MRI-based Response Assessment of Neoadjuvant Systemic Immunotherapy in Muscle-invasive Bladder Cancer: An Analysis of Inter-radiologist Variability and Diagnostic Accuracy in three Prospective Clinical Trials.

We analyzed data from 115 patients across three prospective trials (NABUCCO, TURANDOT, and PURE-01). Patients underwent mpMRI after transurethral resection of bladder tumor and before neoadjuvant immunotherapy, and after neoadjuvant immunotherapy prior to radical cystectomy. Multiple radiologists assessed the radiological response using qualitative (AJCC Staging, nacVI-RADS, Visual Response, and RECIST 1.1) and quantitative (diameter, volumetric) criteria. Using Fleiss' kappa, Krippendorff's alpha, and intraclass-correlation coefficient (ICC), we assessed inter-radiologist variability. ROC-AUC (Receiver operator characteristic-area under the curve) assessed the diagnostic accuracy for pathological complete response (pCR) of the primary tumor, with correlations explored for circulating tumor (ctDNA) and tumor cell density.

Semi-automatic volumetric mpMRI assessment is a reproducible and accurate tool for evaluating local response to neoadjuvant immunotherapy in MIBC. Despite focusing on the primary tumor, these findings support its potential as an imaging biomarker and foundation for future response criteria. However, confirming its role in clinical decision-making requires prospective validation.

Visual assessment demonstrated high inter-radiologist agreement among qualitative methods (α = 0.79, 95% CI: [0.68-0.87]), while semi-automatic volumetric analysis showed high reproducibility and accuracy quantitatively (ICC = 0.93, 95% CI: [0.83-0.95], AUC = 0.8-0.98). Volumetric measurements showed moderate correlation with ctDNA and tumor cell density. All methods exhibited strong predictive performance for pCR, but longitudinal volume changes showed a good combination of reproducibility and accuracy.

For patients with muscle-invasive bladder cancer (MIBC), accurate assessment of neoadjuvant therapy response may allow for bladder-sparing strategies, emphasizing the need for accurate, noninvasive response assessment. Multi-parametric magnetic resonance imaging (mpMRI) has emerged as a promising imaging modality, but its reproducibility and diagnostic performance following neoadjuvant immunotherapy remain underexplored.