Impact of cytoreductive nephrectomy (CN) and treatment (trt) sequence on overall survival (OS) in metastatic non-clear cell renal cell cancer (nccRCC).

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e16543 Background: nccRCC accounts for 25% of kidney cancer diagnoses and encompasses a diverse group of kidney tumors with distinct biology for which trt in the metastatic setting is evolving. The role of CN for nccRCC population in the current trt landscape remains unclear. Methods: We retrospectively identified patients (pts) with nccRCC from The National Cancer Database (NCDB) participant user file (PUF) for Kidney and Renal Pelvis Tumors. Pts with de novo metastatic disease diagnosed between 2015 and 2020, received systemic trt with immunotherapy (IO) or non-immunotherapy (NIO) and underwent or could have undergone a CN were selected. Pts classified as having sarcomatoid histology were excluded. Demographic and disease characteristics were summarized using descriptive statistics. The cumulative incidence of CN was estimated using the Nelson-Aalen estimator. The association of demographic and disease characteristics on the cumulative incidence of CN was evaluated using univariate Fine-Gray regression. The effect of CN on survival was visualized via Simon-Makuch plot. P values were based on Mantel-Byar test. Cox regression with a time-dependent predictor was used to estimate the change in the hazard of death after CN. Results: We identified 982 pts, median age 60 (18 – 90) years, 61% male, 69% Caucasian and 28% African American. nccRCC histology included 66.5% papillary (n=653), 10.4% chromophobe (n=102), 9.9% medullary (n=97), 8.8% collecting duct (n=86), 4.4% unclassified (n= 43). 69% of pts received NIO (n= 676), 14% received IO + NIO (n= 134), 18% received IO only (n= 172). 40% had CN (n=390), the majority of CN (86%) occurred within 3 months of diagnosis. 89% had CN followed by systemic trt (n=348), 4.3% underwent initial systemic trt followed by CN (n=42). Median OS was 11 months for the entire group. For those who had CN, mOS was 13.9 vs 10 months for no CN (p=0.002). CN was associated with improved survival; HR 0.79 (95% CI 0.68,0.92; p=0.002). Median OS for pts who received systemic trt followed by CN was 32.6 vs 12.8 months for those who had CN followed by systemic trt vs 10 months for those who had no CN, (p=0.001). Upfront systemic trt followed by CN and CN followed by systemic trt were both associated with improved survival, HR 0.56 (95% CI 0.36, 0.87; p=0.009) and HR 0.83 (95% CI 0.69,0.99; p= 0.034) respectively. Choice of systemic trt was not associated with improved OS (p = 0.139). Unclassified and medullary histology were associated with worse OS, HR 1.60 (95% CI 1.09, 2.34; p=0.015) and HR 2.04 (95% CI 1.46,2.84; p=0.002) respectively. Conclusions: CN is associated with improved outcomes for pts with de novo metastatic nccRCC. Sequencing upfront systemic trt followed by CN may improve survival. Prospective randomized trials in the modern trt era are needed and ongoing (Ie. PROBE trial NCT04510597) to further assess the timing and sequencing of CN in pts with nccRCC.

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