Urine-derived bladder cancer organoids (urinoids) as tool for cancer longitudinal response monitoring and therapy adaptation

Abstract Bladder cancer is one of the most common cancer-types worldwide. Generally, research relies on invasive sampling strategies. Here, we generate bladder cancer organoids directly from urine ( urinoids ). In this project, we establish 12 urinoid-lines from 22 patients with non-muscle and muscle-invasive bladder tumors, with an efficiency of 55%. The histopathological features of the urinoids accurately resemble those of the original bladder tumors. Genetically there is a high concordance of single nucleotide polymorphisms (92.56%) and insertions and deletions (91.54%) between urinoids and original tumors. Furthermore, urinoids show sensitivity to bladder cancer drugs, similar to their tissue-derived organoid counterparts. Genetic analysis of longitudinally generated urinoids from one patient receiving systemic immunotherapy, identify alterations that may guide the choice for second-line therapy. Successful treatment adaptation was subsequently demonstrated in the urinoid-setting. Therefore, urinoids can advance precision medicine in bladder cancer as a non-invasive platform for tumor pathogenesis, longitudinal drug-response monitoring, and therapy adaptation.