Therapeutic considerations for patients with high-risk, nonmetastatic, prostate cancer.

The management of patients with high-risk, early-stage, prostate cancer represents a major challenge to all disciplines involved in the treatment of this common malignant neoplasm. Definition of the natural history of this disease, including the identification of key prognostic factors, in addition to the availability of active systemic therapeutic modalities for patients with advanced disease, are among the basic requirements that allow for early intervention in high-risk patients. Emerging new antiprogression approaches, targeted at various known stages of the metastatic cascade with the potential benefit of altering the natural history of early prostate cancer are attractive alternatives for early interventions with innovative programs. Studies on the natural history of patients with evidence of biochemical relapse following local treatment provide the basis for appropriate estimation of the risk ratio for development of clinical metastasis and selection of candidates for aggressive implementation of early treatment. The study of new candidate biomarkers of disease activity should be included in the context of clinical trials. Genotypic and phenotypic characterization of patients in clinical trials may enhance future therapeutic prospects in this disease.