Bladder cancer treatment optimization requires considering tumor biological heterogeneity and precise timing. Our multi - cohort study analyzed MIBC prognostic factors and treatment effect heterogeneity, aiming to provide cross - ethnic evidence - based individualized treatment.

Inclusion criteria: Histologically confirmed T2–T4 bladder cancer with surgical intervention and complete baseline data. Cohort 1 (SEER, n=14,829),Cohort 2 (West China Hospita, n=180): Prospectively collected data included surgical records, treatment regimens (e.g., immune checkpoint inhibitors), and survival outcomes. Statistical methods: Logistic regression, PSM, Cox regression, subgroup interaction analysis, and nomogram.

Survival analysis demonstrated superior outcomes with chemoradiotherapy versus monotherapy (both cohorts, p<0.01), while immunotherapy showed preliminary efficacy in Cohort 2. Neoadjuvant radiotherapy (preoperative, Cohort 1) failed to improve survival post-PSM. Subgroup analysis revealed therapeutic heterogeneity: transitional cell carcinoma patients derived significant chemotherapy benefits (HR=0.46, p<0.01), whereas radiotherapy increased mortality risk in small cell carcinoma (HR=4.06, p<0.01) .

Therapeutic effects show significant heterogeneity. Future work should optimize individualized strategies using clinical characteristics, histological subtypes, and molecular classifications, and explore the synergistic effects of combining radiochemotherapy with targeted/immunotherapy.