Clinical Question

Does the use of finasteride (Propecia) affect overall mortality or grade-specific survival rates following a diagnosis of prostate cancer?

Bottom Line

Although finasteride prevents low-grade prostate tumors, it does not affect overall survival or survival after prostate cancer diagnosis. Although high-grade cancers were more common among men taking finasteride, up to 18 years of follow-up failed to show increased mortality in this group. The only potential advantage to using finasteride is that the lower rate of low-grade cancers may reduce the likelihood that men would be treated for a cancer that is highly unlikely to harm them. (Level of Evidence = 1b)

Synopsis

The original Prostate Cancer Prevention Trial (PCPT) randomized 18,880 men from 221 sites (median age = 63 years) to receive 5 mg of finasteride per day or placebo. The men were followed at regular intervals via office visits and telephone calls, and underwent annual prostate-specific antigen tests and digital rectal examinations. Biopsy was recommended for patients with prostate-specific antigen levels higher than 4.0 ng per mL (4.0 mcg per L) and for those with an abnormal rectal examination result. Histologic confirmation classified cancer as low grade (Gleason score = 2 to 6) or high grade (Gleason score = 7 to 10). Previously published PCPT results showed that finasteride decreased the relative risk of prostate cancer by 24.8%, but increased the risk of high-grade prostate tumors by 26.9% compared with placebo.

This study, which collected additional incidence data through 2009, is a post-hoc analysis of overall survival and survival rates after diagnosis of prostate cancer. Cause of death, established through review of clinical summaries and death certificates, was determined by participating PCPT centers and through a search of the Social Security Death Index in May 2012. Men who received finasteride were less likely to be given a diagnosis of prostate cancer than men who received placebo (10.5% vs. 14.9%; relative risk = 0.70; 95% confidence interval [CI], 0.65 to 0.76). High-grade tumors were slightly more common in the finasteride group (3.5% vs. 3.0%; relative risk = 1.17; 95% CI, 1.00 to 1.37). However, there were no differences in all-cause mortality rates between patients who took finasteride vs. placebo (hazard ratio = 1.02; 95% CI, 0.97 to 1.08). Fifteen-year survival rates were 78.0% in the finasteride group and 78.2% in the placebo group. Study enrollment was lower than expected because of unforeseen closure of some of the original study centers. One center did not release Social Security numbers of their participants, resulting in missing data. For many men, cause of death was not readily available, thus prostate cancer–specific mortality could not be calculated. But because all-cause mortality was the same between groups, this is not an important limitation.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (any)

Reference: ThompsonIMJrGoodmanPJTangenCMet alLong-term survival of participants in the prostate cancer prevention trial. N Engl J Med.2013; 369( 7): 603– 610.