Prognosis of patients (pts) with synchronous vs metachronous metastatic or locally advanced urothelial carcinoma (la/mUC).

695 Background: There is relatively limited data regarding the prognostic role of the presence of synchronous metastasis or de novo locally advanced (unresectable) tumor in pts with UC. Ιn this retrospective study, we examined the prognosis of pts with synchronous vs metachronous la/mUC (prior localized tumor) in a real-world cohort. We hypothesized that pts with synchronous la/mUC would have worse prognosis. Methods: We included pts from 26 centers in US and Europe treated with anti-PD(L)1 immune checkpoint inhibitors (ICI) in any therapy setting. We calculated overall survival (OS) from the time of initial diagnosis for pts with synchronous la/mUC, and from the time of diagnosis of advanced disease for pts with metachronous la/mUC, until death using Kaplan-Meier method. Pts with diagnosis of la/mUC ≤12 weeks from the initial UC diagnosis and without receiving any interim treatment, were assigned to the synchronous la/mUC group. We also calculated OS, progression-free survival (PFS) from 1st line (1L) Immune Checkpoint Inhibitor (ICI) start until progression or death for PFS, and until death for OS, as well as overall response rate (ORR) in pts with synchronous vs metachronous la/mUC receiving 1L ICI treatment. Multivariable (MVA) models were adjusted using the Khaki risk factors (ECOG PS ≥2, albumin < 3.5 g/dL, neutrophil/lymphocyte ratio > 5, presence of liver metastases). Results: We identified 1537 pts with la/mUC with median age of UC diagnosis 69 years (75% men, 81% White, 20% upper tract primary tumor, 71% pure UC, 40% visceral metastasis (liver/lungs), 75% ECOG PS 0-1, prior platinum-based chemotherapy [19% as neoadjuvant, 46% as 1L metastatic]). Median follow up from time of initial UC diagnosis was 42 months (mo); 511 pts had synchronous la/mUC and 1026 had prior localized tumor. Median ΟS was 22 (95%CI 20-25) mo with synchronous la/mUC vs 25 (95%CI 23-28) mo with metachronous la/mUC (HR 1.18, 95%CI 1.0-1.4, p = 0.045). OS, PFS and ORR MVA analyses with 1st line ICI monotherapy are shown in Table. Conclusions: We found that synchronous la/mUC was associated with worse prognosis vs metachronous la/mUC, but further validation is needed. Limitations include retrospective design, lack of randomization, selection and confounding biases, while 1L therapy did not include enfortumab/pembrolizumab combination. Our hypothesis-generating data could inform prognostic estimates and stratification factors for clinical trials. N mOS, mo(95%CI) HR([95%CI], p) N PFS, mo(95% CI) HR([95%CI], p) N ORR %([95%Cl]) OR(95%CI, p) 1L ICI Synchronous la/mUC 200 15 (10-20) 1.06 ([0.8-1.4], 0.64) 154 4 (2-6) 0.87 ([0.67-1.1], 0.29) 189 32% (25-38) 1.2 ([0.8-1.08], 0.39) Metachronous la/mUC 560 18 (15-21) ref 439 4 (3-5) ref 541 30% (26-34) ref