Prostate cancer (PCa) is the most common non-dermatologic cancer in the western countries in western countries. High-risk PCa accounts for 15% of the diagnosed cases. In this study, we compare the long-term survival outcomes of radical prostatectomy (RP), radiation therapy (RT), brachytherapy (BT), androgen- deprivation therapy (ADT), and watchful waiting (WW) in high-risk prostate cancer (PCa). Overall, RP/(RT plus ADT) gave the best survival outcome in patients with high-risk PCa, whereas ADT/WW had the worst outcome. The overall priority for treatment strategy could be ranked as follows: RP/(RT plus ADT), RT, and ADT/WW. RP had significant better overall survival (OS) than RT or BT, and RP had significant lower cancer-specific mortality (CSM) than RT (0.51 [95% CI 0.30–0.73], P<0.001). ADT improved the cancer-specific survival (CSS) of RP based on a case-controlled study; added ADT to RT failed to challenge the position of RP but could improve the outcome of RT. In conclusions,RP/(RT plus adjuvant ADT) could both be used for the first-line therapy of high-risk PCa. When encountering an individual patient, urologists should consider various factors like tumors themselves, preferences of individuals, and so on.