Impact of deferred cytoreductive nephrectomy in the era of the immunotherapy in metastatic renal cell carcinoma: A multicenter retrospective study.

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Background: Deferred cytoreductive nephrectomy (dCN) is an emerging, strategy in the management of metastatic renal cell carcinoma (mRCC), applied selectively to patients who demonstrate a favorable response to initial systemic therapy. This study aimed to assess the clinical impact of dCN within the context of sequential treatment management. Methods: A multi-institutional retrospective evaluation. The descriptive analysis was performed to examine the demographic and clinical characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. A level of p < 0.05 was considered significant. Results: With a median follow-up of 19 months (1-174 months), 50 patients were divided into three groups: 46% received IO+TKI, 24% received IO+IO, and 30% received TKI. Of the cohort, 66% were male, with median age of 60.6 years. All had clear cell histology, and 76% were intermediate IMDC risk. The most common metastatic sites were lungs (50%), lymph nodes (36%), and bone (32%). The median time from systemic therapy to cytoreductive nephrectomy (CN) was 6 months. Notably, 26% did not restart treatment post-CN, and 6% discontinued pre-CN (two due to toxicity, one due to progression). Median PFS was 36 months, with a 5-year PFS rate of 40%. Analysis by IMDC risk and type of treatment showed no significant differences. However, patients with a Karnofsky score (KS) ≤80% had a lower risk of progression than those with KS >80% [HR: 0.31, 95% CI (0.13-0.75), p=0.01] and those achieving complete response had a significantly lower risk of progression [HR: 8.59, 95% CI (1.1-67), p=0.042]. Median OS was 91 months, with no significant differences between groups. Conclusions: This study demonstrates that dCN can offer a therapeutic advantage especially in selected patients who achieve favorable responses to upfront systemic therapy. Careful patient selection is crucial to maximize the potential benefits of delayed surgery, reduce perioperative risks and improve oncological outcomes. Larger patient cohorts and well-designed prospective clinical trials are essential to solidify these findings and establish evidence-based guidelines.