Ex Vivo Microtumor Testing to Predict Chemotherapy Responses in Patients with Bladder Cancer

Background Patients with bladder cancer (BC) may receive intravesical or systemic chemotherapy, but predictive biomarkers to guide treatment selection are lacking. Consequently, some patients receive ineffective treatment, resulting in unnecessary toxicity and an increased risk of tumor progression. Objective To evaluate the feasibility of ex vivo micro-tumor testing for predicting chemotherapy response in patients with BC. Design, setting, and participants In this prospective study, 65 patients with BC were enrolled (Institutional Review Board no. MEC-2022-0233). Tumor samples were collected during transurethral resection or radical cystectomy. BC was confirmed by uropathological review, supported by the detection of BC-associated mutations in hTERT, FGFR3, and PIK3CA. Patient-derived micro-tumors were exposed ex vivo to anticancer drugs, and responses were assessed using image-based measurements of viability and morphology. Outcome measurements and statistical analysis The primary outcome was successful completion of ex vivo drug testing within 14 days of tissue collection. The secondary outcome was concordance between ex vivo sensitivity and clinical response to platinum-based chemotherapy. Clinical response data were available for nine patients. Results and limitations Ex vivo drug testing was successful for 48 of 65 patients (74%), with all successful results generated within 14 days of tissue collection. Among the nine patients with evaluable clinical outcomes following platinum-based chemotherapy, ex vivo responses corresponded with observed treatment responses. The main limitations were the small clinical correlation cohort and the limited number of drugs evaluated. Conclusions Ex vivo micro-tumor drug testing is feasible for BC within a clinically relevant timeframe. The observed correspondence between ex vivo and clinical responses to platinum-based chemotherapy supports further investigation of this approach for personalized treatment selection in BC.