Finasteride reduces prostate cancer incidence

Benefits may not be worth the risk, physician says

A recent study shows that finasteride (Proscar) prevents or delays the appearance of prostate cancer. The drug, however, also shows sexual side effects and an increased risk of high-grade prostate cancer.

In the Prostate Cancer Prevention Trial (PCPT), prostate cancer was detected in 18.4% men treated with finasteride as compared to 24.4% of the men in the placebo group, a 24.8% reduction. The study was scheduled to be completed in 2004, but was stopped early because the study objective had been met. The current analysis is based on the 86.3% of men who completed the seven years of the study.

Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of steroid Type II 5a-reductase, an intracellular enzyme that converts the androgen testosterone into 5a-dihydrotestosterone. It is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for surgery, including transurethral resection of the prostate and prostatectomy. (A lower-dose version of finasteride is marketed as Propecia and is indicated for the treatment of male pattern hair loss.) In the PCPT, researchers wanted to see if finasteride might prevent prostate cancer by reducing androgenic stimulation.

To test their hypothesis, researchers randomly assigned 18,882 men 55 years of age or older to a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng/mL or lower to treatment with finasteride (5 mg/day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng/mL or if the digital rectal examination was abnormal. Researchers expected that 60% of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary endpoint was the prevalence of prostate cancer during the seven years of the study.

Although the incidence of prostate cancer was reduced in the finasteride group of participants, this group did have an increase in the rate of high-grade cancers — 6.4% as compared to 5.1% in the placebo group. In addition, sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo.

These study results were published on the web site of the New England Journal of Medicine to coincide with the National Cancer Institute’s announcement of the early termination of this trial. They also appeared in the July 17 issue of the journal.

In an accompanying editorial, a physician argues that finasteride does not seem to be an attractive agent for the chemoprevention of prostate cancer. The reduction of prostate cancer was relative to the incidence in a control group in which biopsy was recommended for all men, regardless of risk factors, says Peter T. Scardino, MD, chairman of the Department of Urology at Memorial Sloan-Kettering Cancer Center in New York City.

In addition, the study results suggest that finasteride may accelerate the growth of high-grade cancers, which may pose a threat to life and health if they are not treated successfully, he continues. The effects of finasteride on sexual function also lessen the attractiveness of the drug as a preventive agent.

In the editorial, Scardino suggests that future studies explore whether finasteride would be more effective if it were given earlier in the course of prostate cancer.