Background: Following CARMENA and SURTIME, upfront cytoreductive nephrectomy (CN) is no longer standard of care. Intermediate and poor risk patients (pts) receive systemic therapy with the PT in place with the option to perform deferred CN in responding pts. This practice has been adopted after the recent shift to immune checkpoint inhibitor combination in frontline for mRCC. We assessed the safety and efficacy of this approach in a real-world population. Methods: A retrospective analysis of a clinical audit from 3 institutional datasets of pts treated with first-line N+I and the PT in place. Pts and tumour characteristics, International Metastatic RCC Database Consortium (IMDC) risk, overall response rate (ORR) in the PT and metastatic sites, time to response (TTR) of the PT, PT- and immune related- (ir) adverse events (AE), deferred CN rate, progression free- (PFS) and overall survival (OS) were assessed. Results: Of 41 pts treated with N+I and the PT in place, 46.3% were IMDC poor risk and 51.2% had > 3 metastatic sites. After a median follow-up of 5.9 (2-10.3) months, 29 had at least 1 CT scan from baseline. Of those, 7 (24.3% [95% confidence interval [CI] 0.10-0.43]) had a partial response (PR) of the PT with a median TTR of 5.3 (2.5-8.6) months. Mean and median PT reduction were 16.9% (+7.6 to -70.3%) and 10% from a baseline mean tumour size of 9.5 (3.8-16.1) cm. Pts with a PT reduction > median (n = 14) had a PR at metastatic sites in 86% (CI 0.57-0.98) and no progressive disease (PD). Pts with PT reduction < median (n = 14) had PR in only 21% and PD at metastatic sites in 57% (CI 0.28-0.82). None of the PT progressed. There was no complete response (CR) at metastatic sites . No CN was performed; 5 pts (12%) developed hematuria grade 1-3, requiring embolisation in 2 (4.9%). Grade 3-4 irAE were observed in 22% of pts. Median PFS and OS are 8.6 months and not reached. Conclusions: N+I with the PT in place is safe and PT reduction is associated with response at metastatic sites. Most PT responded by 6 months. No CR at metastatic sites were observed (compared to a 9% CR rate in the pivotal trial) in this real-world population with a relatively high percentage of poor-risk pts. Furthermore, no deferred CN has been performed, neither for near-CR at metastatic sites nor for PT symptoms.