Post hoc analysis of the finasteride effect on the incidence of prostate cancer stratified by prostate gland volume in the Prostate Cancer Prevention Trials (PCPT)

Purpose: Studies have shown that finasteride may decrease the incidence of prostate cancer (PCa) in general but may increase the incidence of high-grade PCa. There have been conflicting hypotheses attempting to explain this phenomenon. This is the first study stratifying the Prostate Cancer Prevention Trials (PCPT) data based on prostate volume as a moderating variable in the incidence of PCa. Materials and methods: Patients from both the control group and the finasteride treatment arm of the PCPT were included in the analysis. Inclusion criteria consisted of patients with documented biopsies and confirmed cancer status, whereas patients without documented prostate volume measurements were excluded. Simple and multivariable logistic regression analyses including specific biographic parameters were applied. Results: From the PCPT study, 10,279 patients, with a mean age of 63 years, were included in our analysis. For the control cohort, patients with prostate volumes larger than 60 cc showed a statically significant reduction in risk of PCa when compared with those with small prostate volumes under 35 cc (P < 0.001). However, under finasteride, patients with large prostate volumes (>60 cc) had an increased risk of PCa compared with patients with small prostates in the placebo group. Conclusion: The presented data reveal a cancer-protective effect of prostate size for both general and clinically significant PCa. However, finasteride negates this in patients with large prostates when compared with small prostates. This phenomenon may relate to the significant transition zone volume reduction in large prostates under finasteride, allowing more space for glandular tissue proliferation in the peripheral zone, where 80% to 85% of PCa originates.