Real-world bladder cancer survival across the immunotherapy era: Persistent age-, stage-, and race-ethnicity disparities demand precision oncology strategies.

Background: Bladder cancer represents 5% of U.S. malignancies, with 82,000 new cases and 17,000 deaths annually. Most tumors are non-muscle invasive, yet recurrence is common and requires long-term surveillance. Five-year survival is high for non-invasive and localized disease (96% and 70%) but drops sharply for regional (34%) and metastatic stages (5%). Despite advances with platinum regimens and, more recently, immune checkpoint inhibitors (ICIs), mortality gaps persist, especially among older adults, Black patients, and those with advanced diseases. Methods: We assessed relative survival for invasive and in situ bladder cancer using SEER-21 data (2000-2021), stratified by race/ethnicity, age, and SEER summary stage. Hispanic origin followed the NAACCR Hispanic Algorithm; AI/AN estimates were limited to PRCDA regions. Survival from 1-10 years after diagnosis was calculated using expected-survival life tables. Results: Overall five-year survival was 78%. Persistent disparities were noted: • Non-Hispanic White: 79.1%• Hispanic: 74.0% • Asian/Pacific Islander: 77.0% • AI/AN: 70.7% • Non-Hispanic Black: 65.0% Age and stage influenced outcomes, with survival ranging from 86.8% (<50 yrs) to 75.3% (≥65 yrs), and from 71.3% (localized) to 7.5% (distant). Since 2016, ICIs-including atezolizumab, pembrolizumab, nivolumab, durvalumab, and avelumab-have improved response durability, achieving complete responses in ~6% and a median OS of ~15 months in selected patients. Conclusions: Although immunotherapy has expanded options for metastatic urothelial carcinoma, its real-world impact remains uneven. Survival gains are modest, and demographic inequities persist across age, race/ethnicity, and stage. Black and AI/AN patients continue to face the highest mortality, and older adults-who represent most cases-often benefit less due to cisplatin ineligibility, comorbidities, and variable ICI responsiveness. These patterns show that therapeutic advances alone are insufficient; strategies integrating biomarker-based selection, optimized sequencing, and multimodal approaches are urgently needed. Without targeted action, current progress risks widening long-standing disparities in bladder cancer survival. Impact: Closing these gaps requires precision-guided care and equitable access to emerging therapies to ensure survival gains are shared by all patient groups.