Deferred cytoreductive nephrectomy in patients with advanced RCC treated with first-line nivolumab plus ipilimumab: A propensity score-matched analysis from the RENOIR study (KCSG GU22-13).

Despite limited supporting evidence, deferred cytoreductive nephrectomy (dCN) has been regarded a useful therapeutic option in selected patients, particularly those demonstrating a favorable response to upfront systemic therapy in the era of immune-oncology. In this context, present study evaluated the clinical characteristics and role of dCN in patients with advanced renal cell carcinoma (aRCC) treated with 1st-line nivolumab plus ipilimumab (NI) therapy. Methods: Patients with aRCC who underwent dCN during 1st-line NI were identified from the Korean Cancer Study Group study (KCSG GU22-13), a retrospective cohort of 466 patients treated between 2018 and 2022 across 21 centers in Korea. To adjust for baseline differences between the dCN and NI-only groups, 1:3 nearest-neighbor propensity score matching was conducted. Covariates included age, sex, and International Metastatic RCC Database Consortium risk group. The primary endpoint was time to treatment failure (TTF); secondary endpoints included overall survival (OS) and clinical characteristics of patients undergoing dCN. Results: Twenty-four dCN patients were identified. Most had one or two metastatic sites (lung 70.8%, lymph node 66.7%). The median time from NI initiation to dCN was 5.3 months (mo), and the median number of treatment cycles was 20 (range, 2–85). The objective response rate (ORR) was 70.8%, while 12.5% demonstrated initial disease progression, primarily in the kidneys. Most patients underwent dCN for palliation, particularly to control gross hematuria, but one-third (n = 7) were curatively intended based on near complete response (CR) in extrarenal metastatic sites. Two patients discontinued NI postoperatively due to achieving CR. Notably, patients who achieved objective response before dCN showed significantly more favorable survival from the date of dCN (not reached vs. 25.7 mo, p = 0.01), whereas dCN performed in cases of initial progression failed to confer meaningful survival benefits. After matching, 96 patients (24 dCN; 72 NI-only) were analyzed. Compared with NI-only, dCN patients had larger primary tumors (≥7.5 cm; 75.0% vs. 50.0%, p = 0.03), fewer liver metastases (0% vs. 16.7%, p = 0.03), and higher completion of 4 NI induction cycles and ORR (83.3% vs. 56.9%, p = 0.02 and 70.8% vs. 51.4%, p = 0.09). With a median follow-up of 26.2 months, median TTF was longer in the dCN group (49.4 vs. 6.4 mo; p = 0.09), though not statistically significant. Median OS did not differ significantly (not reached vs. 42.8 mo; p = 0.22). Conclusions: In aRCC treated with 1st-line NI, response before dCN predicted post-dCN survival. After matching, dCN showed a trend toward longer TTF, suggesting potential benefit in selected responders.