Genitourinary Cancer

Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.

But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).

The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.

In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.

Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.

"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.

The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.

Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.

But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).

The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.

In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.

Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.

"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.

The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.

Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.

But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).

The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.

In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.

Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.

"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.

The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.

For most men with localized prostate cancer who defer surgery or radiation, primary androgen deprivation therapy offers no mortality benefit, Dr. Arnold L. Potosky reported.

Dr. Potosky of Georgetown University Medical Center, Washington, D.C., and colleagues looked at 15,170 men with newly diagnosed, clinically localized prostate cancer who did not receive curative therapy, including radiation, radical prostatectomy, or chemotherapy (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.2043]).

Overall, 23% of the cohort had primary androgen deprivation therapy (PADT) initiated within the first year of diagnosis. After adjustment for factors including age, baseline prostate-specific antigen, Gleason score, and T stage, the authors found that there was no difference between PADT-treated men and their PADT-naive counterparts in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.97-1.11) or prostate-cancer specific mortality (HR, 1.03; 95% CI, 0.89-1.19).

Indeed, despite its widespread use among patients who do not undergo curative-intent treatments, "the risk of serious adverse events and the high costs associated with its use mitigate any clinical or policy rationale for PADT use in these men," the authors wrote.

They did report a small but significant decreased risk of all-cause mortality (HR, 0.88; 95% CI, 0.78-0.97) in men with high-risk cancer (pretreatment PSA greater than 20; Gleason score, 8-10; clinical stage, T2c-T3a), but "the observed benefit was relatively small and should not be taken as definitive, given the limitations of our data," they noted.

An increased risk of death was reported in men with low-risk cancer (HR, 1.41; 95% CI, 0.99-1.82) and no difference in risk for men with intermediate-risk cancer (HR, 1.12; 95% CI, 0.92-1.32). There were no differences in risk of prostate cancer mortality by risk group category.

The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.

For most men with localized prostate cancer who defer surgery or radiation, primary androgen deprivation therapy offers no mortality benefit, Dr. Arnold L. Potosky reported.

Dr. Potosky of Georgetown University Medical Center, Washington, D.C., and colleagues looked at 15,170 men with newly diagnosed, clinically localized prostate cancer who did not receive curative therapy, including radiation, radical prostatectomy, or chemotherapy (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.2043]).

Overall, 23% of the cohort had primary androgen deprivation therapy (PADT) initiated within the first year of diagnosis. After adjustment for factors including age, baseline prostate-specific antigen, Gleason score, and T stage, the authors found that there was no difference between PADT-treated men and their PADT-naive counterparts in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.97-1.11) or prostate-cancer specific mortality (HR, 1.03; 95% CI, 0.89-1.19).

Indeed, despite its widespread use among patients who do not undergo curative-intent treatments, "the risk of serious adverse events and the high costs associated with its use mitigate any clinical or policy rationale for PADT use in these men," the authors wrote.

They did report a small but significant decreased risk of all-cause mortality (HR, 0.88; 95% CI, 0.78-0.97) in men with high-risk cancer (pretreatment PSA greater than 20; Gleason score, 8-10; clinical stage, T2c-T3a), but "the observed benefit was relatively small and should not be taken as definitive, given the limitations of our data," they noted.

An increased risk of death was reported in men with low-risk cancer (HR, 1.41; 95% CI, 0.99-1.82) and no difference in risk for men with intermediate-risk cancer (HR, 1.12; 95% CI, 0.92-1.32). There were no differences in risk of prostate cancer mortality by risk group category.

The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.

For most men with localized prostate cancer who defer surgery or radiation, primary androgen deprivation therapy offers no mortality benefit, Dr. Arnold L. Potosky reported.

Dr. Potosky of Georgetown University Medical Center, Washington, D.C., and colleagues looked at 15,170 men with newly diagnosed, clinically localized prostate cancer who did not receive curative therapy, including radiation, radical prostatectomy, or chemotherapy (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.2043]).

Overall, 23% of the cohort had primary androgen deprivation therapy (PADT) initiated within the first year of diagnosis. After adjustment for factors including age, baseline prostate-specific antigen, Gleason score, and T stage, the authors found that there was no difference between PADT-treated men and their PADT-naive counterparts in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.97-1.11) or prostate-cancer specific mortality (HR, 1.03; 95% CI, 0.89-1.19).

Indeed, despite its widespread use among patients who do not undergo curative-intent treatments, "the risk of serious adverse events and the high costs associated with its use mitigate any clinical or policy rationale for PADT use in these men," the authors wrote.

They did report a small but significant decreased risk of all-cause mortality (HR, 0.88; 95% CI, 0.78-0.97) in men with high-risk cancer (pretreatment PSA greater than 20; Gleason score, 8-10; clinical stage, T2c-T3a), but "the observed benefit was relatively small and should not be taken as definitive, given the limitations of our data," they noted.

An increased risk of death was reported in men with low-risk cancer (HR, 1.41; 95% CI, 0.99-1.82) and no difference in risk for men with intermediate-risk cancer (HR, 1.12; 95% CI, 0.92-1.32). There were no differences in risk of prostate cancer mortality by risk group category.

The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Extended follow-up confirms that radical prostatectomy continues to substantially reduce mortality from any cause, mortality from prostate cancer, and the risk of developing metastases over the long term, compared with watchful waiting, investigators reported March 5 in the New England Journal of Medicine.

These protective effects were most pronounced in men who were under age 65 at diagnosis, but older men had the additional benefit from radical prostatectomy of improved quality of life, because of a significantly lower risk of palliative care, including androgen-deprivation therapy. "The life experience after the diagnosis of prostate cancer differs substantially between the two study groups and evolves over decades," said Dr. Anna Bill-Axelson of Uppsala (Sweden) University Hospital and her associates.

Between 1989 and 1999, men with localized prostate cancer who were under age 75 and had life expectancies beyond 10 years, were randomly assigned to undergo radical prostatectomy (347 patients) or watchful waiting (348 patients) at 14 medical centers in Sweden, Finland, and Iceland. A total of 447 men (64%) died during extended follow-up lasting until 2012 (median follow-up, 13.4 years).

All-cause mortality was 56.1% in the prostatectomy group, significantly lower than the 68.9% all-cause mortality in the watchful waiting group; the number needed to treat to prevent 1 death at 18 years of follow-up was 8. Similarly, prostate cancer–specific mortality was 17.7% with prostatectomy vs. 28.7% with watchful waiting, and the difference between the two study groups continued to increase over time, the investigators reported (N. Engl. J. Med. 2014 March 5 [doi: 10.1056/NEMoa1311593]).

Among men under age 65 at diagnosis, all-cause mortality was 25.5 percentage points lower, prostate cancer–specific mortality was 15.8 percentage points lower, and risk of metastases was 15.8 percentage points lower with prostatectomy than with watchful waiting. "In this age group, the number needed to treat to prevent 1 death from prostate cancer was 4," Dr. Bill-Axelson and her associates said.

This study was supported by the Swedish Cancer Society, the National Institutes of Health, the Karolinska Institute, the Prostate Cancer Foundation, and the Percy Falk Foundation. The authors reported that they had no financial conflicts of interest.

Extended follow-up confirms that radical prostatectomy continues to substantially reduce mortality from any cause, mortality from prostate cancer, and the risk of developing metastases over the long term, compared with watchful waiting, investigators reported March 5 in the New England Journal of Medicine.

These protective effects were most pronounced in men who were under age 65 at diagnosis, but older men had the additional benefit from radical prostatectomy of improved quality of life, because of a significantly lower risk of palliative care, including androgen-deprivation therapy. "The life experience after the diagnosis of prostate cancer differs substantially between the two study groups and evolves over decades," said Dr. Anna Bill-Axelson of Uppsala (Sweden) University Hospital and her associates.

Between 1989 and 1999, men with localized prostate cancer who were under age 75 and had life expectancies beyond 10 years, were randomly assigned to undergo radical prostatectomy (347 patients) or watchful waiting (348 patients) at 14 medical centers in Sweden, Finland, and Iceland. A total of 447 men (64%) died during extended follow-up lasting until 2012 (median follow-up, 13.4 years).

All-cause mortality was 56.1% in the prostatectomy group, significantly lower than the 68.9% all-cause mortality in the watchful waiting group; the number needed to treat to prevent 1 death at 18 years of follow-up was 8. Similarly, prostate cancer–specific mortality was 17.7% with prostatectomy vs. 28.7% with watchful waiting, and the difference between the two study groups continued to increase over time, the investigators reported (N. Engl. J. Med. 2014 March 5 [doi: 10.1056/NEMoa1311593]).

Among men under age 65 at diagnosis, all-cause mortality was 25.5 percentage points lower, prostate cancer–specific mortality was 15.8 percentage points lower, and risk of metastases was 15.8 percentage points lower with prostatectomy than with watchful waiting. "In this age group, the number needed to treat to prevent 1 death from prostate cancer was 4," Dr. Bill-Axelson and her associates said.

This study was supported by the Swedish Cancer Society, the National Institutes of Health, the Karolinska Institute, the Prostate Cancer Foundation, and the Percy Falk Foundation. The authors reported that they had no financial conflicts of interest.

Extended follow-up confirms that radical prostatectomy continues to substantially reduce mortality from any cause, mortality from prostate cancer, and the risk of developing metastases over the long term, compared with watchful waiting, investigators reported March 5 in the New England Journal of Medicine.

These protective effects were most pronounced in men who were under age 65 at diagnosis, but older men had the additional benefit from radical prostatectomy of improved quality of life, because of a significantly lower risk of palliative care, including androgen-deprivation therapy. "The life experience after the diagnosis of prostate cancer differs substantially between the two study groups and evolves over decades," said Dr. Anna Bill-Axelson of Uppsala (Sweden) University Hospital and her associates.

Between 1989 and 1999, men with localized prostate cancer who were under age 75 and had life expectancies beyond 10 years, were randomly assigned to undergo radical prostatectomy (347 patients) or watchful waiting (348 patients) at 14 medical centers in Sweden, Finland, and Iceland. A total of 447 men (64%) died during extended follow-up lasting until 2012 (median follow-up, 13.4 years).

All-cause mortality was 56.1% in the prostatectomy group, significantly lower than the 68.9% all-cause mortality in the watchful waiting group; the number needed to treat to prevent 1 death at 18 years of follow-up was 8. Similarly, prostate cancer–specific mortality was 17.7% with prostatectomy vs. 28.7% with watchful waiting, and the difference between the two study groups continued to increase over time, the investigators reported (N. Engl. J. Med. 2014 March 5 [doi: 10.1056/NEMoa1311593]).

Among men under age 65 at diagnosis, all-cause mortality was 25.5 percentage points lower, prostate cancer–specific mortality was 15.8 percentage points lower, and risk of metastases was 15.8 percentage points lower with prostatectomy than with watchful waiting. "In this age group, the number needed to treat to prevent 1 death from prostate cancer was 4," Dr. Bill-Axelson and her associates said.

This study was supported by the Swedish Cancer Society, the National Institutes of Health, the Karolinska Institute, the Prostate Cancer Foundation, and the Percy Falk Foundation. The authors reported that they had no financial conflicts of interest.

Montana is expected to have the highest rate of prostate cancer deaths in the United States for 2014, and it will be more than twice as high as that of Texas, which should have the lowest rate, the American Cancer Society reported.

Based on mortality data for 1995-2010 from the National Center for Health Statistics, the ACS estimates put the death rate at 12.8 per 100,000 population for Montana and 6.3 per 100,000 for Texas.

After Texas, Wyoming has the lowest estimated prostate cancer rate for 2014 at 6.9 per 100,000, followed by Utah at 7.2. The District of Columbia has the second-highest rate at 12.4 per 100,000, with Maine third at 12.0, according to the ACS estimates.

Although the number of prostate cancer deaths has been decreasing – dropping by an average of 3.1% per year from 2006 to 2010 – it is still the second-leading cause of cancer death in men. With almost 29,500 deaths expected in the United States this year, the national death rate from prostate cancer for 2014 is estimated to be 9.3 per 100,000, according to the ACS report.

rfranki@frontlinemedcom.com

Montana is expected to have the highest rate of prostate cancer deaths in the United States for 2014, and it will be more than twice as high as that of Texas, which should have the lowest rate, the American Cancer Society reported.

Based on mortality data for 1995-2010 from the National Center for Health Statistics, the ACS estimates put the death rate at 12.8 per 100,000 population for Montana and 6.3 per 100,000 for Texas.

After Texas, Wyoming has the lowest estimated prostate cancer rate for 2014 at 6.9 per 100,000, followed by Utah at 7.2. The District of Columbia has the second-highest rate at 12.4 per 100,000, with Maine third at 12.0, according to the ACS estimates.

Although the number of prostate cancer deaths has been decreasing – dropping by an average of 3.1% per year from 2006 to 2010 – it is still the second-leading cause of cancer death in men. With almost 29,500 deaths expected in the United States this year, the national death rate from prostate cancer for 2014 is estimated to be 9.3 per 100,000, according to the ACS report.

rfranki@frontlinemedcom.com

Montana is expected to have the highest rate of prostate cancer deaths in the United States for 2014, and it will be more than twice as high as that of Texas, which should have the lowest rate, the American Cancer Society reported.

Based on mortality data for 1995-2010 from the National Center for Health Statistics, the ACS estimates put the death rate at 12.8 per 100,000 population for Montana and 6.3 per 100,000 for Texas.

After Texas, Wyoming has the lowest estimated prostate cancer rate for 2014 at 6.9 per 100,000, followed by Utah at 7.2. The District of Columbia has the second-highest rate at 12.4 per 100,000, with Maine third at 12.0, according to the ACS estimates.

Although the number of prostate cancer deaths has been decreasing – dropping by an average of 3.1% per year from 2006 to 2010 – it is still the second-leading cause of cancer death in men. With almost 29,500 deaths expected in the United States this year, the national death rate from prostate cancer for 2014 is estimated to be 9.3 per 100,000, according to the ACS report.

rfranki@frontlinemedcom.com

The use of beta-blockers in men with metastatic and high-risk prostate cancer was associated with a reduced risk of prostate cancer–specific mortality independent of statin or acetylsalicylic acid use, according to a study published in European Urology.

Given these results, beta-blocker use should be further investigated where large registries are available, wrote Dr. Helene Hartvedt Grytli of the Institute of Cancer Research at Oslo University Hospital and her coinvestigators. "This is the first study to assess the association between beta-blocker use and prostate cancer–specific survival in a large cohort of men with known disease aggressiveness at diagnosis," they wrote.

The researchers obtained data from the Cancer Registry of Norway for men diagnosed with prostate cancer between 2004 and 2009. They coupled these data, using participants’ national identification numbers, with information from the Norwegian Prescription Database on filled prescriptions for beta-blockers, statins, and acetylsalicylic acid (ASA). Patients were considered users of these agents if they had filled at least one prescription of the respective drug both before and after diagnosis.

Mortality data were obtained from the Cancer Registry of Norway. A total of 3,561 men were eligible for analysis after exclusion criteria were accounted for; the criteria included having low- or intermediate-risk disease and planned treatment with either radical prostatectomy or radiation therapy.

Beta-blocker use was independently associated with a reduced risk of prostate cancer–specific mortality in a multivariable model (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001). The median follow-up time was 39 months (Eur. Urol. 2014;635-41).

Among beta-blocker users, 72% also used either ASA or statins. The investigators performed a survival analysis, adjusting for the use of these drugs to study any possible confounding effect. Statin use and ASA use were both associated with a reduction in prostate cancer–specific mortality when each drug was analyzed separately. Adjustment for the use of these drug classes did not substantially change the subhazard ratio for beta-blocker use.

The researchers did acknowledge a possible limitation of their study: "Unknown patient characteristics of this patient group might have confounded our results, and additional observation studies are warranted to establish whether beta-blocker use has an independent effect on prostate cancer progression and survival."

The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.

mrajaraman@frontlinemedcom.com

The use of beta-blockers in men with metastatic and high-risk prostate cancer was associated with a reduced risk of prostate cancer–specific mortality independent of statin or acetylsalicylic acid use, according to a study published in European Urology.

Given these results, beta-blocker use should be further investigated where large registries are available, wrote Dr. Helene Hartvedt Grytli of the Institute of Cancer Research at Oslo University Hospital and her coinvestigators. "This is the first study to assess the association between beta-blocker use and prostate cancer–specific survival in a large cohort of men with known disease aggressiveness at diagnosis," they wrote.

The researchers obtained data from the Cancer Registry of Norway for men diagnosed with prostate cancer between 2004 and 2009. They coupled these data, using participants’ national identification numbers, with information from the Norwegian Prescription Database on filled prescriptions for beta-blockers, statins, and acetylsalicylic acid (ASA). Patients were considered users of these agents if they had filled at least one prescription of the respective drug both before and after diagnosis.

Mortality data were obtained from the Cancer Registry of Norway. A total of 3,561 men were eligible for analysis after exclusion criteria were accounted for; the criteria included having low- or intermediate-risk disease and planned treatment with either radical prostatectomy or radiation therapy.

Beta-blocker use was independently associated with a reduced risk of prostate cancer–specific mortality in a multivariable model (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001). The median follow-up time was 39 months (Eur. Urol. 2014;635-41).

Among beta-blocker users, 72% also used either ASA or statins. The investigators performed a survival analysis, adjusting for the use of these drugs to study any possible confounding effect. Statin use and ASA use were both associated with a reduction in prostate cancer–specific mortality when each drug was analyzed separately. Adjustment for the use of these drug classes did not substantially change the subhazard ratio for beta-blocker use.

The researchers did acknowledge a possible limitation of their study: "Unknown patient characteristics of this patient group might have confounded our results, and additional observation studies are warranted to establish whether beta-blocker use has an independent effect on prostate cancer progression and survival."

The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.

mrajaraman@frontlinemedcom.com

The use of beta-blockers in men with metastatic and high-risk prostate cancer was associated with a reduced risk of prostate cancer–specific mortality independent of statin or acetylsalicylic acid use, according to a study published in European Urology.

Given these results, beta-blocker use should be further investigated where large registries are available, wrote Dr. Helene Hartvedt Grytli of the Institute of Cancer Research at Oslo University Hospital and her coinvestigators. "This is the first study to assess the association between beta-blocker use and prostate cancer–specific survival in a large cohort of men with known disease aggressiveness at diagnosis," they wrote.

The researchers obtained data from the Cancer Registry of Norway for men diagnosed with prostate cancer between 2004 and 2009. They coupled these data, using participants’ national identification numbers, with information from the Norwegian Prescription Database on filled prescriptions for beta-blockers, statins, and acetylsalicylic acid (ASA). Patients were considered users of these agents if they had filled at least one prescription of the respective drug both before and after diagnosis.

Mortality data were obtained from the Cancer Registry of Norway. A total of 3,561 men were eligible for analysis after exclusion criteria were accounted for; the criteria included having low- or intermediate-risk disease and planned treatment with either radical prostatectomy or radiation therapy.

Beta-blocker use was independently associated with a reduced risk of prostate cancer–specific mortality in a multivariable model (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001). The median follow-up time was 39 months (Eur. Urol. 2014;635-41).

Among beta-blocker users, 72% also used either ASA or statins. The investigators performed a survival analysis, adjusting for the use of these drugs to study any possible confounding effect. Statin use and ASA use were both associated with a reduction in prostate cancer–specific mortality when each drug was analyzed separately. Adjustment for the use of these drug classes did not substantially change the subhazard ratio for beta-blocker use.

The researchers did acknowledge a possible limitation of their study: "Unknown patient characteristics of this patient group might have confounded our results, and additional observation studies are warranted to establish whether beta-blocker use has an independent effect on prostate cancer progression and survival."

The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.

mrajaraman@frontlinemedcom.com

SAN FRANCISCO – The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is a valid tool for predicting survival in patients starting second-line targeted therapy for this disease, new data show.

In fact, it outperforms the leading model derived a decade ago, researchers reported at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

The new model uses six clinical and laboratory factors to stratify patients into prognostic risk groups. It builds on the widely used three-factor Memorial Sloan-Kettering Cancer Center (MSKCC) second-line prognostic model (J. Clin. Oncol. 2004;22:454-63).

Results of the retrospective cohort study showed that the IMDC model performed well for risk stratification in this setting, with patients in the intermediate- and high-risk groups having roughly two and six times the risk of death, respectively, compared with peers in the favorable risk group, reported Dr. Jenny J. Ko of the British Columbia Cancer Agency, Vancouver. Also, it was superior to the MSKCC model for predicting survival as assessed by three statistical tests.

"The six-factor IMDC prognostic model has been validated in and can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in the first-line targeted therapy and non–clear cell setting," she commented.

"The model fits better into the context of the contemporary treatment era, where targeted therapies are used in a sequential fashion," Dr. Ko added.

The study population was heterogeneous, she acknowledged. But "this can also mean that the cohort was generalizable, as our cohort includes trial and off-trial patients, and it also includes community and academic centers."

Invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia, noted that the durations of second-line therapy and survival after starting this therapy were fairly short, highlighting the need for better therapies.

The choice of first-line therapy for metastatic renal cell carcinoma (mRCC) may shift in the future away from sunitinib (Sutent) and sorafenib (Nexavar), used in the vast majority of the patients studied, he noted.

"My observation is that the medical oncologists that I work with seem to be using pazopanib (Votrient) more now as a first-line therapy because of the improved toxicity," Dr. Canter noted, and doing so may ultimately affect survival. "Obviously, a future question is the role of pazopanib. And ... an algorithm to define second-line choices is clearly something where there is an opportunity for work to be done."

Dr. Ko and her team studied 1,021 consecutive patients with mRCC from 19 centers who were starting second-line targeted therapy. (About a fifth had received immunotherapy before their first-line targeted therapy and were therefore on third-line therapy of any type.)

Eighty-five percent of patients had undergone nephrectomy. Their first-line targeted therapy had most often been sunitinib (67%) or sorafenib (20%).

The second-line therapies given included sorafenib (29%), sunitinib (22%), everolimus (Afinitor) (22%), and temsirolimus (Torisel) (12%), among others.

In a multivariate analysis, five of the six IMDC factors (Karnofsky performance status less than 80%; interval between diagnosis and treatment of less than 1 year; anemia; thrombocytosis; and neutrophilia) individually predicted an elevated risk of death after starting second-line therapy, reported Dr. Ko, who disclosed no conflicts of interest related to the research. Hypercalcemia did not, but few patients had this risk factor.

The median time on second-line targeted therapy was 3.9 months, and the median overall survival after starting this therapy was 12.5 months.

Compared with patients in the favorable IMDC risk group (having none of the risk factors), patients in the intermediate-risk group (having one or two) and patients in the high-risk group (having three or more) had significantly elevated risks of death (hazard ratios, 1.89 and 5.73).

In a likelihood ratio test, comparing the two models, the chi-square value was highly significant, suggesting that inclusion of the three additional factors in the IMDC model enhanced predictive performance over that with the MSKCC model.

Finally, in a reclassification calibration analysis, the chi-square value was much lower for the IMDC model than for the MSKCC model (6.2 vs. 54.2), indicating that the observed vs. predicted number of deaths at 1 year was better for the former.

SAN FRANCISCO – The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is a valid tool for predicting survival in patients starting second-line targeted therapy for this disease, new data show.

In fact, it outperforms the leading model derived a decade ago, researchers reported at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

The new model uses six clinical and laboratory factors to stratify patients into prognostic risk groups. It builds on the widely used three-factor Memorial Sloan-Kettering Cancer Center (MSKCC) second-line prognostic model (J. Clin. Oncol. 2004;22:454-63).

Results of the retrospective cohort study showed that the IMDC model performed well for risk stratification in this setting, with patients in the intermediate- and high-risk groups having roughly two and six times the risk of death, respectively, compared with peers in the favorable risk group, reported Dr. Jenny J. Ko of the British Columbia Cancer Agency, Vancouver. Also, it was superior to the MSKCC model for predicting survival as assessed by three statistical tests.

"The six-factor IMDC prognostic model has been validated in and can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in the first-line targeted therapy and non–clear cell setting," she commented.

"The model fits better into the context of the contemporary treatment era, where targeted therapies are used in a sequential fashion," Dr. Ko added.

The study population was heterogeneous, she acknowledged. But "this can also mean that the cohort was generalizable, as our cohort includes trial and off-trial patients, and it also includes community and academic centers."

Invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia, noted that the durations of second-line therapy and survival after starting this therapy were fairly short, highlighting the need for better therapies.

The choice of first-line therapy for metastatic renal cell carcinoma (mRCC) may shift in the future away from sunitinib (Sutent) and sorafenib (Nexavar), used in the vast majority of the patients studied, he noted.

"My observation is that the medical oncologists that I work with seem to be using pazopanib (Votrient) more now as a first-line therapy because of the improved toxicity," Dr. Canter noted, and doing so may ultimately affect survival. "Obviously, a future question is the role of pazopanib. And ... an algorithm to define second-line choices is clearly something where there is an opportunity for work to be done."

Dr. Ko and her team studied 1,021 consecutive patients with mRCC from 19 centers who were starting second-line targeted therapy. (About a fifth had received immunotherapy before their first-line targeted therapy and were therefore on third-line therapy of any type.)

Eighty-five percent of patients had undergone nephrectomy. Their first-line targeted therapy had most often been sunitinib (67%) or sorafenib (20%).

The second-line therapies given included sorafenib (29%), sunitinib (22%), everolimus (Afinitor) (22%), and temsirolimus (Torisel) (12%), among others.

In a multivariate analysis, five of the six IMDC factors (Karnofsky performance status less than 80%; interval between diagnosis and treatment of less than 1 year; anemia; thrombocytosis; and neutrophilia) individually predicted an elevated risk of death after starting second-line therapy, reported Dr. Ko, who disclosed no conflicts of interest related to the research. Hypercalcemia did not, but few patients had this risk factor.

The median time on second-line targeted therapy was 3.9 months, and the median overall survival after starting this therapy was 12.5 months.

Compared with patients in the favorable IMDC risk group (having none of the risk factors), patients in the intermediate-risk group (having one or two) and patients in the high-risk group (having three or more) had significantly elevated risks of death (hazard ratios, 1.89 and 5.73).

In a likelihood ratio test, comparing the two models, the chi-square value was highly significant, suggesting that inclusion of the three additional factors in the IMDC model enhanced predictive performance over that with the MSKCC model.

Finally, in a reclassification calibration analysis, the chi-square value was much lower for the IMDC model than for the MSKCC model (6.2 vs. 54.2), indicating that the observed vs. predicted number of deaths at 1 year was better for the former.

SAN FRANCISCO – The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is a valid tool for predicting survival in patients starting second-line targeted therapy for this disease, new data show.

In fact, it outperforms the leading model derived a decade ago, researchers reported at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

The new model uses six clinical and laboratory factors to stratify patients into prognostic risk groups. It builds on the widely used three-factor Memorial Sloan-Kettering Cancer Center (MSKCC) second-line prognostic model (J. Clin. Oncol. 2004;22:454-63).

Results of the retrospective cohort study showed that the IMDC model performed well for risk stratification in this setting, with patients in the intermediate- and high-risk groups having roughly two and six times the risk of death, respectively, compared with peers in the favorable risk group, reported Dr. Jenny J. Ko of the British Columbia Cancer Agency, Vancouver. Also, it was superior to the MSKCC model for predicting survival as assessed by three statistical tests.

"The six-factor IMDC prognostic model has been validated in and can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in the first-line targeted therapy and non–clear cell setting," she commented.

"The model fits better into the context of the contemporary treatment era, where targeted therapies are used in a sequential fashion," Dr. Ko added.

The study population was heterogeneous, she acknowledged. But "this can also mean that the cohort was generalizable, as our cohort includes trial and off-trial patients, and it also includes community and academic centers."

Invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia, noted that the durations of second-line therapy and survival after starting this therapy were fairly short, highlighting the need for better therapies.

The choice of first-line therapy for metastatic renal cell carcinoma (mRCC) may shift in the future away from sunitinib (Sutent) and sorafenib (Nexavar), used in the vast majority of the patients studied, he noted.

"My observation is that the medical oncologists that I work with seem to be using pazopanib (Votrient) more now as a first-line therapy because of the improved toxicity," Dr. Canter noted, and doing so may ultimately affect survival. "Obviously, a future question is the role of pazopanib. And ... an algorithm to define second-line choices is clearly something where there is an opportunity for work to be done."

Dr. Ko and her team studied 1,021 consecutive patients with mRCC from 19 centers who were starting second-line targeted therapy. (About a fifth had received immunotherapy before their first-line targeted therapy and were therefore on third-line therapy of any type.)

Eighty-five percent of patients had undergone nephrectomy. Their first-line targeted therapy had most often been sunitinib (67%) or sorafenib (20%).

The second-line therapies given included sorafenib (29%), sunitinib (22%), everolimus (Afinitor) (22%), and temsirolimus (Torisel) (12%), among others.

In a multivariate analysis, five of the six IMDC factors (Karnofsky performance status less than 80%; interval between diagnosis and treatment of less than 1 year; anemia; thrombocytosis; and neutrophilia) individually predicted an elevated risk of death after starting second-line therapy, reported Dr. Ko, who disclosed no conflicts of interest related to the research. Hypercalcemia did not, but few patients had this risk factor.

The median time on second-line targeted therapy was 3.9 months, and the median overall survival after starting this therapy was 12.5 months.

Compared with patients in the favorable IMDC risk group (having none of the risk factors), patients in the intermediate-risk group (having one or two) and patients in the high-risk group (having three or more) had significantly elevated risks of death (hazard ratios, 1.89 and 5.73).

In a likelihood ratio test, comparing the two models, the chi-square value was highly significant, suggesting that inclusion of the three additional factors in the IMDC model enhanced predictive performance over that with the MSKCC model.

Finally, in a reclassification calibration analysis, the chi-square value was much lower for the IMDC model than for the MSKCC model (6.2 vs. 54.2), indicating that the observed vs. predicted number of deaths at 1 year was better for the former.

Among prostate cancers that are judged to be low risk after physical exam and biopsy, and which thus are candidates for active surveillance, 33%-45% are upgraded or upstaged when the patient decides instead to undergo radical prostatectomy, according to a report in the February issue of Journal of Urology.

Researchers analyzed data regarding tumor and patient features for 4,500 cases in a national Swedish database of prostate cancers diagnosed during a 4-year period. All of these cases were judged to be low risk on the basis of Gleason scores, PSA findings, and biopsy results, but all of the men elected to undergo radical prostatectomy, said Dr. Annelies Vellekoop of New York University and Manhattan Veterans Affairs Medical Center, New York, and her associates.

Even though these cases met stringent criteria for active surveillance according to several different protocols, 33%-45% of them (depending on the protocol) were found at surgery to have adverse pathology signaling that the cancers were of higher risk than anticipated (J. Urol. 2014;191:350-7).

Three predictors of upstaging/upgrading – age over 60 years, high PSA level, and stage T2 cancer on biopsy – are already known to raise risk and are included in most risk-assessment criteria. But two other factors – PSA density greater than 0.15 ng/mL and the linear extent of cancer in mm within biopsy specimens – were found to be highly predictive in this study and should be considered as additional criteria to include in risk assessments, the investigators said.

This study was supported by the Swedish Research Council, the Swedish Cancer Foundation, Vasterbotten County Council, and Lion’s Cancer Research Foundation at Umea University. Dr. Vellekoop reported no financial conflicts of interest; one of her associates reported ties to Sanofi.

tor@frontlinemedcom.com

Among prostate cancers that are judged to be low risk after physical exam and biopsy, and which thus are candidates for active surveillance, 33%-45% are upgraded or upstaged when the patient decides instead to undergo radical prostatectomy, according to a report in the February issue of Journal of Urology.

Researchers analyzed data regarding tumor and patient features for 4,500 cases in a national Swedish database of prostate cancers diagnosed during a 4-year period. All of these cases were judged to be low risk on the basis of Gleason scores, PSA findings, and biopsy results, but all of the men elected to undergo radical prostatectomy, said Dr. Annelies Vellekoop of New York University and Manhattan Veterans Affairs Medical Center, New York, and her associates.

Even though these cases met stringent criteria for active surveillance according to several different protocols, 33%-45% of them (depending on the protocol) were found at surgery to have adverse pathology signaling that the cancers were of higher risk than anticipated (J. Urol. 2014;191:350-7).

Three predictors of upstaging/upgrading – age over 60 years, high PSA level, and stage T2 cancer on biopsy – are already known to raise risk and are included in most risk-assessment criteria. But two other factors – PSA density greater than 0.15 ng/mL and the linear extent of cancer in mm within biopsy specimens – were found to be highly predictive in this study and should be considered as additional criteria to include in risk assessments, the investigators said.

This study was supported by the Swedish Research Council, the Swedish Cancer Foundation, Vasterbotten County Council, and Lion’s Cancer Research Foundation at Umea University. Dr. Vellekoop reported no financial conflicts of interest; one of her associates reported ties to Sanofi.

tor@frontlinemedcom.com

Among prostate cancers that are judged to be low risk after physical exam and biopsy, and which thus are candidates for active surveillance, 33%-45% are upgraded or upstaged when the patient decides instead to undergo radical prostatectomy, according to a report in the February issue of Journal of Urology.

Researchers analyzed data regarding tumor and patient features for 4,500 cases in a national Swedish database of prostate cancers diagnosed during a 4-year period. All of these cases were judged to be low risk on the basis of Gleason scores, PSA findings, and biopsy results, but all of the men elected to undergo radical prostatectomy, said Dr. Annelies Vellekoop of New York University and Manhattan Veterans Affairs Medical Center, New York, and her associates.

Even though these cases met stringent criteria for active surveillance according to several different protocols, 33%-45% of them (depending on the protocol) were found at surgery to have adverse pathology signaling that the cancers were of higher risk than anticipated (J. Urol. 2014;191:350-7).

Three predictors of upstaging/upgrading – age over 60 years, high PSA level, and stage T2 cancer on biopsy – are already known to raise risk and are included in most risk-assessment criteria. But two other factors – PSA density greater than 0.15 ng/mL and the linear extent of cancer in mm within biopsy specimens – were found to be highly predictive in this study and should be considered as additional criteria to include in risk assessments, the investigators said.

This study was supported by the Swedish Research Council, the Swedish Cancer Foundation, Vasterbotten County Council, and Lion’s Cancer Research Foundation at Umea University. Dr. Vellekoop reported no financial conflicts of interest; one of her associates reported ties to Sanofi.

tor@frontlinemedcom.com

SAN FRANCISCO – Only selected patients with synchronous metastases from renal cell carcinoma derive a survival benefit from a cytoreductive nephrectomy, a retrospective cohort study showed.

Researchers studied more than 1,600 patients from the International mRCC (metastatic renal cell carcinoma) Database Consortium who developed metastases while their primary tumor was still in place.

The main analyses showed that as a whole, patients who underwent cytoreductive nephrectomy lived longer than their counterparts who did not have this surgery.

However, in stratified analyses, the surgery significantly prolonged survival only among patients who had a life expectancy exceeding 12 months and patients who had three or fewer risk factors by International mRCC Database Consortium (IMDC) criteria.

Risk factors include Karnofsky performance status less than 80%, an interval between diagnosis and treatment of less than 1 year, anemia, thrombocytosis, neutrophilia, and hypercalcemia

"Overall, I think we can say that cytoreductive nephrectomy may be beneficial in the age of targeted therapy. However, not all patients should have it," commented first author Dr. Daniel Y.C. Heng of the University of Calgary (Alta.).

"Patients with four or more IMDC risk factors and patients with limited life expectancy probably shouldn’t have a cytoreductive nephrectomy," he said. "Of course, there are probably exceptions to that rule; if patients are really symptomatic in the primary, for example, or have bleeding, maybe there are exceptions.

"But I think this is a very interesting and useful way to help select our patients for cytoreductive nephrectomy. Certainly, we are awaiting the CARMENA and SURTIME phase III randomized controlled trials to prospectively evaluate this, and hopefully, we will be able to look at the IMDC risk factors to see if they can aid in patient selection in a prospectively validated way," Dr. Heng said at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

Cytoreductive nephrectomy carries risks of morbidity and mortality, and some patients may be unable to go on to receive systemic therapy, noted invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia.

"What I take home as the most important point of this talk is that we need to make better choices and risk stratify these patients before surgery," he said.

A key question arising from the new data is whether the IMDC risk groups should be redefined, according to Dr. Canter; for example, patients with three risk factors are currently placed in the poor risk group, yet they derived significant benefit from surgery in this study. "So is there room for further refinement in this model?" he asked.

"With such a large cohort, I think that adding to this data with complication rates and perioperative mortality would certainly be important in terms of future treatment decision making," he commented.

Session attendee Dr. Adam Metwalli of the National Cancer Institute asked, "Are there specific risk factors that seem to disproportionately cluster among those who have four or five that would help to distinguish them from the ones who have zero to three?"

"By far, the most important prognostic factor is Karnofsky performance status, and that makes sense," Dr. Heng replied. "It’s partially the ‘look test’ and how you think a patient will fare. So, that by far has the biggest contribution."

Introducing the study, he noted that cytoreductive nephrectomy has previously been found to prolong survival by about 6 months in patients with metastatic renal cell carcinoma treated in the immunotherapy era.

"But of course now we are in the age of targeted therapy, with VEGF [vascular endothelial growth factor] inhibitors and mTOR [mammalian target of rapamycin] inhibitors. These are drugs that are much more active than in the era of old immunotherapy. So it begs the question, is cytoreductive nephrectomy still relevant?" Dr. Heng said.

The researchers studied 1,658 patients from 20 institutions who had mRCC with synchronous metastases, of whom 59% underwent cytoreductive nephrectomy.

They had a median age of 59 years, and about half were in the IMDC intermediate-risk group. The most common prior targeted therapy was sunitinib (Sutent), received by about three-fourths, reported Dr. Heng.

In unadjusted analyses, median overall survival was a significant 11 months longer for patients who underwent cytoreductive nephrectomy compared with their counterparts who did not (20.6 vs. 9.5 months). After adjustment for IMDC risk factors, the surgery was associated with a 40% reduction in the risk of death in the entire cohort (hazard ratio, 0.60; P less than .0001).

However, in analyses stratified by patient life expectancy, there was a significant survival benefit of cytoreductive nephrectomy only among patients expected to live 12-18 months (3.3-month incremental benefit; adjusted hazard ratio, 0.85; P = .049) or 18-24 months (5.2-month incremental benefit; adjusted hazard ratio, 0.72; P less than .0001).

Similarly, in analyses stratified by the number of risk factors present out of the six IMDC risk factors, there was a significant survival benefit of cytoreductive nephrectomy only among patients with three or fewer factors (incremental benefit of 6-10 months, P less than .005 for each).

The impact of overall tumor burden and the size of the primary tumor were not considered in this analysis but will be in subsequent analyses, according to Dr. Heng.

He disclosed that he is a consultant/adviser to Aveo, Bayer, Bristol-Myers Squibb, Novartis, and Pfizer.

SAN FRANCISCO – Only selected patients with synchronous metastases from renal cell carcinoma derive a survival benefit from a cytoreductive nephrectomy, a retrospective cohort study showed.

Researchers studied more than 1,600 patients from the International mRCC (metastatic renal cell carcinoma) Database Consortium who developed metastases while their primary tumor was still in place.

The main analyses showed that as a whole, patients who underwent cytoreductive nephrectomy lived longer than their counterparts who did not have this surgery.

However, in stratified analyses, the surgery significantly prolonged survival only among patients who had a life expectancy exceeding 12 months and patients who had three or fewer risk factors by International mRCC Database Consortium (IMDC) criteria.

Risk factors include Karnofsky performance status less than 80%, an interval between diagnosis and treatment of less than 1 year, anemia, thrombocytosis, neutrophilia, and hypercalcemia

"Overall, I think we can say that cytoreductive nephrectomy may be beneficial in the age of targeted therapy. However, not all patients should have it," commented first author Dr. Daniel Y.C. Heng of the University of Calgary (Alta.).

"Patients with four or more IMDC risk factors and patients with limited life expectancy probably shouldn’t have a cytoreductive nephrectomy," he said. "Of course, there are probably exceptions to that rule; if patients are really symptomatic in the primary, for example, or have bleeding, maybe there are exceptions.

"But I think this is a very interesting and useful way to help select our patients for cytoreductive nephrectomy. Certainly, we are awaiting the CARMENA and SURTIME phase III randomized controlled trials to prospectively evaluate this, and hopefully, we will be able to look at the IMDC risk factors to see if they can aid in patient selection in a prospectively validated way," Dr. Heng said at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

Cytoreductive nephrectomy carries risks of morbidity and mortality, and some patients may be unable to go on to receive systemic therapy, noted invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia.

"What I take home as the most important point of this talk is that we need to make better choices and risk stratify these patients before surgery," he said.

A key question arising from the new data is whether the IMDC risk groups should be redefined, according to Dr. Canter; for example, patients with three risk factors are currently placed in the poor risk group, yet they derived significant benefit from surgery in this study. "So is there room for further refinement in this model?" he asked.

"With such a large cohort, I think that adding to this data with complication rates and perioperative mortality would certainly be important in terms of future treatment decision making," he commented.

Session attendee Dr. Adam Metwalli of the National Cancer Institute asked, "Are there specific risk factors that seem to disproportionately cluster among those who have four or five that would help to distinguish them from the ones who have zero to three?"

"By far, the most important prognostic factor is Karnofsky performance status, and that makes sense," Dr. Heng replied. "It’s partially the ‘look test’ and how you think a patient will fare. So, that by far has the biggest contribution."

Introducing the study, he noted that cytoreductive nephrectomy has previously been found to prolong survival by about 6 months in patients with metastatic renal cell carcinoma treated in the immunotherapy era.

"But of course now we are in the age of targeted therapy, with VEGF [vascular endothelial growth factor] inhibitors and mTOR [mammalian target of rapamycin] inhibitors. These are drugs that are much more active than in the era of old immunotherapy. So it begs the question, is cytoreductive nephrectomy still relevant?" Dr. Heng said.

The researchers studied 1,658 patients from 20 institutions who had mRCC with synchronous metastases, of whom 59% underwent cytoreductive nephrectomy.

They had a median age of 59 years, and about half were in the IMDC intermediate-risk group. The most common prior targeted therapy was sunitinib (Sutent), received by about three-fourths, reported Dr. Heng.

In unadjusted analyses, median overall survival was a significant 11 months longer for patients who underwent cytoreductive nephrectomy compared with their counterparts who did not (20.6 vs. 9.5 months). After adjustment for IMDC risk factors, the surgery was associated with a 40% reduction in the risk of death in the entire cohort (hazard ratio, 0.60; P less than .0001).

However, in analyses stratified by patient life expectancy, there was a significant survival benefit of cytoreductive nephrectomy only among patients expected to live 12-18 months (3.3-month incremental benefit; adjusted hazard ratio, 0.85; P = .049) or 18-24 months (5.2-month incremental benefit; adjusted hazard ratio, 0.72; P less than .0001).

Similarly, in analyses stratified by the number of risk factors present out of the six IMDC risk factors, there was a significant survival benefit of cytoreductive nephrectomy only among patients with three or fewer factors (incremental benefit of 6-10 months, P less than .005 for each).

The impact of overall tumor burden and the size of the primary tumor were not considered in this analysis but will be in subsequent analyses, according to Dr. Heng.

He disclosed that he is a consultant/adviser to Aveo, Bayer, Bristol-Myers Squibb, Novartis, and Pfizer.

SAN FRANCISCO – Only selected patients with synchronous metastases from renal cell carcinoma derive a survival benefit from a cytoreductive nephrectomy, a retrospective cohort study showed.

Researchers studied more than 1,600 patients from the International mRCC (metastatic renal cell carcinoma) Database Consortium who developed metastases while their primary tumor was still in place.

The main analyses showed that as a whole, patients who underwent cytoreductive nephrectomy lived longer than their counterparts who did not have this surgery.

However, in stratified analyses, the surgery significantly prolonged survival only among patients who had a life expectancy exceeding 12 months and patients who had three or fewer risk factors by International mRCC Database Consortium (IMDC) criteria.

Risk factors include Karnofsky performance status less than 80%, an interval between diagnosis and treatment of less than 1 year, anemia, thrombocytosis, neutrophilia, and hypercalcemia

"Overall, I think we can say that cytoreductive nephrectomy may be beneficial in the age of targeted therapy. However, not all patients should have it," commented first author Dr. Daniel Y.C. Heng of the University of Calgary (Alta.).

"Patients with four or more IMDC risk factors and patients with limited life expectancy probably shouldn’t have a cytoreductive nephrectomy," he said. "Of course, there are probably exceptions to that rule; if patients are really symptomatic in the primary, for example, or have bleeding, maybe there are exceptions.

"But I think this is a very interesting and useful way to help select our patients for cytoreductive nephrectomy. Certainly, we are awaiting the CARMENA and SURTIME phase III randomized controlled trials to prospectively evaluate this, and hopefully, we will be able to look at the IMDC risk factors to see if they can aid in patient selection in a prospectively validated way," Dr. Heng said at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

Cytoreductive nephrectomy carries risks of morbidity and mortality, and some patients may be unable to go on to receive systemic therapy, noted invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia.

"What I take home as the most important point of this talk is that we need to make better choices and risk stratify these patients before surgery," he said.

A key question arising from the new data is whether the IMDC risk groups should be redefined, according to Dr. Canter; for example, patients with three risk factors are currently placed in the poor risk group, yet they derived significant benefit from surgery in this study. "So is there room for further refinement in this model?" he asked.

"With such a large cohort, I think that adding to this data with complication rates and perioperative mortality would certainly be important in terms of future treatment decision making," he commented.

Session attendee Dr. Adam Metwalli of the National Cancer Institute asked, "Are there specific risk factors that seem to disproportionately cluster among those who have four or five that would help to distinguish them from the ones who have zero to three?"

"By far, the most important prognostic factor is Karnofsky performance status, and that makes sense," Dr. Heng replied. "It’s partially the ‘look test’ and how you think a patient will fare. So, that by far has the biggest contribution."

Introducing the study, he noted that cytoreductive nephrectomy has previously been found to prolong survival by about 6 months in patients with metastatic renal cell carcinoma treated in the immunotherapy era.

"But of course now we are in the age of targeted therapy, with VEGF [vascular endothelial growth factor] inhibitors and mTOR [mammalian target of rapamycin] inhibitors. These are drugs that are much more active than in the era of old immunotherapy. So it begs the question, is cytoreductive nephrectomy still relevant?" Dr. Heng said.

The researchers studied 1,658 patients from 20 institutions who had mRCC with synchronous metastases, of whom 59% underwent cytoreductive nephrectomy.

They had a median age of 59 years, and about half were in the IMDC intermediate-risk group. The most common prior targeted therapy was sunitinib (Sutent), received by about three-fourths, reported Dr. Heng.

In unadjusted analyses, median overall survival was a significant 11 months longer for patients who underwent cytoreductive nephrectomy compared with their counterparts who did not (20.6 vs. 9.5 months). After adjustment for IMDC risk factors, the surgery was associated with a 40% reduction in the risk of death in the entire cohort (hazard ratio, 0.60; P less than .0001).

However, in analyses stratified by patient life expectancy, there was a significant survival benefit of cytoreductive nephrectomy only among patients expected to live 12-18 months (3.3-month incremental benefit; adjusted hazard ratio, 0.85; P = .049) or 18-24 months (5.2-month incremental benefit; adjusted hazard ratio, 0.72; P less than .0001).

Similarly, in analyses stratified by the number of risk factors present out of the six IMDC risk factors, there was a significant survival benefit of cytoreductive nephrectomy only among patients with three or fewer factors (incremental benefit of 6-10 months, P less than .005 for each).

The impact of overall tumor burden and the size of the primary tumor were not considered in this analysis but will be in subsequent analyses, according to Dr. Heng.

He disclosed that he is a consultant/adviser to Aveo, Bayer, Bristol-Myers Squibb, Novartis, and Pfizer.