Stereotactic Body Radiation Therapy Alone or in Combination with Immunotherapy in Kidney Cancer: A Systematic Review

Background and objective: Despite its radioresistant reputation, renal cell carcinoma (RCC) is sensitive to high dose per fraction stereotactic ablative body radiotherapy (SABR). As SABR also triggers immunomodulatory effects, a combination of SABR and immunotherapy for RCC might improve patient outcomes. The current systematic review will discuss all prospective studies on SABR alone or combined with immunotherapy. Methods: A systematic review was conducted in January 2025 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement on the PubMed and Cochrane databases. Thirty-eight studies were included in this review. Key findings and limitations: In the primary setting, 15 prospective studies have proved SABR to be a valuable alternative for (partial) nephrectomy for high-risk or medically inoperable patients, with good tolerability and excellent local control. No prospective studies have reported on SABR combined with immunotherapy in nonmetastatic patients. In the oligometastatic setting, two phase 2 trials have investigated SABR in lieu of systemic treatment. This showed encouraging results, with the majority of patients being free from systemic therapy at 1 yr. SABR combined with immunotherapy in the metastatic setting has been investigated in multiple phase 1 and 2 trials, where the most promising option seems to be SABR to multiple—preferentially all—lesions. Cytoreductive SABR and SABR to oligoprogressive lesions combined with immunotherapy are attractive future strategies. Conclusions and clinical implications: SABR is a valid alternative in localised RCC when (partial) nephrectomy is not an option. In the metastatic setting, several early-phase trials have investigated SABR alone and in combination with immunotherapy, warranting future large, randomised trials.