Extensive necrosis as a prognostic indicator in metastatic RCC patients undergoing deferred cytoreductive nephrectomy after immunologic checkpoint inhibitor treatment.

Abstract

468 Background: The role of cytoreductive nephrectomy (CN) in patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitor (ICI)-based therapies remains under debate. Retrospective cohorts have reported shrinkage in the primary tumors and no residual tumor in primary specimens (pT0), however, the clinical relevance has not been explored. Assessing the pathological outcomes of CN following ICI may provide valuable information. Methods: This is a single-center retrospective analysis of metastatic/locally advanced RCC who underwent CN between May 2017 and September 2024 after ICI-based treatment. Demographic and clinicopathological were collected. The primary endpoint was the rate of patients with extensive necrosis (EN), defined as ≥ 95% of necrosis in the resected primary tumor. Progression-free survival (PFS) was calculated at two timepoints: from the date of ICI initiation (PFS1) and from the date of surgery (PFS2) until event (progression or death) or last follow-up, using the Kaplan-Meier method. Differences between groups (pts with EN in resected kidney vs not) were assed with the log-rank test and hazard ratios were calculated with Cox regression model. Correlations were made with the Fisher test between presence of EN and other categorical variables. Results: Twenty-five pts were identified, with a median age of 62 years (range, 40–83), and median follow-up of 31.5 months after initiating ICI. 84% were metastatic, with 84% receiving first-line ICI-based combinations (5 Ipi/Nivo;16 ICI-TKI), while the remaining 16% had second-line nivolumab. The median ICI exposure before surgery was 10.5 m (range, 2.1–42.7) in the entire cohort, 12.7 m (range, 2.1–28.8) in the EN subgroup and 10.3 m (range, 3.1–42.7) in the non-EN. Best overall radiological response prior to surgery included 4% CR, 68% PR and 28% SD. Pathological assessment revealed 76% clear cell, 16% unclassified and 8% papillary RCC and 16% had a sarcomatoid component. 40% of pts had ≥ 95 % necrosis, with half of these pts (20%) achieving pT0. The median PFS1 was numerically longer in pts with EN, not reached (NR) vs 27.7 m, (HR 0.33; 95% CI, 0.09 -1.26; p = 0.09). The median follow-up after surgery was 10 months, and the median PFS2 was longer in the EN subgroup, NR vs 9.7 m, (HR 0.2; 95% CI, 0.04–0.96; p < 0.05). No significant correlations were found between EN and Fuhrman grade, presence of sarcomatoid differentiation, treatment duration, or radiological response. Conclusions: ICI-based regimens showed activity in primary RCC tumors, leading to EN (≥ 95% of necrosis) in a subset of pts. Those who achieved EN appear to have reduced risk of disease progression.