High-risk prostate cancer (PCa), established according to the d’Amico criteria or other prognostic tools, remains very heterogeneous, including a third of patients with excellent prognosis in whom surgical treatment can result in long-term progression-free survival. In contrast, a substantial proportion of high risk will not be cured by local treatment alone and might benefit from a more aggressive multimodal adjuvant treatment strategy. However, to date, except in one adjuvant radiotherapy series, no neoadjuvant or adjuvant therapy has shown a survival improvement after radical prostatectomy for high-risk PCa. Recent observational studies tend to prove that radical prostatectomy may offer benefits over radiotherapy in disease-free and overall survival. However, good Level 1 evidence is lacking and further prospective studies are warranted to directly compare the outcomes of radical prostatectomy to combined radiation and hormonal therapy in high-risk patients.