Nephrology

DENVER — Use of nonaspirin NSAIDs more than twice per week was associated with a 45% reduction in the risk of developing bladder cancer in a pooled analysis of three prospective cohort studies totaling more than half a million subjects.

The strongest inverse association was seen with daily use, which conferred a 50% reduction in bladder cancer risk among nonsmokers after adjustment for sex, smoking status, body mass index, race, and aspirin use, Sarah Daugherty, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

The use of aspirin proved to be unrelated to bladder cancer risk in this pooled analysis, added Dr. Daugherty of the National Cancer Institute.

The three prospective cohort studies incorporated in this analysis were the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the NIH-AARP Diet and Health Study, and the U.S. Radiologic Technologist Health Study.

Together the three cohorts totaled 508,807 adults, of whom 2,553 developed bladder cancer during a median of 7 years of follow-up.

DENVER — Use of nonaspirin NSAIDs more than twice per week was associated with a 45% reduction in the risk of developing bladder cancer in a pooled analysis of three prospective cohort studies totaling more than half a million subjects.

The strongest inverse association was seen with daily use, which conferred a 50% reduction in bladder cancer risk among nonsmokers after adjustment for sex, smoking status, body mass index, race, and aspirin use, Sarah Daugherty, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

The use of aspirin proved to be unrelated to bladder cancer risk in this pooled analysis, added Dr. Daugherty of the National Cancer Institute.

The three prospective cohort studies incorporated in this analysis were the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the NIH-AARP Diet and Health Study, and the U.S. Radiologic Technologist Health Study.

Together the three cohorts totaled 508,807 adults, of whom 2,553 developed bladder cancer during a median of 7 years of follow-up.

DENVER — Use of nonaspirin NSAIDs more than twice per week was associated with a 45% reduction in the risk of developing bladder cancer in a pooled analysis of three prospective cohort studies totaling more than half a million subjects.

The strongest inverse association was seen with daily use, which conferred a 50% reduction in bladder cancer risk among nonsmokers after adjustment for sex, smoking status, body mass index, race, and aspirin use, Sarah Daugherty, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

The use of aspirin proved to be unrelated to bladder cancer risk in this pooled analysis, added Dr. Daugherty of the National Cancer Institute.

The three prospective cohort studies incorporated in this analysis were the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the NIH-AARP Diet and Health Study, and the U.S. Radiologic Technologist Health Study.

Together the three cohorts totaled 508,807 adults, of whom 2,553 developed bladder cancer during a median of 7 years of follow-up.

DENVER — Prolonged oral glucocorticoid use may be associated with an increased risk of bladder cancer, findings from a population-based case-control study suggest.

The working hypothesis for the observed link is that the immunosuppression induced by prolonged use of oral glucocorticoids results in diminished immunosurveillance against growing tumors, Dr. Karl Dietrich explained at the annual meeting of the American Association for Cancer Research.

He reported on 786 patients with bladder cancer and 1,083 controls who underwent structured personal interviews regarding their history of medication use as well as the prevalence of standard risk factors for bladder cancer. Oral glucocorticoids had been used for 1 month or more by 61 cancer patients and 51 controls.

After adjusting for age, gender, and smoking, current prolonged users of oral glucocorticoids had a 2.2-fold greater risk of bladder cancer than individuals who had not taken the medication for at least 1 month, said Dr. Dietrich of Dartmouth University, Hanover, N.H.

The risk of bladder cancer was greatest in individuals who used oral glucocorticoids for a total of 5 years or more. They had an adjusted 3.4-fold increased risk of the malignancy, compared with nonusers.

Prednisone accounted for close to 90% of all oral glucocorticoid use in the study. Dose information was provide by 63 subjects. Those who took at least 50 mg/day had a 4.1-fold increased risk of bladder cancer; however, patients who took less than 49 mg/day didn't have a significantly greater rate of bladder cancer than nonusers.

Dr. Dietrich noted in an interview that the bladder cancer study is a sequel to earlier groundbreaking work led by Margaret R. Karagas, Ph.D., also of Dartmouth. Her similar population-based case-control study demonstrated that use of glucocorticoids for 1 month or longer was associated with an adjusted 2.3-fold increased risk of cutaneous squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (Br. J. Cancer 2001;85:683-6).

Dr. Karagas was subsequently a coinvestigator in a confirmatory Danish population-based cohort study which concluded that patients with 15 or more filled prescriptions for oral glucocorticoids had a 2.5-fold increased risk of squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (J. Natl. Cancer Inst. 2004;96:709-11).

The bladder cancer study results suggest that the same glucocorticoid-induced reduced immunosurveillance that allows growth and development of skin cancers also confers an increased risk of internal malignancies, Dr. Dietrich said.

The study was partly funded by the National Cancer Institute and National Institute of Environmental Health Sciences.

DENVER — Prolonged oral glucocorticoid use may be associated with an increased risk of bladder cancer, findings from a population-based case-control study suggest.

The working hypothesis for the observed link is that the immunosuppression induced by prolonged use of oral glucocorticoids results in diminished immunosurveillance against growing tumors, Dr. Karl Dietrich explained at the annual meeting of the American Association for Cancer Research.

He reported on 786 patients with bladder cancer and 1,083 controls who underwent structured personal interviews regarding their history of medication use as well as the prevalence of standard risk factors for bladder cancer. Oral glucocorticoids had been used for 1 month or more by 61 cancer patients and 51 controls.

After adjusting for age, gender, and smoking, current prolonged users of oral glucocorticoids had a 2.2-fold greater risk of bladder cancer than individuals who had not taken the medication for at least 1 month, said Dr. Dietrich of Dartmouth University, Hanover, N.H.

The risk of bladder cancer was greatest in individuals who used oral glucocorticoids for a total of 5 years or more. They had an adjusted 3.4-fold increased risk of the malignancy, compared with nonusers.

Prednisone accounted for close to 90% of all oral glucocorticoid use in the study. Dose information was provide by 63 subjects. Those who took at least 50 mg/day had a 4.1-fold increased risk of bladder cancer; however, patients who took less than 49 mg/day didn't have a significantly greater rate of bladder cancer than nonusers.

Dr. Dietrich noted in an interview that the bladder cancer study is a sequel to earlier groundbreaking work led by Margaret R. Karagas, Ph.D., also of Dartmouth. Her similar population-based case-control study demonstrated that use of glucocorticoids for 1 month or longer was associated with an adjusted 2.3-fold increased risk of cutaneous squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (Br. J. Cancer 2001;85:683-6).

Dr. Karagas was subsequently a coinvestigator in a confirmatory Danish population-based cohort study which concluded that patients with 15 or more filled prescriptions for oral glucocorticoids had a 2.5-fold increased risk of squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (J. Natl. Cancer Inst. 2004;96:709-11).

The bladder cancer study results suggest that the same glucocorticoid-induced reduced immunosurveillance that allows growth and development of skin cancers also confers an increased risk of internal malignancies, Dr. Dietrich said.

The study was partly funded by the National Cancer Institute and National Institute of Environmental Health Sciences.

DENVER — Prolonged oral glucocorticoid use may be associated with an increased risk of bladder cancer, findings from a population-based case-control study suggest.

The working hypothesis for the observed link is that the immunosuppression induced by prolonged use of oral glucocorticoids results in diminished immunosurveillance against growing tumors, Dr. Karl Dietrich explained at the annual meeting of the American Association for Cancer Research.

He reported on 786 patients with bladder cancer and 1,083 controls who underwent structured personal interviews regarding their history of medication use as well as the prevalence of standard risk factors for bladder cancer. Oral glucocorticoids had been used for 1 month or more by 61 cancer patients and 51 controls.

After adjusting for age, gender, and smoking, current prolonged users of oral glucocorticoids had a 2.2-fold greater risk of bladder cancer than individuals who had not taken the medication for at least 1 month, said Dr. Dietrich of Dartmouth University, Hanover, N.H.

The risk of bladder cancer was greatest in individuals who used oral glucocorticoids for a total of 5 years or more. They had an adjusted 3.4-fold increased risk of the malignancy, compared with nonusers.

Prednisone accounted for close to 90% of all oral glucocorticoid use in the study. Dose information was provide by 63 subjects. Those who took at least 50 mg/day had a 4.1-fold increased risk of bladder cancer; however, patients who took less than 49 mg/day didn't have a significantly greater rate of bladder cancer than nonusers.

Dr. Dietrich noted in an interview that the bladder cancer study is a sequel to earlier groundbreaking work led by Margaret R. Karagas, Ph.D., also of Dartmouth. Her similar population-based case-control study demonstrated that use of glucocorticoids for 1 month or longer was associated with an adjusted 2.3-fold increased risk of cutaneous squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (Br. J. Cancer 2001;85:683-6).

Dr. Karagas was subsequently a coinvestigator in a confirmatory Danish population-based cohort study which concluded that patients with 15 or more filled prescriptions for oral glucocorticoids had a 2.5-fold increased risk of squamous cell carcinoma and a 1.5-fold increased risk of basal cell carcinoma (J. Natl. Cancer Inst. 2004;96:709-11).

The bladder cancer study results suggest that the same glucocorticoid-induced reduced immunosurveillance that allows growth and development of skin cancers also confers an increased risk of internal malignancies, Dr. Dietrich said.

The study was partly funded by the National Cancer Institute and National Institute of Environmental Health Sciences.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40–79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjusting for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

A randomized, controlled trial is now needed, Dr. Hamilton said. He and his colleagues plan to analyze additional data on this group of patients to look at cholesterol levels, duration of statin use, and dose and statin use after surgery.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

Statins Improve Male Urologic Health

New studies add weight to the possibility of a connection between statins and various aspects of male urologic health.

In addition to studies showing decreased risk of prostate cancer in men taking statins, a Mayo Clinic study using data on 2,447 men aged 40–79 from the Rochester Epidemiology Project revealed an inverse relationship between erectile dysfunction and statin use. A total of 729 (30%) of the men reported taking statin medications. Starting with the sixth year of follow-up and biennially thereafter, patients were asked questions from the Brief Male Sexual Function Inventory. The inverse association was strongest in the oldest men in the study, according to Dr. Ajay Nehra, of the urology department at Mayo. The association was strengthened after adjustment for age at baseline, diabetes, hypertension, coronary heart disease, smoking status, and weight.

In another Mayo Clinic study of the same cohort, statins were associated with a decreased risk of lower urinary tract symptoms and benign prostatic enlargement, as well as a decreased peak urinary flow rate. The combined use of statins and NSAIDs lowered these risks further, Dr. Jennifer L. St. Sauver, also of the Mayo Clinic, and her colleagues reported in a poster.

Dr. St. Sauver had no financial disclosures related to the study. Dr. Nehra is a consultant for Pfizer, GlaxoSmithKline, and Sanofi-Aventis.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40–79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjusting for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

A randomized, controlled trial is now needed, Dr. Hamilton said. He and his colleagues plan to analyze additional data on this group of patients to look at cholesterol levels, duration of statin use, and dose and statin use after surgery.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

Statins Improve Male Urologic Health

New studies add weight to the possibility of a connection between statins and various aspects of male urologic health.

In addition to studies showing decreased risk of prostate cancer in men taking statins, a Mayo Clinic study using data on 2,447 men aged 40–79 from the Rochester Epidemiology Project revealed an inverse relationship between erectile dysfunction and statin use. A total of 729 (30%) of the men reported taking statin medications. Starting with the sixth year of follow-up and biennially thereafter, patients were asked questions from the Brief Male Sexual Function Inventory. The inverse association was strongest in the oldest men in the study, according to Dr. Ajay Nehra, of the urology department at Mayo. The association was strengthened after adjustment for age at baseline, diabetes, hypertension, coronary heart disease, smoking status, and weight.

In another Mayo Clinic study of the same cohort, statins were associated with a decreased risk of lower urinary tract symptoms and benign prostatic enlargement, as well as a decreased peak urinary flow rate. The combined use of statins and NSAIDs lowered these risks further, Dr. Jennifer L. St. Sauver, also of the Mayo Clinic, and her colleagues reported in a poster.

Dr. St. Sauver had no financial disclosures related to the study. Dr. Nehra is a consultant for Pfizer, GlaxoSmithKline, and Sanofi-Aventis.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40–79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjusting for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

A randomized, controlled trial is now needed, Dr. Hamilton said. He and his colleagues plan to analyze additional data on this group of patients to look at cholesterol levels, duration of statin use, and dose and statin use after surgery.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

Statins Improve Male Urologic Health

New studies add weight to the possibility of a connection between statins and various aspects of male urologic health.

In addition to studies showing decreased risk of prostate cancer in men taking statins, a Mayo Clinic study using data on 2,447 men aged 40–79 from the Rochester Epidemiology Project revealed an inverse relationship between erectile dysfunction and statin use. A total of 729 (30%) of the men reported taking statin medications. Starting with the sixth year of follow-up and biennially thereafter, patients were asked questions from the Brief Male Sexual Function Inventory. The inverse association was strongest in the oldest men in the study, according to Dr. Ajay Nehra, of the urology department at Mayo. The association was strengthened after adjustment for age at baseline, diabetes, hypertension, coronary heart disease, smoking status, and weight.

In another Mayo Clinic study of the same cohort, statins were associated with a decreased risk of lower urinary tract symptoms and benign prostatic enlargement, as well as a decreased peak urinary flow rate. The combined use of statins and NSAIDs lowered these risks further, Dr. Jennifer L. St. Sauver, also of the Mayo Clinic, and her colleagues reported in a poster.

Dr. St. Sauver had no financial disclosures related to the study. Dr. Nehra is a consultant for Pfizer, GlaxoSmithKline, and Sanofi-Aventis.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

DENVER — A man's absolute risk of developing prostate cancer over a 20-year period can be estimated by determining the number of risk alleles present on a simple genetic test and then taking family history into account.

It's known that an average 55-year-old man has a 13% risk of developing prostate cancer during the next 20 years. But by adding up how many of 14 known risk alleles the man has on single-nucleotide polymorphisms, his risk can be defined far more accurately.

For example, a man with seven or fewer of the risk alleles plus a negative family history has only an 8% absolute risk of being diagnosed with prostate cancer at age 55–74. The risk shoots up to 52% in a man with 14 risk alleles and a positive family history, Dr. Jianfeng Xu explained at the annual meeting of the American Association for Cancer Research.

This latter highest-risk group includes 8% of the general adult male population, noted Dr. Xu, professor of epidemiology and cancer biology at Wake Forest University, Winston-Salem, N.C.

He and his coworkers developed their risk model by studying 2,893 men with prostate cancer and 1,781 without the disease who had previously participated in a Swedish case-control study. The investigators found that while each of the risk alleles contributed a relatively small increase in risk, the risk was additive.

Moreover, the risk was further enhanced in a predictable way by the presence of a positive family history. For example, the 20-year absolute risk in a man with seven or fewer risk alleles and a negative family history is a mere 8%, but it rises to 17% with a positive family history. At the other extreme, a man possessing 14 risk alleles but a negative family history has a 24% risk of being diagnosed with prostate cancer at age 55–74; having a positive family history increases that risk to 52%.

The investigators subsequently confirmed their findings in a retrospective analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Dr. Xu conceded that the model has a major limitation: It doesn't distinguish between indolent and aggressive forms of prostate cancer. Thus, using the model would likely result in overtreatment of many men identified as being at high absolute risk, but who have indolent disease. The investigators have identified several single-nucleotide polymorphisms that appear to distinguish between nonaggressive and lethal prostate cancer, however, and are now doing confirmatory testing.

Even if these new candidate risk alleles don't pan out, Dr. Xu said he sees the current version of the absolute risk assessment as having potential utility. For example, men identified as high risk might elect to embark on a program of risk reduction through diet and lifestyle modification along with chemoprevention using finasteride, which has been shown to reduce prostate cancer risk by about 25%.

For men at average risk, finasteride could reduce their 20-year absolute risk from 13% to 10% at the cost of roughly $1.6 million per life-year gained. But for men at very high risk, the absolute risk reduction conferred by finasteride would be substantially greater and cost per life-year gained would be lower, Dr. Xu said.

He and his colleagues plan to launch a prospective prostate cancer prevention trial using risk alleles and family history to guide chemoprevention with finasteride.

“More replication is definitely needed before this is ready to go to the clinic, but this is taking us one step closer to the personalized medicine approach,” observed Dr. Peter G. Shields of the department of medicine at Georgetown University Medical Center and deputy director of the Lombardi Comprehensive Cancer Center, Washington.

By adding up how many of 14 known risk alleles the man has, his risk can be defined far more accurately. DR. XU

DENVER — A man's absolute risk of developing prostate cancer over a 20-year period can be estimated by determining the number of risk alleles present on a simple genetic test and then taking family history into account.

It's known that an average 55-year-old man has a 13% risk of developing prostate cancer during the next 20 years. But by adding up how many of 14 known risk alleles the man has on single-nucleotide polymorphisms, his risk can be defined far more accurately.

For example, a man with seven or fewer of the risk alleles plus a negative family history has only an 8% absolute risk of being diagnosed with prostate cancer at age 55–74. The risk shoots up to 52% in a man with 14 risk alleles and a positive family history, Dr. Jianfeng Xu explained at the annual meeting of the American Association for Cancer Research.

This latter highest-risk group includes 8% of the general adult male population, noted Dr. Xu, professor of epidemiology and cancer biology at Wake Forest University, Winston-Salem, N.C.

He and his coworkers developed their risk model by studying 2,893 men with prostate cancer and 1,781 without the disease who had previously participated in a Swedish case-control study. The investigators found that while each of the risk alleles contributed a relatively small increase in risk, the risk was additive.

Moreover, the risk was further enhanced in a predictable way by the presence of a positive family history. For example, the 20-year absolute risk in a man with seven or fewer risk alleles and a negative family history is a mere 8%, but it rises to 17% with a positive family history. At the other extreme, a man possessing 14 risk alleles but a negative family history has a 24% risk of being diagnosed with prostate cancer at age 55–74; having a positive family history increases that risk to 52%.

The investigators subsequently confirmed their findings in a retrospective analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Dr. Xu conceded that the model has a major limitation: It doesn't distinguish between indolent and aggressive forms of prostate cancer. Thus, using the model would likely result in overtreatment of many men identified as being at high absolute risk, but who have indolent disease. The investigators have identified several single-nucleotide polymorphisms that appear to distinguish between nonaggressive and lethal prostate cancer, however, and are now doing confirmatory testing.

Even if these new candidate risk alleles don't pan out, Dr. Xu said he sees the current version of the absolute risk assessment as having potential utility. For example, men identified as high risk might elect to embark on a program of risk reduction through diet and lifestyle modification along with chemoprevention using finasteride, which has been shown to reduce prostate cancer risk by about 25%.

For men at average risk, finasteride could reduce their 20-year absolute risk from 13% to 10% at the cost of roughly $1.6 million per life-year gained. But for men at very high risk, the absolute risk reduction conferred by finasteride would be substantially greater and cost per life-year gained would be lower, Dr. Xu said.

He and his colleagues plan to launch a prospective prostate cancer prevention trial using risk alleles and family history to guide chemoprevention with finasteride.

“More replication is definitely needed before this is ready to go to the clinic, but this is taking us one step closer to the personalized medicine approach,” observed Dr. Peter G. Shields of the department of medicine at Georgetown University Medical Center and deputy director of the Lombardi Comprehensive Cancer Center, Washington.

By adding up how many of 14 known risk alleles the man has, his risk can be defined far more accurately. DR. XU

DENVER — A man's absolute risk of developing prostate cancer over a 20-year period can be estimated by determining the number of risk alleles present on a simple genetic test and then taking family history into account.

It's known that an average 55-year-old man has a 13% risk of developing prostate cancer during the next 20 years. But by adding up how many of 14 known risk alleles the man has on single-nucleotide polymorphisms, his risk can be defined far more accurately.

For example, a man with seven or fewer of the risk alleles plus a negative family history has only an 8% absolute risk of being diagnosed with prostate cancer at age 55–74. The risk shoots up to 52% in a man with 14 risk alleles and a positive family history, Dr. Jianfeng Xu explained at the annual meeting of the American Association for Cancer Research.

This latter highest-risk group includes 8% of the general adult male population, noted Dr. Xu, professor of epidemiology and cancer biology at Wake Forest University, Winston-Salem, N.C.

He and his coworkers developed their risk model by studying 2,893 men with prostate cancer and 1,781 without the disease who had previously participated in a Swedish case-control study. The investigators found that while each of the risk alleles contributed a relatively small increase in risk, the risk was additive.

Moreover, the risk was further enhanced in a predictable way by the presence of a positive family history. For example, the 20-year absolute risk in a man with seven or fewer risk alleles and a negative family history is a mere 8%, but it rises to 17% with a positive family history. At the other extreme, a man possessing 14 risk alleles but a negative family history has a 24% risk of being diagnosed with prostate cancer at age 55–74; having a positive family history increases that risk to 52%.

The investigators subsequently confirmed their findings in a retrospective analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Dr. Xu conceded that the model has a major limitation: It doesn't distinguish between indolent and aggressive forms of prostate cancer. Thus, using the model would likely result in overtreatment of many men identified as being at high absolute risk, but who have indolent disease. The investigators have identified several single-nucleotide polymorphisms that appear to distinguish between nonaggressive and lethal prostate cancer, however, and are now doing confirmatory testing.

Even if these new candidate risk alleles don't pan out, Dr. Xu said he sees the current version of the absolute risk assessment as having potential utility. For example, men identified as high risk might elect to embark on a program of risk reduction through diet and lifestyle modification along with chemoprevention using finasteride, which has been shown to reduce prostate cancer risk by about 25%.

For men at average risk, finasteride could reduce their 20-year absolute risk from 13% to 10% at the cost of roughly $1.6 million per life-year gained. But for men at very high risk, the absolute risk reduction conferred by finasteride would be substantially greater and cost per life-year gained would be lower, Dr. Xu said.

He and his colleagues plan to launch a prospective prostate cancer prevention trial using risk alleles and family history to guide chemoprevention with finasteride.

“More replication is definitely needed before this is ready to go to the clinic, but this is taking us one step closer to the personalized medicine approach,” observed Dr. Peter G. Shields of the department of medicine at Georgetown University Medical Center and deputy director of the Lombardi Comprehensive Cancer Center, Washington.

By adding up how many of 14 known risk alleles the man has, his risk can be defined far more accurately. DR. XU

While rosuvastatin significantly improved the lipid profile of patients with end-stage renal disease, those improvements did not translate into a decrease in the combined rate of heart attack, stroke, or cardiovascular death, a large randomized, controlled trial has confirmed.

“Although the patients tolerated the treatment very well, and it did lower their low-density lipoprotein by the expected amount, rosuvastatin had absolutely no treatment effect on either the composite cardiovascular end point or any of our secondary end points,” Dr. Bengt Fellstrom said at a teleconference held at the annual meeting of the American College of Cardiology.

“We suspect very strongly that the vascular disease they have is quite different from that in patients without end-stage renal disease. It has more to do with endothelial dysfunction and calcification, while cholesterol is not a significant risk factor,” Dr. Fellstrom said.

The 4-year AURORA study randomized 2,776 patients, all of whom had been on regular hemodialysis for at least 3 months, to either rosuvastatin 10 mg per day or placebo. The study's primary end points were time to nonfatal heart attack or stroke, or cardiovascular death. Secondary end points included all-cause mortality, event-free survival, and coronary or peripheral revascularization.

The patients' mean age was 64 years. At baseline, their average total cholesterol level was 175 mg/dL, with an LDL level of 99 mg/dL and HDL level of 45 mg/dL.

By 3 months, patients on rosuvastatin experienced a significantly larger decrease in LDL cholesterol than those taking placebo (43% vs. 2%, respectively). Rosuvastatin also significantly reduced total cholesterol (27% vs. 0.5%, respectively) and triglycerides (16% vs. an increase of 0.9% in placebo group). HDL increased in the active treatment group, but not significantly so.

The primary end point of stroke, heart attack, or death from those causes occurred in 396 patients taking the study drug and 408 taking placebo—not a significant difference. Neither were there any significant differences when the investigators examined the primary end points individually.

Death for any reason occurred in 636 patients taking rosuvastatin and 660 taking placebo, again not a significant difference. None of the prespecified secondary outcomes were significantly affected by the study drug.

The findings echo those of the German Diabetes and Dialysis study, which found that atorvastatin conferred no cardiovascular benefits on dialyzed patients with type 2 diabetes.

“Since that didn't work either, I suspect this is a class effect for all statins,” said Dr. Fellstrom of the University Hospital, Uppsala, Sweden.

AURORA enrolled only statin-naive patients. Dr. Fellstrom noted that the drugs do have an important place in the care of many other patients with end-stage renal disease. “Up to 40% of these patients have been put on statins before going on dialysis, after having a coronary event. Those patients should stay on the treatment.”

The study was published simultaneously online in the New England Journal of Medicine (doi:10.1056/NEJMoa0810177). An accompanying editorial discussed the disappointing finding that yet another possible intervention for improving cardiovascular survival in dialyzed patients had failed (doi:10.1056/NEJMe0901067).

“AURORA has shown that the hope of effective interventions to lower cardiovascular risk among patients undergoing hemodialysis remains unrealized,” wrote Jonathan C. Craig, Ph.D., of the University of Sydney, Australia. “The search is on for more promising interventions for a desperately needy group of people with very poor outcomes. Such interventions need to be based on a more complete understanding of the causal pathway of cardiac disease in patients undergoing dialysis.”

Dr. Fellstrom reported receiving consulting fees from Astra-Zeneca, the maker of rosuvastatin (Crestor), and other large pharmaceutical companies. Dr. Craig reported no conflict of interest.

While rosuvastatin significantly improved the lipid profile of patients with end-stage renal disease, those improvements did not translate into a decrease in the combined rate of heart attack, stroke, or cardiovascular death, a large randomized, controlled trial has confirmed.

“Although the patients tolerated the treatment very well, and it did lower their low-density lipoprotein by the expected amount, rosuvastatin had absolutely no treatment effect on either the composite cardiovascular end point or any of our secondary end points,” Dr. Bengt Fellstrom said at a teleconference held at the annual meeting of the American College of Cardiology.

“We suspect very strongly that the vascular disease they have is quite different from that in patients without end-stage renal disease. It has more to do with endothelial dysfunction and calcification, while cholesterol is not a significant risk factor,” Dr. Fellstrom said.

The 4-year AURORA study randomized 2,776 patients, all of whom had been on regular hemodialysis for at least 3 months, to either rosuvastatin 10 mg per day or placebo. The study's primary end points were time to nonfatal heart attack or stroke, or cardiovascular death. Secondary end points included all-cause mortality, event-free survival, and coronary or peripheral revascularization.

The patients' mean age was 64 years. At baseline, their average total cholesterol level was 175 mg/dL, with an LDL level of 99 mg/dL and HDL level of 45 mg/dL.

By 3 months, patients on rosuvastatin experienced a significantly larger decrease in LDL cholesterol than those taking placebo (43% vs. 2%, respectively). Rosuvastatin also significantly reduced total cholesterol (27% vs. 0.5%, respectively) and triglycerides (16% vs. an increase of 0.9% in placebo group). HDL increased in the active treatment group, but not significantly so.

The primary end point of stroke, heart attack, or death from those causes occurred in 396 patients taking the study drug and 408 taking placebo—not a significant difference. Neither were there any significant differences when the investigators examined the primary end points individually.

Death for any reason occurred in 636 patients taking rosuvastatin and 660 taking placebo, again not a significant difference. None of the prespecified secondary outcomes were significantly affected by the study drug.

The findings echo those of the German Diabetes and Dialysis study, which found that atorvastatin conferred no cardiovascular benefits on dialyzed patients with type 2 diabetes.

“Since that didn't work either, I suspect this is a class effect for all statins,” said Dr. Fellstrom of the University Hospital, Uppsala, Sweden.

AURORA enrolled only statin-naive patients. Dr. Fellstrom noted that the drugs do have an important place in the care of many other patients with end-stage renal disease. “Up to 40% of these patients have been put on statins before going on dialysis, after having a coronary event. Those patients should stay on the treatment.”

The study was published simultaneously online in the New England Journal of Medicine (doi:10.1056/NEJMoa0810177). An accompanying editorial discussed the disappointing finding that yet another possible intervention for improving cardiovascular survival in dialyzed patients had failed (doi:10.1056/NEJMe0901067).

“AURORA has shown that the hope of effective interventions to lower cardiovascular risk among patients undergoing hemodialysis remains unrealized,” wrote Jonathan C. Craig, Ph.D., of the University of Sydney, Australia. “The search is on for more promising interventions for a desperately needy group of people with very poor outcomes. Such interventions need to be based on a more complete understanding of the causal pathway of cardiac disease in patients undergoing dialysis.”

Dr. Fellstrom reported receiving consulting fees from Astra-Zeneca, the maker of rosuvastatin (Crestor), and other large pharmaceutical companies. Dr. Craig reported no conflict of interest.

While rosuvastatin significantly improved the lipid profile of patients with end-stage renal disease, those improvements did not translate into a decrease in the combined rate of heart attack, stroke, or cardiovascular death, a large randomized, controlled trial has confirmed.

“Although the patients tolerated the treatment very well, and it did lower their low-density lipoprotein by the expected amount, rosuvastatin had absolutely no treatment effect on either the composite cardiovascular end point or any of our secondary end points,” Dr. Bengt Fellstrom said at a teleconference held at the annual meeting of the American College of Cardiology.

“We suspect very strongly that the vascular disease they have is quite different from that in patients without end-stage renal disease. It has more to do with endothelial dysfunction and calcification, while cholesterol is not a significant risk factor,” Dr. Fellstrom said.

The 4-year AURORA study randomized 2,776 patients, all of whom had been on regular hemodialysis for at least 3 months, to either rosuvastatin 10 mg per day or placebo. The study's primary end points were time to nonfatal heart attack or stroke, or cardiovascular death. Secondary end points included all-cause mortality, event-free survival, and coronary or peripheral revascularization.

The patients' mean age was 64 years. At baseline, their average total cholesterol level was 175 mg/dL, with an LDL level of 99 mg/dL and HDL level of 45 mg/dL.

By 3 months, patients on rosuvastatin experienced a significantly larger decrease in LDL cholesterol than those taking placebo (43% vs. 2%, respectively). Rosuvastatin also significantly reduced total cholesterol (27% vs. 0.5%, respectively) and triglycerides (16% vs. an increase of 0.9% in placebo group). HDL increased in the active treatment group, but not significantly so.

The primary end point of stroke, heart attack, or death from those causes occurred in 396 patients taking the study drug and 408 taking placebo—not a significant difference. Neither were there any significant differences when the investigators examined the primary end points individually.

Death for any reason occurred in 636 patients taking rosuvastatin and 660 taking placebo, again not a significant difference. None of the prespecified secondary outcomes were significantly affected by the study drug.

The findings echo those of the German Diabetes and Dialysis study, which found that atorvastatin conferred no cardiovascular benefits on dialyzed patients with type 2 diabetes.

“Since that didn't work either, I suspect this is a class effect for all statins,” said Dr. Fellstrom of the University Hospital, Uppsala, Sweden.

AURORA enrolled only statin-naive patients. Dr. Fellstrom noted that the drugs do have an important place in the care of many other patients with end-stage renal disease. “Up to 40% of these patients have been put on statins before going on dialysis, after having a coronary event. Those patients should stay on the treatment.”

The study was published simultaneously online in the New England Journal of Medicine (doi:10.1056/NEJMoa0810177). An accompanying editorial discussed the disappointing finding that yet another possible intervention for improving cardiovascular survival in dialyzed patients had failed (doi:10.1056/NEJMe0901067).

“AURORA has shown that the hope of effective interventions to lower cardiovascular risk among patients undergoing hemodialysis remains unrealized,” wrote Jonathan C. Craig, Ph.D., of the University of Sydney, Australia. “The search is on for more promising interventions for a desperately needy group of people with very poor outcomes. Such interventions need to be based on a more complete understanding of the causal pathway of cardiac disease in patients undergoing dialysis.”

Dr. Fellstrom reported receiving consulting fees from Astra-Zeneca, the maker of rosuvastatin (Crestor), and other large pharmaceutical companies. Dr. Craig reported no conflict of interest.

DENVER — Men on digoxin were roughly one-quarter less likely to be diagnosed with prostate cancer than digoxin nonusers, according to findings from the Health Professionals Follow-Up Study.

The longer the duration of digoxin use, the lower the risk of prostate cancer. Indeed, men on digoxin for at least 10 years had a 42% relative risk reduction for the malignancy compared with never-users, Elizabeth A. Platz, Sc.D., said at the annual meeting of the American Association for Cancer Research.

The Health Professionals Follow-Up Study is a very large, prospective, Harvard University-based cohort investigation. Dr. Platz reported on 4,511 cases of prostate cancer that occurred among 47,759 participating men aged 40–75 years during 745,041 person-years of follow-up.

At baseline, 2% of the participants were on digoxin. Their risk of developing prostate cancer during the follow-up period was 26% lower than in digoxin nonusers, even after adjusting for numerous potential confounders, including dietary differences and the use of other medications, among which were statins and aspirin, explained Dr. Platz, a cancer epidemiologist at Johns Hopkins University, Baltimore.

The association between digoxin use and reduced risk of developing prostate cancer was equally robust among those prescribed the drug for heart failure and those on digoxin for arrhythmias, she added.

Dr. Platz stressed that the digoxin analysis was not a “fishing expedition.” Rather, digoxin came under scrutiny as the result of a multidisciplinary project that began with bench scientists screening literally thousands of Food and Drug Administration-approved medications for their ability to inhibit prostate cancer cell growth in vitro. Digoxin was selected for further investigation because it exhibited moderate antiproliferative activity and is widely enough prescribed that its association with prostate cancer in clinical practice could reasonably be studied.

As an aside, Dr. Platz noted that digoxin's degree of in vitro inhibition of prostate cancer cell growth was even greater than a statin's performance in the same assay. The significance of this observation lies in the fact that a landmark investigation—also conducted using data from the Health Professionals Follow-Up Study cohort—concluded that the multivariate-adjusted relative risk of advanced prostate cancer in current statin users was reduced by 49% and the risk of metastatic or fatal disease was reduced by 61%, compared with nonusers. Dr. Platz was first author of the statin study (J. Natl. Cancer Inst. 2006;98:1819–25).

Encouragingly, the finding that statin therapy was indeed associated with a reduced risk of advanced prostate cancer was subsequently confirmed in three other very large epidemiologic studies published simultaneously: the Cancer Prevention Study II, the California Men's Health Study, and a Finnish study of all cases of prostate cancer diagnosed in that country during a recent 8-year period (Cancer Epidemiol. Biomarkers Prev. 2007;16:2213–7; 2218–25; and 2226–32, respectively).

Dr. Platz and her associates plan to study the mechanism of action by which digoxin prevents prostate cancer. This could perhaps lead to development of a drug targeting the specific pathway influencing cancer risk.

Digoxin could conceivably find a role for chemoprevention in selected high-risk men, or perhaps in the treatment of prostate cancer, but its potent cardiovascular effects make it poorly suited for use in broad-scale chemoprevention, she said.

The study was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute.

DENVER — Men on digoxin were roughly one-quarter less likely to be diagnosed with prostate cancer than digoxin nonusers, according to findings from the Health Professionals Follow-Up Study.

The longer the duration of digoxin use, the lower the risk of prostate cancer. Indeed, men on digoxin for at least 10 years had a 42% relative risk reduction for the malignancy compared with never-users, Elizabeth A. Platz, Sc.D., said at the annual meeting of the American Association for Cancer Research.

The Health Professionals Follow-Up Study is a very large, prospective, Harvard University-based cohort investigation. Dr. Platz reported on 4,511 cases of prostate cancer that occurred among 47,759 participating men aged 40–75 years during 745,041 person-years of follow-up.

At baseline, 2% of the participants were on digoxin. Their risk of developing prostate cancer during the follow-up period was 26% lower than in digoxin nonusers, even after adjusting for numerous potential confounders, including dietary differences and the use of other medications, among which were statins and aspirin, explained Dr. Platz, a cancer epidemiologist at Johns Hopkins University, Baltimore.

The association between digoxin use and reduced risk of developing prostate cancer was equally robust among those prescribed the drug for heart failure and those on digoxin for arrhythmias, she added.

Dr. Platz stressed that the digoxin analysis was not a “fishing expedition.” Rather, digoxin came under scrutiny as the result of a multidisciplinary project that began with bench scientists screening literally thousands of Food and Drug Administration-approved medications for their ability to inhibit prostate cancer cell growth in vitro. Digoxin was selected for further investigation because it exhibited moderate antiproliferative activity and is widely enough prescribed that its association with prostate cancer in clinical practice could reasonably be studied.

As an aside, Dr. Platz noted that digoxin's degree of in vitro inhibition of prostate cancer cell growth was even greater than a statin's performance in the same assay. The significance of this observation lies in the fact that a landmark investigation—also conducted using data from the Health Professionals Follow-Up Study cohort—concluded that the multivariate-adjusted relative risk of advanced prostate cancer in current statin users was reduced by 49% and the risk of metastatic or fatal disease was reduced by 61%, compared with nonusers. Dr. Platz was first author of the statin study (J. Natl. Cancer Inst. 2006;98:1819–25).

Encouragingly, the finding that statin therapy was indeed associated with a reduced risk of advanced prostate cancer was subsequently confirmed in three other very large epidemiologic studies published simultaneously: the Cancer Prevention Study II, the California Men's Health Study, and a Finnish study of all cases of prostate cancer diagnosed in that country during a recent 8-year period (Cancer Epidemiol. Biomarkers Prev. 2007;16:2213–7; 2218–25; and 2226–32, respectively).

Dr. Platz and her associates plan to study the mechanism of action by which digoxin prevents prostate cancer. This could perhaps lead to development of a drug targeting the specific pathway influencing cancer risk.

Digoxin could conceivably find a role for chemoprevention in selected high-risk men, or perhaps in the treatment of prostate cancer, but its potent cardiovascular effects make it poorly suited for use in broad-scale chemoprevention, she said.

The study was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute.

DENVER — Men on digoxin were roughly one-quarter less likely to be diagnosed with prostate cancer than digoxin nonusers, according to findings from the Health Professionals Follow-Up Study.

The longer the duration of digoxin use, the lower the risk of prostate cancer. Indeed, men on digoxin for at least 10 years had a 42% relative risk reduction for the malignancy compared with never-users, Elizabeth A. Platz, Sc.D., said at the annual meeting of the American Association for Cancer Research.

The Health Professionals Follow-Up Study is a very large, prospective, Harvard University-based cohort investigation. Dr. Platz reported on 4,511 cases of prostate cancer that occurred among 47,759 participating men aged 40–75 years during 745,041 person-years of follow-up.

At baseline, 2% of the participants were on digoxin. Their risk of developing prostate cancer during the follow-up period was 26% lower than in digoxin nonusers, even after adjusting for numerous potential confounders, including dietary differences and the use of other medications, among which were statins and aspirin, explained Dr. Platz, a cancer epidemiologist at Johns Hopkins University, Baltimore.

The association between digoxin use and reduced risk of developing prostate cancer was equally robust among those prescribed the drug for heart failure and those on digoxin for arrhythmias, she added.

Dr. Platz stressed that the digoxin analysis was not a “fishing expedition.” Rather, digoxin came under scrutiny as the result of a multidisciplinary project that began with bench scientists screening literally thousands of Food and Drug Administration-approved medications for their ability to inhibit prostate cancer cell growth in vitro. Digoxin was selected for further investigation because it exhibited moderate antiproliferative activity and is widely enough prescribed that its association with prostate cancer in clinical practice could reasonably be studied.

As an aside, Dr. Platz noted that digoxin's degree of in vitro inhibition of prostate cancer cell growth was even greater than a statin's performance in the same assay. The significance of this observation lies in the fact that a landmark investigation—also conducted using data from the Health Professionals Follow-Up Study cohort—concluded that the multivariate-adjusted relative risk of advanced prostate cancer in current statin users was reduced by 49% and the risk of metastatic or fatal disease was reduced by 61%, compared with nonusers. Dr. Platz was first author of the statin study (J. Natl. Cancer Inst. 2006;98:1819–25).

Encouragingly, the finding that statin therapy was indeed associated with a reduced risk of advanced prostate cancer was subsequently confirmed in three other very large epidemiologic studies published simultaneously: the Cancer Prevention Study II, the California Men's Health Study, and a Finnish study of all cases of prostate cancer diagnosed in that country during a recent 8-year period (Cancer Epidemiol. Biomarkers Prev. 2007;16:2213–7; 2218–25; and 2226–32, respectively).

Dr. Platz and her associates plan to study the mechanism of action by which digoxin prevents prostate cancer. This could perhaps lead to development of a drug targeting the specific pathway influencing cancer risk.

Digoxin could conceivably find a role for chemoprevention in selected high-risk men, or perhaps in the treatment of prostate cancer, but its potent cardiovascular effects make it poorly suited for use in broad-scale chemoprevention, she said.

The study was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks after treatment with botulinum neurotoxin type A (Botox) in a randomized trial of 313 patients.

“Botox doses at or above 100 U consistently [provided] meaningful benefit as measured by improvements on these questionnaires,” Dr. David A. Ginsberg and his colleagues reported in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

At baseline, participants (mean age 58.8 years, 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia, said Dr. Ginsberg, who disclosed that he is a consultant for Allergan, which supported the multicenter, double-blind, phase II study.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50 U group to 39.7 in the 300 U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups except those receiving the lowest dose, compared with the placebo group. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the 100 U, 150 U, and 300 U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention over 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U, 100-U, 150-U, 200-U, and 300-U dose groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773–8) reported that more than 2 of 5 patients required clean intermittent self-catheterization following treatment. Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“I tell my patients there is about a 10%–20% risk that they might need [intermittent catheterization] to empty their bladder,” Dr. Ginsberg said.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks after treatment with botulinum neurotoxin type A (Botox) in a randomized trial of 313 patients.

“Botox doses at or above 100 U consistently [provided] meaningful benefit as measured by improvements on these questionnaires,” Dr. David A. Ginsberg and his colleagues reported in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

At baseline, participants (mean age 58.8 years, 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia, said Dr. Ginsberg, who disclosed that he is a consultant for Allergan, which supported the multicenter, double-blind, phase II study.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50 U group to 39.7 in the 300 U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups except those receiving the lowest dose, compared with the placebo group. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the 100 U, 150 U, and 300 U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention over 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U, 100-U, 150-U, 200-U, and 300-U dose groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773–8) reported that more than 2 of 5 patients required clean intermittent self-catheterization following treatment. Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“I tell my patients there is about a 10%–20% risk that they might need [intermittent catheterization] to empty their bladder,” Dr. Ginsberg said.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks after treatment with botulinum neurotoxin type A (Botox) in a randomized trial of 313 patients.

“Botox doses at or above 100 U consistently [provided] meaningful benefit as measured by improvements on these questionnaires,” Dr. David A. Ginsberg and his colleagues reported in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

At baseline, participants (mean age 58.8 years, 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia, said Dr. Ginsberg, who disclosed that he is a consultant for Allergan, which supported the multicenter, double-blind, phase II study.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50 U group to 39.7 in the 300 U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups except those receiving the lowest dose, compared with the placebo group. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the 100 U, 150 U, and 300 U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention over 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U, 100-U, 150-U, 200-U, and 300-U dose groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773–8) reported that more than 2 of 5 patients required clean intermittent self-catheterization following treatment. Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“I tell my patients there is about a 10%–20% risk that they might need [intermittent catheterization] to empty their bladder,” Dr. Ginsberg said.

CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.

The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.

“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.

“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.

Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.

The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.

The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.

The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.

At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).

The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.

This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.

The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”

To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.

The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.

Dr. Penson said that he had no disclosures related to the study.

CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.

The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.

“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.

“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.

Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.

The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.

The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.

The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.

At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).

The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.

This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.

The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”

To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.

The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.

Dr. Penson said that he had no disclosures related to the study.

CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.

The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.

“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.

“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.

Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.

The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.

The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.

The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.

At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).

The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.

This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.

The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”

To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.

The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.

Dr. Penson said that he had no disclosures related to the study.