Chemoprevention of prostate cancer: guidelines for possible intervention strategies

The "natural history" of prostate cancer may bedevil the development of guidelines for chemoprevention interventions. Can strategies be designed to direct agents to those lesions which have the potential to develop localized extension that may become symptomatic or metastatic disease? Of necessity our interventions will focus on the identification and quantification of appropriate biomarkers as intermediate endpoints, although no reliable endpoints for prostate cancer have yet been identified. The reduction of prostate cancer incidence may be the ultimate objective, but a decrease in the progression of microfocal or "latent" cancer may well be just as effective as prevention when the age of the target population and competing causes of death are taken into account. Early intervention strategies must focus on the analysis of the interactions of the chosen chemopreventive agents upon precancerous and cancerous cellular dynamics in the prostate. Whether the requirements of such molecular epidemiology necessitate a more deliberate strategy of Phase II studies or a high risk-high gain strategy of a broad Phase III study is open to debate. Factorial designs for proposed randomized chemoprevention trials may be desirable to test multiple chemopreventive agents simultaneously, provided knowledge of the biochemical synergism of the agents is solid. Stratification of study participants by degree of risk will ameliorate concerns regarding the precision targeting of lesions at different stages in the precancer/cancer continuum.