Clinical and pathological outcomes of nephrectomy/metastasectomy in patients with metastatic renal cell carcinoma after prior immune checkpoint inhibitor exposure.

e16515 Background: The landscape of metastatic renal cell carcinoma (mRCC) treatment has changed with the emergence of immune checkpoint blockade (ICB) which leads to enhanced responses and prolonged survival compared to tyrosine kinase inhibitors (TKI). The higher objective response rates and durable disease control has resulted in consideration of consolidative surgery in a subset of patients. Methods: A single-center retrospective analysis of mRCC patients who had cytoreductive nephrectomy or metastasectomy between October 2017 and January 2024 after prior ICB exposure was conducted. Clinical and pathological characteristics, response to ICB, and safety outcomes were evaluated. We also assessed the time off systemic therapy after surgery. Results: Seventeen patients were identified. The median age was 59 years, and the median follow-up was 24.8 months after starting ICB. 76.5% received combination regimens (six with dual ICB and seven with ICB plus TKI), while the remaining four patients had anti-PD1 monotherapy. Fourteen patients initiated ICB as first- line treatment while the remaining three patients had ICB in the second line. Median ICB exposure time before surgery was 10.9 months (range, 0.8 - 41.5). 70.6% were International mRCC Database Consortium (IMDC) intermediate risk and 29.4% were poor risk. Fifteen patients had radical nephrectomy, and one had a renal bed resection. The best overall response before surgery included 6% complete response, 35.2% partial response, 41.1% stable disease, 17.6% disease progression (PD of primary tumor only). Pathological findings revealed 76.5% clear cell, 11.8% unclassified and 11.8% papillary RCC. 58.8% showed Fuhrman grade 3 or 4 and 11.8% had a sarcomatoid component. Notably, three (17%) patients had a complete pathological response in the primary tumor and 88.2% displayed necrosis. One patient (6%) had a 30-day post-operative complication of deep vein thrombosis. Fourteen (82.4%) patients had residual disease after surgery, but ten patients (58.8%) discontinued systemic treatment. Among the seventeen patients, nine resumed systemic therapy after a median time of 8.3 months off therapy (range, 2.8 -15.5). Conclusions: Surgical consolidation after ICB is safe and may allow patients time off systemic therapy. ICB is active in primary renal tumors, with complete pathological responses and necrosis observed.