In the Prostate Cancer Prevention Trial (PCPT), initially reported in 2003, finasteride significantly reduced the risk of prostate cancer by 24.8% but was associated with a relative 26.9% increase in risk of high-grade disease compared with placebo. In a study reported in The New England Journal of Medicine, Ian M. Thompson, MD, of The University of Texas Health Science Center at San Antonio, and colleagues analyzed survival rates of all subjects and those with prostate cancer in the trial during up to 18 years of follow-up.1 They found that although high-grade cancer was more common in the finasteride group, there were no significant differences between the finasteride and placebo groups in rates of overall survival or survival after diagnosis of prostate cancer.
Analyses of the PCPT have indicated that the use of finasteride improved the sensitivity of prostate-specific antigen (PSA) testing, prostate biopsy, and digital rectal examination for identification of prostate cancer and improved the sensitivity of PSA testing and prostate biopsy for detection of high-grade disease. The improved sensitivity may have reflected reduction of PSA in finasteride recipients who had benign enlargement and subsequent shrinkage of the prostate. Although analyses suggested that such detection bias accounted for at least some of the greater rate of high-grade tumors in the finasteride group, concern over the potential risk with finasteride has resulted in virtual abandonment of its use in prostate cancer prevention.
In the current study, investigators analyzed survival in the two study groups at 18 years after initial randomization to identify evidence of increased risk of death in the finasteride group, since such an increase might be an indicator of increased risk of high-grade cancer. Data on the incidence of prostate cancer among PCPT participants for an additional year after the first study report in 2003 were collected and the Social Security Death Index was searched to assess survival status through October 31, 2011.
Among 18,880 men who were randomly assigned to finasteride or placebo, prostate cancer was diagnosed in 989 (10.5%) of 9,423 in the finasteride group and 1,412 (14.9%) of 9,457 in the placebo group, yielding a relative risk (RR) in the finasteride group of 0.70 (P < .001). Of these cancers, 3.5% of those in the finasteride group and 3.0% of those in placebo group were assessed as high-grade cancer (Gleason score of 7–10; RR = 1.17, P = .05). Risk of low-grade cancer was reduced in the finasteride group (RR = 0.57, P < .001).
In the primary 2003 report, relative risks were 0.75 (P < .001) for any cancer, 0.62 (P < .001) for low-grade cancer, and 1.27 (P = .005) for high-grade cancer.
At the time of randomization, the median age of participants was 63 years. As of October 31, 2011, the median age of those still alive was 79 years. Median age at the time of prostate cancer diagnosis was 70 years in the two groups.
The 15-year survival rate was 78.0% in the finasteride group and 78.2% in the placebo group (unadjusted hazard ratio [HR] 1.02, P = .46; HR adjusted for age, race, and prostate cancer diagnosis 1.03, P = .26). Factors significantly associated with death from any cause were age at randomization (HR = 1.12 as continuous variable, P < .001) and black vs non-black race (HR = 1.48, P < .001).
Among men with prostate cancer, the unadjusted hazard ratio for death in the finasteride group was 1.01 (P = .90) and the hazard ratio adjusted for cancer grade, age at diagnosis, race, and family history of prostate cancer was 0.93 (P = .45). At 10 years, survival rates for men with prostate cancer were 79.3% in the finasteride group and 79.5% in the placebo group, including rates of 83.0% vs 80.9% in those with low-grade cancer and 73.0% vs 73.6% in those with high-grade cancer.
Compared with patients with high-grade cancer in the finasteride group, patients with low-grade cancer and placebo recipients were less likely to die. Hazard ratios for death after diagnosis were 0.64 (P = .001) for finasteride patients with low-grade cancer, 0.94 (P = .68) for placebo patients with high-grade cancer, and 0.73 (P = .01) for placebo patients with low-grade cancer. Age at diagnosis was a significant predictor of death after diagnosis (HR = 1.11, P < .001).
Limitation of the survival analysis to patients diagnosed with prostate cancer at the time of the initial report did not change the results. The test for interaction between treatment and cancer grade was not significant (P = .32), indicating that the between-group difference in risk of death from high-grade cancer was not significant.
The investigators concluded, “Finasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer.” ■
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit www.nejm.org.
1. Thompson IM Jr, Goodman PJ, Tangen CM, et al: Long-term survival of participants in the Prostate Cancer Prevention Trial. N Engl J Med 369:603-610, 2013.
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