Clinical burden of recurrence among older adults with muscle invasive bladder cancer undergoing tri-modal therapy in the real world: A SEER-Medicare, population-level study.

Abstract

679 Background: While radical cystectomy (RC) remains standard of care for muscle-invasive bladder cancer (MIBC), trimodal therapy (TMT) has emerged as a bladder-sparing alternative for select patients, particularly older adults. However, US population-level data on TMT patterns and outcomes remain limited. This study evaluates TMT use and outcomes across the treatment continuum in older adults with MIBC. Methods: SEER-Medicare data (01/01/2007-09/30/2020) were used to identify adults ≥65 years with stage T2-T4a N0M0 MIBC. Eligible patients underwent TMT, defined as maximal transurethral resection of the bladder tumor (TURBT; index) followed within 6 months by concurrent chemoradiotherapy (CRT). Neoadjuvant therapy was identified within 6 months pre-TURBT; adjuvant therapy was captured within 120 days post-TMT. Recurrence was defined based on: (1) cancer-directed treatments received ≥120 days post-TMT (or antibody drug conjugates [ADCs] any time post-TMT); (2) diagnosis of distant metastases or secondary bladder malignancy after 60 days post-TMT; or (3) diagnosis of non-bladder secondary malignancy post-TMT. Categorical data were assessed using chi-square tests at a significance level of α = 0.05. Results: Among 1,032 TMT-treated MIBC patients (median age 79), most were male (71.2%), non-Hispanic (96.2%), and White (92.2%), with clinical stage T2 disease (87.0%). Use of neoadjuvant therapy was rare ( < 1%). Median time from TURBT to CRT initiation was 39 days. During CRT, patients received a median of 34 fractions of radiotherapy; common CRT agents were cisplatin (43.9%, n = 453) and carboplatin (39.3%, n = 406). Adjuvant therapy was administered to 18.6% (n = 192) of patients. Treatment patterns associated with TMT were not significantly different between patients with or without recurrence. Over half of patients (53.5%, n = 552) experienced recurrence (median time to recurrence: 2.5 years). Among these, 134 (24.3%) received intravesical therapy as the first post-recurrence treatment, suggesting non-muscle invasive recurrence. Salvage RC was performed in 10.5% (n = 58) of those with recurrence, and 12 patients received neoadjuvant therapy pre-RC. Over half of the recurrence cohort (n = 330) received post-recurrence systemic treatment, commonly non-cisplatin chemotherapy (n = 176) and ADCs (n = 170). Conclusions: Recurrence was common among older adults with MIBC despite timely initiation of TMT. Most recurrences appeared to be invasive, with high rates of systemic therapy use, underscoring the clinical burden after TMT failure. The absence of differences in TMT patterns between recurrence and non-recurrence cohorts suggests that recurrence risk may be driven by tumor biology rather than care delivery. Further therapeutic strategies are needed to reduce recurrence and improve outcomes in this growing population.