The Emerging Role of Extracranial Stereotactic Ablative Radiotherapy for Metastatic Renal Cell Carcinoma: A Systematic Review.

CONTEXT: Although the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of new systemic agents, still few patients experience a long-term durable response. Stereotactic ablative radiotherapy (SABR) is nowadays commonly used as metastasis-directed therapy (MDT), but limited data exist on how best to implement this strategy as part of a multimodal approach.

OBJECTIVE: To evaluate the potential role of extracranial SABR in mRCC and to identify future therapeutic developments of SABR in different disease settings.

EVIDENCE ACQUISITION: A systematic review was conducted in May 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement on the PubMed database. Thirty-four studies were selected for inclusion in this systematic review.

EVIDENCE SYNTHESIS: SABR has been used with four main goals: (1) eradication of the whole metastatic burden in synchronous and metachronous oligometastatic patients, resulting in a long-term local control (LC) rate of >90% and median progression-free survival (PFS) ranging between 8 and 15 mo; (2) eradication of oligoprogressive lesions, enabling an extension of the duration of the systemic therapy by approximately 9 mo; (3) improvement of the response to systemic therapy in polymetastatic patients, resulting in an overall response rate ranging from 17% to 56%; and (4) cytoreduction in polymetastatic mRCC patients, with LC rates ranging between 71% and 100%, and preservation of the renal function, but unclear PFS and overall survival impact. Overall, the combination of SABR and systemic agents has been associated with overall good tolerance, with grade ≥3 toxicity ranging from 0% to 13%.

CONCLUSIONS: Current data highlight the role of SABR as an emerging MDT treatment option in both oligometastatic and oligoprogressive extracranial mRCC, able to ensure long-term disease control and delay the use of next-line systemic therapies. The use of SABR for cytoreduction in the de novo metastatic disease and as an immunological booster in the polymetastatic setting remains investigational and warrants further investigations.

PATIENT SUMMARY: Radiotherapy delivered with ablative doses (>6 Gy per fraction) is a promising treatment strategy for patients diagnosed with metastatic renal cell carcinoma. Excellent outcome results have been observed in patients with a limited number of metastases, improving metastasis-free survival by several months. For patients with a few metastases progressing under systemic therapy, radiotherapy allows an extension of the duration of the ongoing therapy by several months.