KEY TAKEAWAYS
- The PURE-01 phase 2 study involved mpMRI scans before and after pembro treatment for patients undergoing RC.
- The VI-RADS scores before and after immunotherapy (IO) treatment significantly correlated with pathological downstaging.
- The study suggests that VI-RADS scores can serve as reliable indicators for selecting patients for bladder-sparing strategies in addition to immunotherapy monotherapy.
The PURE-01 study involved multiparametric magnetic resonance imaging (mpMRI) scans administered to patients (pts) before and after three cycles of pembrolizumab (pembro) treatment before radical cystectomy (RC). Logistic regression models were used to analyze VI-RADS scores against pT ≤1 and pT0, wherein VI-RADS scores were categorized into 0-3 (no disease evidence) and 4-5. The models also considered several covariates: cT-stage, age, gender, PD-L1 CPS, and TMB. The model’s effectiveness is currently being tested in the ongoing NureCombo and SURE-01 studies. Transcriptome-wide expression profiling was matched with VI-RADS scores.
In the study,115 pts underwent centrally-reviewed MRI scans, with 230 mpMRI scans conducted from February 2017 to August 2018. Of these pts, 27.8%(n=32) had pure or predominant non-urothelial carcinoma (UC) histology, while 47%(n=54) had a cT3-4N0 MIBC. Before receiving pembro, 18.3% of pts(n=21) had no measurable disease (VI-RADS=0), 32.2%(n=37) had a VI-RADS score of 1-3, and 49.5%(n=57) had a VI-RADS score of 4-5. There was aPembrolizumab, Pembrolizumab (MK-3475) significant decrease in VI-RADS scores from 4-5 to 0-3 post-pembro in 20 pts (17.4%). VI-RADS 4-5 scores before pembro treatment showed higher angiogenesis and epithelial-mesenchymal transition (EMT) activity levels than VI-RADS 0-3 (p=0.011 and 0.033). Both pre-pembro and post-pembro VI-RADS 0-3 scores were significant predictors of the pT ≤1 endpoint in multivariable analyses (MVA). Post -pembro VI-RADS 0-3 had the most substantial effect against pT ≤1 response (OR: 23.4, 95% CI: 7-95.3, p<0.0001). The model had an impressive AUC of 0.90 and supported the 10-80% range for model-based decisions. Stromal signature scores were significantly higher for post-pembro VI-RADS 4-5 than VI-RADS 0-3. In the combined NureCombo+SURE-01 cohort, 90% of pts underwent post-therapy VI-RADS testing (totaling 34 mpMRI scans) and received a score of 0-3 showing a pT ≤1 stage at radical cystectomy.
The VI-RADS scores in MIBC reflect unique biological characteristics and tissue biomarkers of IO response. After IO treatment, the VI-RADS scores strongly correlate with pathological downstaging and serve as a reliable indicator for selecting pts for bladder-sparing strategies. These findings should be considered for other neoadjuvant therapies in addition to IO monotherapy.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003426.12
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02736266
Necchi, Andrea; Basile, Giuseppe; Gibb, Ewan; Calareso, Giuseppina; Padua, Tiago; Patanè, Damiano; Crupi, Emanuele; Mercinelli, Chiara; Del Prete, Andrea; Giannatempo, Patrizia; Moschini, Marco; Ross, Jeffrey; Briganti, Alberto; Montorsi, Francesco; Messina, Antonella; De Cobelli, Francesco; Brembilla, Giorgio LBA03-12 BIOLOGY AND PERFORMANCE OF PRE- AND POST-PEMBROLIZUMAB (PEMBRO) VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) TO PREDICT THE PATHOLOGICAL RESPONSE IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIBC): FULL DATA ANALYSIS FROM A CLINICAL TRIALS PIPELINE, Journal of Urology: April 2023 – Volume 209 – Issue Supplement 4 Pembrolizumab (MK-3475)doi: 10.1097/JU.0000000000003426.12
