Tumor resection followed by adjuvant bacillus Calmette-Guérin (BCG) bladder instillations is currently the recommended treatment for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC), yet only 50% of patients benefit from this therapy. Advanced disease progression can lead to morbidity and poor clinical outcomes for patients.
A group of researchers from the Cedars-Sinai Cancer Center set out to determine which types of tumors are unlikely to respond positively to BCG so that alternative treatments such as early cystectomy, targeted therapy, or immunotherapy can be administered to patients.
Molecular profiling was carried out on 132 patients with BCG-naïve HR-NMIBC and 44 patients who had experienced recurrences after BCG. Three different BCG response subtypes were found: BRS1, BRS2, and BRS3.
Patients with BRS3 tumors were found to have reduced recurrence-free and progression-free survival compared with those with BRS1/2 tumors. BRS3 tumors were also found to have an immunosuppressive profile. BRS stratification was performed in another cohort of 151 BCG-naïve patients with HR-NMIBC, where the subtypes outperformed guideline-recommended risk stratification based on clinicopathological variables.
A commercially approved assay was confirmed to be able to predict BRS3 tumors. The BCG response subtypes will enable improved identification of patients with HR-NMIBC, as well as the selection of more appropriate treatments for those unlikely to respond to BCG.