Impact of Time to Metastasis (Synchronous vs. Metachronous) on Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with First Line Immune-Checkpoint Inhibitors (ICI)-based Combinations

Abstract Background Metastatic renal cell carcinoma (RCC) can present as synchronous metastatic disease, where primary metastases are detected at the time of diagnosis, or metachronous appear during follow-up after initial RCC diagnosis. The effect to metastasis on patient outcomes is not well characterized in era immune checkpoint inhibitor (ICI)-based combinations. Herein, we assess differences clinical between patients with and mRCC. Methods Data for mRCC treated first line ICI-based combination therapies 2014 2023 were retrospectively collected from two NCI-designated comprehensive cancer centers. Patients categorized having disease based presentation metastases. Synchronous was defined presence diagnosis within 3 months thereafter. study endpoints treatment failure (TTF), overall survival (OS), control rate (DCR). TTF OS estimated by Kaplan-Meier method compared using log-rank tests. Univariable multivariable Cox proportional hazard models logistic regression used examine impact sex, IMDC risk score, histology, age start TTF, DCR. Results A total 223 (126 97 metachronous) diagnosed included analysis. No significant difference seen gender distribution these groups. Although statistically significant, group had a higher proportion non-clear histology those (21% vs. 11%, P = 0.057). median shorter but did reach statistical significance (9 19.8 metachronous, respectively, HR 1.37, 95% CI [0.98, 1.92], 0.064). Median significantly (28.0 50.9 months, adjusted 2.23, [1.36, 3.65], 0.001). Similarly, lower DCR than (58.7% vs 78.4%, odds ratio (OR) 0.29, [0.13, 0.64], 0.002). In analysis, remained an independent factor associated worse Conclusions who combinations have poorer OS, develop follow-up. further validation needed, findings could be valuable designing trials selecting escalation closer CDMRP DOD Funding: no