Untreated advanced urothelial carcinoma (aUC) in the modern treatment era: Patterns of care from a decade-long national cohort.

4570 Background: Over the past decade, the therapeutic landscape for locally advanced/unresectable and de novo metastatic urothelial cancer (aUC) has transformed with the introduction of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs). These agents offer a more favorable benefit-risk and superior efficacy vs historical chemotherapy. We hypothesized that the proportion of untreated patients with aUC has declined over time, reflecting increased uptake of novel therapeutics. Methods: We analyzed the U.S. Flatiron Health EHR-derived de-identified database. We included patients diagnosed with aUC between Jan 1, 2011 and April 30, 2025. Patients were classified as treated if they received first-line (1L) systemic therapy within 6 months of advanced diagnosis. Calendar time was divided into three clinically relevant eras: pre-ICI approval (2011-2016), post-ICI but pre-ADC approval (2017-2019), and post-ADC approval (2020-2025). Outcomes included proportion untreated and time to treatment initiation (TTI) from advanced diagnosis. We estimated the cumulative incidence of treatment initiation using competing-risk methods, treating death before initiating as a competing event. Subgroup analyses evaluated patients with de novo stage IV disease at initial diagnosis. Results: We identified 12,849 patients with aUC (median age 73, 72.9% male, 78.7% white, 57.5% cis-ineligible, 78.3% bladder primary site). The proportion remaining untreated 6 months post advanced diagnosis declined across therapeutic eras: 36.8% untreated in the pre-ICI era, 27.4% in the post-ICI, pre-ADC era, and 22.7% untreated in the post-ADC era. Year-specific analysis showed steady improvement in treatment uptake: treatment within 6 months rose from 56% in 2011 to 79% in 2024 (Table). In the TTI analysis, overall, 25.1% had not initiated 1L therapy before death or data cutoff. Median TTI shortened across eras (63 days, 49 days, 45 days) and competing-risk cumulative incidence initiating therapy increased over time. For example, the probability of initiating 1L therapy within 90 days of aUC diagnosis across eras was 55.9% (pre-ICI), 66.1% (post-ICI, pre-ADC) and 70.7% (post ADC). Conclusions: In a large national cohort, untreated rates among patients with aUC declined markedly from 2011-2025 paralleling the introduction of ICIs and ADCs. Novel, better-tolerated therapies appear to have expanded real-world treatment eligibility and reduced early attrition. Temporal trends in treatment rates. Year 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 3 months 0.48 0.53 0.54 0.57 0.58 0.61 0.68 0.65 0.67 0.69 0.69 0.72 0.7 0.74 6 months 0.56 0.6 0.61 0.63 0.65 0.69 0.73 0.7 0.74 0.76 0.76 0.78 0.78 0.79 1 year 0.58 0.63 0.64 0.66 0.67 0.71 0.75 0.72 0.77 0.77 0.77 0.79 0.8 0.81