PURPOSE OF REVIEW: The landscape of therapy for metastatic castration-resistant prostate cancer (mCRPC) has seen an unprecedented transformation with the emergence of combination therapies. This review summarizes the current findings from randomized controlled trials (RCTs) assessing the oncologic outcomes of mCRPC. RECENT FINDINGS: In the first-line, treatment-naïve setting, recent RCTs demonstrated the oncologic benefit of adding AKT inhibitors or poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors to abiraterone in terms of radiographical progression-free survival. Although this is a strong surrogate endpoint, these agents have not yet shown overall survival (OS) improvement. In the second- or later-line settings, olaparib improved OS in patients with at least one alteration in BRCA1 , BRCA2 , or ATM gene and lutetium-177-prostate-specific membrane antigen-617 [177-Lu-prostate-specific membrane antigen (PSMA)-617] were superior to repeat androgen receptor signaling inhibitor (ARSI) therapy. In addition, 177-Lu-PSMA-617 had better progression-free survival compared with cabazitaxel but failed to result in an OS benefit. To date, there is no evidence for effective immune checkpoint inhibitor regimens/combinations for mCRPC. SUMMARY: According to recent RCTs, several novel agents and/or combinations exhibit promising oncologic outcomes. In the first-line setting, OS benefits compared with currently available regimens are still missing. Results from ongoing/well-designed phase 3 RCTs and real-world data regarding the sequential impact of currently available agents on outcomes of mCRPC patients after ARSI-based combination therapy for metastatic hormone-sensitive prostate cancer are awaited. Such data will improve clinical decision-making in the ever-intensifying treatment era.

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology The Jikei University School of Medicine Tokyo

Department of Urology University of Texas Southwestern Medical Center Dallas Texas USA

Department of Urology Weill Cornell Medical College New York New York USA

Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

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