Pathologic findings and clinical outcomes after immune checkpoint blockade in renal cell carcinoma patients undergoing deferred consolidative nephrectomy.

Abstract

525 Background: Consolidative nephrectomy (CN) is undertaken in selected patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockade (ICB). However, patient selection and post-operative management (e.g. treatment discontinuation) remains controversial. Standardized pathological response assessment may provide prognostic insight. We evaluated the association between pathological features and clinical outcome in patients undergoing CN after ICB. Methods: A multicenter retrospective study of patients with locally advanced or mRCC who underwent CN following ICB between 2018 – 2025 across five US centers was performed. Clinical and pathological features (tabulated by institutional genitourinary pathologist and oncologist) were collected both at baseline and during follow-up. The primary endpoint was 18-month progression-free survival (PFS) from CN by pT0 status (no residual viable tumor). Secondary endpoints included 18-month PFS according to major pathological response (MPR), defined as ≤ 10% residual viable tumor, residual sarcomatoid component (yes/no), and post-operative residual measurable disease. PFS was estimated from the date of surgery until progression or last follow-up using Kaplan-Meier method and differences in 18-month PFS between subgroups were compared using a two-sample z-test. Results: 137 patients were included; median age 63 years, 78% had stage IV disease; 87% clear cell RCC. Median follow-up was 34 months since start of ICB and 22 months after CN. ICB regimens included anti-PD1 + CTLA4 (42%), anti-PD1 + TKI (50%), and anti-PD1 monotherapy (7%). Median ICB duration prior to CN was 5.6 (IQR 2.8 – 12) months and median time to CN from last treatment was 1.2 months. Overall radiological objective response per investigator-assessed RECIST 1.1 pre-CN included CR 0.7%, PR 44%, SD 46%, PD 3.5% and median primary tumor shrinkage was 17.6%. On pathology, 12% achieved pT0, 22% MPR, 75% had histologic grade ≥3, and 14% had sarcomatoid features. Among pT0 patients, 29% received anti-PD1 + CTLA4 and 59% IO-TKI. At 18-months post-CN, the PFS was 100% for pT0 vs. 55% for non-pT0 (p < 0.01). Patients without sarcomatoid component (68% vs. 27%) showed significantly improved 18-month PFS (p < 0.01) and those with a MPR showed a trend toward longer 18-month PFS (72% vs. 55%, p = 0.14). Among stage IV patients, the absence of postoperative measurable disease (n = 51) was associated with superior 18-month PFS (70% vs. 43%, p < 0.01). Immediately after CN, 49% discontinued ICB and 54% discontinued TKI. Conclusions: Pathologic complete response was associated with longer PFS among patients undergoing deferred CN after ICB. These findings highlight the clinical relevance of standardized pathologic assessment in RCC and suggest that selected patients may achieve durable disease control following surgery.