Invasive urothelial carcinoma of the urinary bladder is a highly aggressive malignancy with significant morbidity and mortality. Current treatment guidelines recommend radical cystectomy combined with systemic chemotherapy to improve survival outcomes. Several clinical trials have demonstrated the survival benefits of neoadjuvant chemotherapy (NAC) administered before surgery; however, the role of adjuvant chemotherapy (AC) post-surgery remains debated. Comparative studies assessing the effectiveness of NAC versus AC in real-world populations are limited. This study utilized the TriNetX global health research network, a large, de-identified electronic medical record database, to evaluate overall survival outcomes between these two treatment approaches.

Two cohorts were established within the TriNetX platform. Cohort 1 included patients diagnosed with invasive urothelial carcinoma of the urinary bladder who received neoadjuvant chemotherapy prior to surgery. Cohort 2 comprised patients who received adjuvant chemotherapy following surgery. Additionally, patients from both cohorts with liver metastasis were identified for subgroup analysis. Kaplan-Meier analysis was used to compare the overall survival (OS) between groups.

After applying inclusion criteria and propensity score matching, a total of 402 patients were included in each cohort. The median OS was 2,136 days in the AC group, while the NAC group did not reach median OS, suggesting a potential survival advantage. Kaplan-Meier analysis revealed a significantly improved OS in the NAC group compared to the AC group (p < 0.0001, HR = 0.528, 95% CI: 0.413–0.676). In the liver metastasis subgroup, 30 patients in the NAC group and 93 in the AC group were identified. The NAC group again demonstrated a significant OS benefit (HR = 0.284, 95% CI: 0.188–0.428).

Neoadjuvant chemotherapy is associated with improved overall survival compared to adjuvant chemotherapy in patients with invasive urothelial carcinoma of the urinary bladder. These results support the continued use of NAC and warrant further prospective studies for validation.