Volume 9, Supplement 2Review ArticlesHigh-Risk, Clinically Localized Prostate Cancer: Is Monotherapy Adequate?Androgen-Independent Prostate CancerMark H KatzJames M McKiernanHigh-risk, clinically localized prostate cancer represents a diverse disease entity. Patients who are considered to be at highest risk for biochemical failure after localized treatments may not be at significant risk for diseasespecific mortality. In this review, an attempt will be made to define high-risk status and help identify patients at high risk for mortality after a diagnosis of localized prostate cancer. Subsequently, a review of monotherapy approaches as well as previously successful strategies utilizing multimodality therapy for high-risk disease will be presented. Finally, a synopsis will be given of several ongoing randomized clinical trials using the most effective systemic therapies in the adjuvant setting following thorough local treatments such as radical prostatectomy. This review will provide a glimpse into the future and describe the tools that it is hoped will improve further upon the results of surgical monotherapy for high-risk, localized prostate cancer. [Rev Urol. 2007;9(suppl 2):S19-S27]Prostate cancerRadical prostatectomyHigh-risk, localized prostate cancerMortality riskMultimodality therapy