CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies. OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients. EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators. EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively. CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain. PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.

Department of Biomedical Informatics College of Medicine Konyang University Daejeon Republic of Korea

Department of Biostatistics and Translational Medicine Medical University of Lodz Lodz Poland

Department of Radiation Oncology Brigham and Women's Hospital and Dana Farber Cancer Institute Harvard Medical School Boston MA USA

Department of Radiation Oncology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Radiation Oncology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; 3rd Radiotherapy and Chemotherapy Department Maria Skłodowska Curie National Research Institute of Oncology Gliwice Poland

Department of Radiation Oncology Iridium Network Wilrijk Belgium

Department of Radiation Oncology Oncological Institute of Southern Switzerland Bellinzona Switzerland

Department of Radiotherapy ICO René Gauducheau Saint Herblain France

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Dentistry and Pharmaceutical Sciences Okayama University Graduate School of Medicine Okayama Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; Division of Urology Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan; Department of Urology Weill Cornell Medical College New York NY USA; Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Hospital Clínico San Carlos Madrid Spain

Department of Urology La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology St Antonius Hospital Utrecht The Netherlands

Division of Urological Surgery and Center for Surgery and Public Health Brigham and Women's Hospital Harvard Medical School Boston MA USA

Unit of Urology Division of Oncology IRCCS Ospedale San Raffaele Milan Italy

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Metastasis-directed therapy in oligometastatic prostate cancer