“Intravesical BCG therapy is the standard-of-care for patients with high-risk NMIBC, but only delivers clinical benefits in 50% of the patients undergoing this treatment,” clarified Mr Florus de Jong (Erasmus University Medical Center, the Netherlands). The current study aimed to improve risk stratification of high-risk NMIBC and to identify molecular subtypes related to BCG treatment response. RNA sequencing was performed on the tumour tissue of 2 patient groups (cohort A, n=132; cohort B, n=151). The primary outcome of the study was progression-free survival (PFS).
Three molecular subtypes were related to BCG response in cohort A, named BCG-response subtype (BRS)1, 2, and 3. Patients with BRS3 displayed a reduced PFS compared with patients with BRS1 (P=0.003) or BRS2 (P=0.017). These findings were confirmed in cohort B. BRS3 tumours were characterised by high levels of EMT-basal markers and displayed an immunosuppressive profile, added Mr de Jong.
BRS3 tumours could be identified with high accuracy (AUROC 0.87) using a commercially approved qPCR-based assay, providing options to use this improved risk stratification method in clinical practice and thus select patients who may benefit from early radical cystectomy. The authors also found that recurring BRS3 tumours after BCG treatment were highly enriched. In these patients, several druggable regulators (TGFβ, DDR2) were upregulated after BCG treatment.
Reference:
1. De Jong, FC, et al. Non-muscle invasive bladder cancer subtypes with differential response to intravesical bacillus Calmette-Guerin treatment. Abstract 0068, EAU 2022, 01–04 July.