CHEMOPREVENTION FOR PROSTATIC INTRAEPITHELIAL NEOPLASIA

Objectives: To evaluate the potential application of chemoprevention s trategies in prostatic intraepithelial neoplasia. Methods: Review of r elevant Literature on chemoprevention with emphasis on prostate cancer and premalignant lesions. Results: Chemoprevention represents a strat egy designed to inhibit or reverse the process of carcinogenesis by ad ministering one or several noncytotoxic chemical compounds. The epidem iology of prostate carcinoma indicates that this cancer is a prime can didate for a strategy aimed at prevention due to the extremely high pr evalence rate, rising annual incidence, and long latent interval betwe en the cancer-initiating events and the development of invasive diseas e. Chemopreventive agents may exert their inhibitory effects at differ ent stages of the multistep carcinogenic process broadly categorized a s initiation, promotion, and progression. The synthetic retinoids, pol yamine synthesis inhibitors, and antiandrogens are among the compounds shown to have in vitro or in vivo chemopreventive effects in prostate carcinogenesis. A major limitation in the evaluation of such agents i n a human prostate cancer is the long duration of clinical trials requ ired to assess the efficacy with an endpoint of cancer development. Pr emalignant epithelial changes such as prostate intraepithelial neoplas ia, or PIN, are highly associated with prostate cancer, and share many molecular features of invasive cancer. If the reversal or inhibition of intraepithelial neoplasia translates to a concomitant reduction in clinically relevant prostate cancer, then the pharmacological modulati on of PIN may provide a rapid means to evaluate the effects and benefi ts of potential chemopreventive agents. Conclusion: Men with PIN may r epresent ideal candidates for chemoprevention protocols. The ideal age nt and duration of therapy remains to be defined.