What a Surgeon Needs to Know about Cytoreductive Nephrectomy in the Immunotherapy Era: A Comprehensive Narrative Review

Abstract

Cytoreductive nephrectomy in metastatic renal cell carcinoma has been redefined by the results of the CARMENA and SURTIME trials and, more recently, by the introduction of immune checkpoint inhibitor-based combination regimens. Although systemic therapy has improved survival outcomes, important uncertainty remains regarding patient selection, timing of surgery, operative strategy, and postoperative integration of cytoreductive nephrectomy within multimodal care. This narrative review summarizes contemporary evidence on cytoreductive nephrectomy in the immunotherapy era, with a focus on patient selection, treatment sequencing, surgical management, and postoperative decision-making. Current real-world, registry-based, and meta-analytic data suggest that cytoreductive nephrectomy may still have a role in carefully selected patients, particularly those with favorable or selected intermediate-risk disease, limited metastatic burden, preserved performance status, and disease control after initial systemic therapy. Deferred cytoreductive nephrectomy has gained increasing attention as a response-adapted strategy that may allow biologic selection of patients more likely to benefit from surgery, whereas upfront cytoreductive nephrectomy may still be appropriate in selected favorable-risk cases or when local symptom control is required. Radical nephrectomy remains the standard surgical approach for most patients, while partial nephrectomy and minimally invasive techniques may be considered in highly selected settings. However, most available evidence remains retrospective and subject to important bias. Overall, cytoreductive nephrectomy should be regarded as a selective, risk-adapted, and strategically timed component of multidisciplinary metastatic renal cell carcinoma management in the immunotherapy era, although its optimal role remains to be defined by ongoing prospective trials.