PD42-04 TUMOR MICROBIOME ASSOCIATED WITH BCG RESPONSE IN NON-MUSCLE INVASIVE BLADDER CANCER

Abstract

INTRODUCTION AND OBJECTIVE: M. bovis Bacillus Calmette-Guerin (BCG) is the standard of care for high-risk non-muscle invasive bladder cancer. Despite well-established efficacy, no clinical marker has been identified to reliably predict durable response to BCG. A potential marker may be the local urinary microbiome, which has been closely tied to the host immune system and implicated in genitourinary disease. Our objective was to characterize the urinary microbiome in bladder tumors from BCG responders and non-responders. METHODS: We conducted microbiome analyses on formalinfixed bladder tumor tissue from patients who subsequently received intravesical BCG therapy for bladder cancer. Patients were identified as BCG responders or non-responders, with BCG response defined as no disease two years from induction BCG. Paired tumor specimens were also included for non-responders who underwent cystectomy after BCG failure. DNA was extracted for 16S high-throughput sequencing (Illumina MiSeq). Sequence reads were assigned to genus-level amplicon sequence variants (ASVs) in DADA2 and analyzed in Phyloseq. Statistical tests included paired t-test and Permanova analysis. RESULTS: Species richness was not significantly different between BCG responders (n=14) and non-responders (n=12) (p=0.196). However, overall microbiome composition did differ significantly (p=0.011), with enrichment of Corynebacterium and Pseudomonas in responders vs. non-responders. In paired nonresponder samples before BCG (n=12) and at cystectomy (n=9), there were no significant differences in species richness (p=0.489) or overall composition (p=0.107). However, the microbiome after BCG failure demonstrated differential enrichment in Acinetobacter, Lactobaccilus, Corynebacterium, Pseudomonas, and Staphylococcus. In targeted analysis, M. bovis was enriched in non-responder tumors after BCG failure. CONCLUSIONS: The bladder tumor microbiome may be associated with response to BCG therapy. Enrichment of Corynebacterium in responders is notable given taxonomic similarities with M. bovis. Enrichment in certain ASVs after BCG suggests this therapy alters the composition of the local microbiome. The presence of M. bovis in nonresponders after therapy suggests BCG can persist and may have implications for immune tolerance in the setting of non-response. (Table Presented).