BCG treatment is the gold-standard therapy for high-grade intermediate-risk and high-risk non-muscle-invasive bladder cancer (NMIBC). However, ~30−40% of patients who receive BCG experience treatment failure, and the mechanisms by which it acts are not well understood. Thus, the role of the tumour microbiome in bladder cancer treatment response has gained increasing interest. Now, new data have provided insight into differences in microbiome species richness and diversity between BCG responders and BCG non-responders and enabled identification of possible mechanistic pathways.

In this study, both retrospectively collected and prospectively collected samples were analysed. In the retrospective analysis, 47 archival formalin-fixed paraffin-embedded (FFPE) tissue samples from transurethral resection of the bladder tumour (TURBT) and 14 paired radical cystectomy specimens collected between 2012 and 2018 were identified and compared for BCG response. All patients had received at least induction and six instillations of BCG. Responders were defined as having no evidence of disease for at least 2 years after one course of induction with or without maintenance therapy — 23 were identified in total. Non-responders were defined as experiencing progression to muscle-invasive bladder cancer, having persistent high-grade T1 disease or progressing to high-grade T1 disease within 3 months of completing induction BCG, or having persistent high-grade TA disease or carcinoma in situ despite two cycles of induction BCG, based on the AUA–SUO guidelines — 24 were identified in total, 14 of whom had paired radical cystectomy samples.