The high risk patient with clinically local-regional prostate cancer has a number of treatment options. The classification of high risk will be delineated. The level I evidence has documented the efficacy of external beam radiotherapy (EBRT) dose escalation, while support for pelvic lymph node therapy has not yet been garnered. The data will be summarized and compared to the very favorable results with brachytherapy-based methods. The side effects of these treatments are fairly low using modern techniques and will be summarized. The use of conventional EBRT doses and androgen deprivation therapy (ADT) has been studied extensively in Phase III clinical trials and found to improve survival over EBRT alone. The impact of ADT on quality of life is substantial, however. A key question is whether ADT is necessary in the setting of RT dose escalation — the related findings will be discussed. Another combined modality approach is prostatectomy followed by post-operative RT adjuvantly or for salvage. Level I evidence demonstrates that adjuvant and salvage radiotherapy result in consistent reductions in biochemical failure, as well as distant metastasis andin one study, mortality. At the conclusion of this activity, the learner will be able to do the following: 1. Discuss the role of radiation dose escalation, including brachytherapy, and the gains from lymph node treatment. 2. Review the role of the addition androgen deprivation to radiotherapy and the side effects of androgen deprivation. 3. Explain the gains from post-prostatectomy radiotherapy given adjuvantly and for salvage.