INTRODUCTION: The management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with the development of androgen receptor axis-targeted (ARAT) agents. The updated results with final overall survival (OS) data of the phase III PROSPER, SPARTAN, and ARAMIS trials have recently been reported. Therefore, we performed an updated meta-analysis and network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. EVIDENCE ACQUISITION: Multiple databases were searched for articles published before January 2021. Studies that compared OS and adverse events (AEs) in patients with nmCRPC were considered eligible. EVIDENCE SYNTHESIS: Three studies (N.=4117) met our eligibility criteria. Formal network meta-analyses were conducted. ARAT agent is associated with significantly longer OS compared to placebo (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001), with similar results shown for patients with both N1 and N0 disease (pooled HR 0.61 and pooled HR 0.76, respectively). In the network meta-analysis, apalutamide, darolutamide, and enzalutamide were more effective than placebo, with similar efficacies in terms of OS. For AEs (including any AEs, grade 3 or grade 4 AEs, grade 5 AEs, serious AEs, and AEs leading to treatment discontinuation), darolutamide was shown to be likely well tolerated. Quality of Life was preserved in treatment arms irrespective of the drug. CONCLUSIONS: All three ARAT agents are efficacious options for the treatment of nmCRPC, whereas darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

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

Department of Urology Campus Bio Medico University Rome Italy

Department of Urology IRCCS San Raffaele Hospital Vita Salute San Raffaele University Milan Italy

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology La Croix du Sud Hospital Quint Fonsegrives France

Department of Urology La Paz University Hospital Madrid Spain

Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology University Hospital Zurich Zurich Switzerland

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

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

European Society of Residents in Urology Arnhem the Netherlands

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

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Men's Health and Reproductive Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran

Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

School of Medicine Department of Urology Jikei University Tokyo Japan

School of Medicine Division of Urology Department of Oncology San Luigi Hospital University of Turin Orbassano Turin Italy

Minerva Urol Nephrol. 2022 Jun;74(3):360-362. doi: 10.23736/S2724-6051.22.04948-5. PubMed

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