Local treatment for metastatic and primary sites in metastatic renal cell carcinoma in the combination immunotherapy era: a narrative review

Advances in immuno-oncology (IO)-based systemic therapies have improved treatment outcomes for patients with metastatic renal cell carcinoma (mRCC). However, long-term survival of these patients remains challenging, highlighting the need to reassess the role of local and metastasis-directed treatments. Cytoreductive nephrectomy (CN) has traditionally been a part of the therapeutic armamentarium for mRCC, and evidence from the targeted therapy era-most notably the CARMENA and SURTIME trials-indicates that deferred CN after initial systemic therapy may benefit carefully selected patients. In the IO era, prospective evidence regarding CN is lacking, although ongoing trials, such as NORDIC-SUN and PROBE, are expected to refine patient selection and optimal timing. Real-world analysis reveals a significant decline in conducting CN since 2018. However, CN remains associated with improved overall survival of patients who received several IO-based first-line regimens after adjustment for baseline characteristics. Metastasis-directed treatments, including metastasectomy and local interventions for bone metastases, continue to exhibit potential survival benefits and may maintain functional status when complete resection of lesions is achievable. Considering the absence of definitive prospective data applicable to routine clinical practice, individualized treatment strategies should consider CN and local therapies alongside systemic treatment response, tumor biology, and patient-specific prognostic factors.