Background: With the approval of more effective systemic treatments (syst Rx) such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI), the impact of cytoreductive nephrectomy (CN) on response to Rx and survival remains unknown. The majority of patients (pts) previously enrolled in clinical trials have had radical nephrectomy (RN) or CN prior to syst Rx. Therefore, the response of the P-Rmass to ICIs and the effect of intact P-Rmass on response to syst Rx is not well described. Methods: A retrospective review of 209 pts with mRCC who were treated with ICI in the first or second-line was conducted. Following the appropriate regulatory process, collaborators from 5 US sites collected clinical, pathological, and outcome data via chart review. The response was investigator-assessed for all pts with at least one post-treatment scan or evidence of clinical progression after treatment initiation. Overall radiographic response (ORR) includes complete response (CR) and radiographic response (Rad-resp) to treatment. Disease control rate (DCR) includes CR, Rad-resp, and stable disease. Results: Median age at diagnosis was 63 yrs and 69% were male. 102 pts (49%) had localized disease at diagnosis and underwent radical or partial nephrectomy, 3 (1%) had ablation/radiation of P-Rmass, 26 (12%) had CN, 9 (4%) had CN after an excellent response to syst Rx, 12 (6%) had a previous nephrectomy but developed a new Rmass (measurable target lesion), and 57 (27%) did not have CN and had an intact P-Rmass. 176 (84%) pts had clear cell histology. 27 (14%) and 23 (12%) had known sarcomatoid and rhabdoid features, respectively. Overall, 77 (37%) pts had a measurable Rmass while receiving syst Rx. 84 (40%), 93 (45%), and 10 (5%) pts received ICI (Ipilimumab/Nivolumab or Nivo), TKI, or Pembrolizumab/Axitinib in the first-line. 143 (68%) and 70 (33%) pts received second- and third-line treatment. 103 (72%) and 28 (19%) pts received ICI and TKI in the second-line, respectively. The best ORR and the Rad-resp in the intact P-Rmass in evaluable pts are summarized in the table below. ORR to ICI in the first or second-line were numerically higher in pts with an intact P-Rmass compared to pts who had nephrectomy, but this difference was not statistically significant (p= .38 and .35 respectively). Conclusions: The intact P-Rmass had a good response (62-70%) to the first-line syst Rx. Although the overall Rad-resp rates to ICI are numerically higher in pts with intact P-Rmass, this difference was not statistically significant.