Nephrology

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Adding the investigational agent vandetanib to docetaxel added toxicity but little clinical benefit in a double-blind, multicenter study of 142 patients with platinum-pretreated metastatic urothelial cancer.

The primary end point of median progression-free survival reached 1.58 months with placebo plus docetaxel (Taxotere) and 2.56 months with vandetanib plus docetaxel (hazard ratio 1.02). Median overall survival was actually longer with placebo at 7.03 months vs. 5.85 months with vandetanib (HR 1.21).

Treatment-related all-grade toxicity was reported in 66% of the vandetanib vs. 44% in the placebo arm (P = .012), and high-grade toxicity in 60% vs. 36% (P = .007), lead author Dr. Toni K. Choueiri reported in a late-breaking abstract at the Genitourinary Cancers Symposium.

"The addition of vandetanib, a dual EGFR/VEGFR antagonist, to docetaxel did not result in any benefit in terms of progression-free survival, response rate, or overall survival as compared to placebo plus docetaxel," he concluded. "Toxicities ran higher, but [were] manageable."

Vandetanib was an attractive agent to evaluate because it blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor 2, two pathways that play an important role in urothelial cancer.

The researchers had hypothesized that simultaneous blockade of the pathways, in addition to the taxane docetaxel, might provide additional benefit, compared with chemotherapy alone. There is no standard of care for metastatic urothelial cancer that has progressed after treatment with a platinum-containing regimen. Taxanes often are used in the salvage setting, but with minimal activity, he said.

AstraZeneca is seeking approval of vandetanib for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer. A Food and Drug Administration panel voted in late December that the risk-benefit profile of vandetanib is acceptable for patients with progressive, symptomatic medullary thyroid cancer, and added restrictive language to the proposed indication in light of toxicity concerns, particularly the possibility of QTc prolongation. On Jan. 7, the FDA extended the review time line for the new drug application to April 7, 2011.

In 2009, AstraZeneca filed for an advanced non–small cell lung cancer indication for vandetanib (under the proposed trade name Zactima) in the United States and Europe, but quickly withdrew the applications after preliminary feedback from regulators indicated progression-free survival data were not sufficient to support approval.

Dr. Choueiri and his associates assessed long-term outcomes among 142 patients with metastatic bladder cancer who had failed first-line platinum-based chemotherapy and received up to three prior systemic therapies including paclitaxel. They had a performance status of 0 or 1, and brain metastases were allowed.

Patients were randomized to docetaxel 75 mg/m² every 21 days plus oral vandetanib 100 mg once daily or the same docetaxel regimen plus oral placebo until disease progression. Patients on the placebo arm were allowed to cross over to single-agent vandetanib.

Only 8 of the 72 (11%) placebo patients and 5 of the 70 (7%) vandetanib patients responded to treatment, Dr. Choueiri reported.

In all, 25% of the placebo arm experienced a grade 3/4 treatment-related nonhematologic adverse event vs. 50% of the vandetanib arm, including significantly more rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%).

Single-agent activity with vandetanib was limited, said Dr. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. A crossover analysis among 37 patients revealed one partial response and stable disease in 5 patients, with a median overall survival of 5.2 months. Two patients were unevaluable, and one patient recently crossed over without response data.

Exploratory analyses among all patients revealed no preferential activity with vandetanib for any subgroup with regard to progression-free or overall survival, Dr. Choueiri said.

"Clinical trials of rational drugs and combinations are urgently needed in this setting," he said.

The Dana-Farber Cancer Institute sponsored the study. Dr. Choueiri reported consultant/advisory roles with Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx Pharmaceuticals, and Pfizer.

ORLANDO – Adding the investigational agent vandetanib to docetaxel added toxicity but little clinical benefit in a double-blind, multicenter study of 142 patients with platinum-pretreated metastatic urothelial cancer.

The primary end point of median progression-free survival reached 1.58 months with placebo plus docetaxel (Taxotere) and 2.56 months with vandetanib plus docetaxel (hazard ratio 1.02). Median overall survival was actually longer with placebo at 7.03 months vs. 5.85 months with vandetanib (HR 1.21).

Treatment-related all-grade toxicity was reported in 66% of the vandetanib vs. 44% in the placebo arm (P = .012), and high-grade toxicity in 60% vs. 36% (P = .007), lead author Dr. Toni K. Choueiri reported in a late-breaking abstract at the Genitourinary Cancers Symposium.

"The addition of vandetanib, a dual EGFR/VEGFR antagonist, to docetaxel did not result in any benefit in terms of progression-free survival, response rate, or overall survival as compared to placebo plus docetaxel," he concluded. "Toxicities ran higher, but [were] manageable."

Vandetanib was an attractive agent to evaluate because it blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor 2, two pathways that play an important role in urothelial cancer.

The researchers had hypothesized that simultaneous blockade of the pathways, in addition to the taxane docetaxel, might provide additional benefit, compared with chemotherapy alone. There is no standard of care for metastatic urothelial cancer that has progressed after treatment with a platinum-containing regimen. Taxanes often are used in the salvage setting, but with minimal activity, he said.

AstraZeneca is seeking approval of vandetanib for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer. A Food and Drug Administration panel voted in late December that the risk-benefit profile of vandetanib is acceptable for patients with progressive, symptomatic medullary thyroid cancer, and added restrictive language to the proposed indication in light of toxicity concerns, particularly the possibility of QTc prolongation. On Jan. 7, the FDA extended the review time line for the new drug application to April 7, 2011.

In 2009, AstraZeneca filed for an advanced non–small cell lung cancer indication for vandetanib (under the proposed trade name Zactima) in the United States and Europe, but quickly withdrew the applications after preliminary feedback from regulators indicated progression-free survival data were not sufficient to support approval.

Dr. Choueiri and his associates assessed long-term outcomes among 142 patients with metastatic bladder cancer who had failed first-line platinum-based chemotherapy and received up to three prior systemic therapies including paclitaxel. They had a performance status of 0 or 1, and brain metastases were allowed.

Patients were randomized to docetaxel 75 mg/m² every 21 days plus oral vandetanib 100 mg once daily or the same docetaxel regimen plus oral placebo until disease progression. Patients on the placebo arm were allowed to cross over to single-agent vandetanib.

Only 8 of the 72 (11%) placebo patients and 5 of the 70 (7%) vandetanib patients responded to treatment, Dr. Choueiri reported.

In all, 25% of the placebo arm experienced a grade 3/4 treatment-related nonhematologic adverse event vs. 50% of the vandetanib arm, including significantly more rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%).

Single-agent activity with vandetanib was limited, said Dr. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. A crossover analysis among 37 patients revealed one partial response and stable disease in 5 patients, with a median overall survival of 5.2 months. Two patients were unevaluable, and one patient recently crossed over without response data.

Exploratory analyses among all patients revealed no preferential activity with vandetanib for any subgroup with regard to progression-free or overall survival, Dr. Choueiri said.

"Clinical trials of rational drugs and combinations are urgently needed in this setting," he said.

The Dana-Farber Cancer Institute sponsored the study. Dr. Choueiri reported consultant/advisory roles with Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx Pharmaceuticals, and Pfizer.

ORLANDO – Adding the investigational agent vandetanib to docetaxel added toxicity but little clinical benefit in a double-blind, multicenter study of 142 patients with platinum-pretreated metastatic urothelial cancer.

The primary end point of median progression-free survival reached 1.58 months with placebo plus docetaxel (Taxotere) and 2.56 months with vandetanib plus docetaxel (hazard ratio 1.02). Median overall survival was actually longer with placebo at 7.03 months vs. 5.85 months with vandetanib (HR 1.21).

Treatment-related all-grade toxicity was reported in 66% of the vandetanib vs. 44% in the placebo arm (P = .012), and high-grade toxicity in 60% vs. 36% (P = .007), lead author Dr. Toni K. Choueiri reported in a late-breaking abstract at the Genitourinary Cancers Symposium.

"The addition of vandetanib, a dual EGFR/VEGFR antagonist, to docetaxel did not result in any benefit in terms of progression-free survival, response rate, or overall survival as compared to placebo plus docetaxel," he concluded. "Toxicities ran higher, but [were] manageable."

Vandetanib was an attractive agent to evaluate because it blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor 2, two pathways that play an important role in urothelial cancer.

The researchers had hypothesized that simultaneous blockade of the pathways, in addition to the taxane docetaxel, might provide additional benefit, compared with chemotherapy alone. There is no standard of care for metastatic urothelial cancer that has progressed after treatment with a platinum-containing regimen. Taxanes often are used in the salvage setting, but with minimal activity, he said.

AstraZeneca is seeking approval of vandetanib for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer. A Food and Drug Administration panel voted in late December that the risk-benefit profile of vandetanib is acceptable for patients with progressive, symptomatic medullary thyroid cancer, and added restrictive language to the proposed indication in light of toxicity concerns, particularly the possibility of QTc prolongation. On Jan. 7, the FDA extended the review time line for the new drug application to April 7, 2011.

In 2009, AstraZeneca filed for an advanced non–small cell lung cancer indication for vandetanib (under the proposed trade name Zactima) in the United States and Europe, but quickly withdrew the applications after preliminary feedback from regulators indicated progression-free survival data were not sufficient to support approval.

Dr. Choueiri and his associates assessed long-term outcomes among 142 patients with metastatic bladder cancer who had failed first-line platinum-based chemotherapy and received up to three prior systemic therapies including paclitaxel. They had a performance status of 0 or 1, and brain metastases were allowed.

Patients were randomized to docetaxel 75 mg/m² every 21 days plus oral vandetanib 100 mg once daily or the same docetaxel regimen plus oral placebo until disease progression. Patients on the placebo arm were allowed to cross over to single-agent vandetanib.

Only 8 of the 72 (11%) placebo patients and 5 of the 70 (7%) vandetanib patients responded to treatment, Dr. Choueiri reported.

In all, 25% of the placebo arm experienced a grade 3/4 treatment-related nonhematologic adverse event vs. 50% of the vandetanib arm, including significantly more rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%).

Single-agent activity with vandetanib was limited, said Dr. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. A crossover analysis among 37 patients revealed one partial response and stable disease in 5 patients, with a median overall survival of 5.2 months. Two patients were unevaluable, and one patient recently crossed over without response data.

Exploratory analyses among all patients revealed no preferential activity with vandetanib for any subgroup with regard to progression-free or overall survival, Dr. Choueiri said.

"Clinical trials of rational drugs and combinations are urgently needed in this setting," he said.

The Dana-Farber Cancer Institute sponsored the study. Dr. Choueiri reported consultant/advisory roles with Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx Pharmaceuticals, and Pfizer.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Periodic breaks from androgen suppression therapy did not impact survival in men with prostate-specific antigen progression after radical therapy for prostate cancer.

In a phase III study involving 1,386 men, median overall survival was 9.1 years with continuous androgen deprivation and 8.8 years with intermittent androgen suppression (P value .009, hazard ratio 1.02), lead author Dr. Laurence Klotz said at the Genitourinary Cancers Symposium. Median follow-up was 6.9 years.

"Based on this study, which is really, I think a pivotal, definitive trial of this question, IAS [intermittent androgen suppression] should be the standard of care for most patients with PSA [prostate-specific antigen] recurrence after radiation, who are initiating androgen deprivation therapy," he said.

The inter-group study, which was stopped early based on the interim analysis, answers the long-standing question of survival for a therapeutic approach that is increasingly popular among clinicians and patients.

Intermittent androgen suppression was first described in a report by Dr. Klotz in 1986 and since then has been the subject of 17 phase II and nine phase III studies. Although previous studies reported favorable results, they were either too small to determine survival non-inferiority or included patients with both metastatic and non-metastatic disease, he said.

The current study included men without metastatic disease who had a rising serum prostate-specific antigen of more than 3 ng/ml and serum testosterone of more than 5 nmol/L at one year after undergoing radiation therapy, either as primary management or post radical prostatectomy. PSA testing was performed every 2 months.

In the randomized multi-center trial, 696 patients received initial flare blockade with an anti-androgen (AA) and therapy with a luteinizing hormone-releasing hormone (LHRH) analog until castrate resistance and 690 patients received initial AA and LHRH for 8 months, at which time therapy was stopped if PSA levels became normal. If PSA rose to more than 10 mg/ml, the 8 months of therapy was repeated. Patients were switched to continuous androgen deprivation at disease progression or with a PSA of more than 10 ng/ml within 2 months of discontinuing therapy.

Dr. Christopher Logothetis, chair of genitourinary medical oncology at MD Anderson Cancer Center in Houston, said in an interview that another trial is unlikely to be conducted and that the current findings make intermittent therapy the preferred treatment. He has been using intermittent androgen suppression for more than 5 years in his patients and said the difference in quality of life is striking for these men.

"I’m not sure that the side effect profile he [Dr. Klotz] described captures the degree of benefit that patients feel when they have a normal testosterone – this general sense of well-being, a sort of equanimity they experience and return to life and engagement," he said. "My own view of life is that the benefits are underestimated."

Significant adverse events were similar between the intermittent androgen suppression and continuous androgen deprivation patients, including erectile dysfunction (86% vs. 88%), libido (79% both groups), urine frequency/urgency (61% vs. 57%), fatigue (59% both groups), myocardial ischemia/infarction (10% vs. 11%), and osteoporotic fracture (4% vs. 3%). The only real difference was in hot flashes, favoring the intermittent androgen suppression arm at 90% vs. 93% (P = .04), said Dr. Klotz, chief of urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Quality-of-life studies, which will address off-treatment events, will be reported at a future meeting.

The median time to castration resistance was 10 years with continuous androgen deprivation and 9.8 years with intermittent androgen suppression, although a stratified log-rank analysis favored the intermittent arm (P = .024, HR 0.80). This finding may reflect the study design, which was biased toward a longer time of castrate resistance in the intermittent arm because patients off treatment had to be retreated before they could be defined as castrate resistant, he said.

There were 9% more prostate cancer deaths on intermittent androgen suppression and 8% more non-prostate cancer deaths on continuous androgen deprivation. Seven-year disease-specific mortality was 18% in the intermittent androgen suppression arm vs. 15% in the continuous arm (P = .24, HR 1.18).

Dr. Klotz suggested that the increase in non-prostate cancer deaths in the continuous androgen deprivation arm may be related to the metabolic effects of long-term continuous androgen deprivation. The increase in prostate cancer deaths in the intermittent arm "is going to be a matter, I think, for some discussion and controversy," even though it was statistically insignificant and "a very secondary point compared to the observation of no difference in overall survival," he added.

Surprisingly, the average on-treatment time was only 27% on average in the intermittent arm, with men spending a median of 15.4 months on therapy and 37.6 months off therapy. Dr. Klotz pointed out that this contrasts with an on-treatment time of 50% observed in most of the phase II studies.

"This is actually quite reassuring and I think important data that, at least in this scenario, patients tend to stay off treatment for a much longer period of time," he said at the symposium, co-sponsored by the American Society for Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, said the question of survival with intermittent therapy has now been answered, and that it is very reasonable for intermittent therapy to be considered the standard of care in these patients.

"The only caveat is that you do have to monitor this; you just can’t send them out the door and say, ‘I’ll see you in a year,’ " said Dr. Sartor, who has been using intermittent therapy for the past decade in his patients to reduce adverse events. "I will be monitoring, typically, every 2 months."

In an interview, Dr. Klotz described the results as a win-win for patients and may also save them money. Although significantly less costly than many of the newer targeted therapies, a monthly injection costs about $350. He speculated that in treatment-naïve patients, the investigational agent MDV3100 and intermittent androgen deprivation may be a good partnership, but did not recommend this approach with abiraterone acetate should it gain approval this year, as is anticipated.

Of the 1,368 men evaluated, 11% had undergone a prior prostatectomy, and for 78%, it had been at least 3 years since radiation therapy. They had a median age of 74 years, 81% had a performance status of 0, and 23% had a PSA of more than 15 ng/ml when entering the trial, which was sponsored by several research groups including the National Cancer Institute Clinical Trials Group and Southwest Oncology Group.

Dr. Klotz and his co-authors disclosed no conflicts. Dr. Logothetis disclosed consulting for and honoraria and research funding from several drug companies. Dr. Sartor disclosed honoraria from Sanofi-Aventis as well as consulting for and receiving research funding from multiple drug companies.

ORLANDO – Periodic breaks from androgen suppression therapy did not impact survival in men with prostate-specific antigen progression after radical therapy for prostate cancer.

In a phase III study involving 1,386 men, median overall survival was 9.1 years with continuous androgen deprivation and 8.8 years with intermittent androgen suppression (P value .009, hazard ratio 1.02), lead author Dr. Laurence Klotz said at the Genitourinary Cancers Symposium. Median follow-up was 6.9 years.

"Based on this study, which is really, I think a pivotal, definitive trial of this question, IAS [intermittent androgen suppression] should be the standard of care for most patients with PSA [prostate-specific antigen] recurrence after radiation, who are initiating androgen deprivation therapy," he said.

The inter-group study, which was stopped early based on the interim analysis, answers the long-standing question of survival for a therapeutic approach that is increasingly popular among clinicians and patients.

Intermittent androgen suppression was first described in a report by Dr. Klotz in 1986 and since then has been the subject of 17 phase II and nine phase III studies. Although previous studies reported favorable results, they were either too small to determine survival non-inferiority or included patients with both metastatic and non-metastatic disease, he said.

The current study included men without metastatic disease who had a rising serum prostate-specific antigen of more than 3 ng/ml and serum testosterone of more than 5 nmol/L at one year after undergoing radiation therapy, either as primary management or post radical prostatectomy. PSA testing was performed every 2 months.

In the randomized multi-center trial, 696 patients received initial flare blockade with an anti-androgen (AA) and therapy with a luteinizing hormone-releasing hormone (LHRH) analog until castrate resistance and 690 patients received initial AA and LHRH for 8 months, at which time therapy was stopped if PSA levels became normal. If PSA rose to more than 10 mg/ml, the 8 months of therapy was repeated. Patients were switched to continuous androgen deprivation at disease progression or with a PSA of more than 10 ng/ml within 2 months of discontinuing therapy.

Dr. Christopher Logothetis, chair of genitourinary medical oncology at MD Anderson Cancer Center in Houston, said in an interview that another trial is unlikely to be conducted and that the current findings make intermittent therapy the preferred treatment. He has been using intermittent androgen suppression for more than 5 years in his patients and said the difference in quality of life is striking for these men.

"I’m not sure that the side effect profile he [Dr. Klotz] described captures the degree of benefit that patients feel when they have a normal testosterone – this general sense of well-being, a sort of equanimity they experience and return to life and engagement," he said. "My own view of life is that the benefits are underestimated."

Significant adverse events were similar between the intermittent androgen suppression and continuous androgen deprivation patients, including erectile dysfunction (86% vs. 88%), libido (79% both groups), urine frequency/urgency (61% vs. 57%), fatigue (59% both groups), myocardial ischemia/infarction (10% vs. 11%), and osteoporotic fracture (4% vs. 3%). The only real difference was in hot flashes, favoring the intermittent androgen suppression arm at 90% vs. 93% (P = .04), said Dr. Klotz, chief of urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Quality-of-life studies, which will address off-treatment events, will be reported at a future meeting.

The median time to castration resistance was 10 years with continuous androgen deprivation and 9.8 years with intermittent androgen suppression, although a stratified log-rank analysis favored the intermittent arm (P = .024, HR 0.80). This finding may reflect the study design, which was biased toward a longer time of castrate resistance in the intermittent arm because patients off treatment had to be retreated before they could be defined as castrate resistant, he said.

There were 9% more prostate cancer deaths on intermittent androgen suppression and 8% more non-prostate cancer deaths on continuous androgen deprivation. Seven-year disease-specific mortality was 18% in the intermittent androgen suppression arm vs. 15% in the continuous arm (P = .24, HR 1.18).

Dr. Klotz suggested that the increase in non-prostate cancer deaths in the continuous androgen deprivation arm may be related to the metabolic effects of long-term continuous androgen deprivation. The increase in prostate cancer deaths in the intermittent arm "is going to be a matter, I think, for some discussion and controversy," even though it was statistically insignificant and "a very secondary point compared to the observation of no difference in overall survival," he added.

Surprisingly, the average on-treatment time was only 27% on average in the intermittent arm, with men spending a median of 15.4 months on therapy and 37.6 months off therapy. Dr. Klotz pointed out that this contrasts with an on-treatment time of 50% observed in most of the phase II studies.

"This is actually quite reassuring and I think important data that, at least in this scenario, patients tend to stay off treatment for a much longer period of time," he said at the symposium, co-sponsored by the American Society for Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, said the question of survival with intermittent therapy has now been answered, and that it is very reasonable for intermittent therapy to be considered the standard of care in these patients.

"The only caveat is that you do have to monitor this; you just can’t send them out the door and say, ‘I’ll see you in a year,’ " said Dr. Sartor, who has been using intermittent therapy for the past decade in his patients to reduce adverse events. "I will be monitoring, typically, every 2 months."

In an interview, Dr. Klotz described the results as a win-win for patients and may also save them money. Although significantly less costly than many of the newer targeted therapies, a monthly injection costs about $350. He speculated that in treatment-naïve patients, the investigational agent MDV3100 and intermittent androgen deprivation may be a good partnership, but did not recommend this approach with abiraterone acetate should it gain approval this year, as is anticipated.

Of the 1,368 men evaluated, 11% had undergone a prior prostatectomy, and for 78%, it had been at least 3 years since radiation therapy. They had a median age of 74 years, 81% had a performance status of 0, and 23% had a PSA of more than 15 ng/ml when entering the trial, which was sponsored by several research groups including the National Cancer Institute Clinical Trials Group and Southwest Oncology Group.

Dr. Klotz and his co-authors disclosed no conflicts. Dr. Logothetis disclosed consulting for and honoraria and research funding from several drug companies. Dr. Sartor disclosed honoraria from Sanofi-Aventis as well as consulting for and receiving research funding from multiple drug companies.

ORLANDO – Periodic breaks from androgen suppression therapy did not impact survival in men with prostate-specific antigen progression after radical therapy for prostate cancer.

In a phase III study involving 1,386 men, median overall survival was 9.1 years with continuous androgen deprivation and 8.8 years with intermittent androgen suppression (P value .009, hazard ratio 1.02), lead author Dr. Laurence Klotz said at the Genitourinary Cancers Symposium. Median follow-up was 6.9 years.

"Based on this study, which is really, I think a pivotal, definitive trial of this question, IAS [intermittent androgen suppression] should be the standard of care for most patients with PSA [prostate-specific antigen] recurrence after radiation, who are initiating androgen deprivation therapy," he said.

The inter-group study, which was stopped early based on the interim analysis, answers the long-standing question of survival for a therapeutic approach that is increasingly popular among clinicians and patients.

Intermittent androgen suppression was first described in a report by Dr. Klotz in 1986 and since then has been the subject of 17 phase II and nine phase III studies. Although previous studies reported favorable results, they were either too small to determine survival non-inferiority or included patients with both metastatic and non-metastatic disease, he said.

The current study included men without metastatic disease who had a rising serum prostate-specific antigen of more than 3 ng/ml and serum testosterone of more than 5 nmol/L at one year after undergoing radiation therapy, either as primary management or post radical prostatectomy. PSA testing was performed every 2 months.

In the randomized multi-center trial, 696 patients received initial flare blockade with an anti-androgen (AA) and therapy with a luteinizing hormone-releasing hormone (LHRH) analog until castrate resistance and 690 patients received initial AA and LHRH for 8 months, at which time therapy was stopped if PSA levels became normal. If PSA rose to more than 10 mg/ml, the 8 months of therapy was repeated. Patients were switched to continuous androgen deprivation at disease progression or with a PSA of more than 10 ng/ml within 2 months of discontinuing therapy.

Dr. Christopher Logothetis, chair of genitourinary medical oncology at MD Anderson Cancer Center in Houston, said in an interview that another trial is unlikely to be conducted and that the current findings make intermittent therapy the preferred treatment. He has been using intermittent androgen suppression for more than 5 years in his patients and said the difference in quality of life is striking for these men.

"I’m not sure that the side effect profile he [Dr. Klotz] described captures the degree of benefit that patients feel when they have a normal testosterone – this general sense of well-being, a sort of equanimity they experience and return to life and engagement," he said. "My own view of life is that the benefits are underestimated."

Significant adverse events were similar between the intermittent androgen suppression and continuous androgen deprivation patients, including erectile dysfunction (86% vs. 88%), libido (79% both groups), urine frequency/urgency (61% vs. 57%), fatigue (59% both groups), myocardial ischemia/infarction (10% vs. 11%), and osteoporotic fracture (4% vs. 3%). The only real difference was in hot flashes, favoring the intermittent androgen suppression arm at 90% vs. 93% (P = .04), said Dr. Klotz, chief of urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Quality-of-life studies, which will address off-treatment events, will be reported at a future meeting.

The median time to castration resistance was 10 years with continuous androgen deprivation and 9.8 years with intermittent androgen suppression, although a stratified log-rank analysis favored the intermittent arm (P = .024, HR 0.80). This finding may reflect the study design, which was biased toward a longer time of castrate resistance in the intermittent arm because patients off treatment had to be retreated before they could be defined as castrate resistant, he said.

There were 9% more prostate cancer deaths on intermittent androgen suppression and 8% more non-prostate cancer deaths on continuous androgen deprivation. Seven-year disease-specific mortality was 18% in the intermittent androgen suppression arm vs. 15% in the continuous arm (P = .24, HR 1.18).

Dr. Klotz suggested that the increase in non-prostate cancer deaths in the continuous androgen deprivation arm may be related to the metabolic effects of long-term continuous androgen deprivation. The increase in prostate cancer deaths in the intermittent arm "is going to be a matter, I think, for some discussion and controversy," even though it was statistically insignificant and "a very secondary point compared to the observation of no difference in overall survival," he added.

Surprisingly, the average on-treatment time was only 27% on average in the intermittent arm, with men spending a median of 15.4 months on therapy and 37.6 months off therapy. Dr. Klotz pointed out that this contrasts with an on-treatment time of 50% observed in most of the phase II studies.

"This is actually quite reassuring and I think important data that, at least in this scenario, patients tend to stay off treatment for a much longer period of time," he said at the symposium, co-sponsored by the American Society for Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, said the question of survival with intermittent therapy has now been answered, and that it is very reasonable for intermittent therapy to be considered the standard of care in these patients.

"The only caveat is that you do have to monitor this; you just can’t send them out the door and say, ‘I’ll see you in a year,’ " said Dr. Sartor, who has been using intermittent therapy for the past decade in his patients to reduce adverse events. "I will be monitoring, typically, every 2 months."

In an interview, Dr. Klotz described the results as a win-win for patients and may also save them money. Although significantly less costly than many of the newer targeted therapies, a monthly injection costs about $350. He speculated that in treatment-naïve patients, the investigational agent MDV3100 and intermittent androgen deprivation may be a good partnership, but did not recommend this approach with abiraterone acetate should it gain approval this year, as is anticipated.

Of the 1,368 men evaluated, 11% had undergone a prior prostatectomy, and for 78%, it had been at least 3 years since radiation therapy. They had a median age of 74 years, 81% had a performance status of 0, and 23% had a PSA of more than 15 ng/ml when entering the trial, which was sponsored by several research groups including the National Cancer Institute Clinical Trials Group and Southwest Oncology Group.

Dr. Klotz and his co-authors disclosed no conflicts. Dr. Logothetis disclosed consulting for and honoraria and research funding from several drug companies. Dr. Sartor disclosed honoraria from Sanofi-Aventis as well as consulting for and receiving research funding from multiple drug companies.

Use of robotic prostatectomy has mushroomed in the United States, but new data suggest it is best left in the hands of expert surgeons.

A multicenter analysis of 3,794 cases of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by three experienced surgeons found that at least 1,500-1,600 cases were needed to achieve a positive surgical margin (PSM) rate of less than 10%, which is widely accepted in the surgical literature as a sign of excellence.

"We recommend that this operation should not be done by all urologists in small community hospitals, but should be focused and concentrated into those high-volume centers of excellence where the operation can be done by surgeons doing a large number of cases, very frequently, in order that they can achieve the best possible cancer-control results for their patients," lead author Dr. Prasanna Sooriakumaran said during a Feb. 15 press briefing for a symposium on genitourinary cancers.

Of the roughly 90,000 radical prostatectomies performed each year in the United States to treat prostate cancer, more than 70,000 are robot assisted and more than 70% of these are performed by surgeons who do fewer than 100 cases of RALP per year, he said.

The growing popularity of RALP was stoked by reports that the learning curve with regard to safety is around 25-40 cases. There is no good evidence in the literature, however, as to how long it takes to achieve expert level or optimal results for the patient, said Dr. Sooriakumaran, a visiting fellow in urology at the Weill Cornell Medical College in New York.

The researchers divided the cases based on surgeon experience, beginning at fewer than 50 cases and progressing to more than 1,000 cases performed. The median preoperative prostate-specific antigen level (range 4.7-5.4 ng/mL) and median age at surgery (range 60-61 years) remained relatively constant with increasing surgeon experience.

As surgeon experience increased, however, the number of patients with high-grade cancer, defined by a Gleason score of more than 7, decreased from 8.2% to 5.6%, and the number of patients with extracapsular invasion or pT3 disease decreased from 27% to 16%, suggesting that patients should have better results since the cases were getting more curable with time, Dr. Sooriakumaran said.

PSM rates for all patients start off at about 20% when surgeons begin learning the procedure, and it takes about 1,500-1,600 cases for margin rates to reach less than 10%. Notably, margin rates continue to fall beyond 1,600 cases, suggesting that the learning curve continues, even when PSM rates fall below 10%, he said.

When only patients with pT3 disease were evaluated, the learning curve starts to plateau after 1,000-1,500 cases, which is to be expected because these patients have prostate cancer outside the prostate, and therefore an operation to simply remove the prostate is more likely to leave cancer cells behind, Dr. Sooriakumaran said.

Operating times for the three surgeons started off at 3 hours and plateaued at around 2 hours after 750-1,000 cases, regardless of whether patients had extracapsular extension or not.

When asked how surgeons at community hospitals should gain experience if the procedure is limited to high-volume centers, Dr. Sooriakumaran said there has to be a balance and likened the situation to what is occurring with laparoscopic radical prostatectomy, which was popularized in the United States but was found to be a difficult operation to perform safely and is now done by only a few expert surgeons.

Press briefing moderator Dr. Nicholas Vogelzang, who is with US Oncology, said this scenario is already playing out in Las Vegas, where internal discussions among 40-45 urologists have delineated the use of RALP to 4 or 5 who will become experts in the procedure.

When asked if it was fair to extrapolate the experiences of three surgeons to all surgeons with regard to RALP proficiency, Dr. Sooriakumaran said the three physicians studied were all experienced, high-volume surgeons at centers in the United States and Europe.

The study will be formally presented at the symposium, which is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

Dr. Sooriakumaran disclosed no conflicts. Coauthor Dr. Ashutosh Tewari disclosed research funding from Intuitive Surgical Inc. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Use of robotic prostatectomy has mushroomed in the United States, but new data suggest it is best left in the hands of expert surgeons.

A multicenter analysis of 3,794 cases of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by three experienced surgeons found that at least 1,500-1,600 cases were needed to achieve a positive surgical margin (PSM) rate of less than 10%, which is widely accepted in the surgical literature as a sign of excellence.

"We recommend that this operation should not be done by all urologists in small community hospitals, but should be focused and concentrated into those high-volume centers of excellence where the operation can be done by surgeons doing a large number of cases, very frequently, in order that they can achieve the best possible cancer-control results for their patients," lead author Dr. Prasanna Sooriakumaran said during a Feb. 15 press briefing for a symposium on genitourinary cancers.

Of the roughly 90,000 radical prostatectomies performed each year in the United States to treat prostate cancer, more than 70,000 are robot assisted and more than 70% of these are performed by surgeons who do fewer than 100 cases of RALP per year, he said.

The growing popularity of RALP was stoked by reports that the learning curve with regard to safety is around 25-40 cases. There is no good evidence in the literature, however, as to how long it takes to achieve expert level or optimal results for the patient, said Dr. Sooriakumaran, a visiting fellow in urology at the Weill Cornell Medical College in New York.

The researchers divided the cases based on surgeon experience, beginning at fewer than 50 cases and progressing to more than 1,000 cases performed. The median preoperative prostate-specific antigen level (range 4.7-5.4 ng/mL) and median age at surgery (range 60-61 years) remained relatively constant with increasing surgeon experience.

As surgeon experience increased, however, the number of patients with high-grade cancer, defined by a Gleason score of more than 7, decreased from 8.2% to 5.6%, and the number of patients with extracapsular invasion or pT3 disease decreased from 27% to 16%, suggesting that patients should have better results since the cases were getting more curable with time, Dr. Sooriakumaran said.

PSM rates for all patients start off at about 20% when surgeons begin learning the procedure, and it takes about 1,500-1,600 cases for margin rates to reach less than 10%. Notably, margin rates continue to fall beyond 1,600 cases, suggesting that the learning curve continues, even when PSM rates fall below 10%, he said.

When only patients with pT3 disease were evaluated, the learning curve starts to plateau after 1,000-1,500 cases, which is to be expected because these patients have prostate cancer outside the prostate, and therefore an operation to simply remove the prostate is more likely to leave cancer cells behind, Dr. Sooriakumaran said.

Operating times for the three surgeons started off at 3 hours and plateaued at around 2 hours after 750-1,000 cases, regardless of whether patients had extracapsular extension or not.

When asked how surgeons at community hospitals should gain experience if the procedure is limited to high-volume centers, Dr. Sooriakumaran said there has to be a balance and likened the situation to what is occurring with laparoscopic radical prostatectomy, which was popularized in the United States but was found to be a difficult operation to perform safely and is now done by only a few expert surgeons.

Press briefing moderator Dr. Nicholas Vogelzang, who is with US Oncology, said this scenario is already playing out in Las Vegas, where internal discussions among 40-45 urologists have delineated the use of RALP to 4 or 5 who will become experts in the procedure.

When asked if it was fair to extrapolate the experiences of three surgeons to all surgeons with regard to RALP proficiency, Dr. Sooriakumaran said the three physicians studied were all experienced, high-volume surgeons at centers in the United States and Europe.

The study will be formally presented at the symposium, which is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

Dr. Sooriakumaran disclosed no conflicts. Coauthor Dr. Ashutosh Tewari disclosed research funding from Intuitive Surgical Inc. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Use of robotic prostatectomy has mushroomed in the United States, but new data suggest it is best left in the hands of expert surgeons.

A multicenter analysis of 3,794 cases of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by three experienced surgeons found that at least 1,500-1,600 cases were needed to achieve a positive surgical margin (PSM) rate of less than 10%, which is widely accepted in the surgical literature as a sign of excellence.

"We recommend that this operation should not be done by all urologists in small community hospitals, but should be focused and concentrated into those high-volume centers of excellence where the operation can be done by surgeons doing a large number of cases, very frequently, in order that they can achieve the best possible cancer-control results for their patients," lead author Dr. Prasanna Sooriakumaran said during a Feb. 15 press briefing for a symposium on genitourinary cancers.

Of the roughly 90,000 radical prostatectomies performed each year in the United States to treat prostate cancer, more than 70,000 are robot assisted and more than 70% of these are performed by surgeons who do fewer than 100 cases of RALP per year, he said.

The growing popularity of RALP was stoked by reports that the learning curve with regard to safety is around 25-40 cases. There is no good evidence in the literature, however, as to how long it takes to achieve expert level or optimal results for the patient, said Dr. Sooriakumaran, a visiting fellow in urology at the Weill Cornell Medical College in New York.

The researchers divided the cases based on surgeon experience, beginning at fewer than 50 cases and progressing to more than 1,000 cases performed. The median preoperative prostate-specific antigen level (range 4.7-5.4 ng/mL) and median age at surgery (range 60-61 years) remained relatively constant with increasing surgeon experience.

As surgeon experience increased, however, the number of patients with high-grade cancer, defined by a Gleason score of more than 7, decreased from 8.2% to 5.6%, and the number of patients with extracapsular invasion or pT3 disease decreased from 27% to 16%, suggesting that patients should have better results since the cases were getting more curable with time, Dr. Sooriakumaran said.

PSM rates for all patients start off at about 20% when surgeons begin learning the procedure, and it takes about 1,500-1,600 cases for margin rates to reach less than 10%. Notably, margin rates continue to fall beyond 1,600 cases, suggesting that the learning curve continues, even when PSM rates fall below 10%, he said.

When only patients with pT3 disease were evaluated, the learning curve starts to plateau after 1,000-1,500 cases, which is to be expected because these patients have prostate cancer outside the prostate, and therefore an operation to simply remove the prostate is more likely to leave cancer cells behind, Dr. Sooriakumaran said.

Operating times for the three surgeons started off at 3 hours and plateaued at around 2 hours after 750-1,000 cases, regardless of whether patients had extracapsular extension or not.

When asked how surgeons at community hospitals should gain experience if the procedure is limited to high-volume centers, Dr. Sooriakumaran said there has to be a balance and likened the situation to what is occurring with laparoscopic radical prostatectomy, which was popularized in the United States but was found to be a difficult operation to perform safely and is now done by only a few expert surgeons.

Press briefing moderator Dr. Nicholas Vogelzang, who is with US Oncology, said this scenario is already playing out in Las Vegas, where internal discussions among 40-45 urologists have delineated the use of RALP to 4 or 5 who will become experts in the procedure.

When asked if it was fair to extrapolate the experiences of three surgeons to all surgeons with regard to RALP proficiency, Dr. Sooriakumaran said the three physicians studied were all experienced, high-volume surgeons at centers in the United States and Europe.

The study will be formally presented at the symposium, which is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

Dr. Sooriakumaran disclosed no conflicts. Coauthor Dr. Ashutosh Tewari disclosed research funding from Intuitive Surgical Inc. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Use of robotic prostatectomy has mushroomed in the United States, but new data suggest it is best left in the hands of expert surgeons.

A multicenter analysis of 3,794 cases of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by three experienced surgeons found that at least 1,500-1,600 cases were needed to achieve a positive surgical margin (PSM) rate of less than 10%, which is widely accepted in the surgical literature as a sign of excellence.

"We recommend that this operation should not be done by all urologists in small community hospitals, but should be focused and concentrated into those high-volume centers of excellence where the operation can be done by surgeons doing a large number of cases, very frequently, in order that they can achieve the best possible cancer-control results for their patients," lead author Dr. Prasanna Sooriakumaran said during a Feb. 15 press briefing for a symposium on genitourinary cancers.

Of the roughly 90,000 radical prostatectomies performed each year in the United States to treat prostate cancer, more than 70,000 are robot assisted and more than 70% of these are performed by surgeons who do fewer than 100 cases of RALP per year, he said.

The growing popularity of RALP was stoked by reports that the learning curve with regard to safety is around 25-40 cases. There is no good evidence in the literature, however, as to how long it takes to achieve expert level or optimal results for the patient, said Dr. Sooriakumaran, a visiting fellow in urology at the Weill Cornell Medical College in New York.

The researchers divided the cases based on surgeon experience, beginning at fewer than 50 cases and progressing to more than 1,000 cases performed. The median preoperative prostate-specific antigen level (range 4.7-5.4 ng/mL) and median age at surgery (range 60-61 years) remained relatively constant with increasing surgeon experience.

As surgeon experience increased, however, the number of patients with high-grade cancer, defined by a Gleason score of more than 7, decreased from 8.2% to 5.6%, and the number of patients with extracapsular invasion or pT3 disease decreased from 27% to 16%, suggesting that patients should have better results since the cases were getting more curable with time, Dr. Sooriakumaran said.

PSM rates for all patients start off at about 20% when surgeons begin learning the procedure, and it takes about 1,500-1,600 cases for margin rates to reach less than 10%. Notably, margin rates continue to fall beyond 1,600 cases, suggesting that the learning curve continues, even when PSM rates fall below 10%, he said.

When only patients with pT3 disease were evaluated, the learning curve starts to plateau after 1,000-1,500 cases, which is to be expected because these patients have prostate cancer outside the prostate, and therefore an operation to simply remove the prostate is more likely to leave cancer cells behind, Dr. Sooriakumaran said.

Operating times for the three surgeons started off at 3 hours and plateaued at around 2 hours after 750-1,000 cases, regardless of whether patients had extracapsular extension or not.

When asked how surgeons at community hospitals should gain experience if the procedure is limited to high-volume centers, Dr. Sooriakumaran said there has to be a balance and likened the situation to what is occurring with laparoscopic radical prostatectomy, which was popularized in the United States but was found to be a difficult operation to perform safely and is now done by only a few expert surgeons.

Press briefing moderator Dr. Nicholas Vogelzang, who is with US Oncology, said this scenario is already playing out in Las Vegas, where internal discussions among 40-45 urologists have delineated the use of RALP to 4 or 5 who will become experts in the procedure.

When asked if it was fair to extrapolate the experiences of three surgeons to all surgeons with regard to RALP proficiency, Dr. Sooriakumaran said the three physicians studied were all experienced, high-volume surgeons at centers in the United States and Europe.

The study will be formally presented at the symposium, which is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

Dr. Sooriakumaran disclosed no conflicts. Coauthor Dr. Ashutosh Tewari disclosed research funding from Intuitive Surgical Inc. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Use of robotic prostatectomy has mushroomed in the United States, but new data suggest it is best left in the hands of expert surgeons.

A multicenter analysis of 3,794 cases of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by three experienced surgeons found that at least 1,500-1,600 cases were needed to achieve a positive surgical margin (PSM) rate of less than 10%, which is widely accepted in the surgical literature as a sign of excellence.

"We recommend that this operation should not be done by all urologists in small community hospitals, but should be focused and concentrated into those high-volume centers of excellence where the operation can be done by surgeons doing a large number of cases, very frequently, in order that they can achieve the best possible cancer-control results for their patients," lead author Dr. Prasanna Sooriakumaran said during a Feb. 15 press briefing for a symposium on genitourinary cancers.

Of the roughly 90,000 radical prostatectomies performed each year in the United States to treat prostate cancer, more than 70,000 are robot assisted and more than 70% of these are performed by surgeons who do fewer than 100 cases of RALP per year, he said.

The growing popularity of RALP was stoked by reports that the learning curve with regard to safety is around 25-40 cases. There is no good evidence in the literature, however, as to how long it takes to achieve expert level or optimal results for the patient, said Dr. Sooriakumaran, a visiting fellow in urology at the Weill Cornell Medical College in New York.

The researchers divided the cases based on surgeon experience, beginning at fewer than 50 cases and progressing to more than 1,000 cases performed. The median preoperative prostate-specific antigen level (range 4.7-5.4 ng/mL) and median age at surgery (range 60-61 years) remained relatively constant with increasing surgeon experience.

As surgeon experience increased, however, the number of patients with high-grade cancer, defined by a Gleason score of more than 7, decreased from 8.2% to 5.6%, and the number of patients with extracapsular invasion or pT3 disease decreased from 27% to 16%, suggesting that patients should have better results since the cases were getting more curable with time, Dr. Sooriakumaran said.

PSM rates for all patients start off at about 20% when surgeons begin learning the procedure, and it takes about 1,500-1,600 cases for margin rates to reach less than 10%. Notably, margin rates continue to fall beyond 1,600 cases, suggesting that the learning curve continues, even when PSM rates fall below 10%, he said.

When only patients with pT3 disease were evaluated, the learning curve starts to plateau after 1,000-1,500 cases, which is to be expected because these patients have prostate cancer outside the prostate, and therefore an operation to simply remove the prostate is more likely to leave cancer cells behind, Dr. Sooriakumaran said.

Operating times for the three surgeons started off at 3 hours and plateaued at around 2 hours after 750-1,000 cases, regardless of whether patients had extracapsular extension or not.

When asked how surgeons at community hospitals should gain experience if the procedure is limited to high-volume centers, Dr. Sooriakumaran said there has to be a balance and likened the situation to what is occurring with laparoscopic radical prostatectomy, which was popularized in the United States but was found to be a difficult operation to perform safely and is now done by only a few expert surgeons.

Press briefing moderator Dr. Nicholas Vogelzang, who is with US Oncology, said this scenario is already playing out in Las Vegas, where internal discussions among 40-45 urologists have delineated the use of RALP to 4 or 5 who will become experts in the procedure.

When asked if it was fair to extrapolate the experiences of three surgeons to all surgeons with regard to RALP proficiency, Dr. Sooriakumaran said the three physicians studied were all experienced, high-volume surgeons at centers in the United States and Europe.

The study will be formally presented at the symposium, which is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

Dr. Sooriakumaran disclosed no conflicts. Coauthor Dr. Ashutosh Tewari disclosed research funding from Intuitive Surgical Inc. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Use of robotic prostatectomy has mushroomed in the United States, but new data suggest it is best left in the hands of expert surgeons.

A multicenter analysis of 3,794 cases of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by three experienced surgeons found that at least 1,500-1,600 cases were needed to achieve a positive surgical margin (PSM) rate of less than 10%, which is widely accepted in the surgical literature as a sign of excellence.

"We recommend that this operation should not be done by all urologists in small community hospitals, but should be focused and concentrated into those high-volume centers of excellence where the operation can be done by surgeons doing a large number of cases, very frequently, in order that they can achieve the best possible cancer-control results for their patients," lead author Dr. Prasanna Sooriakumaran said during a Feb. 15 press briefing for a symposium on genitourinary cancers.

Of the roughly 90,000 radical prostatectomies performed each year in the United States to treat prostate cancer, more than 70,000 are robot assisted and more than 70% of these are performed by surgeons who do fewer than 100 cases of RALP per year, he said.

The growing popularity of RALP was stoked by reports that the learning curve with regard to safety is around 25-40 cases. There is no good evidence in the literature, however, as to how long it takes to achieve expert level or optimal results for the patient, said Dr. Sooriakumaran, a visiting fellow in urology at the Weill Cornell Medical College in New York.

The researchers divided the cases based on surgeon experience, beginning at fewer than 50 cases and progressing to more than 1,000 cases performed. The median preoperative prostate-specific antigen level (range 4.7-5.4 ng/mL) and median age at surgery (range 60-61 years) remained relatively constant with increasing surgeon experience.

As surgeon experience increased, however, the number of patients with high-grade cancer, defined by a Gleason score of more than 7, decreased from 8.2% to 5.6%, and the number of patients with extracapsular invasion or pT3 disease decreased from 27% to 16%, suggesting that patients should have better results since the cases were getting more curable with time, Dr. Sooriakumaran said.

PSM rates for all patients start off at about 20% when surgeons begin learning the procedure, and it takes about 1,500-1,600 cases for margin rates to reach less than 10%. Notably, margin rates continue to fall beyond 1,600 cases, suggesting that the learning curve continues, even when PSM rates fall below 10%, he said.

When only patients with pT3 disease were evaluated, the learning curve starts to plateau after 1,000-1,500 cases, which is to be expected because these patients have prostate cancer outside the prostate, and therefore an operation to simply remove the prostate is more likely to leave cancer cells behind, Dr. Sooriakumaran said.

Operating times for the three surgeons started off at 3 hours and plateaued at around 2 hours after 750-1,000 cases, regardless of whether patients had extracapsular extension or not.

When asked how surgeons at community hospitals should gain experience if the procedure is limited to high-volume centers, Dr. Sooriakumaran said there has to be a balance and likened the situation to what is occurring with laparoscopic radical prostatectomy, which was popularized in the United States but was found to be a difficult operation to perform safely and is now done by only a few expert surgeons.

Press briefing moderator Dr. Nicholas Vogelzang, who is with US Oncology, said this scenario is already playing out in Las Vegas, where internal discussions among 40-45 urologists have delineated the use of RALP to 4 or 5 who will become experts in the procedure.

When asked if it was fair to extrapolate the experiences of three surgeons to all surgeons with regard to RALP proficiency, Dr. Sooriakumaran said the three physicians studied were all experienced, high-volume surgeons at centers in the United States and Europe.

The study will be formally presented at the symposium, which is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

Dr. Sooriakumaran disclosed no conflicts. Coauthor Dr. Ashutosh Tewari disclosed research funding from Intuitive Surgical Inc. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

An initial prostate-specific antigen level of less than 3.0 ng/mL can be safely used to stratify men at low risk of developing prostate cancer, according to data from a large, European population-based study.

The overall risk of prostate cancer death in 15,758 middle-age and elderly men with a PSA level of less than 3.0 ng/mL was 0.14/1,000 life-years, which is 3.5-fold lower than the population-based risk of 0.49/1,000 life-years.

In addition, the risk of prostate cancer death within this low-risk group increased with higher baseline PSA values, senior investigator Monique J. Roobol, Ph.D., said during a Feb. 15 press briefing for the symposium on genitourinary cancers in Orlando, where the data will be formally presented.

Prostate-specific deaths increased fourfold among those with PSA levels between 1.0-1.9 ng/mL and 7.6-fold amongst those with PSAs between 2.0-2.9 ng/mL when they were compared with men who had an initial PSA below 1 ng/mL (0.17% vs. 0.35% vs. 04%, respectively). The median time from diagnosis to death was 8.3 years among men in the lowest PSA group.

The results justify using the PSA threshold of 3.0 ng/mL or more as an indication for biopsy and contribute to risk stratification and management of men in PSA-based screening programs, she said. For example, the favorable outcome in men with initial PSA values of less than 1.0 ng/mL supports prolonging the screening interval for up to 8 years.

Press briefing moderator Nicholas Vogelzang of US Oncology said men with a PSA value less than 1 ng/mL and probably those with a PSA less than 2 ng/mL could be considered for substantially longer intervals of PSA screening.

"I believe this study gives us some confidence that annual PSA screening is going to soon become a thing of the past," Dr. Vogelzang said.

The study, which is part of the larger European Randomized Study of Screening for Prostate Cancer, screened 19,950 men between ages 55 and 74 years and recommended biopsies only for those with PSA levels of 3.0 ng/mL or more. Cancers were identified at rescreens conducted every 4 years or clinically during screening intervals. The median follow-up was 11 years.

Of the 19,950 men screened, 15,758 (almost 80%) had a PSA level less than 3.0 ng/mL, observed Dr. Roobol, an epidemiologist in the department of urology at Erasmus University Medical Center in Rotterdam, the Netherlands. In all, 915 of the 15,758 men (5.5%) were diagnosed with prostate cancer, and 23 died (0.14%) from the disease.

Men with a PSA level of less than 1.0 ng/mL were 2.7-fold less likely than were those with a PSA of 1.0-1.9 ng/mL to develop aggressive prostate cancer, and 6.2-fold less likely to do so than were their counterparts with a PSA of 2.0-2.9 ng/mL.

When asked whether patient age at the time of the initial PSA affects the findings, Dr. Roobol acknowledged that the age range in the study was not very broad but said that the PSA range is much more predictive than age.

Fellow presenter Dr. Neil Fleshner, head of urology at the University Health Network in Toronto pointed out that growing evidence suggests that the PSA test is better in younger men than in older patients where there is confounding with benign prosthetic hyperplasia. He also noted that the entire screening process will be refined with the emergence of new biomarkers in the coming decade.

Dr. Roobol responded that the PSA is very valuable in identifying men at low risk of prostate cancer and can remove almost half of men aged 55 to 74 years from the need for continued testing. Once that’s done, clinicians can use better biomarkers to increase detection in the remaining half.

"I think PSA is a very good first step," she said.

Dr. Meelan Bul, lead author, who is also from Erasmus University Medical Center, will present the study at the symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Dr. Roobol disclosed a consultant/advisory role with Bechman Coulter, GlaxoSmithKline and Gen-Probe. Coauthor Dr. Fritz H. Schroder also disclosed consulting/advising for GSK. Dr. Vogelzang disclosed relationships with multiple pharmaceutical companies.

An initial prostate-specific antigen level of less than 3.0 ng/mL can be safely used to stratify men at low risk of developing prostate cancer, according to data from a large, European population-based study.

The overall risk of prostate cancer death in 15,758 middle-age and elderly men with a PSA level of less than 3.0 ng/mL was 0.14/1,000 life-years, which is 3.5-fold lower than the population-based risk of 0.49/1,000 life-years.

In addition, the risk of prostate cancer death within this low-risk group increased with higher baseline PSA values, senior investigator Monique J. Roobol, Ph.D., said during a Feb. 15 press briefing for the symposium on genitourinary cancers in Orlando, where the data will be formally presented.

Prostate-specific deaths increased fourfold among those with PSA levels between 1.0-1.9 ng/mL and 7.6-fold amongst those with PSAs between 2.0-2.9 ng/mL when they were compared with men who had an initial PSA below 1 ng/mL (0.17% vs. 0.35% vs. 04%, respectively). The median time from diagnosis to death was 8.3 years among men in the lowest PSA group.

The results justify using the PSA threshold of 3.0 ng/mL or more as an indication for biopsy and contribute to risk stratification and management of men in PSA-based screening programs, she said. For example, the favorable outcome in men with initial PSA values of less than 1.0 ng/mL supports prolonging the screening interval for up to 8 years.

Press briefing moderator Nicholas Vogelzang of US Oncology said men with a PSA value less than 1 ng/mL and probably those with a PSA less than 2 ng/mL could be considered for substantially longer intervals of PSA screening.

"I believe this study gives us some confidence that annual PSA screening is going to soon become a thing of the past," Dr. Vogelzang said.

The study, which is part of the larger European Randomized Study of Screening for Prostate Cancer, screened 19,950 men between ages 55 and 74 years and recommended biopsies only for those with PSA levels of 3.0 ng/mL or more. Cancers were identified at rescreens conducted every 4 years or clinically during screening intervals. The median follow-up was 11 years.

Of the 19,950 men screened, 15,758 (almost 80%) had a PSA level less than 3.0 ng/mL, observed Dr. Roobol, an epidemiologist in the department of urology at Erasmus University Medical Center in Rotterdam, the Netherlands. In all, 915 of the 15,758 men (5.5%) were diagnosed with prostate cancer, and 23 died (0.14%) from the disease.

Men with a PSA level of less than 1.0 ng/mL were 2.7-fold less likely than were those with a PSA of 1.0-1.9 ng/mL to develop aggressive prostate cancer, and 6.2-fold less likely to do so than were their counterparts with a PSA of 2.0-2.9 ng/mL.

When asked whether patient age at the time of the initial PSA affects the findings, Dr. Roobol acknowledged that the age range in the study was not very broad but said that the PSA range is much more predictive than age.

Fellow presenter Dr. Neil Fleshner, head of urology at the University Health Network in Toronto pointed out that growing evidence suggests that the PSA test is better in younger men than in older patients where there is confounding with benign prosthetic hyperplasia. He also noted that the entire screening process will be refined with the emergence of new biomarkers in the coming decade.

Dr. Roobol responded that the PSA is very valuable in identifying men at low risk of prostate cancer and can remove almost half of men aged 55 to 74 years from the need for continued testing. Once that’s done, clinicians can use better biomarkers to increase detection in the remaining half.

"I think PSA is a very good first step," she said.

Dr. Meelan Bul, lead author, who is also from Erasmus University Medical Center, will present the study at the symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Dr. Roobol disclosed a consultant/advisory role with Bechman Coulter, GlaxoSmithKline and Gen-Probe. Coauthor Dr. Fritz H. Schroder also disclosed consulting/advising for GSK. Dr. Vogelzang disclosed relationships with multiple pharmaceutical companies.

An initial prostate-specific antigen level of less than 3.0 ng/mL can be safely used to stratify men at low risk of developing prostate cancer, according to data from a large, European population-based study.

The overall risk of prostate cancer death in 15,758 middle-age and elderly men with a PSA level of less than 3.0 ng/mL was 0.14/1,000 life-years, which is 3.5-fold lower than the population-based risk of 0.49/1,000 life-years.

In addition, the risk of prostate cancer death within this low-risk group increased with higher baseline PSA values, senior investigator Monique J. Roobol, Ph.D., said during a Feb. 15 press briefing for the symposium on genitourinary cancers in Orlando, where the data will be formally presented.

Prostate-specific deaths increased fourfold among those with PSA levels between 1.0-1.9 ng/mL and 7.6-fold amongst those with PSAs between 2.0-2.9 ng/mL when they were compared with men who had an initial PSA below 1 ng/mL (0.17% vs. 0.35% vs. 04%, respectively). The median time from diagnosis to death was 8.3 years among men in the lowest PSA group.

The results justify using the PSA threshold of 3.0 ng/mL or more as an indication for biopsy and contribute to risk stratification and management of men in PSA-based screening programs, she said. For example, the favorable outcome in men with initial PSA values of less than 1.0 ng/mL supports prolonging the screening interval for up to 8 years.

Press briefing moderator Nicholas Vogelzang of US Oncology said men with a PSA value less than 1 ng/mL and probably those with a PSA less than 2 ng/mL could be considered for substantially longer intervals of PSA screening.

"I believe this study gives us some confidence that annual PSA screening is going to soon become a thing of the past," Dr. Vogelzang said.

The study, which is part of the larger European Randomized Study of Screening for Prostate Cancer, screened 19,950 men between ages 55 and 74 years and recommended biopsies only for those with PSA levels of 3.0 ng/mL or more. Cancers were identified at rescreens conducted every 4 years or clinically during screening intervals. The median follow-up was 11 years.

Of the 19,950 men screened, 15,758 (almost 80%) had a PSA level less than 3.0 ng/mL, observed Dr. Roobol, an epidemiologist in the department of urology at Erasmus University Medical Center in Rotterdam, the Netherlands. In all, 915 of the 15,758 men (5.5%) were diagnosed with prostate cancer, and 23 died (0.14%) from the disease.

Men with a PSA level of less than 1.0 ng/mL were 2.7-fold less likely than were those with a PSA of 1.0-1.9 ng/mL to develop aggressive prostate cancer, and 6.2-fold less likely to do so than were their counterparts with a PSA of 2.0-2.9 ng/mL.

When asked whether patient age at the time of the initial PSA affects the findings, Dr. Roobol acknowledged that the age range in the study was not very broad but said that the PSA range is much more predictive than age.

Fellow presenter Dr. Neil Fleshner, head of urology at the University Health Network in Toronto pointed out that growing evidence suggests that the PSA test is better in younger men than in older patients where there is confounding with benign prosthetic hyperplasia. He also noted that the entire screening process will be refined with the emergence of new biomarkers in the coming decade.

Dr. Roobol responded that the PSA is very valuable in identifying men at low risk of prostate cancer and can remove almost half of men aged 55 to 74 years from the need for continued testing. Once that’s done, clinicians can use better biomarkers to increase detection in the remaining half.

"I think PSA is a very good first step," she said.

Dr. Meelan Bul, lead author, who is also from Erasmus University Medical Center, will present the study at the symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Dr. Roobol disclosed a consultant/advisory role with Bechman Coulter, GlaxoSmithKline and Gen-Probe. Coauthor Dr. Fritz H. Schroder also disclosed consulting/advising for GSK. Dr. Vogelzang disclosed relationships with multiple pharmaceutical companies.

An initial prostate-specific antigen level of less than 3.0 ng/mL can be safely used to stratify men at low risk of developing prostate cancer, according to data from a large, European population-based study.

The overall risk of prostate cancer death in 15,758 middle-age and elderly men with a PSA level of less than 3.0 ng/mL was 0.14/1,000 life-years, which is 3.5-fold lower than the population-based risk of 0.49/1,000 life-years.

In addition, the risk of prostate cancer death within this low-risk group increased with higher baseline PSA values, senior investigator Monique J. Roobol, Ph.D., said during a Feb. 15 press briefing for the symposium on genitourinary cancers in Orlando, where the data will be formally presented.

Prostate-specific deaths increased fourfold among those with PSA levels between 1.0-1.9 ng/mL and 7.6-fold amongst those with PSAs between 2.0-2.9 ng/mL when they were compared with men who had an initial PSA below 1 ng/mL (0.17% vs. 0.35% vs. 04%, respectively). The median time from diagnosis to death was 8.3 years among men in the lowest PSA group.

The results justify using the PSA threshold of 3.0 ng/mL or more as an indication for biopsy and contribute to risk stratification and management of men in PSA-based screening programs, she said. For example, the favorable outcome in men with initial PSA values of less than 1.0 ng/mL supports prolonging the screening interval for up to 8 years.

Press briefing moderator Nicholas Vogelzang of US Oncology said men with a PSA value less than 1 ng/mL and probably those with a PSA less than 2 ng/mL could be considered for substantially longer intervals of PSA screening.

"I believe this study gives us some confidence that annual PSA screening is going to soon become a thing of the past," Dr. Vogelzang said.

The study, which is part of the larger European Randomized Study of Screening for Prostate Cancer, screened 19,950 men between ages 55 and 74 years and recommended biopsies only for those with PSA levels of 3.0 ng/mL or more. Cancers were identified at rescreens conducted every 4 years or clinically during screening intervals. The median follow-up was 11 years.

Of the 19,950 men screened, 15,758 (almost 80%) had a PSA level less than 3.0 ng/mL, observed Dr. Roobol, an epidemiologist in the department of urology at Erasmus University Medical Center in Rotterdam, the Netherlands. In all, 915 of the 15,758 men (5.5%) were diagnosed with prostate cancer, and 23 died (0.14%) from the disease.

Men with a PSA level of less than 1.0 ng/mL were 2.7-fold less likely than were those with a PSA of 1.0-1.9 ng/mL to develop aggressive prostate cancer, and 6.2-fold less likely to do so than were their counterparts with a PSA of 2.0-2.9 ng/mL.

When asked whether patient age at the time of the initial PSA affects the findings, Dr. Roobol acknowledged that the age range in the study was not very broad but said that the PSA range is much more predictive than age.

Fellow presenter Dr. Neil Fleshner, head of urology at the University Health Network in Toronto pointed out that growing evidence suggests that the PSA test is better in younger men than in older patients where there is confounding with benign prosthetic hyperplasia. He also noted that the entire screening process will be refined with the emergence of new biomarkers in the coming decade.

Dr. Roobol responded that the PSA is very valuable in identifying men at low risk of prostate cancer and can remove almost half of men aged 55 to 74 years from the need for continued testing. Once that’s done, clinicians can use better biomarkers to increase detection in the remaining half.

"I think PSA is a very good first step," she said.

Dr. Meelan Bul, lead author, who is also from Erasmus University Medical Center, will present the study at the symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Dr. Roobol disclosed a consultant/advisory role with Bechman Coulter, GlaxoSmithKline and Gen-Probe. Coauthor Dr. Fritz H. Schroder also disclosed consulting/advising for GSK. Dr. Vogelzang disclosed relationships with multiple pharmaceutical companies.

An initial prostate-specific antigen level of less than 3.0 ng/mL can be safely used to stratify men at low risk of developing prostate cancer, according to data from a large, European population-based study.

The overall risk of prostate cancer death in 15,758 middle-age and elderly men with a PSA level of less than 3.0 ng/mL was 0.14/1,000 life-years, which is 3.5-fold lower than the population-based risk of 0.49/1,000 life-years.

In addition, the risk of prostate cancer death within this low-risk group increased with higher baseline PSA values, senior investigator Monique J. Roobol, Ph.D., said during a Feb. 15 press briefing for the symposium on genitourinary cancers in Orlando, where the data will be formally presented.

Prostate-specific deaths increased fourfold among those with PSA levels between 1.0-1.9 ng/mL and 7.6-fold amongst those with PSAs between 2.0-2.9 ng/mL when they were compared with men who had an initial PSA below 1 ng/mL (0.17% vs. 0.35% vs. 04%, respectively). The median time from diagnosis to death was 8.3 years among men in the lowest PSA group.

The results justify using the PSA threshold of 3.0 ng/mL or more as an indication for biopsy and contribute to risk stratification and management of men in PSA-based screening programs, she said. For example, the favorable outcome in men with initial PSA values of less than 1.0 ng/mL supports prolonging the screening interval for up to 8 years.

Press briefing moderator Nicholas Vogelzang of US Oncology said men with a PSA value less than 1 ng/mL and probably those with a PSA less than 2 ng/mL could be considered for substantially longer intervals of PSA screening.

"I believe this study gives us some confidence that annual PSA screening is going to soon become a thing of the past," Dr. Vogelzang said.

The study, which is part of the larger European Randomized Study of Screening for Prostate Cancer, screened 19,950 men between ages 55 and 74 years and recommended biopsies only for those with PSA levels of 3.0 ng/mL or more. Cancers were identified at rescreens conducted every 4 years or clinically during screening intervals. The median follow-up was 11 years.

Of the 19,950 men screened, 15,758 (almost 80%) had a PSA level less than 3.0 ng/mL, observed Dr. Roobol, an epidemiologist in the department of urology at Erasmus University Medical Center in Rotterdam, the Netherlands. In all, 915 of the 15,758 men (5.5%) were diagnosed with prostate cancer, and 23 died (0.14%) from the disease.

Men with a PSA level of less than 1.0 ng/mL were 2.7-fold less likely than were those with a PSA of 1.0-1.9 ng/mL to develop aggressive prostate cancer, and 6.2-fold less likely to do so than were their counterparts with a PSA of 2.0-2.9 ng/mL.

When asked whether patient age at the time of the initial PSA affects the findings, Dr. Roobol acknowledged that the age range in the study was not very broad but said that the PSA range is much more predictive than age.

Fellow presenter Dr. Neil Fleshner, head of urology at the University Health Network in Toronto pointed out that growing evidence suggests that the PSA test is better in younger men than in older patients where there is confounding with benign prosthetic hyperplasia. He also noted that the entire screening process will be refined with the emergence of new biomarkers in the coming decade.

Dr. Roobol responded that the PSA is very valuable in identifying men at low risk of prostate cancer and can remove almost half of men aged 55 to 74 years from the need for continued testing. Once that’s done, clinicians can use better biomarkers to increase detection in the remaining half.

"I think PSA is a very good first step," she said.

Dr. Meelan Bul, lead author, who is also from Erasmus University Medical Center, will present the study at the symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Dr. Roobol disclosed a consultant/advisory role with Bechman Coulter, GlaxoSmithKline and Gen-Probe. Coauthor Dr. Fritz H. Schroder also disclosed consulting/advising for GSK. Dr. Vogelzang disclosed relationships with multiple pharmaceutical companies.

An initial prostate-specific antigen level of less than 3.0 ng/mL can be safely used to stratify men at low risk of developing prostate cancer, according to data from a large, European population-based study.

The overall risk of prostate cancer death in 15,758 middle-age and elderly men with a PSA level of less than 3.0 ng/mL was 0.14/1,000 life-years, which is 3.5-fold lower than the population-based risk of 0.49/1,000 life-years.

In addition, the risk of prostate cancer death within this low-risk group increased with higher baseline PSA values, senior investigator Monique J. Roobol, Ph.D., said during a Feb. 15 press briefing for the symposium on genitourinary cancers in Orlando, where the data will be formally presented.

Prostate-specific deaths increased fourfold among those with PSA levels between 1.0-1.9 ng/mL and 7.6-fold amongst those with PSAs between 2.0-2.9 ng/mL when they were compared with men who had an initial PSA below 1 ng/mL (0.17% vs. 0.35% vs. 04%, respectively). The median time from diagnosis to death was 8.3 years among men in the lowest PSA group.

The results justify using the PSA threshold of 3.0 ng/mL or more as an indication for biopsy and contribute to risk stratification and management of men in PSA-based screening programs, she said. For example, the favorable outcome in men with initial PSA values of less than 1.0 ng/mL supports prolonging the screening interval for up to 8 years.

Press briefing moderator Nicholas Vogelzang of US Oncology said men with a PSA value less than 1 ng/mL and probably those with a PSA less than 2 ng/mL could be considered for substantially longer intervals of PSA screening.

"I believe this study gives us some confidence that annual PSA screening is going to soon become a thing of the past," Dr. Vogelzang said.

The study, which is part of the larger European Randomized Study of Screening for Prostate Cancer, screened 19,950 men between ages 55 and 74 years and recommended biopsies only for those with PSA levels of 3.0 ng/mL or more. Cancers were identified at rescreens conducted every 4 years or clinically during screening intervals. The median follow-up was 11 years.

Of the 19,950 men screened, 15,758 (almost 80%) had a PSA level less than 3.0 ng/mL, observed Dr. Roobol, an epidemiologist in the department of urology at Erasmus University Medical Center in Rotterdam, the Netherlands. In all, 915 of the 15,758 men (5.5%) were diagnosed with prostate cancer, and 23 died (0.14%) from the disease.

Men with a PSA level of less than 1.0 ng/mL were 2.7-fold less likely than were those with a PSA of 1.0-1.9 ng/mL to develop aggressive prostate cancer, and 6.2-fold less likely to do so than were their counterparts with a PSA of 2.0-2.9 ng/mL.

When asked whether patient age at the time of the initial PSA affects the findings, Dr. Roobol acknowledged that the age range in the study was not very broad but said that the PSA range is much more predictive than age.

Fellow presenter Dr. Neil Fleshner, head of urology at the University Health Network in Toronto pointed out that growing evidence suggests that the PSA test is better in younger men than in older patients where there is confounding with benign prosthetic hyperplasia. He also noted that the entire screening process will be refined with the emergence of new biomarkers in the coming decade.

Dr. Roobol responded that the PSA is very valuable in identifying men at low risk of prostate cancer and can remove almost half of men aged 55 to 74 years from the need for continued testing. Once that’s done, clinicians can use better biomarkers to increase detection in the remaining half.

"I think PSA is a very good first step," she said.

Dr. Meelan Bul, lead author, who is also from Erasmus University Medical Center, will present the study at the symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Dr. Roobol disclosed a consultant/advisory role with Bechman Coulter, GlaxoSmithKline and Gen-Probe. Coauthor Dr. Fritz H. Schroder also disclosed consulting/advising for GSK. Dr. Vogelzang disclosed relationships with multiple pharmaceutical companies.