ABSTRACT
Prostate cancer has a high prevalence and a rising incidence in many parts of the world. Although many screen-detected prostate cancers may be indolent, prostate cancer remains a major contributor to mortality in men. Therefore, the appropriate diagnosis and treatment of localized prostate cancer with lethal potential are of great importance. High-risk, localized prostate cancer has multiple definitions. Treatment options that should be individualized to each patient include observation, radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation, and combined modality treatment. Specific outcomes of radical prostatectomy and combined modality treatment for high-risk prostate cancer are reviewed. The rationale for extended pelvic lymphadenectomy at the time of surgery is discussed, as is the role for surgery in the setting of node-positive, high-risk disease. There is not yet a biomarker that accurately identifies lethal prostate cancer, but rigorous clinical studies have identified methods of optimizing oncologic outcomes in high-risk men.