Overall Survival After Neoadjuvant Versus Adjuvant Chemotherapy for Invasive Urothelial Carcinoma of the Bladder: A Real-world Multicenter Cohort Study

Background/Aim: Invasive urothelial carcinoma of the urinary bladder carries a high risk of micrometastatic spread, and perioperative chemotherapy is a key component of curative-intent treatment. Neoadjuvant chemotherapy (NAC) has the strongest supporting evidence, whereas the role of adjuvant chemotherapy (AC) remains debated and real-world comparisons are limited. We compared overall survival (OS) and the development of liver metastasis between patients treated with NAC and those treated with AC who underwent radical cystectomy. Patients and Methods: Using the TriNetX U.S. Collaborative Network, we identified adults with bladder cancer who underwent radical cystectomy and received cisplatin or carboplatin within 1 year before (NAC) or within 1 year after (AC) surgery. The two cohorts were balanced by 1:1 propensity score-matching for age, sex, and race. OS (primary endpoint) and time to liver metastasis (secondary endpoint) were estimated by the Kaplan-Meier method and compared with the log-rank test. Results: After matching, 402 patients were included in each group. Median OS was 2,136 days for the AC group and was not reached for the NAC group. NAC was associated with significantly longer OS than AC (hazard ratio=0.528, 95% confidence interval=0.413-0.676, p<0.0001). Liver metastasis developed in 30 (7.5%) patients in the NAC group and 93 (23.1%) in the AC group, and NAC was associated with a lower risk of liver metastasis (hazard ratio=0.284, 95% confidence interval=0.188-0.428, p<0.0001). Conclusion: In this real-world cohort, NAC was associated with significantly longer OS and a lower risk of liver metastasis than AC in patients undergoing radical cystectomy for invasive bladder cancer. These hypothesis-generating findings support the preferential use of NAC when feasible and warrant prospective validation.