Vesical Imaging‐Reporting and Data System use predicting the outcome of neoadjuvant pembrolizumab in muscle‐invasive bladder cancer

Objective To evaluate the predictive capability of the pre‐ and post‐pembrolizumab Vesical Imaging–Reporting and Data System (VI‐RADS) to identify ypT0N0 or ypT≤1N0 response in muscle‐invasive bladder cancer (MIBC) within the PURE‐01 trial (ClinicalTrials.gov identifier: NCT02736266). Patients and Methods Patients were staged with bladder multiparametric magnetic resonance imaging (mpMRI) before and after treatment (three cycles of pembrolizumab) prior to radical cystectomy (RC). Logistic regression models were used to analyse the pre‐ and post‐ pembrolizumab VI‐RADS against ypT≤1N0 and ypT0N0 response. The VI‐RADS scores were dichotomised between 0 and 3 (0 = no evidence of disease) and 4–5. Event‐free survival (EFS) and overall survival (OS) analyses were performed. Comprehensive genomic profiling and transcriptome‐wide expression profiling data were matched with the VI‐RADS scores. Results In total, 110 patients underwent centrally reviewed scans ( N = 220 mpMRI), treated between February 2017 and July 2020. Both pre‐ and post‐pembrolizumab VI‐RADS 0–3 scores were the only significant covariates that predicted the ypT≤1N0 endpoint in multivariable analyses, and the strongest effect was seen with post‐pembrolizumab VI‐RADS 0–3 predicting the ypT≤1N0 response ( P < 0.001). The area under the curve for this model was 0.90. Post‐pembrolizumab VI‐RADS 0–3 also predicted a longer EFS ( P < 0.001) and OS ( P = 0.044). The scores of several gene signatures from baseline tumours differed between the pre‐pembrolizumab VI‐RADS 0–3 and 4–5 categories. Conclusion Post‐pembrolizumab VI‐RADS scores are strongly associated with pathological downstaging and survival. VI‐RADS scores were also characterised by distinct biomarker features. These results indicate that the VI‐RADS is emerging as an important tool for designing next‐generation trials for MIBC.