Neoadjuvant Surgical Enablement in Renal Cell Carcinoma: Systematic Review and Meta-analysis

Neoadjuvant systemic therapy is increasingly considered for selected patients with localized or locally advanced renal cell carcinoma (RCC) when the intended value is not merely tumor shrinkage but surgical enablement, including partial nephrectomy achievement, venous tumor thrombus downstaging, or simplification of the planned operation. We synthesized the evidence on neoadjuvant or preoperative systemic therapy as a surgical-enabling strategy in RCC. PubMed/MEDLINE, Web of Science Core Collection, the Cochrane Library, and Embase were searched from inception to 1 May 2026. Eligible reports included adults with localized or locally advanced RCC treated with neoadjuvant or preoperative systemic therapy before surgery or surgical reassessment and reporting extractable surgical, radiographic, pathologic, or safety outcomes. Random-effects single-arm meta-analyses used non-overlapping outcome-level denominators. Thirty-four eligible study records were included. Pooled rates were 0.80 for partial nephrectomy achievement, 0.32 for objective response, 0.44 for venous tumor thrombus or Mayo-level downstaging, 0.42 for surgical strategy simplification, and 0.11 for pathologic complete response or ypT0. Grade ≥ 3 treatment-related adverse events occurred at a pooled rate of 0.28; among operated patients, Clavien-Dindo grade ≥ III postoperative complications occurred at a pooled rate of 0.13. Certainty was low or very low. Neoadjuvant systemic therapy may support individualized surgical enablement in selected RCC patients, but current evidence does not justify routine use outside carefully defined multidisciplinary decision-making or prospective trials.