Genitourinary Cancer

The Food and Drug Administration has approved bevacizumab as a treatment for ovarian cancer, in combination with chemotherapy, based on the results of the AURELIA study, according to a Nov. 14 announcement by Genentech.

The approved indication is bevacizumab – in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy – for the treatment of women with platinum-resistant, recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received no more than two prior chemotherapy regimens.

Bevacizumab, marketed as Avastin, a vascular endothelial growth factor–specific angiogenesis inhibitor, administered intravenously, is also approved for colon, lung, kidney, and cervical cancer indications. For the ovarian cancer indication, it is administered at a dose of 10 mg/kg IV every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or weekly topotecan; or 15 mg/kg IV every 3 weeks with topotecan given every 3 weeks, according to the updated prescribing information.

In the AURELIA study, a phase III open-label study, 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer and whom had been treated with more than two treatment regimens, were randomized to one of six treatment arms (paclitaxel, topotecan, or pegylated liposomal doxorubicin), with or without bevacizumab. In the intent-to-treat population, the primary endpoint, progression-free survival as assessed by the investigator, was 6.8 months among those on bevacizumab plus chemotherapy, compared with 3.4 months among those on chemotherapy alone, a highly statistically significant difference (hazard ratio, 0.38). Overall survival (a median of 16.6 months vs. 13.3 months) and overall response rates (28% vs. 13%) also favored those in the bevacizumab plus chemotherapy group.

Adverse events were consistent with those seen in studies of bevacizumab for the previously approved indications, “but also included high blood pressure and pain, redness or swelling of the hands or feet,” the company statement said. Grade 3-4 adverse events that affected at least 2% of women on bevacizumab were high blood pressure (6.7% among those on bevacizumab vs. 1.1% of those on chemotherapy alone) and hand-foot syndrome (4.5% vs. 1.7%) .

The bevacizumab label includes a boxed warning about the risk of gastrointestinal perforations, surgery and wound healing complications and hemorrhage associated with treatment.

Genentech, which sponsored the Aurelia study, is a member of the Roche group. The updated Avastin label is available at the FDA.

Serious adverse events associated with bevacizumab should be reported to the FDA’s MedWatch programonline or at 800-332-1088.

emechcatie@frontlinemedcom.com

The Food and Drug Administration has approved bevacizumab as a treatment for ovarian cancer, in combination with chemotherapy, based on the results of the AURELIA study, according to a Nov. 14 announcement by Genentech.

The approved indication is bevacizumab – in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy – for the treatment of women with platinum-resistant, recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received no more than two prior chemotherapy regimens.

Bevacizumab, marketed as Avastin, a vascular endothelial growth factor–specific angiogenesis inhibitor, administered intravenously, is also approved for colon, lung, kidney, and cervical cancer indications. For the ovarian cancer indication, it is administered at a dose of 10 mg/kg IV every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or weekly topotecan; or 15 mg/kg IV every 3 weeks with topotecan given every 3 weeks, according to the updated prescribing information.

In the AURELIA study, a phase III open-label study, 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer and whom had been treated with more than two treatment regimens, were randomized to one of six treatment arms (paclitaxel, topotecan, or pegylated liposomal doxorubicin), with or without bevacizumab. In the intent-to-treat population, the primary endpoint, progression-free survival as assessed by the investigator, was 6.8 months among those on bevacizumab plus chemotherapy, compared with 3.4 months among those on chemotherapy alone, a highly statistically significant difference (hazard ratio, 0.38). Overall survival (a median of 16.6 months vs. 13.3 months) and overall response rates (28% vs. 13%) also favored those in the bevacizumab plus chemotherapy group.

Adverse events were consistent with those seen in studies of bevacizumab for the previously approved indications, “but also included high blood pressure and pain, redness or swelling of the hands or feet,” the company statement said. Grade 3-4 adverse events that affected at least 2% of women on bevacizumab were high blood pressure (6.7% among those on bevacizumab vs. 1.1% of those on chemotherapy alone) and hand-foot syndrome (4.5% vs. 1.7%) .

The bevacizumab label includes a boxed warning about the risk of gastrointestinal perforations, surgery and wound healing complications and hemorrhage associated with treatment.

Genentech, which sponsored the Aurelia study, is a member of the Roche group. The updated Avastin label is available at the FDA.

Serious adverse events associated with bevacizumab should be reported to the FDA’s MedWatch programonline or at 800-332-1088.

emechcatie@frontlinemedcom.com

The Food and Drug Administration has approved bevacizumab as a treatment for ovarian cancer, in combination with chemotherapy, based on the results of the AURELIA study, according to a Nov. 14 announcement by Genentech.

The approved indication is bevacizumab – in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy – for the treatment of women with platinum-resistant, recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received no more than two prior chemotherapy regimens.

Bevacizumab, marketed as Avastin, a vascular endothelial growth factor–specific angiogenesis inhibitor, administered intravenously, is also approved for colon, lung, kidney, and cervical cancer indications. For the ovarian cancer indication, it is administered at a dose of 10 mg/kg IV every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or weekly topotecan; or 15 mg/kg IV every 3 weeks with topotecan given every 3 weeks, according to the updated prescribing information.

In the AURELIA study, a phase III open-label study, 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer and whom had been treated with more than two treatment regimens, were randomized to one of six treatment arms (paclitaxel, topotecan, or pegylated liposomal doxorubicin), with or without bevacizumab. In the intent-to-treat population, the primary endpoint, progression-free survival as assessed by the investigator, was 6.8 months among those on bevacizumab plus chemotherapy, compared with 3.4 months among those on chemotherapy alone, a highly statistically significant difference (hazard ratio, 0.38). Overall survival (a median of 16.6 months vs. 13.3 months) and overall response rates (28% vs. 13%) also favored those in the bevacizumab plus chemotherapy group.

Adverse events were consistent with those seen in studies of bevacizumab for the previously approved indications, “but also included high blood pressure and pain, redness or swelling of the hands or feet,” the company statement said. Grade 3-4 adverse events that affected at least 2% of women on bevacizumab were high blood pressure (6.7% among those on bevacizumab vs. 1.1% of those on chemotherapy alone) and hand-foot syndrome (4.5% vs. 1.7%) .

The bevacizumab label includes a boxed warning about the risk of gastrointestinal perforations, surgery and wound healing complications and hemorrhage associated with treatment.

Genentech, which sponsored the Aurelia study, is a member of the Roche group. The updated Avastin label is available at the FDA.

Serious adverse events associated with bevacizumab should be reported to the FDA’s MedWatch programonline or at 800-332-1088.

emechcatie@frontlinemedcom.com

Dr. Benjamin Davies has responded to advertising claims that recently ran in the Sunday New York Times Magazine and the New Yorker with an article in Forbes entitled “Prostate Cancer Advertising: Lies And The Damn Lies (Part 1).”

“I have a rating system for prostate cancer advertisements based on two self-evident tenets. First, cancer advertising should be scrupulously true and evidence based. Second, cancer patients are uniquely vulnerable to “hopeful” advertising (or “hopeium”) since often they face devastating odds of survival. We should all – collectively – shun advertisers that take advantage of these patients,” he wrote in the first of several articles. “I have no gripe with advertising your cancer care – just be horribly honest.”

Dr. Davies is associate professor of urology and director of the urologic oncology fellowship at the University of Pittsburgh. You can see the advertisements and read his articles here.

lnikolaides@frontlinemedcom.com

On Twitter @nikolaideslaura

Dr. Benjamin Davies has responded to advertising claims that recently ran in the Sunday New York Times Magazine and the New Yorker with an article in Forbes entitled “Prostate Cancer Advertising: Lies And The Damn Lies (Part 1).”

“I have a rating system for prostate cancer advertisements based on two self-evident tenets. First, cancer advertising should be scrupulously true and evidence based. Second, cancer patients are uniquely vulnerable to “hopeful” advertising (or “hopeium”) since often they face devastating odds of survival. We should all – collectively – shun advertisers that take advantage of these patients,” he wrote in the first of several articles. “I have no gripe with advertising your cancer care – just be horribly honest.”

Dr. Davies is associate professor of urology and director of the urologic oncology fellowship at the University of Pittsburgh. You can see the advertisements and read his articles here.

lnikolaides@frontlinemedcom.com

On Twitter @nikolaideslaura

Dr. Benjamin Davies has responded to advertising claims that recently ran in the Sunday New York Times Magazine and the New Yorker with an article in Forbes entitled “Prostate Cancer Advertising: Lies And The Damn Lies (Part 1).”

“I have a rating system for prostate cancer advertisements based on two self-evident tenets. First, cancer advertising should be scrupulously true and evidence based. Second, cancer patients are uniquely vulnerable to “hopeful” advertising (or “hopeium”) since often they face devastating odds of survival. We should all – collectively – shun advertisers that take advantage of these patients,” he wrote in the first of several articles. “I have no gripe with advertising your cancer care – just be horribly honest.”

Dr. Davies is associate professor of urology and director of the urologic oncology fellowship at the University of Pittsburgh. You can see the advertisements and read his articles here.

lnikolaides@frontlinemedcom.com

On Twitter @nikolaideslaura

Androgen-deprivation therapy for prostate cancer may increase the risk of cardiac death among men who have congestive heart failure or who have experienced a previous myocardial infarction, a retrospective cohort study has found.

The study of 5,077 men, whose prostate cancer was treated with brachytherapy with or without neoadjuvant androgen-deprivation therapy (ADT), showed that ADT was associated with a greater-than-threefold increase in the risk of cardiac specific mortality among men with heart failure or myocardial infarction (adjusted hazard ratio, 3.28; 95% confidence interval, 1.01-10.64; P = .048), representing a 5% increase in absolute risk over 5 years.

However, researchers saw no association between ADT and cardiac death among men with no cardiac risk factors, or those with diabetes mellitus, hypertension, or hypercholesterolemia, according to a paper published online Oct. 29 in BJU International (2014 [doi:10.1111/bju.12905]).

“These results add vital detail to past work that showed that the delivery of ADT to men with moderate to severe comorbidity is associated with no survival benefit, and that delivery of ADT to men with [HF] or past MI is associated with increased risk of death from any cause,” wrote Dr. David R. Ziehr from Harvard Medical School, Boston, and his colleagues.

The study was supported by Fitz’s CancerWarriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. Some authors declared consultancies, lectureships, and advisory board positions for pharmaceutical companies.

Androgen-deprivation therapy for prostate cancer may increase the risk of cardiac death among men who have congestive heart failure or who have experienced a previous myocardial infarction, a retrospective cohort study has found.

The study of 5,077 men, whose prostate cancer was treated with brachytherapy with or without neoadjuvant androgen-deprivation therapy (ADT), showed that ADT was associated with a greater-than-threefold increase in the risk of cardiac specific mortality among men with heart failure or myocardial infarction (adjusted hazard ratio, 3.28; 95% confidence interval, 1.01-10.64; P = .048), representing a 5% increase in absolute risk over 5 years.

However, researchers saw no association between ADT and cardiac death among men with no cardiac risk factors, or those with diabetes mellitus, hypertension, or hypercholesterolemia, according to a paper published online Oct. 29 in BJU International (2014 [doi:10.1111/bju.12905]).

“These results add vital detail to past work that showed that the delivery of ADT to men with moderate to severe comorbidity is associated with no survival benefit, and that delivery of ADT to men with [HF] or past MI is associated with increased risk of death from any cause,” wrote Dr. David R. Ziehr from Harvard Medical School, Boston, and his colleagues.

The study was supported by Fitz’s CancerWarriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. Some authors declared consultancies, lectureships, and advisory board positions for pharmaceutical companies.

Androgen-deprivation therapy for prostate cancer may increase the risk of cardiac death among men who have congestive heart failure or who have experienced a previous myocardial infarction, a retrospective cohort study has found.

The study of 5,077 men, whose prostate cancer was treated with brachytherapy with or without neoadjuvant androgen-deprivation therapy (ADT), showed that ADT was associated with a greater-than-threefold increase in the risk of cardiac specific mortality among men with heart failure or myocardial infarction (adjusted hazard ratio, 3.28; 95% confidence interval, 1.01-10.64; P = .048), representing a 5% increase in absolute risk over 5 years.

However, researchers saw no association between ADT and cardiac death among men with no cardiac risk factors, or those with diabetes mellitus, hypertension, or hypercholesterolemia, according to a paper published online Oct. 29 in BJU International (2014 [doi:10.1111/bju.12905]).

“These results add vital detail to past work that showed that the delivery of ADT to men with moderate to severe comorbidity is associated with no survival benefit, and that delivery of ADT to men with [HF] or past MI is associated with increased risk of death from any cause,” wrote Dr. David R. Ziehr from Harvard Medical School, Boston, and his colleagues.

The study was supported by Fitz’s CancerWarriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. Some authors declared consultancies, lectureships, and advisory board positions for pharmaceutical companies.

Adding abiraterone to standard neoadjuvant therapy using luteinizing hormone-releasing hormone agonists induces markedly more effective androgen suppression within the prostate tissue in men who have high-risk localized prostate cancer, according to a report published online Oct. 13 in the Journal of Clinical Oncology.

Patients with localized high-risk prostate cancer show the highest recurrence rates after prostatectomy, with PSA relapse ranging from 40% to 65%. Abiraterone intensifies androgen deprivation therapy because it inhibits all sources of androgens: testicular, adrenal, prostate, and (presumably) tumor, said Dr. Mary-Ellen Taplin of the Dana-Farber Cancer Institute, Boston, and her associates.

In an open-label phase II clinical trial, Dr. Taplin and colleagues assessed 58 men who had localized prostate cancer plus PSA levels above 10 ng/ml, a PSA velocity greater than 2 ng/ml during the preceding year, and/or a Gleason score of 7 or higher. These participants were randomly assigned to receive 12 weeks of either LHRH agonists alone (28 men) or LHRH agonists plus abiraterone (30 men) in the randomized portion of the study. Then participants who had not received the abiraterone crossed over, and all the participants received another 12 weeks of abiraterone before undergoing prostatectomy (J. Clin. Oncol. 2014 October 13 [doi:10.1200/JCO.2013.53.4578]).

In biopsies taken at 12 weeks, the addition of abiraterone reduced median levels of testosterone within the prostate by 37% and reduced median levels of dihydrotestosterone by 86%. Further study is needed to determine whether this laboratory response indicating reduced tumor burden translates into a clinical response of improved survival or quality of life, Dr. Taplin and her associates said.

Adding abiraterone to standard neoadjuvant therapy using luteinizing hormone-releasing hormone agonists induces markedly more effective androgen suppression within the prostate tissue in men who have high-risk localized prostate cancer, according to a report published online Oct. 13 in the Journal of Clinical Oncology.

Patients with localized high-risk prostate cancer show the highest recurrence rates after prostatectomy, with PSA relapse ranging from 40% to 65%. Abiraterone intensifies androgen deprivation therapy because it inhibits all sources of androgens: testicular, adrenal, prostate, and (presumably) tumor, said Dr. Mary-Ellen Taplin of the Dana-Farber Cancer Institute, Boston, and her associates.

In an open-label phase II clinical trial, Dr. Taplin and colleagues assessed 58 men who had localized prostate cancer plus PSA levels above 10 ng/ml, a PSA velocity greater than 2 ng/ml during the preceding year, and/or a Gleason score of 7 or higher. These participants were randomly assigned to receive 12 weeks of either LHRH agonists alone (28 men) or LHRH agonists plus abiraterone (30 men) in the randomized portion of the study. Then participants who had not received the abiraterone crossed over, and all the participants received another 12 weeks of abiraterone before undergoing prostatectomy (J. Clin. Oncol. 2014 October 13 [doi:10.1200/JCO.2013.53.4578]).

In biopsies taken at 12 weeks, the addition of abiraterone reduced median levels of testosterone within the prostate by 37% and reduced median levels of dihydrotestosterone by 86%. Further study is needed to determine whether this laboratory response indicating reduced tumor burden translates into a clinical response of improved survival or quality of life, Dr. Taplin and her associates said.

Adding abiraterone to standard neoadjuvant therapy using luteinizing hormone-releasing hormone agonists induces markedly more effective androgen suppression within the prostate tissue in men who have high-risk localized prostate cancer, according to a report published online Oct. 13 in the Journal of Clinical Oncology.

Patients with localized high-risk prostate cancer show the highest recurrence rates after prostatectomy, with PSA relapse ranging from 40% to 65%. Abiraterone intensifies androgen deprivation therapy because it inhibits all sources of androgens: testicular, adrenal, prostate, and (presumably) tumor, said Dr. Mary-Ellen Taplin of the Dana-Farber Cancer Institute, Boston, and her associates.

In an open-label phase II clinical trial, Dr. Taplin and colleagues assessed 58 men who had localized prostate cancer plus PSA levels above 10 ng/ml, a PSA velocity greater than 2 ng/ml during the preceding year, and/or a Gleason score of 7 or higher. These participants were randomly assigned to receive 12 weeks of either LHRH agonists alone (28 men) or LHRH agonists plus abiraterone (30 men) in the randomized portion of the study. Then participants who had not received the abiraterone crossed over, and all the participants received another 12 weeks of abiraterone before undergoing prostatectomy (J. Clin. Oncol. 2014 October 13 [doi:10.1200/JCO.2013.53.4578]).

In biopsies taken at 12 weeks, the addition of abiraterone reduced median levels of testosterone within the prostate by 37% and reduced median levels of dihydrotestosterone by 86%. Further study is needed to determine whether this laboratory response indicating reduced tumor burden translates into a clinical response of improved survival or quality of life, Dr. Taplin and her associates said.

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Men who undergo radiation therapy for high-risk prostate cancer are less likely to have a recurrence and to die if they also receive long-duration androgen deprivation therapy. A long duration roughly half of that typically used appears to strike a good balance between efficacy and quality of life.

These were among the key findings of a pair of phase III randomized trials reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Quantity of life became the most important piece for us as we were trying to control prostate cancer. But today, so many of our localized prostate cancer patients are going to survive their illness that quality of life becomes exceedingly important,” said Dr. Colleen Lawton, vice chair and clinical director of the department of radiation oncology at the Medical College of Wisconsin, Milwaukee, and moderator of a related press briefing.

Efficacy data support long-duration ADT

In the first trial, called DART 01/05 (or AADLPC) and supported in part by the AstraZeneca Fund, investigators led by Dr. Almudena Zapatero, a radiation oncologist at Hospital Universitario de la Princesa, Madrid, studied 355 patients with intermediate- or high-risk prostate cancer.

The patients were randomized evenly to high-dose radiation therapy of at least 76 Gy, plus either short-duration ADT (4 months before and during radiation only) or long-duration ADT (4 months before and during radiation and 24 months afterward).

With a median follow-up of 63 months, relative to short-duration ADT, long-duration ADT was associated with better 5-year rates of biochemical disease–free survival according to the Phoenix definition (89.8% vs. 81.3%), overall survival (94.8% vs. 86.1%), and metastasis-free survival (93.6% vs. 83.4%), reported Dr. Zapatero. However, in stratified analyses, these benefits were seen only in the men with high-risk disease.

The two treatment groups did not differ significantly with respect to rates of acute and late rectal and urinary toxicity.

The study is noteworthy as it supports use of more costly high-dose radiation and hormonal therapy, said Dr. Zapatero. “We have demonstrated that we can get a 10% absolute benefit in PSA [prostate-specific antigen] control and overall survival and cancer-specific survival with acceptably low complications for high-risk disease. This is what we know now. We now know that … intermediate-risk disease probably doesn’t need any complementary [hormone therapy],” she said.

“We await longer follow-up to confirm these results and to determine the impact of long-term hormones according to the risk subgroup,” added Dr. Zapatero, noting that high-risk patients can be further stratified according to T3 stage, high Gleason score, and undifferentiated tumor histology. “Probably, if you have one factor, you are going to need less long of a duration of hormones, probably close to 18 months. And if you have two or three, what we call very high risk disease, you are going to need longer hormone therapy and the highest radiation [dose].”

Explaining the importance of the findings, Dr. Lawton, the press briefing moderator, said, “We have shown over time that increasing the dose [of radiation] to the prostate and immediate surrounding tissues improves outcomes. We have also shown for our high-risk patients that adding hormone therapy improves outcomes. But what we have yet to show is … do you really need the hormone therapy if you use dose escalation? And the answer is yes.”

Shortening duration of ADT improves testosterone recovery

In the second trial, known as PCS IV, investigators led by Dr. Abdenour Nabid, a radiation oncologist at Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada, studied 561 men with high-risk prostate cancer who had been treated with radiation therapy (44 Gy to the whole pelvis and 70 Gy to the prostate) and randomized to 18 months or 36 months of ADT. AstraZeneca collaborated on the trial.

Previously reported results suggested that 18 months was just as efficacious as 36 months for overall survival and cancer-specific survival (ASCO 2013 Annual Meeting. Abstract LBA4510).

With a median follow-up of 84 months, relative to counterparts who had received ADT for 36 months, patients who had received ADT for 18 months were more likely to have recovery of testosterone values into the normal range (55.7% vs. 44.9%, P = .01) and had a shorter median time to recovery (47.2 vs. 73.2 months, P less than .001).

Relative to counterparts who did not have testosterone recovery, patients who did had significantly better scores on 18 of 30 items on the European Organization for Research and Treatment of Cancer’s global quality of life questionnaire (EORTC30) (P less than .01 for each) and on 10 of 25 items on the related Prostate Module (PR25) (P less than .01 for each).

Clinically relevant differences, defined as ones of at least 10 points on the 100-point linearly transformed scales, were seen between men who did and did not have testosterone recovery for two of the global quality of life items – trouble doing strenuous activities and trouble taking long walks – and three of the prostate-related quality of life items – hot flushes, interest in sex, and sexual activity.

“In high-risk prostate cancer treated with radiation therapy and ADT, patients who recover normal testosterone levels have a better quality of life,” said Dr. Nabid. “There is a major advantage in the use of 18 months of ADT instead of 36 months since a higher proportion of patients recovered normal testosterone levels in a much shorter time without any apparent detriment in long-term outcomes.”

“If we succeed to demonstrate that 18 months is at least equal to 36 months, it’s a big jump because it’s a matter of quality of life, it’s a matter of cost also,” he added. The investigators expect to be able to publish final efficacy and quality of life results next year.

In the meantime, clinicians can follow national guidelines, according to Dr. Nabid. “If you look at the guidelines, like the NCCN guidelines for the U.S., what is written is that the long-term [ADT] could be between 24 and 36 months. So my advice would be, even if you wait for the final paper, to go for 24 months. It’s a good beginning,” he asserted.

However, “you have to use your clinical judgment,” he added, agreeing that disease factors can be used to further stratify high-risk patients; additionally, age, comorbidities, and other factors will play a role in tailoring the duration of ADT. And importantly, “one has to discuss this with his patients.”

Dr. Lawton noted that the definition of long-duration ADT has varied by world region, and has typically been 28 months in the United States and 36 months in Europe. On the basis of this trial’s findings, “I do think that 18 months is potentially our new long-term hormone therapy option. That data isn’t out in print yet, other than in abstract form, But I think going forward, the question for us should be, can we shorten it from there,” she said. “I don’t know that we’ve nailed [the optimal long duration], but we are certainly heading in the right direction.”

Dr. Zapatero disclosed no conflicts of interest; the trial was supported in part by the AstraZeneca Fund. Dr. Nabid disclosed ties with AstraZeneca and Sanofi; AstraZeneca collaborated on the trial.

SAN FRANCISCO – Men who undergo radiation therapy for high-risk prostate cancer are less likely to have a recurrence and to die if they also receive long-duration androgen deprivation therapy. A long duration roughly half of that typically used appears to strike a good balance between efficacy and quality of life.

These were among the key findings of a pair of phase III randomized trials reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Quantity of life became the most important piece for us as we were trying to control prostate cancer. But today, so many of our localized prostate cancer patients are going to survive their illness that quality of life becomes exceedingly important,” said Dr. Colleen Lawton, vice chair and clinical director of the department of radiation oncology at the Medical College of Wisconsin, Milwaukee, and moderator of a related press briefing.

Efficacy data support long-duration ADT

In the first trial, called DART 01/05 (or AADLPC) and supported in part by the AstraZeneca Fund, investigators led by Dr. Almudena Zapatero, a radiation oncologist at Hospital Universitario de la Princesa, Madrid, studied 355 patients with intermediate- or high-risk prostate cancer.

The patients were randomized evenly to high-dose radiation therapy of at least 76 Gy, plus either short-duration ADT (4 months before and during radiation only) or long-duration ADT (4 months before and during radiation and 24 months afterward).

With a median follow-up of 63 months, relative to short-duration ADT, long-duration ADT was associated with better 5-year rates of biochemical disease–free survival according to the Phoenix definition (89.8% vs. 81.3%), overall survival (94.8% vs. 86.1%), and metastasis-free survival (93.6% vs. 83.4%), reported Dr. Zapatero. However, in stratified analyses, these benefits were seen only in the men with high-risk disease.

The two treatment groups did not differ significantly with respect to rates of acute and late rectal and urinary toxicity.

The study is noteworthy as it supports use of more costly high-dose radiation and hormonal therapy, said Dr. Zapatero. “We have demonstrated that we can get a 10% absolute benefit in PSA [prostate-specific antigen] control and overall survival and cancer-specific survival with acceptably low complications for high-risk disease. This is what we know now. We now know that … intermediate-risk disease probably doesn’t need any complementary [hormone therapy],” she said.

“We await longer follow-up to confirm these results and to determine the impact of long-term hormones according to the risk subgroup,” added Dr. Zapatero, noting that high-risk patients can be further stratified according to T3 stage, high Gleason score, and undifferentiated tumor histology. “Probably, if you have one factor, you are going to need less long of a duration of hormones, probably close to 18 months. And if you have two or three, what we call very high risk disease, you are going to need longer hormone therapy and the highest radiation [dose].”

Explaining the importance of the findings, Dr. Lawton, the press briefing moderator, said, “We have shown over time that increasing the dose [of radiation] to the prostate and immediate surrounding tissues improves outcomes. We have also shown for our high-risk patients that adding hormone therapy improves outcomes. But what we have yet to show is … do you really need the hormone therapy if you use dose escalation? And the answer is yes.”

Shortening duration of ADT improves testosterone recovery

In the second trial, known as PCS IV, investigators led by Dr. Abdenour Nabid, a radiation oncologist at Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada, studied 561 men with high-risk prostate cancer who had been treated with radiation therapy (44 Gy to the whole pelvis and 70 Gy to the prostate) and randomized to 18 months or 36 months of ADT. AstraZeneca collaborated on the trial.

Previously reported results suggested that 18 months was just as efficacious as 36 months for overall survival and cancer-specific survival (ASCO 2013 Annual Meeting. Abstract LBA4510).

With a median follow-up of 84 months, relative to counterparts who had received ADT for 36 months, patients who had received ADT for 18 months were more likely to have recovery of testosterone values into the normal range (55.7% vs. 44.9%, P = .01) and had a shorter median time to recovery (47.2 vs. 73.2 months, P less than .001).

Relative to counterparts who did not have testosterone recovery, patients who did had significantly better scores on 18 of 30 items on the European Organization for Research and Treatment of Cancer’s global quality of life questionnaire (EORTC30) (P less than .01 for each) and on 10 of 25 items on the related Prostate Module (PR25) (P less than .01 for each).

Clinically relevant differences, defined as ones of at least 10 points on the 100-point linearly transformed scales, were seen between men who did and did not have testosterone recovery for two of the global quality of life items – trouble doing strenuous activities and trouble taking long walks – and three of the prostate-related quality of life items – hot flushes, interest in sex, and sexual activity.

“In high-risk prostate cancer treated with radiation therapy and ADT, patients who recover normal testosterone levels have a better quality of life,” said Dr. Nabid. “There is a major advantage in the use of 18 months of ADT instead of 36 months since a higher proportion of patients recovered normal testosterone levels in a much shorter time without any apparent detriment in long-term outcomes.”

“If we succeed to demonstrate that 18 months is at least equal to 36 months, it’s a big jump because it’s a matter of quality of life, it’s a matter of cost also,” he added. The investigators expect to be able to publish final efficacy and quality of life results next year.

In the meantime, clinicians can follow national guidelines, according to Dr. Nabid. “If you look at the guidelines, like the NCCN guidelines for the U.S., what is written is that the long-term [ADT] could be between 24 and 36 months. So my advice would be, even if you wait for the final paper, to go for 24 months. It’s a good beginning,” he asserted.

However, “you have to use your clinical judgment,” he added, agreeing that disease factors can be used to further stratify high-risk patients; additionally, age, comorbidities, and other factors will play a role in tailoring the duration of ADT. And importantly, “one has to discuss this with his patients.”

Dr. Lawton noted that the definition of long-duration ADT has varied by world region, and has typically been 28 months in the United States and 36 months in Europe. On the basis of this trial’s findings, “I do think that 18 months is potentially our new long-term hormone therapy option. That data isn’t out in print yet, other than in abstract form, But I think going forward, the question for us should be, can we shorten it from there,” she said. “I don’t know that we’ve nailed [the optimal long duration], but we are certainly heading in the right direction.”

Dr. Zapatero disclosed no conflicts of interest; the trial was supported in part by the AstraZeneca Fund. Dr. Nabid disclosed ties with AstraZeneca and Sanofi; AstraZeneca collaborated on the trial.

SAN FRANCISCO – Men who undergo radiation therapy for high-risk prostate cancer are less likely to have a recurrence and to die if they also receive long-duration androgen deprivation therapy. A long duration roughly half of that typically used appears to strike a good balance between efficacy and quality of life.

These were among the key findings of a pair of phase III randomized trials reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Quantity of life became the most important piece for us as we were trying to control prostate cancer. But today, so many of our localized prostate cancer patients are going to survive their illness that quality of life becomes exceedingly important,” said Dr. Colleen Lawton, vice chair and clinical director of the department of radiation oncology at the Medical College of Wisconsin, Milwaukee, and moderator of a related press briefing.

Efficacy data support long-duration ADT

In the first trial, called DART 01/05 (or AADLPC) and supported in part by the AstraZeneca Fund, investigators led by Dr. Almudena Zapatero, a radiation oncologist at Hospital Universitario de la Princesa, Madrid, studied 355 patients with intermediate- or high-risk prostate cancer.

The patients were randomized evenly to high-dose radiation therapy of at least 76 Gy, plus either short-duration ADT (4 months before and during radiation only) or long-duration ADT (4 months before and during radiation and 24 months afterward).

With a median follow-up of 63 months, relative to short-duration ADT, long-duration ADT was associated with better 5-year rates of biochemical disease–free survival according to the Phoenix definition (89.8% vs. 81.3%), overall survival (94.8% vs. 86.1%), and metastasis-free survival (93.6% vs. 83.4%), reported Dr. Zapatero. However, in stratified analyses, these benefits were seen only in the men with high-risk disease.

The two treatment groups did not differ significantly with respect to rates of acute and late rectal and urinary toxicity.

The study is noteworthy as it supports use of more costly high-dose radiation and hormonal therapy, said Dr. Zapatero. “We have demonstrated that we can get a 10% absolute benefit in PSA [prostate-specific antigen] control and overall survival and cancer-specific survival with acceptably low complications for high-risk disease. This is what we know now. We now know that … intermediate-risk disease probably doesn’t need any complementary [hormone therapy],” she said.

“We await longer follow-up to confirm these results and to determine the impact of long-term hormones according to the risk subgroup,” added Dr. Zapatero, noting that high-risk patients can be further stratified according to T3 stage, high Gleason score, and undifferentiated tumor histology. “Probably, if you have one factor, you are going to need less long of a duration of hormones, probably close to 18 months. And if you have two or three, what we call very high risk disease, you are going to need longer hormone therapy and the highest radiation [dose].”

Explaining the importance of the findings, Dr. Lawton, the press briefing moderator, said, “We have shown over time that increasing the dose [of radiation] to the prostate and immediate surrounding tissues improves outcomes. We have also shown for our high-risk patients that adding hormone therapy improves outcomes. But what we have yet to show is … do you really need the hormone therapy if you use dose escalation? And the answer is yes.”

Shortening duration of ADT improves testosterone recovery

In the second trial, known as PCS IV, investigators led by Dr. Abdenour Nabid, a radiation oncologist at Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada, studied 561 men with high-risk prostate cancer who had been treated with radiation therapy (44 Gy to the whole pelvis and 70 Gy to the prostate) and randomized to 18 months or 36 months of ADT. AstraZeneca collaborated on the trial.

Previously reported results suggested that 18 months was just as efficacious as 36 months for overall survival and cancer-specific survival (ASCO 2013 Annual Meeting. Abstract LBA4510).

With a median follow-up of 84 months, relative to counterparts who had received ADT for 36 months, patients who had received ADT for 18 months were more likely to have recovery of testosterone values into the normal range (55.7% vs. 44.9%, P = .01) and had a shorter median time to recovery (47.2 vs. 73.2 months, P less than .001).

Relative to counterparts who did not have testosterone recovery, patients who did had significantly better scores on 18 of 30 items on the European Organization for Research and Treatment of Cancer’s global quality of life questionnaire (EORTC30) (P less than .01 for each) and on 10 of 25 items on the related Prostate Module (PR25) (P less than .01 for each).

Clinically relevant differences, defined as ones of at least 10 points on the 100-point linearly transformed scales, were seen between men who did and did not have testosterone recovery for two of the global quality of life items – trouble doing strenuous activities and trouble taking long walks – and three of the prostate-related quality of life items – hot flushes, interest in sex, and sexual activity.

“In high-risk prostate cancer treated with radiation therapy and ADT, patients who recover normal testosterone levels have a better quality of life,” said Dr. Nabid. “There is a major advantage in the use of 18 months of ADT instead of 36 months since a higher proportion of patients recovered normal testosterone levels in a much shorter time without any apparent detriment in long-term outcomes.”

“If we succeed to demonstrate that 18 months is at least equal to 36 months, it’s a big jump because it’s a matter of quality of life, it’s a matter of cost also,” he added. The investigators expect to be able to publish final efficacy and quality of life results next year.

In the meantime, clinicians can follow national guidelines, according to Dr. Nabid. “If you look at the guidelines, like the NCCN guidelines for the U.S., what is written is that the long-term [ADT] could be between 24 and 36 months. So my advice would be, even if you wait for the final paper, to go for 24 months. It’s a good beginning,” he asserted.

However, “you have to use your clinical judgment,” he added, agreeing that disease factors can be used to further stratify high-risk patients; additionally, age, comorbidities, and other factors will play a role in tailoring the duration of ADT. And importantly, “one has to discuss this with his patients.”

Dr. Lawton noted that the definition of long-duration ADT has varied by world region, and has typically been 28 months in the United States and 36 months in Europe. On the basis of this trial’s findings, “I do think that 18 months is potentially our new long-term hormone therapy option. That data isn’t out in print yet, other than in abstract form, But I think going forward, the question for us should be, can we shorten it from there,” she said. “I don’t know that we’ve nailed [the optimal long duration], but we are certainly heading in the right direction.”

Dr. Zapatero disclosed no conflicts of interest; the trial was supported in part by the AstraZeneca Fund. Dr. Nabid disclosed ties with AstraZeneca and Sanofi; AstraZeneca collaborated on the trial.

Men with a combination of frontal and moderate vertex baldness at age 45 were at a significantly increased risk of having aggressive prostate cancer in a large prospective cohort study, according to investigators.

“Although the effect is moderate, it supports the possibility of overlapping pathogenesis between male pattern baldness and prostate cancer,” Cindy Ke Zhou of the National Cancer Institute, Bethesda, Md., and her associates wrote in their analysis (Sept. 15, J. Clin. Onc. 2014 Sept. 15 [doi: 10.1200/JCO.2014.55.4279])

Courtesy American Society of Clinical Oncology

The results of previous studies ­evaluating the association between male pattern baldness and prostate cancer – mostly small cross-sectional or case-control studies – have been inconsistent. Unlike those studies, this study looked at subtypes of prostate cancer among 39,070 mostly white men enrolled at aged 55-74 in a large prospective cohort cancer screening study, who had not been diagnosed with cancer. About half reported being bald at age 45.

Over a median of almost 3 years, 1,138 prostate cancers were diagnosed, including 571 that were aggressive. There was no significant association between having frontal plus moderate vertex baldness (affecting both the front and the crown of the head) at age 45 years and prostate cancer overall (hazard ratio, 1.19) or with prostate cancer that was not aggressive (HR, 0.97), when compared with men who were not bald at that age.

However, compared with men who were not bald, this particular pattern of male baldness was associated with a nearly 40% increased risk of aggressive prostate cancer (HR, 1.39), which was statistically significant. There was no association with an increased risk for overall or any subtype of prostate cancer and other hair loss patterns.

“While our data show a strong possibility for a link between the development of baldness and aggressive prostate cancer, it’s too soon to apply these findings to patient care,” the study’s senior author, Michael Cook, Ph.D., of the NCI’s Division of Cancer Epidemiology and Genetics, said in a statement issued by the American Society of Clinical Oncology, the publisher of the journal. But if the results are confirmed, he added, baldness may be a possible way to help identify men who could be at an increased risk of having aggressive prostate cancer.

The study was funded by the NCI’s intramural program of the Division of Cancer Epidemiology and Genetics. None of the authors had disclosures.

emechcatie@frontlinemedcom.com

Men with a combination of frontal and moderate vertex baldness at age 45 were at a significantly increased risk of having aggressive prostate cancer in a large prospective cohort study, according to investigators.

“Although the effect is moderate, it supports the possibility of overlapping pathogenesis between male pattern baldness and prostate cancer,” Cindy Ke Zhou of the National Cancer Institute, Bethesda, Md., and her associates wrote in their analysis (Sept. 15, J. Clin. Onc. 2014 Sept. 15 [doi: 10.1200/JCO.2014.55.4279])

Courtesy American Society of Clinical Oncology

The results of previous studies ­evaluating the association between male pattern baldness and prostate cancer – mostly small cross-sectional or case-control studies – have been inconsistent. Unlike those studies, this study looked at subtypes of prostate cancer among 39,070 mostly white men enrolled at aged 55-74 in a large prospective cohort cancer screening study, who had not been diagnosed with cancer. About half reported being bald at age 45.

Over a median of almost 3 years, 1,138 prostate cancers were diagnosed, including 571 that were aggressive. There was no significant association between having frontal plus moderate vertex baldness (affecting both the front and the crown of the head) at age 45 years and prostate cancer overall (hazard ratio, 1.19) or with prostate cancer that was not aggressive (HR, 0.97), when compared with men who were not bald at that age.

However, compared with men who were not bald, this particular pattern of male baldness was associated with a nearly 40% increased risk of aggressive prostate cancer (HR, 1.39), which was statistically significant. There was no association with an increased risk for overall or any subtype of prostate cancer and other hair loss patterns.

“While our data show a strong possibility for a link between the development of baldness and aggressive prostate cancer, it’s too soon to apply these findings to patient care,” the study’s senior author, Michael Cook, Ph.D., of the NCI’s Division of Cancer Epidemiology and Genetics, said in a statement issued by the American Society of Clinical Oncology, the publisher of the journal. But if the results are confirmed, he added, baldness may be a possible way to help identify men who could be at an increased risk of having aggressive prostate cancer.

The study was funded by the NCI’s intramural program of the Division of Cancer Epidemiology and Genetics. None of the authors had disclosures.

emechcatie@frontlinemedcom.com

Men with a combination of frontal and moderate vertex baldness at age 45 were at a significantly increased risk of having aggressive prostate cancer in a large prospective cohort study, according to investigators.

“Although the effect is moderate, it supports the possibility of overlapping pathogenesis between male pattern baldness and prostate cancer,” Cindy Ke Zhou of the National Cancer Institute, Bethesda, Md., and her associates wrote in their analysis (Sept. 15, J. Clin. Onc. 2014 Sept. 15 [doi: 10.1200/JCO.2014.55.4279])

Courtesy American Society of Clinical Oncology

The results of previous studies ­evaluating the association between male pattern baldness and prostate cancer – mostly small cross-sectional or case-control studies – have been inconsistent. Unlike those studies, this study looked at subtypes of prostate cancer among 39,070 mostly white men enrolled at aged 55-74 in a large prospective cohort cancer screening study, who had not been diagnosed with cancer. About half reported being bald at age 45.

Over a median of almost 3 years, 1,138 prostate cancers were diagnosed, including 571 that were aggressive. There was no significant association between having frontal plus moderate vertex baldness (affecting both the front and the crown of the head) at age 45 years and prostate cancer overall (hazard ratio, 1.19) or with prostate cancer that was not aggressive (HR, 0.97), when compared with men who were not bald at that age.

However, compared with men who were not bald, this particular pattern of male baldness was associated with a nearly 40% increased risk of aggressive prostate cancer (HR, 1.39), which was statistically significant. There was no association with an increased risk for overall or any subtype of prostate cancer and other hair loss patterns.

“While our data show a strong possibility for a link between the development of baldness and aggressive prostate cancer, it’s too soon to apply these findings to patient care,” the study’s senior author, Michael Cook, Ph.D., of the NCI’s Division of Cancer Epidemiology and Genetics, said in a statement issued by the American Society of Clinical Oncology, the publisher of the journal. But if the results are confirmed, he added, baldness may be a possible way to help identify men who could be at an increased risk of having aggressive prostate cancer.

The study was funded by the NCI’s intramural program of the Division of Cancer Epidemiology and Genetics. None of the authors had disclosures.

emechcatie@frontlinemedcom.com