Real-world overall survival (OS) improvements in metastatic urothelial carcinoma (mUC) across three key therapeutic eras.

Abstract

686 Background: Over the past 3 decades, treatment of mUC has been transformed by 3 landmark backbone therapies: platinum-based chemotherapy (PBC), immune-checkpoint inhibitors (ICIs), and antibody–drug conjugates (ADCs), either alone or in combination therapies. Temporal trends of OS improvement in patients (pts) with mUC are instrumental to identify research gaps and unmet needs. Methods: We used the TriNetX research database to conduct a retrospective, large-scale outcome analysis of pts with mUC who received ≥1 line of treatment across worldwide healthcare institutions. Pts were stratified into 3 therapeutic temporal periods: PBC era (1999–2015), ICIs era (2016–2018), and ADC era (2019–2025). Baseline clinical and demographic characteristics were compared using standard statistics. Kaplan–Meier analysis estimated OS, and propensity score matching (PSM) adjusted for sex, age, stage at diagnosis, lines of treatment and comorbidities. Results: Among 4,720 pts with mUC, 2,383 received 1st-line therapy between 1999 and 2025 and were included in the analysis. Overall, 783, 663, and 937 pts were treated in the PBC, ICI, and ADC eras. Median age was 70 years across PBC, ICI, and ADC eras, respectively; the proportion of male pts was 72.9%, 69.4%, and 73.1%. Across treatment eras, 51.7% of pts in PBC era received PBC (49.3% non-PBC), 32% in the ICI era received ICIs (35.3% only PBC, 32.6% non-PBC), and 20% in the ADC era received ADCs (20.9% only PBC, 30.2% only non-PBC, 28.9% ICIs). Regarding subsequent therapies, in the PBC, ICI, and ADC eras, 51.4%, 52.6%, and 53.2% of pts received 2nd-line and 25.4%, 25.9%, and 26.7% 3rd-line therapy, respectively. The three cohorts yielded no significant differences in sex, race, comorbidities, lines of treatment, or stage at diagnosis (all p > 0.05). Median OS was 13.5 months (mo) in the PBC era, 17.5 mo in the ICIs era, and 21.1 mo in the ADC era with a significant difference between the ADC vs PBC eras (p = 0.0017). After PSM, median OS was 13.4, 17.3, and 22.3 mo in the PBC, ICI, and ADC eras, respectively, with the difference between the PBC vs ADC eras remaining significant (p = 0.005). Notably, a subgroup analysis of pts who received only chemotherapy (PBC or non-PBC) in their respective temporal period showed a median of OS 13.5, 14.6, and 17.1 mo in the PBC, ICI, and ADC eras, respectively, with a trend toward significance for the PBC vs ADC eras comparison (p = 0.006). Conclusions: OS in mUC has significantly improved over the past 3 decades, with the greatest gains observed in the ADC era during which an over 7.5 month improvement in median OS was observed (vs PBC era). Notably, improvements were seen even among many pts not receiving era-specific systemic therapies, suggesting that advances in diagnostics, staging, supportive care, and healthcare delivery —should be considered when interpreting real-world survival gains.