An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer

Jacob Knorr; Zaeem Lone; Glenn Werneburg; Ava Adler; Jose Agudelo; Mangesh Suryavanshi; Rebecca A Campbell; Kyle Ericson; Hong Qiu; Petar Bajic; Georges-Pascal Haber; Christopher J Weight; Philip P Ahern; Nima Almassi; Aaron W Miller; Byron H Lee

doi:10.1016/j.urolonc.2024.04.011

An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer

Urol Oncol. 2024 Apr 24:S1078-1439(24)00430-7. doi: 10.1016/j.urolonc.2024.04.011. Online ahead of print.

Authors

Affiliations

¹ Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH.
² Cleveland Clinic Lerner College of Medicine, Cleveland, OH.
³ Cleveland Clinic Lerner Research Institute, Cleveland, OH.
⁴ Univeristy Hospitals Department of Urology, Cleveland, OH.
⁵ Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH; Cleveland Clinic Lerner Research Institute, Cleveland, OH. Electronic address: millera25@ccf.org.
⁶ University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: bhlee@mdanderson.org.

PMID: 38664180
DOI: 10.1016/j.urolonc.2024.04.011

Abstract

Purpose: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response.

Materials and methods: Patients with archival pre-treatment biopsy samples (2012-2018) were identified retrospectively. Prospectively, urine and fresh tumor samples were collected from individuals with high-risk NMIBC (2020-2023). BCG response was defined as tumor-free 2 years from induction therapy. Extracted DNA was sequenced for 16S rRNA and shotgun metagenomics. Primary outcomes were species richness (α-diversity) and microbial composition (β-diversity). Paired t-tests were performed for α-diversity (Observed species/Margalef). Statistical analysis for β-diversity (weighted and unweighted UniFrac distances, weighted Bray-Curtis dissimilarity) were conducted through Permanova, with 999 permutations.

Results: Microbial species richness (P < 0.001) and composition (P = 0.001) differed between BCG responders and non-responders. Lactobacillus spp. were significantly enriched in BCG-responders. Shotgun metagenomics identified possible mechanistic pathways such as assimilatory sulfate reduction.

Conclusion: A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders.

Keywords: BCG; Bladder cancer; Microbiome.