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Introduction Recent breakthrough recognition of metastasis-free survival as a clinically relevant endpoint has opened a new era in the management of advanced prostate cancer. The need for new, intermediate endpoints is the logical consequence of scientific advances in prostate carcinoma. The treatment algorithms for non-metastatic castration-resistant prostate cancer (M0 CRPC) have recently been updated by adding novel anti-androgen apalutamide, and also enzalutamide for high-risk patients. Objective To review clinical evidence of metas