What question did this study set out to answer?

To assess the utility of TURBT-derived patient-derived organoids (PDOs) for predicting postoperative chemotherapy outcomes in bladder cancer.

May 30, 2026

Clinically actionable TURBT-derived bladder cancer organoid pharmacotyping as a predictor of postoperative outcomes in a prospective multicenter study.

Key Points

To assess the utility of TURBT-derived patient-derived organoids (PDOs) for predicting postoperative chemotherapy outcomes in bladder cancer.
Conducted a prospective multicenter study (NCT06662071) involving 63 TURBT specimens from 4 centers generating organoids.
Evaluated drug responses using IC50 and nAUC across eight chemotherapy agents and classified responses using six strategies.
Analyzed the concordance of PDO drug profiling results with postoperative outcomes in treated patients.
Successfully established 41 PDO lines from 37 patients with a success rate of 65.1%.
IC50 values for drug sensitivity varied, with pirarubicin showing an IC50 of 0.080 µM and gemcitabine reaching up to 369.500 µM.
IC50-based Jenks classification exhibited high specificity (0.933) and accuracy (0.882) in predicting clinical outcomes.

Abstract

e16613 Background: Post-TURBT chemotherapy is largely empiric despite marked inter-patient heterogeneity in bladder cancer drug sensitivity. We evaluated a multicenter TURBT-derived PDO pharmacotyping workflow and its concordance with postoperative outcomes. Methods: In a prospective multicenter study (NCT06662071), TURBT bladder cancer specimens were used to generate patient-derived organoids (PDOs), with histologic fidelity assessed by H 72-hour exposure) across eight clinically used agents/regimens; viability (CellTiter-Glo 3D) was used to derive IC50 and nAUC (plus viability at Cmax). Six response-classification strategies (Jenks vs tertiles × IC50/nAUC/Cmax viability) were compared, and concordance with postoperative chemotherapy outcomes (recurrence/progression on surveillance follow-up) was summarized by specificity and accuracy. Results: From 4 centers, 63 TURBT specimens yielded 41 PDO lines from 37 patients (65.1% success). Successful establishment correlated with higher post-digestion viability (p < 0.01) and cell yield (p < 0.05). Drug profiling was completed in 35/41 lines (85.4%). IC50 values spanned submicromolar medians for anthracyclines/pirarubicin (pirarubicin 0.080 µM; doxorubicin 0.540 µM; epirubicin 0.508 µM) to higher micromolar medians for platinum/antimetabolites (cisplatin 20.245 µM; gemcitabine 16.913 µM; methotrexate 61.205 µM), with gemcitabine showing the widest range (0.004–369.500 µM). Of six strategies, IC50-based Jenks natural breaks (Sensitive/Intermediate/Resistant) best matched clinical outcomes (specificity 0.933; accuracy 0.882). Clinical concordance was assessed in 15 treated patients (17 PDO–patient pairs); 2/15 (13.3%) recurred/progressed. Illustrative concordant cases included pirarubicin sensitivity (IC50 0.12 µM) with recurrence-free follow-up and gemcitabine resistance (IC50 227.7 µM) with early recurrence/progression after GC-based management. Conclusions: This multicenter TURBT-derived bladder cancer PDO study establishes a clinically actionable pharmacotyping workflow. PDOs can be generated from routine specimens, capture marked inter-patient drug-response heterogeneity, and provide drug-specific sensitivity tiers that align with postoperative outcomes with high specificity for identifying potentially ineffective therapy. These data support prospective validation of PDO-guided regimen selection to reduce futile treatment and individualize postoperative bladder cancer care.

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