Long-term survival of participants in the prostate cancer prevention trial

Abstract

Background: In the Prostate Cancer Prevention Trial (PCPT), finasteride significantly reduced the risk of prostate cancer but was associated with an increased risk of high-grade disease. With up to 18 years of follow-up, we analyzed rates of survival among all study participants and among those with prostate cancer.

Methods: We collected data on the incidence of prostate cancer among PCPT participants for an additional year after our first report was published in 2003 and searched the Social Security Death Index to assess survival status through October 31, 2011.

Results: Among 18,880 eligible men who underwent randomization, prostate cancer was diagnosed in 989 of 9423 (10.5%) in the finasteride group and 1412 of 9457 (14.9%) in the placebo group (relative risk in the finasteride group, 0.70; 95% confidence interval [CI], 0.65 to 0.76; P<0.001). Of the men who were evaluated, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Of the men who died, 2538 were in the finasteride group and 2496 were in the placebo group, for 15-year survival rates of 78.0% and 78.2%, respectively. The unadjusted hazard ratio for death in the finasteride group was 1.02 (95% CI, 0.97 to 1.08; P=0.46). Ten-year survival rates were 83.0% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73.0% and 73.6%, respectively, for those with high-grade prostate cancer.

Conclusions: 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. (Funded by the National Cancer Institute.).

Figure 1. Enrollment and Outcomes

Data in the boxes with shading were included in the primary 2003 report of the Prostate Cancer Prevention Trial (PCPT). All other results are from the current follow-up study. Men with a negative biopsy result underwent the procedure before March 2003, the month in which data were censored for the primary report. Men who were presumed not to have prostate cancer did not undergo a biopsy at the end of the study. One participant in the finasteride group who was classified as having low-grade prostate cancer in the primary report was subsequently reclassified as having high-grade prostatic intraepithelial neoplasia. Among men who were included in the primary report, some prostate-cancer grades were changed after further central pathological review; the values presented here are the final confirmed values. Cancers that did not undergo central pathological review were classified as having an unknown grade. A total of 390 men (196 in the finasteride group and 194 in the placebo group) were evaluated at a single study center that prohibited the release of the study participant's full name and Social Security number. Data for these men were censored on the last date they were known to be alive on the basis of PCPT follow-up data.

Figure 2

Kaplan–Meier Curves for Overall Survival.

Figure 3. Overall Survival of Men with Prostate Cancer, According to Cancer Grade

Low-grade cancers had a Gleason score of 2 to 6; high-grade cancers had a Gleason score of 7 to 10. A total of 163 cancers with an unknown grade were excluded from this analysis. Estimates of survival were reported at 10 years (rather than 15 years, as in Fig. 2) because of the small number of men who were evaluated at 15 years.