BackgroundThe effectiveness of the clinical outcome of CN (Cytoreductive Nephrectomy) in cases of mccRCC (Metastatic Clear Cell Renal cell Carcinoma) is still uncertain despite two trials, SURTIME and CARMENA. These trials, conducted with Sunitinib as the standard treatment, did not provide evidence supporting the use of CN. MethodsWe queried the NCDB for stage IV mccRCC patients between the years of 2004-2020, who received (immunotherapy) IO with or without nephrectomy. Overall survival (OS) was calculated among three groups of IO alone, IO followed by CN (IOCN), CN followed by IO (CNIO). Cox models compared OS by treatment group after adjusting for sociodemographic, health, and facility variables. ResultsFrom 1,549,101 renal cancer cases, 7,983 clear and non-clear cell renal cell carcinoma cases were identified. After adjusting for sociodemographic and health covariates, patients who received IO followed by CN or CN followed by IO had a respective 64% (adjusted Hazard Ratio [aHR]= 0.36, 95% CI =0.30-0.43, p= 0.006] and 47% (aHR=0.53, 95% CI=0.49-0.56, p=0.001) mortality risk reduction respectively compared to patients who received IO alone. Compared to White adults, individuals who identified as Black exhibited 17% higher risk mortality (aHR= 1.17, 95% CI= 1.06-1.30, p=0.002). Patients who received CN prior to IO had a 59% associated mortality risk compared to patients who received IO followed by CN who had a lower risk, 35.7% (p<.001). ConclusionsPatients receiving CN regardless of sequence with IO did better than IO alone in this national registry-based adjusted analysis for mccRCC. Presently available data indicates that the combination of CN and IO holds promise for enhancing clinical results in patients with mRCC. MicroabstractThis study investigates the effectiveness of combining surgery, Cytoreductive Nephrectomy (CN), with immunotherapy (IO) in metastatic clear cell renal cell carcinoma (mccRCC). Using data from the National Cancer Database, outcomes were compared among patients receiving IO alone, IO followed by CN, and CN followed by IO. Results reveal a significant mortality risk reduction for patients undergoing CN in combination with IO, underscoring the potential clinical benefit in mccRCC management.