Exploring the influence of the bladder microbiome on BCG immunotherapy outcomes for high-risk non muscle invasive bladder cancer

Abstract

BACKGROUND: Intravesical Bacillus Calmette-Guérin (BCG) is an established adjuvant therapy for high-risk superficial bladder cancer, though its efficacy varies among patients. Recent interest in the urinary microbiome comprising microorganisms inhabiting the urinary tract stems from its potential impact on various urological conditions, including bladder cancer. Our study investigates the possible relationship between the bladder microbiome and BCG therapy outcomes in a preliminary and explorative analysis. METHODS: We conducted a retrospective, descriptive study involving 31 high-risk bladder cancer (BC) patients treated with BCG. BC tissues were collected pre-treatment, and formalin-fixed paraffin-embedded (FFPE) samples were analyzed. DNA extracted from these samples underwent high-throughput 16S rRNA amplicon sequencing targeting the V1-V3 regions. RESULTS: Our cohort consisted of 15 BCG-resistant patients and 16 responders. Median instillation numbers were six (IQR: 6-9) for resistant patients and twelve (IQR: 14-15) for responders, with a median follow-up length of six months (IQR: 3.3-9.5) and 43 months (IQR: 24-55), respectively. Significant differences were observed in the microbiome: BCG responders showed higher median percentages of Firmicutes (1.1 vs. 0.3, P=0.0293) and Verrucomicrobiota (0.9 vs. 0.1, P=0.0285). Additionally, Fusobacteriota was more prevalent among responders (75% vs. 33.3%, P=0.0198), while Cyanobacteria were more common in resistant patients (73.3% vs. 31.3%, P=0.0191). CONCLUSIONS: Our preliminary findings illuminate the bladder microbiome's role in influencing BCG therapy outcomes, underscoring the complex microbial interplay affecting treatment efficacy in urological diseases. This explorative study sets the groundwork for ongoing data collection and future research pathways aimed at further delineating these relationships.