Prostate cancer is a disease associated with
androgens. It has been hypothesized that reducing the conversion of
testosterone (T) to
dihydrotestosterone (DHT) in the prostate by the use of the
drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of
prostate cancer. We investigated the chemopreventive potential of
finasteride by evaluating its effect on the prostate gland of men with elevated serum
prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for
cancer were randomized to receive
finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of
cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade
prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to
proliferating cell nuclear antigen (
PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the
finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the
finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the
finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with
finasteride treatment.
Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with
finasteride, eight (30%) had
adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six
cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no
cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two
cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one
cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of
prostate cancer, provides little evidence that
finasteride is an effective chemopreventive agent for
prostate cancer in men with elevated PSA.