Genitourinary Cancer

Intermittent androgen deprivation fell short of proving its noninferiority in a 10-year study comparing survival outcomes for intermittent and standard continuous androgen deprivation in men with metastatic hormone-sensitive prostate cancer.

In the international randomized clinical trial designed to test the noninferiority of intermittent androgen deprivation, the findings were "statistically inconclusive," according to a report published online April 3 in the New England Journal of Medicine.

In short, "the trial results are inconclusive," said Dr. Maha Hussain of the division of hematology/oncology, University of Michigan, Ann Arbor, and her associates. "The median survival after randomization was 5.1 years in the intermittent-therapy group, as compared with 5.8 years in the continuous-therapy group."

The researchers also cautioned that "the lack of a significant difference between the groups does not imply similar survival."

Intermittent therapy might even compromise survival, they said, as a 10% relative increase in the risk of death was associated with that treatment approach. And statistically, a possible 20% relative rise in mortality risk could not be ruled out.

It was hoped that intermittent androgen deprivation would improve patients’ quality of life by reducing adverse effects from the treatment and would improve survival by staving off the androgen resistance, which eventually develops in most patients.

Dr. Hussain and her colleagues compared intermittent with continuous androgen deprivation in 1,749 men enrolled during 1995-2008 at multiple sites across the United States, the United Kingdom, and Canada.

The study subjects all had newly diagnosed, metastatic, hormone-sensitive prostate cancer and a prostate-specific antigen (PSA) level of 5 ng/mL or higher. All had responded to a 7-month induction course of goserelin, bicalutamide, or a similar agent.

The study subjects were stratified by their performance status, prior hormone therapy, and the extent of their metastatic disease. Cancer confined to the spine, pelvic bones, or lymph nodes was considered minimal while that involving the ribs, long bones, or visceral organs was considered extensive.

The subjects were then randomly assigned to receive either intermittent or standard, continuous androgen-deprivation therapy.

In intermittent therapy, treatment was suspended until PSA values returned to baseline levels or to 20 ng/mL. At the discretion of the researchers, androgen deprivation also could be resumed when PSA levels reached 10 ng/mL or when symptoms developed. If patients responded to a subsequent 7-month course of the therapy, another off-treatment interval was begun.

The study subjects were followed for a median of 9.8 years.

Overall median survival was 3.7 years. There were 445 deaths in the continuous-therapy group and 483 deaths in the intermittent-therapy group. Deaths were cancer-related in approximately 80% of the members of both groups, the investigators reported (N. Engl. J. Med. 2013 April 3 [doi: 10.1056/NEJMoa1212299]).

The researchers were unable to show that intermittent androgen-deprivation therapy was either noninferior or inferior to continuous androgen-deprivation therapy.

Treatment effects were "generally consistent" across all subgroups of patients in a post hoc analysis of the data. For example, there was no significant difference in survival between patients who were alive before 2004, when treatment with docetaxel was approved, and those who were alive in 2004 or later. However, "caution should be taken not to overinterpret the results of the subgroup analyses," Dr. Hussain and her associates noted.

The two study groups differed in quality-of-life measures at 3 months after randomization. Men assigned to intermittent therapy were significantly less likely to report impotence and had significantly better mental health scores than did those assigned to continuous androgen deprivation. The intermittent-therapy group also tended to have higher scores for libido, but that difference did not reach statistical significance.

The advantage in quality-of-life measures persisted at 9 months after randomization but gradually declined. By 15 months, the only quality-of-life measure that scored better in the intermittent-therapy group was overall physical functioning.

There was a "remarkably similar" number of grade 3 and grade 4 adverse events in both study groups, the researchers said.

This study was funded by the U.S. National Cancer Institute, the U.S. Public Health Service, and AstraZeneca. AstraZeneca donated goserelin and bicalutamide used in this study but had no role in the study design, data collection or analysis, or writing the manuscript. Dr. Hussain reported ties to AstraZeneca, and her associates reported ties to numerous industry sources.

Intermittent androgen deprivation fell short of proving its noninferiority in a 10-year study comparing survival outcomes for intermittent and standard continuous androgen deprivation in men with metastatic hormone-sensitive prostate cancer.

In the international randomized clinical trial designed to test the noninferiority of intermittent androgen deprivation, the findings were "statistically inconclusive," according to a report published online April 3 in the New England Journal of Medicine.

In short, "the trial results are inconclusive," said Dr. Maha Hussain of the division of hematology/oncology, University of Michigan, Ann Arbor, and her associates. "The median survival after randomization was 5.1 years in the intermittent-therapy group, as compared with 5.8 years in the continuous-therapy group."

The researchers also cautioned that "the lack of a significant difference between the groups does not imply similar survival."

Intermittent therapy might even compromise survival, they said, as a 10% relative increase in the risk of death was associated with that treatment approach. And statistically, a possible 20% relative rise in mortality risk could not be ruled out.

It was hoped that intermittent androgen deprivation would improve patients’ quality of life by reducing adverse effects from the treatment and would improve survival by staving off the androgen resistance, which eventually develops in most patients.

Dr. Hussain and her colleagues compared intermittent with continuous androgen deprivation in 1,749 men enrolled during 1995-2008 at multiple sites across the United States, the United Kingdom, and Canada.

The study subjects all had newly diagnosed, metastatic, hormone-sensitive prostate cancer and a prostate-specific antigen (PSA) level of 5 ng/mL or higher. All had responded to a 7-month induction course of goserelin, bicalutamide, or a similar agent.

The study subjects were stratified by their performance status, prior hormone therapy, and the extent of their metastatic disease. Cancer confined to the spine, pelvic bones, or lymph nodes was considered minimal while that involving the ribs, long bones, or visceral organs was considered extensive.

The subjects were then randomly assigned to receive either intermittent or standard, continuous androgen-deprivation therapy.

In intermittent therapy, treatment was suspended until PSA values returned to baseline levels or to 20 ng/mL. At the discretion of the researchers, androgen deprivation also could be resumed when PSA levels reached 10 ng/mL or when symptoms developed. If patients responded to a subsequent 7-month course of the therapy, another off-treatment interval was begun.

The study subjects were followed for a median of 9.8 years.

Overall median survival was 3.7 years. There were 445 deaths in the continuous-therapy group and 483 deaths in the intermittent-therapy group. Deaths were cancer-related in approximately 80% of the members of both groups, the investigators reported (N. Engl. J. Med. 2013 April 3 [doi: 10.1056/NEJMoa1212299]).

The researchers were unable to show that intermittent androgen-deprivation therapy was either noninferior or inferior to continuous androgen-deprivation therapy.

Treatment effects were "generally consistent" across all subgroups of patients in a post hoc analysis of the data. For example, there was no significant difference in survival between patients who were alive before 2004, when treatment with docetaxel was approved, and those who were alive in 2004 or later. However, "caution should be taken not to overinterpret the results of the subgroup analyses," Dr. Hussain and her associates noted.

The two study groups differed in quality-of-life measures at 3 months after randomization. Men assigned to intermittent therapy were significantly less likely to report impotence and had significantly better mental health scores than did those assigned to continuous androgen deprivation. The intermittent-therapy group also tended to have higher scores for libido, but that difference did not reach statistical significance.

The advantage in quality-of-life measures persisted at 9 months after randomization but gradually declined. By 15 months, the only quality-of-life measure that scored better in the intermittent-therapy group was overall physical functioning.

There was a "remarkably similar" number of grade 3 and grade 4 adverse events in both study groups, the researchers said.

This study was funded by the U.S. National Cancer Institute, the U.S. Public Health Service, and AstraZeneca. AstraZeneca donated goserelin and bicalutamide used in this study but had no role in the study design, data collection or analysis, or writing the manuscript. Dr. Hussain reported ties to AstraZeneca, and her associates reported ties to numerous industry sources.

Intermittent androgen deprivation fell short of proving its noninferiority in a 10-year study comparing survival outcomes for intermittent and standard continuous androgen deprivation in men with metastatic hormone-sensitive prostate cancer.

In the international randomized clinical trial designed to test the noninferiority of intermittent androgen deprivation, the findings were "statistically inconclusive," according to a report published online April 3 in the New England Journal of Medicine.

In short, "the trial results are inconclusive," said Dr. Maha Hussain of the division of hematology/oncology, University of Michigan, Ann Arbor, and her associates. "The median survival after randomization was 5.1 years in the intermittent-therapy group, as compared with 5.8 years in the continuous-therapy group."

The researchers also cautioned that "the lack of a significant difference between the groups does not imply similar survival."

Intermittent therapy might even compromise survival, they said, as a 10% relative increase in the risk of death was associated with that treatment approach. And statistically, a possible 20% relative rise in mortality risk could not be ruled out.

It was hoped that intermittent androgen deprivation would improve patients’ quality of life by reducing adverse effects from the treatment and would improve survival by staving off the androgen resistance, which eventually develops in most patients.

Dr. Hussain and her colleagues compared intermittent with continuous androgen deprivation in 1,749 men enrolled during 1995-2008 at multiple sites across the United States, the United Kingdom, and Canada.

The study subjects all had newly diagnosed, metastatic, hormone-sensitive prostate cancer and a prostate-specific antigen (PSA) level of 5 ng/mL or higher. All had responded to a 7-month induction course of goserelin, bicalutamide, or a similar agent.

The study subjects were stratified by their performance status, prior hormone therapy, and the extent of their metastatic disease. Cancer confined to the spine, pelvic bones, or lymph nodes was considered minimal while that involving the ribs, long bones, or visceral organs was considered extensive.

The subjects were then randomly assigned to receive either intermittent or standard, continuous androgen-deprivation therapy.

In intermittent therapy, treatment was suspended until PSA values returned to baseline levels or to 20 ng/mL. At the discretion of the researchers, androgen deprivation also could be resumed when PSA levels reached 10 ng/mL or when symptoms developed. If patients responded to a subsequent 7-month course of the therapy, another off-treatment interval was begun.

The study subjects were followed for a median of 9.8 years.

Overall median survival was 3.7 years. There were 445 deaths in the continuous-therapy group and 483 deaths in the intermittent-therapy group. Deaths were cancer-related in approximately 80% of the members of both groups, the investigators reported (N. Engl. J. Med. 2013 April 3 [doi: 10.1056/NEJMoa1212299]).

The researchers were unable to show that intermittent androgen-deprivation therapy was either noninferior or inferior to continuous androgen-deprivation therapy.

Treatment effects were "generally consistent" across all subgroups of patients in a post hoc analysis of the data. For example, there was no significant difference in survival between patients who were alive before 2004, when treatment with docetaxel was approved, and those who were alive in 2004 or later. However, "caution should be taken not to overinterpret the results of the subgroup analyses," Dr. Hussain and her associates noted.

The two study groups differed in quality-of-life measures at 3 months after randomization. Men assigned to intermittent therapy were significantly less likely to report impotence and had significantly better mental health scores than did those assigned to continuous androgen deprivation. The intermittent-therapy group also tended to have higher scores for libido, but that difference did not reach statistical significance.

The advantage in quality-of-life measures persisted at 9 months after randomization but gradually declined. By 15 months, the only quality-of-life measure that scored better in the intermittent-therapy group was overall physical functioning.

There was a "remarkably similar" number of grade 3 and grade 4 adverse events in both study groups, the researchers said.

This study was funded by the U.S. National Cancer Institute, the U.S. Public Health Service, and AstraZeneca. AstraZeneca donated goserelin and bicalutamide used in this study but had no role in the study design, data collection or analysis, or writing the manuscript. Dr. Hussain reported ties to AstraZeneca, and her associates reported ties to numerous industry sources.

Baldness seems to confer a significantly increased risk of prostate cancer upon black men – particularly if they lose their hair before age 60 years.

Different patterns of baldness were also related to different grades of cancer, Charnita Zeigler-Johnson, Ph.D., and her colleagues reported in the March 26 online issue of Cancer, Epidemiology, Biomarkers, and Prevention (Canc. Ep. Biomark. Prev. 2013;22: 589-96).Those with frontal baldness were more than twice as likely to have high-grade and high-stage disease at diagnosis than were those with other hair loss patterns, wrote Dr. Zeigler-Johnson of the University of Pennsylvania, Philadelphia, and her coauthors.

The researchers’ case-control study comprised 318 black patients with prostate cancer and 219 black controls. The subjects were matched for age and other baseline characteristics. However, patients were significantly older than controls (60 vs. 57 years), and more likely to report a family history of prostate cancer (36% vs. 27%). Any form of baldness occurred in significantly more patients than in controls (20% vs.13%).

When the investigators conducted a multivariate analysis, they found a number of significant associations between the cancer and hair loss. Compared with those without hair loss, men with any form of baldness were 69% more likely to have prostate cancer. Frontal baldness was associated with more than a doubling in the risk of both high-stage and high-grade disease (odds ratio, 2.61 and 2.20, respectively).

Men with vertex balding who developed prostate cancer were significantly more likely to present with a low-grade tumor (OR, 1.45).

When the authors broke the groups down by age, they found no significant associations with disease severity among men older than 60 years. Instead, these risks were concentrated in men younger than 60 years. Among these, baldness increased the risk of high-stage cancer by more than three times (OR, 3.43) and more than doubled the risk high-grade disease (OR, 2.33). Frontal baldness was a particularly ominous risk factor for younger men, being associated with more than six times the risk of high-stage disease and more than four times the risk of high-grade disease (OR, 6.51 and 4.23, respectively).

There were also significant relationships observed between baldness and prostate specific antigen levels at diagnosis among younger men. Any baldness was associated with a tripling in the risk of a high PSA (10 ng/mL or more) at diagnosis. The association was stronger for men with frontal-only baldness (OR, 5.29).

The authors speculated that the elevated risks are related to genetically determined androgen metabolism. "There are differences in the prevalence of genotypes that metabolize testosterone and influence dihydrotestosterone (DHT) levels," they wrote. "High DHT levels have been associated with both early pattern baldness and prostate cancer processes, including increases in PSA levels."

In particular, they noted, four genes known to be associated with early-onset baldness are also involved in pathways of androgen metabolism, hair development, and age-related neurodegenerative disease.

"Given the high prevalence of prostate cancer in African Americans, early-onset baldness may be a particularly relevant indicator of risk that deserves attention in future studies as we seek to advance our knowledge about high-risk populations."

None of the authors had any financial disclosures. The work was funded by the Department of Defense and the Public Health Service.

msullivan@frontlinemedcom.com

Baldness seems to confer a significantly increased risk of prostate cancer upon black men – particularly if they lose their hair before age 60 years.

Different patterns of baldness were also related to different grades of cancer, Charnita Zeigler-Johnson, Ph.D., and her colleagues reported in the March 26 online issue of Cancer, Epidemiology, Biomarkers, and Prevention (Canc. Ep. Biomark. Prev. 2013;22: 589-96).Those with frontal baldness were more than twice as likely to have high-grade and high-stage disease at diagnosis than were those with other hair loss patterns, wrote Dr. Zeigler-Johnson of the University of Pennsylvania, Philadelphia, and her coauthors.

The researchers’ case-control study comprised 318 black patients with prostate cancer and 219 black controls. The subjects were matched for age and other baseline characteristics. However, patients were significantly older than controls (60 vs. 57 years), and more likely to report a family history of prostate cancer (36% vs. 27%). Any form of baldness occurred in significantly more patients than in controls (20% vs.13%).

When the investigators conducted a multivariate analysis, they found a number of significant associations between the cancer and hair loss. Compared with those without hair loss, men with any form of baldness were 69% more likely to have prostate cancer. Frontal baldness was associated with more than a doubling in the risk of both high-stage and high-grade disease (odds ratio, 2.61 and 2.20, respectively).

Men with vertex balding who developed prostate cancer were significantly more likely to present with a low-grade tumor (OR, 1.45).

When the authors broke the groups down by age, they found no significant associations with disease severity among men older than 60 years. Instead, these risks were concentrated in men younger than 60 years. Among these, baldness increased the risk of high-stage cancer by more than three times (OR, 3.43) and more than doubled the risk high-grade disease (OR, 2.33). Frontal baldness was a particularly ominous risk factor for younger men, being associated with more than six times the risk of high-stage disease and more than four times the risk of high-grade disease (OR, 6.51 and 4.23, respectively).

There were also significant relationships observed between baldness and prostate specific antigen levels at diagnosis among younger men. Any baldness was associated with a tripling in the risk of a high PSA (10 ng/mL or more) at diagnosis. The association was stronger for men with frontal-only baldness (OR, 5.29).

The authors speculated that the elevated risks are related to genetically determined androgen metabolism. "There are differences in the prevalence of genotypes that metabolize testosterone and influence dihydrotestosterone (DHT) levels," they wrote. "High DHT levels have been associated with both early pattern baldness and prostate cancer processes, including increases in PSA levels."

In particular, they noted, four genes known to be associated with early-onset baldness are also involved in pathways of androgen metabolism, hair development, and age-related neurodegenerative disease.

"Given the high prevalence of prostate cancer in African Americans, early-onset baldness may be a particularly relevant indicator of risk that deserves attention in future studies as we seek to advance our knowledge about high-risk populations."

None of the authors had any financial disclosures. The work was funded by the Department of Defense and the Public Health Service.

msullivan@frontlinemedcom.com

Baldness seems to confer a significantly increased risk of prostate cancer upon black men – particularly if they lose their hair before age 60 years.

Different patterns of baldness were also related to different grades of cancer, Charnita Zeigler-Johnson, Ph.D., and her colleagues reported in the March 26 online issue of Cancer, Epidemiology, Biomarkers, and Prevention (Canc. Ep. Biomark. Prev. 2013;22: 589-96).Those with frontal baldness were more than twice as likely to have high-grade and high-stage disease at diagnosis than were those with other hair loss patterns, wrote Dr. Zeigler-Johnson of the University of Pennsylvania, Philadelphia, and her coauthors.

The researchers’ case-control study comprised 318 black patients with prostate cancer and 219 black controls. The subjects were matched for age and other baseline characteristics. However, patients were significantly older than controls (60 vs. 57 years), and more likely to report a family history of prostate cancer (36% vs. 27%). Any form of baldness occurred in significantly more patients than in controls (20% vs.13%).

When the investigators conducted a multivariate analysis, they found a number of significant associations between the cancer and hair loss. Compared with those without hair loss, men with any form of baldness were 69% more likely to have prostate cancer. Frontal baldness was associated with more than a doubling in the risk of both high-stage and high-grade disease (odds ratio, 2.61 and 2.20, respectively).

Men with vertex balding who developed prostate cancer were significantly more likely to present with a low-grade tumor (OR, 1.45).

When the authors broke the groups down by age, they found no significant associations with disease severity among men older than 60 years. Instead, these risks were concentrated in men younger than 60 years. Among these, baldness increased the risk of high-stage cancer by more than three times (OR, 3.43) and more than doubled the risk high-grade disease (OR, 2.33). Frontal baldness was a particularly ominous risk factor for younger men, being associated with more than six times the risk of high-stage disease and more than four times the risk of high-grade disease (OR, 6.51 and 4.23, respectively).

There were also significant relationships observed between baldness and prostate specific antigen levels at diagnosis among younger men. Any baldness was associated with a tripling in the risk of a high PSA (10 ng/mL or more) at diagnosis. The association was stronger for men with frontal-only baldness (OR, 5.29).

The authors speculated that the elevated risks are related to genetically determined androgen metabolism. "There are differences in the prevalence of genotypes that metabolize testosterone and influence dihydrotestosterone (DHT) levels," they wrote. "High DHT levels have been associated with both early pattern baldness and prostate cancer processes, including increases in PSA levels."

In particular, they noted, four genes known to be associated with early-onset baldness are also involved in pathways of androgen metabolism, hair development, and age-related neurodegenerative disease.

"Given the high prevalence of prostate cancer in African Americans, early-onset baldness may be a particularly relevant indicator of risk that deserves attention in future studies as we seek to advance our knowledge about high-risk populations."

None of the authors had any financial disclosures. The work was funded by the Department of Defense and the Public Health Service.

msullivan@frontlinemedcom.com

An alteration in the gene that regulates the G-protein signaling pathway has been linked to a reduced risk for bladder cancer in a case-control study.

The single nucleotide polymorphism (SNP) rs10759 found on the RGS4 gene conferred a 0.77-fold reduced risk for nonmuscle-invasive bladder cancer (NMIBC).

Other alterations in the regulator of the G-protein signaling (RGS) pathway were linked to NMIBC recurrence and progression and to patient survival in muscle-invasive bladder cancer (MIBC).

"Our current findings have significant clinical implications in personalized medicine," Dr. Eugene Lee and his colleagues report in an early online edition of Cancer (March 25; doi:10.1002/cncr.27871).

"By identifying individuals at increased risk for bladder cancer, we have the ability to initiate comprehensive screening," wrote the authors from the University of Texas MD Anderson Cancer Center in Houston. In addition, the findings could lead to better treatment, with the potential to target patients who may require earlier systemic chemotherapy or treatment with novel targeted agents.

"Furthermore," Dr. Lee noted in a press statement, "we can identify patients who already have a diagnosis of bladder cancer that are at increased risk of worsening of disease or dying."

The ultimate goal, he adds, "is to find as many genetic alterations that confer risk and create a panel of markers that would aid in diagnosis, treatment, and follow-up."

The RGS pathway produces a heterogeneous group of proteins that are involved in cell signaling. Genetic alterations in the pathway have already been linked to several tumors, including breast, prostate, lung cancers, and squamous cell cancer of the head and neck.

The study population consisted of 1,606 individuals, 803 of whom had newly-diagnosed, histologically confirmed, untreated bladder cancer. Each of these individuals was matched, based on age, gender, and ethnicity, to a healthy individual without a history of cancer.

Cases and controls were demographically similar, with a mean age of about 64 years; 79% of participants in each group were men and all were white. Not surprisingly, a higher percentage of patients than of controls were current (23% vs. 8%) or former (50% vs. 47%) smokers.

A total of 85 SNPs in 17 RGS genes were assessed for their potential association with bladder cancer risk, recurrence and progression in nonmuscle-invasive disease, and survival in muscle-invasive.

Bladder cancer risk was associated with six SNPs, including rs10759, which had the only, and the strongest, association for a positive outcome. Individuals with two or more of the five unfavorable SNPs were twice as likely as those without the SNPs to have bladder cancer. The presence of all five unfavorable SNPs increased four-fold the risk for bladder cancer.

NMIBC affected just more than half (52%; n = 421) of the bladder cancer patients, with 11 SNPs linked to disease recurrence and 13 to disease progression to MIBC.

Of patients who presented with MIBC, 10 SNPs were found that either increased or decreased the risk of death. Of these, two SNPs, and rs234473 on the RGS5 gene in particular, conferred the greatest risk of a poor survival outcome. Indeed, patients who had rs234473 had a lower median overall survival of 13.3 months, compared with 81.9 months in those where the genetic variant was absent.

The study was funded by several grants from the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.

The study was funded by the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.

An alteration in the gene that regulates the G-protein signaling pathway has been linked to a reduced risk for bladder cancer in a case-control study.

The single nucleotide polymorphism (SNP) rs10759 found on the RGS4 gene conferred a 0.77-fold reduced risk for nonmuscle-invasive bladder cancer (NMIBC).

Other alterations in the regulator of the G-protein signaling (RGS) pathway were linked to NMIBC recurrence and progression and to patient survival in muscle-invasive bladder cancer (MIBC).

"Our current findings have significant clinical implications in personalized medicine," Dr. Eugene Lee and his colleagues report in an early online edition of Cancer (March 25; doi:10.1002/cncr.27871).

"By identifying individuals at increased risk for bladder cancer, we have the ability to initiate comprehensive screening," wrote the authors from the University of Texas MD Anderson Cancer Center in Houston. In addition, the findings could lead to better treatment, with the potential to target patients who may require earlier systemic chemotherapy or treatment with novel targeted agents.

"Furthermore," Dr. Lee noted in a press statement, "we can identify patients who already have a diagnosis of bladder cancer that are at increased risk of worsening of disease or dying."

The ultimate goal, he adds, "is to find as many genetic alterations that confer risk and create a panel of markers that would aid in diagnosis, treatment, and follow-up."

The RGS pathway produces a heterogeneous group of proteins that are involved in cell signaling. Genetic alterations in the pathway have already been linked to several tumors, including breast, prostate, lung cancers, and squamous cell cancer of the head and neck.

The study population consisted of 1,606 individuals, 803 of whom had newly-diagnosed, histologically confirmed, untreated bladder cancer. Each of these individuals was matched, based on age, gender, and ethnicity, to a healthy individual without a history of cancer.

Cases and controls were demographically similar, with a mean age of about 64 years; 79% of participants in each group were men and all were white. Not surprisingly, a higher percentage of patients than of controls were current (23% vs. 8%) or former (50% vs. 47%) smokers.

A total of 85 SNPs in 17 RGS genes were assessed for their potential association with bladder cancer risk, recurrence and progression in nonmuscle-invasive disease, and survival in muscle-invasive.

Bladder cancer risk was associated with six SNPs, including rs10759, which had the only, and the strongest, association for a positive outcome. Individuals with two or more of the five unfavorable SNPs were twice as likely as those without the SNPs to have bladder cancer. The presence of all five unfavorable SNPs increased four-fold the risk for bladder cancer.

NMIBC affected just more than half (52%; n = 421) of the bladder cancer patients, with 11 SNPs linked to disease recurrence and 13 to disease progression to MIBC.

Of patients who presented with MIBC, 10 SNPs were found that either increased or decreased the risk of death. Of these, two SNPs, and rs234473 on the RGS5 gene in particular, conferred the greatest risk of a poor survival outcome. Indeed, patients who had rs234473 had a lower median overall survival of 13.3 months, compared with 81.9 months in those where the genetic variant was absent.

The study was funded by several grants from the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.

The study was funded by the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.

An alteration in the gene that regulates the G-protein signaling pathway has been linked to a reduced risk for bladder cancer in a case-control study.

The single nucleotide polymorphism (SNP) rs10759 found on the RGS4 gene conferred a 0.77-fold reduced risk for nonmuscle-invasive bladder cancer (NMIBC).

Other alterations in the regulator of the G-protein signaling (RGS) pathway were linked to NMIBC recurrence and progression and to patient survival in muscle-invasive bladder cancer (MIBC).

"Our current findings have significant clinical implications in personalized medicine," Dr. Eugene Lee and his colleagues report in an early online edition of Cancer (March 25; doi:10.1002/cncr.27871).

"By identifying individuals at increased risk for bladder cancer, we have the ability to initiate comprehensive screening," wrote the authors from the University of Texas MD Anderson Cancer Center in Houston. In addition, the findings could lead to better treatment, with the potential to target patients who may require earlier systemic chemotherapy or treatment with novel targeted agents.

"Furthermore," Dr. Lee noted in a press statement, "we can identify patients who already have a diagnosis of bladder cancer that are at increased risk of worsening of disease or dying."

The ultimate goal, he adds, "is to find as many genetic alterations that confer risk and create a panel of markers that would aid in diagnosis, treatment, and follow-up."

The RGS pathway produces a heterogeneous group of proteins that are involved in cell signaling. Genetic alterations in the pathway have already been linked to several tumors, including breast, prostate, lung cancers, and squamous cell cancer of the head and neck.

The study population consisted of 1,606 individuals, 803 of whom had newly-diagnosed, histologically confirmed, untreated bladder cancer. Each of these individuals was matched, based on age, gender, and ethnicity, to a healthy individual without a history of cancer.

Cases and controls were demographically similar, with a mean age of about 64 years; 79% of participants in each group were men and all were white. Not surprisingly, a higher percentage of patients than of controls were current (23% vs. 8%) or former (50% vs. 47%) smokers.

A total of 85 SNPs in 17 RGS genes were assessed for their potential association with bladder cancer risk, recurrence and progression in nonmuscle-invasive disease, and survival in muscle-invasive.

Bladder cancer risk was associated with six SNPs, including rs10759, which had the only, and the strongest, association for a positive outcome. Individuals with two or more of the five unfavorable SNPs were twice as likely as those without the SNPs to have bladder cancer. The presence of all five unfavorable SNPs increased four-fold the risk for bladder cancer.

NMIBC affected just more than half (52%; n = 421) of the bladder cancer patients, with 11 SNPs linked to disease recurrence and 13 to disease progression to MIBC.

Of patients who presented with MIBC, 10 SNPs were found that either increased or decreased the risk of death. Of these, two SNPs, and rs234473 on the RGS5 gene in particular, conferred the greatest risk of a poor survival outcome. Indeed, patients who had rs234473 had a lower median overall survival of 13.3 months, compared with 81.9 months in those where the genetic variant was absent.

The study was funded by several grants from the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.

The study was funded by the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.

ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.

In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.

Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.

The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m²) on days 1, 15, and 22; vinblastine (3 mg/m²) on days 2, 15, and 22; Adriamycin (30 mg/m²) on day 2; and cisplatin (70 mg/m²) on day 2.

Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.

"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."

Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.

The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.

Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).

At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).

Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.

nmiller@frontlinemedcom.com

On Twitter @naseemsmiller

ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.

In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.

Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.

The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m²) on days 1, 15, and 22; vinblastine (3 mg/m²) on days 2, 15, and 22; Adriamycin (30 mg/m²) on day 2; and cisplatin (70 mg/m²) on day 2.

Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.

"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."

Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.

The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.

Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).

At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).

Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.

nmiller@frontlinemedcom.com

On Twitter @naseemsmiller

ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.

In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.

Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.

The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m²) on days 1, 15, and 22; vinblastine (3 mg/m²) on days 2, 15, and 22; Adriamycin (30 mg/m²) on day 2; and cisplatin (70 mg/m²) on day 2.

Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.

"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."

Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.

The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.

Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).

At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).

Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.

nmiller@frontlinemedcom.com

On Twitter @naseemsmiller

ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.

Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.

With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.

In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m², three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).

There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.

The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.

Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.

The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.

Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.

Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).

Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.

Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.

With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.

In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m², three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).

There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.

The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.

Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.

The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.

Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.

Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).

Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.

Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.

With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.

In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m², three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).

There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.

The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.

Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.

The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.

Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.

Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).

Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.

The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.

Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m² IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.

The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.

The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.

Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).

The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).

Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.

Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.

Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

nmiller@frontlinemedcom.com

On Twitter @naseemsmiller

Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.

The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.

Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m² IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.

The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.

The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.

Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).

The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).

Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.

Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.

Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

nmiller@frontlinemedcom.com

On Twitter @naseemsmiller

Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.

The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.

Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m² IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.

The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.

The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.

Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).

The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).

Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.

Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.

Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

nmiller@frontlinemedcom.com

On Twitter @naseemsmiller

The 2013 ASCO Genitourinary Cancers Symposium was more about expansion of knowledge than major practice changers. In an interview Dr. Nicholas Vogelzang of the Comprehensive Cancer Centers of Nevada touches upon this year's major studies on GU cancers and predicts what's in the store for the coming year.

The 2013 ASCO Genitourinary Cancers Symposium was more about expansion of knowledge than major practice changers. In an interview Dr. Nicholas Vogelzang of the Comprehensive Cancer Centers of Nevada touches upon this year's major studies on GU cancers and predicts what's in the store for the coming year.

The 2013 ASCO Genitourinary Cancers Symposium was more about expansion of knowledge than major practice changers. In an interview Dr. Nicholas Vogelzang of the Comprehensive Cancer Centers of Nevada touches upon this year's major studies on GU cancers and predicts what's in the store for the coming year.

When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.

Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.

This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.

Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.

"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.

For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.

Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression

At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).

Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.

Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.

The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.

At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.

Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.

n.miller@elsevier.com

On Twitter @naseemsmiller

When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.

Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.

This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.

Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.

"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.

For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.

Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression

At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).

Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.

Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.

The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.

At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.

Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.

n.miller@elsevier.com

On Twitter @naseemsmiller

When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.

Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.

This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.

Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.

"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.

For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.

Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression

At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).

Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.

Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.

The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.

At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.

Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.

n.miller@elsevier.com

On Twitter @naseemsmiller

Older patients with small kidney tumors are up to 70% less likely to die from any cause when managed by watchful waiting rather than by surgery, based on findings from a large retrospective study.

Surveillance appears to be safe for these small lesions, with a kidney cancer mortality of just 3% over a 5-year period. In addition, watchful waiting seems to confer a cardiovascular benefit; these patients had a 49% lower cardiac mortality risk compared with that for patients who had kidney surgery, said lead author Dr. William C. Huang of New York University Medical Center.

The link between kidney surgery and heart problems is probably mediated by compromised kidney function, Dr. Huang said. "It’s believed that when surgery takes excess normal kidney tissue, it hastens the acceleration of kidney failure," leading to cardiovascular problems, he said.

The study findings are going to be increasingly valuable as imaging turns up more and more incidental asymptomatic kidney tumors. Last year alone, about 65,000 of these lesions were diagnosed, most of them during a work-up for other abdominal complaints.

While the trend toward surveillance of small asymptomatic lesions is growing, Dr. Huang said surgery is still the treatment mode for more than half of cases. Most procedures in the retrospective study were radical nephrectomies, with kidney removal in about half of those. "The majority of these small lesions could be removed laparoscopically, but even then you’re taking out normal kidney tissue that you might really want back someday," he said at a press briefing at the Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Physicians can comfortably tell an elderly patient, especially a patient who is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives," he said. "However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery."

The study examined mortality data in the Surveillance, Epidemiology, and End Results database for 8,317 patients, aged 66 years or older, who were diagnosed from 2002 to 2007 with kidney tumors smaller than 1.5 cm. The patients were followed for a median of 59 months; 78% were managed with surgery and 22%, with surveillance. The use of surveillance increased over the course of the study, from about 25% in 2002 to almost 40% in 2007.

Over the study period, 2,078 (25%) of the patients died, including 277 (3%) who died of kidney cancer. At least one cardiovascular event occurred in 24% of the patients.

Kidney cancer mortality rates did not vary between the treatment groups. However, surgical patients had a significantly increased risk of death from any cause. At 7-36 months, those who had surveillance were 30% less likely to have died than those managed by surgery (hazard ratio, 0.70). After 36 months, patients were 63% less likely to have died if their tumors were managed by surveillance instead of surgery (HR, 0.37).

Dr. Huang also demonstrated that those in the surveillance group experienced a significant cardiovascular benefit as well. By the end of the study, 25% of the deaths were due to a cardiovascular event. Patients in the surveillance group had a 49% reduction in the chance of an event.

Dr. Huang said he had no relevant financial disclosures.

michele.sullivan@elsevier.com

Older patients with small kidney tumors are up to 70% less likely to die from any cause when managed by watchful waiting rather than by surgery, based on findings from a large retrospective study.

Surveillance appears to be safe for these small lesions, with a kidney cancer mortality of just 3% over a 5-year period. In addition, watchful waiting seems to confer a cardiovascular benefit; these patients had a 49% lower cardiac mortality risk compared with that for patients who had kidney surgery, said lead author Dr. William C. Huang of New York University Medical Center.

The link between kidney surgery and heart problems is probably mediated by compromised kidney function, Dr. Huang said. "It’s believed that when surgery takes excess normal kidney tissue, it hastens the acceleration of kidney failure," leading to cardiovascular problems, he said.

The study findings are going to be increasingly valuable as imaging turns up more and more incidental asymptomatic kidney tumors. Last year alone, about 65,000 of these lesions were diagnosed, most of them during a work-up for other abdominal complaints.

While the trend toward surveillance of small asymptomatic lesions is growing, Dr. Huang said surgery is still the treatment mode for more than half of cases. Most procedures in the retrospective study were radical nephrectomies, with kidney removal in about half of those. "The majority of these small lesions could be removed laparoscopically, but even then you’re taking out normal kidney tissue that you might really want back someday," he said at a press briefing at the Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Physicians can comfortably tell an elderly patient, especially a patient who is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives," he said. "However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery."

The study examined mortality data in the Surveillance, Epidemiology, and End Results database for 8,317 patients, aged 66 years or older, who were diagnosed from 2002 to 2007 with kidney tumors smaller than 1.5 cm. The patients were followed for a median of 59 months; 78% were managed with surgery and 22%, with surveillance. The use of surveillance increased over the course of the study, from about 25% in 2002 to almost 40% in 2007.

Over the study period, 2,078 (25%) of the patients died, including 277 (3%) who died of kidney cancer. At least one cardiovascular event occurred in 24% of the patients.

Kidney cancer mortality rates did not vary between the treatment groups. However, surgical patients had a significantly increased risk of death from any cause. At 7-36 months, those who had surveillance were 30% less likely to have died than those managed by surgery (hazard ratio, 0.70). After 36 months, patients were 63% less likely to have died if their tumors were managed by surveillance instead of surgery (HR, 0.37).

Dr. Huang also demonstrated that those in the surveillance group experienced a significant cardiovascular benefit as well. By the end of the study, 25% of the deaths were due to a cardiovascular event. Patients in the surveillance group had a 49% reduction in the chance of an event.

Dr. Huang said he had no relevant financial disclosures.

michele.sullivan@elsevier.com

Older patients with small kidney tumors are up to 70% less likely to die from any cause when managed by watchful waiting rather than by surgery, based on findings from a large retrospective study.

Surveillance appears to be safe for these small lesions, with a kidney cancer mortality of just 3% over a 5-year period. In addition, watchful waiting seems to confer a cardiovascular benefit; these patients had a 49% lower cardiac mortality risk compared with that for patients who had kidney surgery, said lead author Dr. William C. Huang of New York University Medical Center.

The link between kidney surgery and heart problems is probably mediated by compromised kidney function, Dr. Huang said. "It’s believed that when surgery takes excess normal kidney tissue, it hastens the acceleration of kidney failure," leading to cardiovascular problems, he said.

The study findings are going to be increasingly valuable as imaging turns up more and more incidental asymptomatic kidney tumors. Last year alone, about 65,000 of these lesions were diagnosed, most of them during a work-up for other abdominal complaints.

While the trend toward surveillance of small asymptomatic lesions is growing, Dr. Huang said surgery is still the treatment mode for more than half of cases. Most procedures in the retrospective study were radical nephrectomies, with kidney removal in about half of those. "The majority of these small lesions could be removed laparoscopically, but even then you’re taking out normal kidney tissue that you might really want back someday," he said at a press briefing at the Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Physicians can comfortably tell an elderly patient, especially a patient who is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives," he said. "However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery."

The study examined mortality data in the Surveillance, Epidemiology, and End Results database for 8,317 patients, aged 66 years or older, who were diagnosed from 2002 to 2007 with kidney tumors smaller than 1.5 cm. The patients were followed for a median of 59 months; 78% were managed with surgery and 22%, with surveillance. The use of surveillance increased over the course of the study, from about 25% in 2002 to almost 40% in 2007.

Over the study period, 2,078 (25%) of the patients died, including 277 (3%) who died of kidney cancer. At least one cardiovascular event occurred in 24% of the patients.

Kidney cancer mortality rates did not vary between the treatment groups. However, surgical patients had a significantly increased risk of death from any cause. At 7-36 months, those who had surveillance were 30% less likely to have died than those managed by surgery (hazard ratio, 0.70). After 36 months, patients were 63% less likely to have died if their tumors were managed by surveillance instead of surgery (HR, 0.37).

Dr. Huang also demonstrated that those in the surveillance group experienced a significant cardiovascular benefit as well. By the end of the study, 25% of the deaths were due to a cardiovascular event. Patients in the surveillance group had a 49% reduction in the chance of an event.

Dr. Huang said he had no relevant financial disclosures.

michele.sullivan@elsevier.com

Men who underwent radiotherapy for localized high-risk prostate cancer and had 18 months of androgen blockade did just as well as comparable men who had 3 years of androgen blockade.

The finding of nearly identical overall and disease-free survival with traditional and shortened hormone therapy is "practice changing," Dr. Bruce Roth said during a press briefing at the 2013 Genitourinary Cancers Symposium.

"I would be willing to change the way I treat my patients," based on the results of the phase III study, said Dr. Roth of Washington University, St. Louis. "The consequences of long-term androgen deprivation are often more striking than the positive aspects of prolonging it. If treatment time can be safely halved, patients will enjoy a much better quality of life."

Dr. Abdenour Nabid of the Centre Hospitalier Universitaire de Sherbrooke, Canada, headed the study. It randomized 630 men with node-negative high-risk prostate cancer to radiation therapy plus either 36 or 18 months of androgen blockade. The hormone therapy consisted of bicalutamide 50 mg/day for 1 month plus goserelin 10.8 mg given as an injection once every 3 months.

At baseline, the patients were a median of 71 years old; the median prostate specific antigen (PSA) level was 16 ng/mL, and the median Gleason score was 8. Most had T2-T3 disease.

The median follow-up period was about 77 months. At that point, 23% of patients in the extended therapy group and 24% in the abbreviated therapy group had died. Of these 147 patients, 116 (79%) had died from causes other than prostate cancer.

Fifty patients developed bone metastases, Dr. Nabid said, but there was not a significant between-group difference in this outcome. Nor were there differences in biochemical failure, regional or distant recurrence, pelvic metastases, or the need for a second course of androgen blockade.

When Dr. Nabid broke the data out by 5- and 10-year follow-up points, the survival results were similar. At 5 years, overall survival was 92% in the 36-month group and 87% in the 18-month group; disease specific survival was 98% and 96%, respectively. At 10 years, overall survival was 64% vs. 63%, and disease-specific survival was 87% in both groups.

He said the study will follow all patients through 10 years, adding "I am convinced this finding won’t change."

Decreasing the length of androgen blockade could avoid some cases of permanent castration syndrome, Dr. Roth said. "The longer the hormone therapy, the less chance that testosterone will recover when it’s finished. With 3 years of hormone therapy, you might be inducing a lifetime of hormone suppression" and a host of problems including sexual dysfunction, loss of muscle tone, and increased visceral fat. These consequences are in turn associated with significantly increased rates of metabolic syndrome, diabetes, myocardial infarction, and coronary heart disease.

"If a patient has several decades left of life and his testosterone levels are lowered to the point of castration syndrome, there is a price to pay," Dr. Roth said. "If this patient dies of a heart attack 10 years before he would have died of prostate cancer, we have not really provided good anticancer therapy."

This is the first study showing that short-term androgen blockade is both safe and effective. "Could we get by with less?" Dr. Nabid asked. "We don’t know. Previous trials have shown that 6 months of hormone treatment is inferior to 24 months, but we don’t know what the effect of 12 months would be. Still, we are excited to see this, and our hope is that this will change the standard of care for this stage of disease."

Dr. Nabid had no financial disclosures.

michele.sullivan@elsevier.com

Men who underwent radiotherapy for localized high-risk prostate cancer and had 18 months of androgen blockade did just as well as comparable men who had 3 years of androgen blockade.

The finding of nearly identical overall and disease-free survival with traditional and shortened hormone therapy is "practice changing," Dr. Bruce Roth said during a press briefing at the 2013 Genitourinary Cancers Symposium.

"I would be willing to change the way I treat my patients," based on the results of the phase III study, said Dr. Roth of Washington University, St. Louis. "The consequences of long-term androgen deprivation are often more striking than the positive aspects of prolonging it. If treatment time can be safely halved, patients will enjoy a much better quality of life."

Dr. Abdenour Nabid of the Centre Hospitalier Universitaire de Sherbrooke, Canada, headed the study. It randomized 630 men with node-negative high-risk prostate cancer to radiation therapy plus either 36 or 18 months of androgen blockade. The hormone therapy consisted of bicalutamide 50 mg/day for 1 month plus goserelin 10.8 mg given as an injection once every 3 months.

At baseline, the patients were a median of 71 years old; the median prostate specific antigen (PSA) level was 16 ng/mL, and the median Gleason score was 8. Most had T2-T3 disease.

The median follow-up period was about 77 months. At that point, 23% of patients in the extended therapy group and 24% in the abbreviated therapy group had died. Of these 147 patients, 116 (79%) had died from causes other than prostate cancer.

Fifty patients developed bone metastases, Dr. Nabid said, but there was not a significant between-group difference in this outcome. Nor were there differences in biochemical failure, regional or distant recurrence, pelvic metastases, or the need for a second course of androgen blockade.

When Dr. Nabid broke the data out by 5- and 10-year follow-up points, the survival results were similar. At 5 years, overall survival was 92% in the 36-month group and 87% in the 18-month group; disease specific survival was 98% and 96%, respectively. At 10 years, overall survival was 64% vs. 63%, and disease-specific survival was 87% in both groups.

He said the study will follow all patients through 10 years, adding "I am convinced this finding won’t change."

Decreasing the length of androgen blockade could avoid some cases of permanent castration syndrome, Dr. Roth said. "The longer the hormone therapy, the less chance that testosterone will recover when it’s finished. With 3 years of hormone therapy, you might be inducing a lifetime of hormone suppression" and a host of problems including sexual dysfunction, loss of muscle tone, and increased visceral fat. These consequences are in turn associated with significantly increased rates of metabolic syndrome, diabetes, myocardial infarction, and coronary heart disease.

"If a patient has several decades left of life and his testosterone levels are lowered to the point of castration syndrome, there is a price to pay," Dr. Roth said. "If this patient dies of a heart attack 10 years before he would have died of prostate cancer, we have not really provided good anticancer therapy."

This is the first study showing that short-term androgen blockade is both safe and effective. "Could we get by with less?" Dr. Nabid asked. "We don’t know. Previous trials have shown that 6 months of hormone treatment is inferior to 24 months, but we don’t know what the effect of 12 months would be. Still, we are excited to see this, and our hope is that this will change the standard of care for this stage of disease."

Dr. Nabid had no financial disclosures.

michele.sullivan@elsevier.com

Men who underwent radiotherapy for localized high-risk prostate cancer and had 18 months of androgen blockade did just as well as comparable men who had 3 years of androgen blockade.

The finding of nearly identical overall and disease-free survival with traditional and shortened hormone therapy is "practice changing," Dr. Bruce Roth said during a press briefing at the 2013 Genitourinary Cancers Symposium.

"I would be willing to change the way I treat my patients," based on the results of the phase III study, said Dr. Roth of Washington University, St. Louis. "The consequences of long-term androgen deprivation are often more striking than the positive aspects of prolonging it. If treatment time can be safely halved, patients will enjoy a much better quality of life."

Dr. Abdenour Nabid of the Centre Hospitalier Universitaire de Sherbrooke, Canada, headed the study. It randomized 630 men with node-negative high-risk prostate cancer to radiation therapy plus either 36 or 18 months of androgen blockade. The hormone therapy consisted of bicalutamide 50 mg/day for 1 month plus goserelin 10.8 mg given as an injection once every 3 months.

At baseline, the patients were a median of 71 years old; the median prostate specific antigen (PSA) level was 16 ng/mL, and the median Gleason score was 8. Most had T2-T3 disease.

The median follow-up period was about 77 months. At that point, 23% of patients in the extended therapy group and 24% in the abbreviated therapy group had died. Of these 147 patients, 116 (79%) had died from causes other than prostate cancer.

Fifty patients developed bone metastases, Dr. Nabid said, but there was not a significant between-group difference in this outcome. Nor were there differences in biochemical failure, regional or distant recurrence, pelvic metastases, or the need for a second course of androgen blockade.

When Dr. Nabid broke the data out by 5- and 10-year follow-up points, the survival results were similar. At 5 years, overall survival was 92% in the 36-month group and 87% in the 18-month group; disease specific survival was 98% and 96%, respectively. At 10 years, overall survival was 64% vs. 63%, and disease-specific survival was 87% in both groups.

He said the study will follow all patients through 10 years, adding "I am convinced this finding won’t change."

Decreasing the length of androgen blockade could avoid some cases of permanent castration syndrome, Dr. Roth said. "The longer the hormone therapy, the less chance that testosterone will recover when it’s finished. With 3 years of hormone therapy, you might be inducing a lifetime of hormone suppression" and a host of problems including sexual dysfunction, loss of muscle tone, and increased visceral fat. These consequences are in turn associated with significantly increased rates of metabolic syndrome, diabetes, myocardial infarction, and coronary heart disease.

"If a patient has several decades left of life and his testosterone levels are lowered to the point of castration syndrome, there is a price to pay," Dr. Roth said. "If this patient dies of a heart attack 10 years before he would have died of prostate cancer, we have not really provided good anticancer therapy."

This is the first study showing that short-term androgen blockade is both safe and effective. "Could we get by with less?" Dr. Nabid asked. "We don’t know. Previous trials have shown that 6 months of hormone treatment is inferior to 24 months, but we don’t know what the effect of 12 months would be. Still, we are excited to see this, and our hope is that this will change the standard of care for this stage of disease."

Dr. Nabid had no financial disclosures.

michele.sullivan@elsevier.com