levels, did not have Gleason 3 + 4 disease, and were more likely to have AJCC T1c [American Joint Committee on Cancer T1c] disease, all of which could have caused men with favorable intermediate-risk PC to have a higher risk of PCSM,” wrote Dr. Ann C. Raldow from the Brigham and Women’s Hospital, Boston, and her coauthors.

There were no conflicts of interest declared.

Men with favorable intermediate-risk prostate cancer could be considered for active surveillance, say the authors of a study, published in JAMA Oncology, showing no significant increase in prostate cancer–specific mortality in this group, compared with those with low-risk disease.

The prospective cohort study in 5,580 men with brachytherapy-treated localized adenocarcinoma of the prostate defined favorable intermediate-risk disease as a Gleason score of 3 + 4 or less, below 50% positive biopsy scores, and one or fewer National Comprehensive Cancer Network determinants of intermediate-risk prostate cancer.

Researchers found no significant increases in prostate cancer–specific or all-cause mortality in the favorable intermediate-risk group, compared with the low-risk group (JAMA Oncology 2015 Feb. 19 [doi:10.1001/jamaoncol.2014.284]).

“This lack of a significant difference in the risk of PCSM [prostate cancer–specific mortality] was evident even though men with low-risk PC had lower median PSA levels, did not have Gleason 3 + 4 disease, and were more likely to have AJCC T1c [American Joint Committee on Cancer T1c] disease, all of which could have caused men with favorable intermediate-risk PC to have a higher risk of PCSM,” wrote Dr. Ann C. Raldow from the Brigham and Women’s Hospital, Boston, and her coauthors.

There were no conflicts of interest declared.

Men with favorable intermediate-risk prostate cancer could be considered for active surveillance, say the authors of a study, published in JAMA Oncology, showing no significant increase in prostate cancer–specific mortality in this group, compared with those with low-risk disease.

The prospective cohort study in 5,580 men with brachytherapy-treated localized adenocarcinoma of the prostate defined favorable intermediate-risk disease as a Gleason score of 3 + 4 or less, below 50% positive biopsy scores, and one or fewer National Comprehensive Cancer Network determinants of intermediate-risk prostate cancer.

Researchers found no significant increases in prostate cancer–specific or all-cause mortality in the favorable intermediate-risk group, compared with the low-risk group (JAMA Oncology 2015 Feb. 19 [doi:10.1001/jamaoncol.2014.284]).

“This lack of a significant difference in the risk of PCSM [prostate cancer–specific mortality] was evident even though men with low-risk PC had lower median PSA levels, did not have Gleason 3 + 4 disease, and were more likely to have AJCC T1c [American Joint Committee on Cancer T1c] disease, all of which could have caused men with favorable intermediate-risk PC to have a higher risk of PCSM,” wrote Dr. Ann C. Raldow from the Brigham and Women’s Hospital, Boston, and her coauthors.

There were no conflicts of interest declared.

Watchful waiting or active surveillance is underused in men with indolent prostate cancer, according to the authors of a study that found radiation therapy was the most common treatment regardless of stage, prostate-specific antigen level, grade, or risk.

The population-based study of 37,261 men with prostate cancer, published in JAMA Oncology, found that the use of watchful waiting or active surveillance increased in men aged over 70, but was significantly lower in men of Asian descent and married men.

Radiation therapy was the most common treatment (57.9%) – followed by radical prostatectomy (19.1% and watching waiting or active surveillance (9.6%) – and its use increased with age, comorbidities, tumor characteristics, and referral to a radiation oncologist (JAMA Oncol. 2015 Feb. 19 [doi:10.1001/jamaoncol.2014.192]).

“Our finding that increased use of radiotherapy among patients with indolent disease portends to a collaborative need for increased dissemination of prostate cancer treatment guidelines among our radiation oncology colleagues,” wrote Dr. Karim Chamie of the University of California, Los Angeles, and coauthors.

The study was supported by the Department of Defense Prostate Cancer Physician Training Award and the National Institutes of Health. No other conflicts of interest were declared.

Watchful waiting or active surveillance is underused in men with indolent prostate cancer, according to the authors of a study that found radiation therapy was the most common treatment regardless of stage, prostate-specific antigen level, grade, or risk.

The population-based study of 37,261 men with prostate cancer, published in JAMA Oncology, found that the use of watchful waiting or active surveillance increased in men aged over 70, but was significantly lower in men of Asian descent and married men.

Radiation therapy was the most common treatment (57.9%) – followed by radical prostatectomy (19.1% and watching waiting or active surveillance (9.6%) – and its use increased with age, comorbidities, tumor characteristics, and referral to a radiation oncologist (JAMA Oncol. 2015 Feb. 19 [doi:10.1001/jamaoncol.2014.192]).

“Our finding that increased use of radiotherapy among patients with indolent disease portends to a collaborative need for increased dissemination of prostate cancer treatment guidelines among our radiation oncology colleagues,” wrote Dr. Karim Chamie of the University of California, Los Angeles, and coauthors.

The study was supported by the Department of Defense Prostate Cancer Physician Training Award and the National Institutes of Health. No other conflicts of interest were declared.

Watchful waiting or active surveillance is underused in men with indolent prostate cancer, according to the authors of a study that found radiation therapy was the most common treatment regardless of stage, prostate-specific antigen level, grade, or risk.

The population-based study of 37,261 men with prostate cancer, published in JAMA Oncology, found that the use of watchful waiting or active surveillance increased in men aged over 70, but was significantly lower in men of Asian descent and married men.

Radiation therapy was the most common treatment (57.9%) – followed by radical prostatectomy (19.1% and watching waiting or active surveillance (9.6%) – and its use increased with age, comorbidities, tumor characteristics, and referral to a radiation oncologist (JAMA Oncol. 2015 Feb. 19 [doi:10.1001/jamaoncol.2014.192]).

“Our finding that increased use of radiotherapy among patients with indolent disease portends to a collaborative need for increased dissemination of prostate cancer treatment guidelines among our radiation oncology colleagues,” wrote Dr. Karim Chamie of the University of California, Los Angeles, and coauthors.

The study was supported by the Department of Defense Prostate Cancer Physician Training Award and the National Institutes of Health. No other conflicts of interest were declared.

Adding radiotherapy to androgen-deprivation therapy for locally advanced prostate cancer improves overall survival 30% in the long term, according to a report published online Feb. 17 in the Journal of Clinical Oncology.

Radiotherapy also improves disease-specific outcomes when added to androgen-deprivation therapy (ADT), and its benefits “are achieved without major detriment in terms of long-term toxicity,” said Dr. Malcolm D. Mason of Cardiff University and Velindre Hospital, Wales, and his associates.

These long-term results from this international randomized, controlled trial confirm that the previously reported short-term survival benefits are maintained for a median follow-up of 8 years and “firmly establish the role of radiotherapy” for locally advanced prostate cancer, they said.

“Recent data suggest that some men with T3-4 disease are still being managed with ADT alone. Although there are undoubtedly patients for whom [radiotherapy] or indeed any curative therapy would be inappropriate because of age, comorbidity, or other factors, we conclude that patients with clinically node-negative, locally advanced prostate cancer who are suitable for additional radiotherapy should be offered that option – an opinion shared by European and North American guidelines,” Dr. Mason and his associates noted.

The trial, which the investigators described as the largest to compare the two approaches to prostate cancer, enrolled 1,205 patients during 1995-2005 and followed them through the end of 2010. The median patient age at baseline was 70 years. There were 465 deaths.

A total of 260 deaths occurred with ADT alone, compared with 205 with ADT plus radiotherapy. Median overall survival time was 9.7 years for ADT alone, compared with 10.9 years for ADT plus radiotherapy. Ten-year overall survival was 49% for ADT alone, compared with 55% for ADT plus radiotherapy.

Prostate cancer–specific mortality also declined markedly with the addition of radiotherapy to ADT (hazard ratio, 0.46). Time to disease progression was extended with radiotherapy. And the rate of progression-free survival at 10 years was 46% with ADT alone, compared with 74% when radiotherapy was added, Dr. Mason and his associates said (J. Clin. Oncol. 2015 Feb. 17 [doi:10.1200/JCO.2014.57.7510]).

“The radiotherapy technique used in our trial reflects the prevailing treatment philosophies of the time. The study predated outcome data from randomized trials of dose-escalated radiotherapy, and the radiotherapy doses used here are modest by modern standards,” they noted.

The addition of radiotherapy had “a detectable, although modest” impact on toxicity, with small increases in the number of patients who experienced impotence, urinary frequency, ischemia, or hypertension. Bowel-related adverse effects were more frequent with the addition of radiotherapy, but most were grade 1 or 2. Any toxic effects of grade 3 or higher were of short duration, “and we would suggest that the toxicity of radiotherapy should not be regarded as a barrier to its routine use in this patient population,” the researchers said.

The National Cancer Institute, the Canadian Cancer Society Research Institute, the United Kingdom Medical Research Council, and the United Kingdom National Cancer Research Network supported the study. Dr. Mason disclosed ties to Sanofi and Dendreon; his associates reported ties to MIOT Institute Chennai, BiPar/Sanofi-Aventis, Novartis, Pfizer, Janssen Pharmaceuticals, Astellas Pharma, and B&C.

Adding radiotherapy to androgen-deprivation therapy for locally advanced prostate cancer improves overall survival 30% in the long term, according to a report published online Feb. 17 in the Journal of Clinical Oncology.

Radiotherapy also improves disease-specific outcomes when added to androgen-deprivation therapy (ADT), and its benefits “are achieved without major detriment in terms of long-term toxicity,” said Dr. Malcolm D. Mason of Cardiff University and Velindre Hospital, Wales, and his associates.

These long-term results from this international randomized, controlled trial confirm that the previously reported short-term survival benefits are maintained for a median follow-up of 8 years and “firmly establish the role of radiotherapy” for locally advanced prostate cancer, they said.

“Recent data suggest that some men with T3-4 disease are still being managed with ADT alone. Although there are undoubtedly patients for whom [radiotherapy] or indeed any curative therapy would be inappropriate because of age, comorbidity, or other factors, we conclude that patients with clinically node-negative, locally advanced prostate cancer who are suitable for additional radiotherapy should be offered that option – an opinion shared by European and North American guidelines,” Dr. Mason and his associates noted.

The trial, which the investigators described as the largest to compare the two approaches to prostate cancer, enrolled 1,205 patients during 1995-2005 and followed them through the end of 2010. The median patient age at baseline was 70 years. There were 465 deaths.

A total of 260 deaths occurred with ADT alone, compared with 205 with ADT plus radiotherapy. Median overall survival time was 9.7 years for ADT alone, compared with 10.9 years for ADT plus radiotherapy. Ten-year overall survival was 49% for ADT alone, compared with 55% for ADT plus radiotherapy.

Prostate cancer–specific mortality also declined markedly with the addition of radiotherapy to ADT (hazard ratio, 0.46). Time to disease progression was extended with radiotherapy. And the rate of progression-free survival at 10 years was 46% with ADT alone, compared with 74% when radiotherapy was added, Dr. Mason and his associates said (J. Clin. Oncol. 2015 Feb. 17 [doi:10.1200/JCO.2014.57.7510]).

“The radiotherapy technique used in our trial reflects the prevailing treatment philosophies of the time. The study predated outcome data from randomized trials of dose-escalated radiotherapy, and the radiotherapy doses used here are modest by modern standards,” they noted.

The addition of radiotherapy had “a detectable, although modest” impact on toxicity, with small increases in the number of patients who experienced impotence, urinary frequency, ischemia, or hypertension. Bowel-related adverse effects were more frequent with the addition of radiotherapy, but most were grade 1 or 2. Any toxic effects of grade 3 or higher were of short duration, “and we would suggest that the toxicity of radiotherapy should not be regarded as a barrier to its routine use in this patient population,” the researchers said.

The National Cancer Institute, the Canadian Cancer Society Research Institute, the United Kingdom Medical Research Council, and the United Kingdom National Cancer Research Network supported the study. Dr. Mason disclosed ties to Sanofi and Dendreon; his associates reported ties to MIOT Institute Chennai, BiPar/Sanofi-Aventis, Novartis, Pfizer, Janssen Pharmaceuticals, Astellas Pharma, and B&C.

Adding radiotherapy to androgen-deprivation therapy for locally advanced prostate cancer improves overall survival 30% in the long term, according to a report published online Feb. 17 in the Journal of Clinical Oncology.

Radiotherapy also improves disease-specific outcomes when added to androgen-deprivation therapy (ADT), and its benefits “are achieved without major detriment in terms of long-term toxicity,” said Dr. Malcolm D. Mason of Cardiff University and Velindre Hospital, Wales, and his associates.

These long-term results from this international randomized, controlled trial confirm that the previously reported short-term survival benefits are maintained for a median follow-up of 8 years and “firmly establish the role of radiotherapy” for locally advanced prostate cancer, they said.

“Recent data suggest that some men with T3-4 disease are still being managed with ADT alone. Although there are undoubtedly patients for whom [radiotherapy] or indeed any curative therapy would be inappropriate because of age, comorbidity, or other factors, we conclude that patients with clinically node-negative, locally advanced prostate cancer who are suitable for additional radiotherapy should be offered that option – an opinion shared by European and North American guidelines,” Dr. Mason and his associates noted.

The trial, which the investigators described as the largest to compare the two approaches to prostate cancer, enrolled 1,205 patients during 1995-2005 and followed them through the end of 2010. The median patient age at baseline was 70 years. There were 465 deaths.

A total of 260 deaths occurred with ADT alone, compared with 205 with ADT plus radiotherapy. Median overall survival time was 9.7 years for ADT alone, compared with 10.9 years for ADT plus radiotherapy. Ten-year overall survival was 49% for ADT alone, compared with 55% for ADT plus radiotherapy.

Prostate cancer–specific mortality also declined markedly with the addition of radiotherapy to ADT (hazard ratio, 0.46). Time to disease progression was extended with radiotherapy. And the rate of progression-free survival at 10 years was 46% with ADT alone, compared with 74% when radiotherapy was added, Dr. Mason and his associates said (J. Clin. Oncol. 2015 Feb. 17 [doi:10.1200/JCO.2014.57.7510]).

“The radiotherapy technique used in our trial reflects the prevailing treatment philosophies of the time. The study predated outcome data from randomized trials of dose-escalated radiotherapy, and the radiotherapy doses used here are modest by modern standards,” they noted.

The addition of radiotherapy had “a detectable, although modest” impact on toxicity, with small increases in the number of patients who experienced impotence, urinary frequency, ischemia, or hypertension. Bowel-related adverse effects were more frequent with the addition of radiotherapy, but most were grade 1 or 2. Any toxic effects of grade 3 or higher were of short duration, “and we would suggest that the toxicity of radiotherapy should not be regarded as a barrier to its routine use in this patient population,” the researchers said.

The National Cancer Institute, the Canadian Cancer Society Research Institute, the United Kingdom Medical Research Council, and the United Kingdom National Cancer Research Network supported the study. Dr. Mason disclosed ties to Sanofi and Dendreon; his associates reported ties to MIOT Institute Chennai, BiPar/Sanofi-Aventis, Novartis, Pfizer, Janssen Pharmaceuticals, Astellas Pharma, and B&C.

PARIS – Using chemotherapy earlier in the treatment of patients with metastatic prostate cancer could maximize its benefits on patients’ overall survival, a leading expert said at an international congress on anticancer treatment.

“Survival benefit is related to the number of life-extending therapies received, and you should not miss the ‘window of opportunity’ to use chemotherapy early,” Dr. Stéphane Oudard of Georges Pompidou Hospital, René Descartes University, Paris, advised attendees during an educational lecture at the  meeting.

© alexdans/Thinkstock

The treatment of advanced prostate cancer usually starts with hormonal or antiandrogen therapies before the disease becomes castrate resistant. Chemotherapy with docetaxel is then a standard first-line choice and cabazitaxel a second-line chemotherapy option when the disease becomes castrate resistant.

The prostate cancer vaccine sipuleucel-T (Provenge) can also be used first-line, with abiraterone (Zytiga), enzalutamide (Xtandi), and radium-223 possible other first- or second-line choices. All of these treatments have different targets and have been shown in phase III clinical trials to increase survival by around 3-5 months more than control treatments have.

Evidence suggests that overall survival may be at its highest, however, when docetaxel is used first before abiraterone, enzalutamide, and cabazitaxel in the metastatic castration-resistant prostate cancer (mCRPC) setting. Furthermore, recent findings of the CHAARTED trial (J. Clin. Oncol. 2014;32-5s: Abstr, LBA2) suggest that combining docetaxel with androgen deprivation therapy (ADT) in castrate-sensitive disease could dramatically up overall survival by around 14 months vs. ADT alone.

Tailoring treatment in mCRPC

During his talk, Dr. Oudard generally discussed how clinicians might interpret available clinical trial data to help them decide which treatment approach to use for individual patients.

First, he looked at post hoc analysis data from the IMPACT study (Urology 2013;81:1297-302) with sipuleucel-T. In this trial, immunotherapy-treated patients had a median overall survival gain of 13 months over controls, when their baseline prostate-specific antigen (PSA) levels were 22.1 mg/mL or lower. As PSA levels increased, however, survival gains were substantially decreased, with a gain of just 2.8 months when PSA was over 134.1 ng/mL.

“So it means if you want to use immunotherapy you perhaps need to use it in asymptomatic patients with a low disease burden,” Dr. Oudard suggested.

Predicting response to treatment

Looking at the use of abiraterone acetate and enzalutamide after docetaxel, he noted that primary resistance to these agents develops in one-third to one-quarter of patients. This usually happens at around the 3-month mark, so it would be advisable to stop using androgen receptor (AR)-targeted agents at this point and find an alternative approach.

Combining AR-targeted agents might seem like a potential option, but data suggest that this approach does not overcome primary resistance, and research has focused on trying to determine which patients will and will not respond to AR-targeted agents.

Results of this research suggest that the duration of response to first-line ADT might be predictive of the risk for primary resistance to AR-targeted agents, with a shorter (12 months) ADT response, but not the duration of hormonal therapy, being associated with a lower response to subsequent ADT.

Another interesting parameter that might help predict response and outcome to treatment is the neutrophil/lymphocyte ratio, with the higher the ratio, the lower the overall survival to abiraterone, docetaxel, and cabazitaxel.

High residual baseline testosterone, below the level of castration, also seems a promising way to predict better response to endocrine therapies, Dr. Oudard observed, but this requires further validation.

And the presence of a genetic anomaly (the AR-V7 splice variant) in circulating tumor cells is “very promising but requires methodology validation” for use as a marker of abiraterone and enzalutamide resistance (N. Engl. J. Med. 2014;371:1028-38).

Treating refractory patients

So what are the options for patients who are refractory to first-line treatments? Data suggest that better overall survival can be achieved if patients who are “truly refractory to docetaxel” are treated with cabazitaxel rather than an AR-targeted agent, Dr. Oudard said.

It also appears that overall survival is better if docetaxel is used before abiraterone than if it is used after, and “interesting” in vitro data show that cabazitaxel seems to have greater antitumor activity than does docetaxel in enzalutamide-resistant xenografts.

Dr. Oudard also presented data showing that the PSA response achieved with cabazitaxel does not appear to be influenced by the prior use of AR-targeted agents.

Higher overall survival can be achieved in the post-docetaxel setting if cabazitaxel is used before abiraterone than if it was used after, he observed, His own data have shown a trend for better survival if the sequence of treatment starts with docetaxel, changes to cabazitaxel, and then goes to abiraterone rather than if patients receive abiraterone before cabazitaxel. The sequence of these three drugs also seems preferable rather than using docetaxel followed by cabazitaxel, he said. Large retrospective or observational studies need to address these points.

“We need to think about the sequence of treatment as early as possible,” Dr. Oudard concluded. Considering the CHAARTED study findings, he added: “We maybe need to propose chemotherapy much earlier” in order to overcome resistance. “The difference in using docetaxel much earlier is huge in terms of overall survival outcome.”

Dr. Oudard has consulting agreements with Bayer, GSK, Janssen, Keocyt, Novartis, Pfizer, Roche, Sanofi, and Takeda.

PARIS – Using chemotherapy earlier in the treatment of patients with metastatic prostate cancer could maximize its benefits on patients’ overall survival, a leading expert said at an international congress on anticancer treatment.

“Survival benefit is related to the number of life-extending therapies received, and you should not miss the ‘window of opportunity’ to use chemotherapy early,” Dr. Stéphane Oudard of Georges Pompidou Hospital, René Descartes University, Paris, advised attendees during an educational lecture at the  meeting.

© alexdans/Thinkstock

The treatment of advanced prostate cancer usually starts with hormonal or antiandrogen therapies before the disease becomes castrate resistant. Chemotherapy with docetaxel is then a standard first-line choice and cabazitaxel a second-line chemotherapy option when the disease becomes castrate resistant.

The prostate cancer vaccine sipuleucel-T (Provenge) can also be used first-line, with abiraterone (Zytiga), enzalutamide (Xtandi), and radium-223 possible other first- or second-line choices. All of these treatments have different targets and have been shown in phase III clinical trials to increase survival by around 3-5 months more than control treatments have.

Evidence suggests that overall survival may be at its highest, however, when docetaxel is used first before abiraterone, enzalutamide, and cabazitaxel in the metastatic castration-resistant prostate cancer (mCRPC) setting. Furthermore, recent findings of the CHAARTED trial (J. Clin. Oncol. 2014;32-5s: Abstr, LBA2) suggest that combining docetaxel with androgen deprivation therapy (ADT) in castrate-sensitive disease could dramatically up overall survival by around 14 months vs. ADT alone.

Tailoring treatment in mCRPC

During his talk, Dr. Oudard generally discussed how clinicians might interpret available clinical trial data to help them decide which treatment approach to use for individual patients.

First, he looked at post hoc analysis data from the IMPACT study (Urology 2013;81:1297-302) with sipuleucel-T. In this trial, immunotherapy-treated patients had a median overall survival gain of 13 months over controls, when their baseline prostate-specific antigen (PSA) levels were 22.1 mg/mL or lower. As PSA levels increased, however, survival gains were substantially decreased, with a gain of just 2.8 months when PSA was over 134.1 ng/mL.

“So it means if you want to use immunotherapy you perhaps need to use it in asymptomatic patients with a low disease burden,” Dr. Oudard suggested.

Predicting response to treatment

Looking at the use of abiraterone acetate and enzalutamide after docetaxel, he noted that primary resistance to these agents develops in one-third to one-quarter of patients. This usually happens at around the 3-month mark, so it would be advisable to stop using androgen receptor (AR)-targeted agents at this point and find an alternative approach.

Combining AR-targeted agents might seem like a potential option, but data suggest that this approach does not overcome primary resistance, and research has focused on trying to determine which patients will and will not respond to AR-targeted agents.

Results of this research suggest that the duration of response to first-line ADT might be predictive of the risk for primary resistance to AR-targeted agents, with a shorter (12 months) ADT response, but not the duration of hormonal therapy, being associated with a lower response to subsequent ADT.

Another interesting parameter that might help predict response and outcome to treatment is the neutrophil/lymphocyte ratio, with the higher the ratio, the lower the overall survival to abiraterone, docetaxel, and cabazitaxel.

High residual baseline testosterone, below the level of castration, also seems a promising way to predict better response to endocrine therapies, Dr. Oudard observed, but this requires further validation.

And the presence of a genetic anomaly (the AR-V7 splice variant) in circulating tumor cells is “very promising but requires methodology validation” for use as a marker of abiraterone and enzalutamide resistance (N. Engl. J. Med. 2014;371:1028-38).

Treating refractory patients

So what are the options for patients who are refractory to first-line treatments? Data suggest that better overall survival can be achieved if patients who are “truly refractory to docetaxel” are treated with cabazitaxel rather than an AR-targeted agent, Dr. Oudard said.

It also appears that overall survival is better if docetaxel is used before abiraterone than if it is used after, and “interesting” in vitro data show that cabazitaxel seems to have greater antitumor activity than does docetaxel in enzalutamide-resistant xenografts.

Dr. Oudard also presented data showing that the PSA response achieved with cabazitaxel does not appear to be influenced by the prior use of AR-targeted agents.

Higher overall survival can be achieved in the post-docetaxel setting if cabazitaxel is used before abiraterone than if it was used after, he observed, His own data have shown a trend for better survival if the sequence of treatment starts with docetaxel, changes to cabazitaxel, and then goes to abiraterone rather than if patients receive abiraterone before cabazitaxel. The sequence of these three drugs also seems preferable rather than using docetaxel followed by cabazitaxel, he said. Large retrospective or observational studies need to address these points.

“We need to think about the sequence of treatment as early as possible,” Dr. Oudard concluded. Considering the CHAARTED study findings, he added: “We maybe need to propose chemotherapy much earlier” in order to overcome resistance. “The difference in using docetaxel much earlier is huge in terms of overall survival outcome.”

Dr. Oudard has consulting agreements with Bayer, GSK, Janssen, Keocyt, Novartis, Pfizer, Roche, Sanofi, and Takeda.

PARIS – Using chemotherapy earlier in the treatment of patients with metastatic prostate cancer could maximize its benefits on patients’ overall survival, a leading expert said at an international congress on anticancer treatment.

“Survival benefit is related to the number of life-extending therapies received, and you should not miss the ‘window of opportunity’ to use chemotherapy early,” Dr. Stéphane Oudard of Georges Pompidou Hospital, René Descartes University, Paris, advised attendees during an educational lecture at the  meeting.

© alexdans/Thinkstock

The treatment of advanced prostate cancer usually starts with hormonal or antiandrogen therapies before the disease becomes castrate resistant. Chemotherapy with docetaxel is then a standard first-line choice and cabazitaxel a second-line chemotherapy option when the disease becomes castrate resistant.

The prostate cancer vaccine sipuleucel-T (Provenge) can also be used first-line, with abiraterone (Zytiga), enzalutamide (Xtandi), and radium-223 possible other first- or second-line choices. All of these treatments have different targets and have been shown in phase III clinical trials to increase survival by around 3-5 months more than control treatments have.

Evidence suggests that overall survival may be at its highest, however, when docetaxel is used first before abiraterone, enzalutamide, and cabazitaxel in the metastatic castration-resistant prostate cancer (mCRPC) setting. Furthermore, recent findings of the CHAARTED trial (J. Clin. Oncol. 2014;32-5s: Abstr, LBA2) suggest that combining docetaxel with androgen deprivation therapy (ADT) in castrate-sensitive disease could dramatically up overall survival by around 14 months vs. ADT alone.

Tailoring treatment in mCRPC

During his talk, Dr. Oudard generally discussed how clinicians might interpret available clinical trial data to help them decide which treatment approach to use for individual patients.

First, he looked at post hoc analysis data from the IMPACT study (Urology 2013;81:1297-302) with sipuleucel-T. In this trial, immunotherapy-treated patients had a median overall survival gain of 13 months over controls, when their baseline prostate-specific antigen (PSA) levels were 22.1 mg/mL or lower. As PSA levels increased, however, survival gains were substantially decreased, with a gain of just 2.8 months when PSA was over 134.1 ng/mL.

“So it means if you want to use immunotherapy you perhaps need to use it in asymptomatic patients with a low disease burden,” Dr. Oudard suggested.

Predicting response to treatment

Looking at the use of abiraterone acetate and enzalutamide after docetaxel, he noted that primary resistance to these agents develops in one-third to one-quarter of patients. This usually happens at around the 3-month mark, so it would be advisable to stop using androgen receptor (AR)-targeted agents at this point and find an alternative approach.

Combining AR-targeted agents might seem like a potential option, but data suggest that this approach does not overcome primary resistance, and research has focused on trying to determine which patients will and will not respond to AR-targeted agents.

Results of this research suggest that the duration of response to first-line ADT might be predictive of the risk for primary resistance to AR-targeted agents, with a shorter (12 months) ADT response, but not the duration of hormonal therapy, being associated with a lower response to subsequent ADT.

Another interesting parameter that might help predict response and outcome to treatment is the neutrophil/lymphocyte ratio, with the higher the ratio, the lower the overall survival to abiraterone, docetaxel, and cabazitaxel.

High residual baseline testosterone, below the level of castration, also seems a promising way to predict better response to endocrine therapies, Dr. Oudard observed, but this requires further validation.

And the presence of a genetic anomaly (the AR-V7 splice variant) in circulating tumor cells is “very promising but requires methodology validation” for use as a marker of abiraterone and enzalutamide resistance (N. Engl. J. Med. 2014;371:1028-38).

Treating refractory patients

So what are the options for patients who are refractory to first-line treatments? Data suggest that better overall survival can be achieved if patients who are “truly refractory to docetaxel” are treated with cabazitaxel rather than an AR-targeted agent, Dr. Oudard said.

It also appears that overall survival is better if docetaxel is used before abiraterone than if it is used after, and “interesting” in vitro data show that cabazitaxel seems to have greater antitumor activity than does docetaxel in enzalutamide-resistant xenografts.

Dr. Oudard also presented data showing that the PSA response achieved with cabazitaxel does not appear to be influenced by the prior use of AR-targeted agents.

Higher overall survival can be achieved in the post-docetaxel setting if cabazitaxel is used before abiraterone than if it was used after, he observed, His own data have shown a trend for better survival if the sequence of treatment starts with docetaxel, changes to cabazitaxel, and then goes to abiraterone rather than if patients receive abiraterone before cabazitaxel. The sequence of these three drugs also seems preferable rather than using docetaxel followed by cabazitaxel, he said. Large retrospective or observational studies need to address these points.

“We need to think about the sequence of treatment as early as possible,” Dr. Oudard concluded. Considering the CHAARTED study findings, he added: “We maybe need to propose chemotherapy much earlier” in order to overcome resistance. “The difference in using docetaxel much earlier is huge in terms of overall survival outcome.”

Dr. Oudard has consulting agreements with Bayer, GSK, Janssen, Keocyt, Novartis, Pfizer, Roche, Sanofi, and Takeda.

A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.

The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.

The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).

Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.

The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.

The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.

“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.

“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”

While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.

Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.

“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.

Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.

A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.

The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.

The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).

Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.

The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.

The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.

“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.

“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”

While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.

Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.

“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.

Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.

A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.

The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.

The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).

Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.

The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.

The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.

“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.

“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”

While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.

Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.

“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.

Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.