Impact of cytoreductive nephrectomy (CRN) on overall survival (OS) in metastatic nonclear cell renal cancer (nccRCC).

730 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for 25% of kidney cancer diagnoses and encompasses a diverse group of kidney tumors with distinct biology for which treatment in the metastatic setting is evolving. The role of CRN for nccRCC population in the current treatment 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 2006 and 2017, received systemic treatment (trt) with immunotherapy (IO) or non-immunotherapy (NIO) and either underwent or could have undergone a CRN were selected. Demographic and disease characteristics were summarized using descriptive statistics. The cumulative incidence of CRN with death without CRN as a competing risk, was estimated using the Nelson-Aalen estimator. The association of each demographic and disease characteristic on the cumulative incidence of CRN was evaluated using univariate Fine-Gray regression. The effect of CRN on survival was visualized using a 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 CRN. Results: We identified 3644 pts, 72% male, mean age 61 ±13 years. Nearly 40% of pts (n=1453) had sarcomatoid histology, followed by 30% with papillary (n=1075). Most pts, 96% (n=3489) received NIO systemic trt and only 9% were treated with IO (n=319). Nearly half of the study population (45%) underwent CRN (n=1642). Of these, 95% received NIO trt (n=1564) and 9% received IO (n=152). Pts who underwent CRN were younger and less likely to have bone, brain or liver metastases. Minority pts were less likely to undergo CRN. Mean time from dx to surgery was 1.1 ±1.7 months. For all pts, mOS was 9 months (95% CI: 8.6-9.4). OS was improved for pts who underwent CRN vs those who did not (11.3 vs 7.5 months, p<0.0001). In multivariate analysis, cytoreductive nephrectomy was associated with a reduction in the risk of death, HR 0.73 (95% CI: 0.68, 0.80, p<.0001). Conclusions: For pts with de novo metastatic nccRCC, CRN is associated with improved outcomes. Further analysis regarding the effect of treatment regimens on survival outcomes is warranted and planned. Prospective randomized trials in the modern treatment era are needed to further assess the timing and impact of CRN on outcomes in pts with metastatic nccRCC. [Table: see text]