Patient-derived organoids enable ex vivo drug-response profiling for precision medicine in bladder cancer

Abstract Patient-derived organoids (PDOs) represent a promising precision medicine approach for replicating primary tumor characteristics and facilitating drug testing across various cancers, although clinical evidence in bladder cancer remains limited. This study evaluates the impact of incorporating PDOs into clinical practice on treatment efficacy in bladder cancer patients. Surgical specimens were used to establish PDOs, which were systematically characterized and compared to parental tumors in terms of histological morphology and genomic features. Based on standard clinical regimens, customized drug combinations were designed for ex vivo drug-response profiling, and the resultant profiles were correlated with individual patients’ clinical responses. Nineteen bladder cancer PDOs were successfully established with an 86.4% success rate, and they closely resembled the parental tumors histopathologically and genetically. Drug sensitivity screening was performed for chemotherapy agents and antibody–drug conjugates (ADCs) using the established PDOs, and the results revealed individual heterogeneity among patients. In an exploratory cohort, ex vivo PDO drug-response profiles were concordant with postoperative clinical outcomes in 9 of 10 evaluable patients (90.0%), supporting the potential clinical relevance of PDO-based drug-response profiling. This study establishes a bladder cancer organoid biobank and highlights the potential of this platform to support personalized treatment strategies and precision medicine in bladder cancer.