Outcomes of delayed cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma treated with immune checkpoint inhibitor therapy.

462 Background: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has evolved in the immune checkpoint inhibitor (ICI) era. We evaluated outcomes of patients with clear cell mRCC treated with first-line ICI therapy who subsequently underwent delayed CN. Methods: Using the Canadian Kidney Cancer information system (CKCis), a multi-institutional database, we retrospectively identified patients with clear cell mRCC treated with first-line ICI-based therapy who subsequently underwent CN. Clinical characteristics, treatment details, use of metastasis-directed therapy, and survival outcomes were collected. Descriptive statistics were applied and Kaplan–Meier methods were used to estimate progression-free survival (PFS) and overall survival (OS). Results: A total of 61 patients underwent delayed CN from January 2017 to June 2024 from a cohort of 1560 patients. Median age at CN was 64 years; 84% were male. All patients had intermediate (47%) or poor-risk (53%) by IMDC criteria. Sarcomatoid features were present in 22%. Lung (77%), lymph node (48%), and bone (18%) were the most common metastatic sites. Most patients had less than 3 sites of disease (65.6%). The most common ICI regime was ipilimumab + nivolumab (85%). Median time from ICI therapy initiation to CN was 11.5 months. A total of 38 patients (62%) who received first-line ICI therapy have discontinued treatment and remain alive, with only 20% (N = 12) requiring second-line therapy. With a median follow-up of 44 months, median OS was not reached; 2- and 5-year OS rates were 88% and 74%, respectively. Median PFS was 35 months, with 2- and 3-year PFS of 61% and 50%. Conclusions: In this retrospective series, delayed CN following ICI therapy in carefully selected patients was associated with durable disease control and encouraging long-term survival. Future analyses will explore pathologic response. These results highlight the need for randomized trials of deferred CN in the ICI era. Characteristic (N=61) Value Ipilimumab + Nivolumab 52 (85%) Pembrolizumab + Axitinib 9 (15%) Metastasis Directed Therapy Radiation therapy 18 (30%) Metastasectomy 12 (20%) Complete Response pre-CN 8 (13%) Discontinuation of systemic therapy 38 (62%) 5-year OS 74% 5-year PFS 50%