5-ARI cuts prostate cancer risk by one-third

After 18 years of follow-up, new findings from the Prostate Cancer Prevention Trial show that the 5-alpha-reductase inhibitor finasteride (Proscar) reduces the risk of prostate cancer by about one-third but has no effect on mortality risk.

Among nearly 19,000 eligible men who underwent randomization, prostate cancer was diagnosed in 10.5% of those in the finasteride group and 14.9% of those in the placebo group, representing a 30% reduction in risk, researchers reported in the New England Journal of Medicine (2013; 369:603-10). The risk of low-grade tumors was cut by 43%.

“If you look at the number of prostate cancers that are diagnosed annually and multiply that by 30%, that’s the number of cancers we might be able to prevent each year. That’s more than 71,000 men. That’s more than 175 jumbo jets full of men who won’t get cancer, who won’t face treatments with side effects like sexual dysfunction,” said lead author Ian M. Thompson, Jr., MD, of the University of Texas Health Science Center at San Antonio.

During the Prostate Cancer Prevention Trial, a slightly higher percentage of those on finasteride developed high-grade cancer than those taking placebo (although this difference shrank in the follow-up analysis). Multiple studies addressing this concern ultimately concluded that detection bias accounted, at least in part, for the increase in the rate of high-grade tumors in finasteride recipients. Nevertheless, in 2011, the FDA added a warning to the label about this risk, and use of finasteride for prostate cancer prevention has been limited.

In the most recent analysis, 3.5% of men in the finasteride group and 3% in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI: 1.00-1.37; p=.05). Ten-year survival rates were 83% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73% and 73.6%, respectively, for those with high-grade prostate cancer.

The 18-year follow-up showed no impact on either overall survival or survival after prostate cancer diagnosis, Dr. Thompson and colleagues reported.

Many men with even low-grade tumors are treated unnecessarily, Dr. Thompson noted, and those treatments carry a considerable burden for the patient and for society.

“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 death and suffering from disease.”

In an accompanying editorial, Michael LeFevre, MD, MSPH, of the University of Missouri, Columbia, pointed out that among men screened for prostate cancer, finasteride meaningfully reduces prostate cancer risk and the morbidity associated with treatment.

“Whether the use of the drug has either a positive or a negative effect on prostate-cancer–specific mortality remains unknown, but either way the effect is probably very small and does not result in any difference in life expectancy,” wrote Dr. LeFevre, who served on the U.S. Preventive Services Task Force on prostate cancer screening. “Men who are aware of and understand the benefits, risks, and uncertainties associated with the use of finasteride for prevention may make a rational decision to take the drug to reduce the harm of screening. Of course, another way to reduce the harm of screening is to choose not to be screened.”

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