Long-term data confirm the finding that finasteride reduces the risk for prostate cancer by about a third, but they also show no effect on overall survival or on survival after a diagnosis of prostate cancer.
The new data, from an 18-year follow-up of men taking part in the Prostate Cancer Prevention Trial (PCPT), are published in the August 15 issue of the New England Journal of Medicine.
The new data should reopen the debate about using finasteride for the prevention of prostate cancer, says Eric Klein, MD, from the Cleveland Clinic, in Ohio, who was not involved in the study.
A major stumbling block to the use of finasteride (and also the similar drug dutasteride) in healthy men for preventing prostate cancer was a finding that emerged from the prevention clinical trials. Although both drugs significantly reduced the risk of being diagnosed with prostate cancer, paradoxically, they also increased the risk of being diagnosed with a high-grade prostate cancer (Gleason score 7 - 10).
It was this finding that scuppered the chances of these drugs being used for chemoprevention. A US Food and Drug Administration (FDA) advisory committee meetingrecommended against approval of this indication (both drugs are already marketed for benign prostatic hyperplasia and male-pattern baldness). The FDA also mandated that the finding of an increased risk of being diagnosed with high-risk prostate cancer was highlighted in a black box warning in the product labeling.
"I think this was an over-reaction," Dr. Klein told Medscape Medical News. He said the black box warning was "sensationalist...suggesting that it put men's lives at risk," whereas there was no evidence at the time that men were harmed, he said.
The new long-term data from the PCTP trial shows that there was no difference in overall survival between the 2 arms of the trial. "This is indisputable evidence that it's safe to take these drugs and they don't make people die," Dr. Klein said in an interview.
The National Cancer Institute, which sponsored the PCPT, said in a statement that this lack of a survival difference between the 2 groups provides "reassurance" that the small excess of higher-grade tumors in men who took finasteride did not translate into an increased risk for death.
New Data Show No Survival Difference
The new analysis, headed by Ian Thompson Jr, MD, director of the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio, set out specifically to look at whether there was an increased risk for death with finasteride.
The PCTP was a 7-year study conducted in 18,880 healthy men (median age, 63.2 years) who were randomly assigned to receive either finasteride or placebo.
Prostate cancer was diagnosed in 10.5% of the men in the finasteride group (989 of 9423 men) and in 14.9% of the men in the placebo group (P < .001), a reduction in risk of 30%. However, there was also a significant increase in the percentage of tumors that were high grade among the men who took finasteride (3.5% vs 3% in the placebo group, P = .05).
The main explanation for this finding of an increase in high-grade prostate cancer has been detection bias, in which the drug's effect of shrinking the prostate gland makes detection of high-grade cancer more likely.
However, there was a lingering concern that these high-grade cancers detected in men receiving finasteride would be clinically more aggressive and thus more lethal, the authors comment. They quote from a review article that suggested that "if the increase in high-grade prostate cancers was not a finasteride-driven artifact of detection but rather reflected new high-grade cancers induced by finasteride, some increase in mortality among men receiving finasteride should become obvious during long-term follow-up."
The new analysis, with follow-up data of up to 18 years, shows no increase in mortality. The 15-year survival rate was 78% for finasteride and 78.2% for placebo.
In addition, the authors report 10-year survival data for the 2 different grades of cancer. Men who were diagnosed with low-grade prostate cancer had 10-year survival rates of 83% on finasteride and 80.9% on placebo, whereas men diagnosed with high-grade prostate cancer had 10-year survival rates of 73% on finasteride and 73.6% on placebo.
Taking finasteride has no impact on lifespan, Dr. Thompson concluded.
"So what's the point of going on that therapy?" asks another prostate cancer expert. Discussing the new survival data from PCTP in a recent Medscape Medical News videoblog, Gerald Chodak, MD, director at the Midwest Prostate and Urology Health Center, Michiana Shores, Indiana, pointed out that men who took finasteride were less likely to be diagnosed with prostate cancer, but they lived just as long as men who did not take the drug. "The bottom line here is that with the more mature data, it is difficult to make a strong recommendation for the use of finasteride to prevent prostate cancer," he said.
Dr. Klein disagrees; he hopes that the new survival data will allay previous concerns and will reignite enthusiasm for chemoprevention for prostate cancer. "This is the only intervention we have that has shown in a high-quality clinical trial to reduce a man's likelihood of getting prostate cancer," he said. Prevention trials with selenium and vitamin E failed. He suggested that it is an intervention that would be appropriate for men with a high risk for prostate cancer, for example, because of family history or ethnicity (African American race), and also for use in men who are found to have a rising prostate-specific antigen (PSA) level but who have a negative biopsy result.
Dr. Thompson suggests that use of chemoprevention could save thousands of men from undergoing unnecessary treatment.
"In men who take finasteride, a third fewer will be diagnosed with prostate cancer," he said in a statement. Extrapolating nationwide, use of the drug could prevent 71,000 cases annually in the United States, he suggested.
The reduction in risk was due entirely to a reduction in the risk for low-grade cancer among the men receiving finasteride compared with the men receiving placebo, Dr. Thompson and colleagues note in the article.
In the current medical climate, many men with low-grade prostate cancer are treated unnecessarily. "If we can free thousands of men each year from that unnecessary burden," he said, "we could use those resources for other important medical interventions."
Reducing Harm in Screened Men
Writing in the accompanying editorial, Michael LeFevre, MD, MSPH, from the Department of Family and Community Medicine at the University of Missouri, in Columbia, emphasized that all the men participating in the PCPT were being actively screened for cancer (using the PSA test).
"For men who choose regular prostate-cancer screening, the use of finasteride meaningfully reduces the risk of prostate cancer and thus the morbidity associated with the disease," Dr. LeFevre writes.
The drug may reduce the harm of screening, he concludes.
"Of course, another way to reduce the harm of screening is to choose not to be screened," he adds.
Dr. LeFevre pointed out that the United States Preventive Services Task Force (USPSTF), on which he serves, recently recommended against routine screening after concluding that the potential benefits of prostate cancer screening do not outweigh the potential harms.
Dr. Thompson reports receiving consulting fees from Ferring and being a named inventor on 2 products currently in development, a prostate cancer diagnostic test and a penile prosthesis. Coauthor Catherine M. Tangen, DrPH, reports receiving consulting frees from Amgen and Eli Lilly. Dr. Chodak reports consulting for Watson Ferring, Amgen, and GlaxoSmithKline. Dr. LeFevre is co–vice chair of the USPSTF. Dr. Klein reports no relevant financial relationships.
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