Background: Recent data showed that cytoreductive nephrectomy (CN) should not be performed prior to systemic therapy in intermediate and poor risk groups. Immune checkpoint inhibitors (ICI) are now approved in first and second line in mRCC, but ICI effect on the primary tumor is unknown. Methods: All patients (pts) treated with ICI for mRCC without prior CN were retrospectively collected and sequential computed tomography (CT) scan evaluated for response. Primary objective was Objective Response Rate (ORR) in the primary renal tumor in the primary RECIST 1.1. Secondary objective included systemic ORR and nephrometry score changes. Results: A total of 20 pts were treated with ICI with primary tumor in situ between 12/2012 and 10/2018. Among these, CT scans were available for evaluation of response for 19 primary tumors in 18 pts. Median age was 59.5 years. Pathology was 16 clear cell RCC, 2 translocation RCC, 1 Collecting duct carcinoma. Baseline median primary renal tumor size was 7.3 cm. ICI was used in first line setting in 7 pts, in second line or beyond in 13 pts. IMDC risk group at ICI start was favourable in 2 pts, intermediate in 9 pts and poor in 9 pts. ICI used was NIVOLUMAB(N) single agent in 13 pts or in combination in 7 pts (6 N-IPILIMUMAB and 1 N-VEGFRTKI). After a median follow up of 6.5 month from ICI start and a median duration of immunotherapy of 3.0 month, ORR on the primary tumor, was 3/19 (16%) (1 CR and 2 PR), 14 tumors (74%) were stable, and 2 had PD as best response. Median change in primary renal tumor was -1%. ICI use did not change nephrometry score. At extra renal assessment, ORR (systemic) was 5/18 (28%), (2 CR, 3 PR), 5 (28%) SD, and 8 (44%) PD (including 1 with new lesion and 1 with non-target lesion PD). Interestingly, 4 pts/18 (22%) had mixed response with opposite response between primary and systemic response. Furthermore, 11/18 (61%) would not classified in same RECIST group (CR, PR, SD, PD) between primary and metastatic sites assessment. Conclusions: To our knowledge, we report the first cohort of patients treated with ICI investigating the response on the primary tumor. ICI can induce a significant reduction in primary renal tumor, especially complete response and therefore raise the question of delayed CN in responders under ICI.