CONTEXT: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. EVIDENCE ACQUISITION: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. EVIDENCE SYNTHESIS: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01-0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95-0.99; n = 293) and 0.97 (95%CI: 0.93-0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88-0.98; n = 294) and 0.86 (95%CI: 0.77-0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. CONCLUSIONS: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients.

2nd Department of Urology Centre of Postgraduate Medical Education 01 813 Warsaw Poland

3 Department of Radiotherapy and Chemotherapy Maria Skłodowska Curie National Research Institute of Oncology 44 102 Gliwice Poland

Brachytherapy Department Saint John's Cancer Center 20 090 Lublin Poland

Collegium Medicum Faculty of Medicine WSB University 41 300 Dąbrowa Górnicza Poland

Department of Biochemical Science Humanitas University 20072 Milan Italy

Department of Experimental and Clinical Medicine University of Florence 50139 Florence Italy

Department of Radiation Oncology University Medical Center 3584 Utrecht The Netherlands

Department of Radiotherapy Medical University of Lublin 20 059 Lublin Poland

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna 1090 Vienna Austria

Department of Urology Humanitas Clinical and Research Institute IRCCS 20089 Milan Italy

Department of Urology Jagiellonian University Medical College 30 688 Krakow Poland

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

Department of Urology Medical University of Silesia 40 800 Zabrze Poland

Department of Urology Semmelweis University 1083 Budapest Hungary

Department of Urology Shimane University Faculty of Medicine Izumo 693 8504 Japan

Department of Urology University Medical Center Hamburg Eppendorf 20251 Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX 75390 USA

Department of Urology Weill Cornell Medical College New York NY 10065 USA

Division of Urology Department of Special Surgery University of Jordan Amman 11942 Jordan

Institute for Urology and Reproductive Health Sechenov University 119992 Moscow Russia

Karl Landsteiner Institute of Urology and Andrology 1010 Vienna Austria

Radiotherapy Department Maria Skłodowska Curie National Research Institute of Oncology 44 102 Gliwice Poland

Radiotherapy Department Saint John's Cancer Center 20 090 Lublin Poland

Research Centre for Evidence Medicine Urology Department Tabriz University of Medical Sciences Tabriz 5166 15731 Iran

Unit of Urological Robotic Surgery and Renal Transplantation University of Florence Careggi Hospital 50134 Florence Italy

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