672 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) is standard of care for cisplatin-eligible (CE) patients (pts) with muscle-invasive bladder cancer (MIBC). Many pts are deemed cisplatin-ineligible (Cis-I) due to impaired renal function, poor performance status, or comorbidities, and optimal management strategies for this population remain unclear. This study aimed to assess real-world (rw) NAC utilization in Cis-I pts and evaluate the impact of NAC receipt on outcomes. Methods: This retrospective cohort study used the US-based, EHR-derived deidentified Flatiron Health Research Database containing data from > 20,000 pts with bladder cancer (cutoff: May 31, 2025). Pts with MIBC diagnosed on or after 2015 who had primary surgery were included. Cisplatin eligibility was based on baseline creatinine clearance (CrCl) and ECOG performance status (ECOG PS). The effect of cisplatin-based NAC vs no NAC on rw overall survival (rwOS, from MIBC diagnosis) and rw disease-free survival (rwDFS, from primary surgery) was assessed in Cis-I pts using unadjusted Kaplan-Meier curves and Cox proportional hazards models adjusted for age, sex, race, ECOG PS, CrCl, practice type, T stage, histology, and residual disease status (rwDFS only). Results: Of 5016 pts with MIBC who underwent surgery, 26.9% were CE, 10.2% Cis-I, and 62.9% indeterminate. Median rwOS and rwDFS (95% CI) were longer in CE vs Cis-I pts: 74.7 (69.6-86.6) vs 39.9 months (30.9-48.2), and 59.7 (52.3-63.8) vs 17.0 months (13.7-23.0), respectively. Among Cis-I pts, 45.2% (n = 231) received cisplatin-based NAC and 32.9% (n = 168) did not receive NAC. Pts who received cisplatin-based NAC were younger, had better performance status and higher baseline CrCl, were more likely to present with T2 (vs T3/4) disease, and less frequently had upper tract disease compared to Cis-I pts who did not receive NAC. Median rwOS (95% CI) was 48.2 months (30.9-67.6) in CI pts who received cisplatin-based NAC and 29.6 months (20.4-46.1) in those who did not; median rwDFS (95% CI) was 21.1 months (14.3-34.2) with NAC and 15.0 months (11.7-21.3) without. In the adjusted Cox PH analysis, receipt of cisplatin-based NAC vs no NAC was suggestive of a lower hazard of death (HR 0.75; 95% CI: 0.55-1.04) in Cis-I patients during follow-up; rwDFS was similar between groups (HR 1.00; 95% CI: 0.73-1.37). Conclusions: Inferior clinical outcomes were observed in Cis-I compared to CE pts. Nearly half of Cis-I pts still received cisplatin-based NAC, reflecting rw extension of therapy to selected pts. The trend toward improved OS associated with receipt of cisplatin-based NAC in Cis-I pts suggests that carefully selected pts may benefit from this treatment. Further research is needed to better understand the optimal treatment strategies for Cis-I pts to address the unmet needs in this population.
Patel et al. (Sun,) studied this question.