(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC H2X 0A9 Canada

Clinic of Urology and Urological Oncology Jagiellonian University 30 688 Krakow Poland

Department of Urology 2nd Faculty of Medicine Charles University 15006 Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Wahringer Gurtel 18 20 1090 Vienna Austria

Department of Urology Faculty of Medicine and University Hospital of Cologne 50937 Cologne Germany

Department of Urology Hillel Yaffe Medical Center 169 Hadera 38100 Israel

Department of Urology Medical University of Silesia 41 800 Zabrze Poland

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama 700 8530 Japan

Department of Urology The Jikei University School of Medicine Tokyo 105 8461 Japan

Department of Urology University Medical Center Hamburg Eppendorf 20251 Hamburg Germany

Department of Urology University of Texas Southwestern Medical Center Dallas TX 75390 USA

Department of Urology Weill Cornell Medical College New York NY 10021 USA

Division of Urology Department of Special Surgery The University of Jordan Amman 19328 Jordan

Institute for Urology and Reproductive Health Sechenov University 119435 Moscow Russia

Karl Landsteiner Institute of Urology and Andrology 1090 Vienna Austria

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