Exploring the utility of a NGS multigene panel to predict BCG response in patients with non-muscle invasive bladder cancer

Background: The therapeutic gold standard for patients with high-risk non-muscle invasive bladder cancer (NMIBC) is intravesical therapy with Bacillus Calmette-Guérin (BCG). Although a long-lasting therapeutic response can be observed in most patients, BCG failure occurs in 30-50% of patients and a progression to muscle invasive disease is found in 10-15%. Therefore, predicting high-risk patients who might not benefit from BCG treatment is critical. The purpose of this study was to identify whether the presence of specific oncogenic mutations might be indicative of BCG treatment response. Methods: High-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided in responders and non-responders. Tissue samples from transurethral resection of bladder cancer performed before starting therapy were examined using a multigene sequencing panel. Results: Mutations in TP53, FGFR3, PIK3CA, KRAS, CTNNB1, ALK and DDR2 genes were detected. TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort (31.6% and 26.3%, respectively), followed by PIK3CA (15.8%). In BCG-responsive patient group, 90% of samples were found to have genes mutated, with about almost 50% of them showing mutations in RTKs and CTNNB1 genes; in the BCG-unresponsive group, we found mutations in 44.4% of samples, mainly in TP53 gene. Conclusions: Our findings suggest that a NGS multigene panel is useful in predicting BCG response in patients with NMIBC.