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Urinary microbiome variations associated with response to BCG therapy for bladder cancer
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NATIONAL HARBOR, Md. — There is an association between certain types of commensal urinary microbiome bacteria found in the urinary tract and a clinical response to bacillus Calmette-Guérin immunotherapy for patients with early-stage urothelial bladder cancer, according to results of an investigator-initiated, single institution pilot study presented at Society for Immunotherapy of Cancer Annual Meeting.
The investigators found that an abundance of Proteobacteria was higher in patients with urothelial bladder cancer who had disease recurrence after immunotherapy with bacillus Calmette-Guérin (BCG).
“Up to 50% of high-grade, non-muscle invasive bladder cancers will recur despite treatment with intravesical BCG immunotherapy,” Randy F. Sweis, MD, a HemOnc Today Next Gen Innovator and assistant professor of medicine in the section of hematology/oncology at University of Chicago Medicine, told Cell Therapy Next. “We aimed to understand whether the commensal microbiome in the urine could impact and predict BCG responsiveness,” he added.
Sweis is one of the study’s co-authors and said that this is the first study to examine the impact of the urine microbiome on the efficacy of immunotherapy. “Variation in the commensal urinary microbiome was linked to BCG response,” was the key takeaway from this study, according to Sweis.
Patient characteristics
Patients with a new diagnosis of bladder cancer were enrolled into the study before receiving first-line treatment with either transurethral resection or BCG immunotherapy. Participants’ urine was collected via sterile catheterization and was used to determine rRNA gene sequencing and subsequent urinary cytokine analysis.
The study comprised 31 patients (median age 69 years; range, 46-87; 71% men; 35% smokers) and the median follow up was 12 months (range, 3-24). Patients with no evidence of urinary infection were included in the study, along with patients who had not received previous BCG immunotherapy. Ten patients had their disease recur during the study follow-up period.
Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Tenericutes comprised greater than 99% of the phyla detected in the urine among the overall study population.
“I was surprised to observe the diversity of bacteria present in the urine of patients,” Sweis said. “Historically, the dogma has been that the urine is sterile in patients without urinary tract infections.”
Urinary microbiome and BCG efficacy
The study’s analysis was done by distance matrix calculation, which indicated an overall significant difference between patients with and without disease recurrence after BCG immunotherapy (Bonferroni-corrected P = .017).
An abundance of Proteobacteria in the urine was higher in patients who had disease recurrence after BCG immunotherapy (P = .035). There were stronger differences observed for specific taxa, such as the Gammaproteobacteria class (P = .0025) and the Enterobacteriaceae family (P = .001).
Patients who did not experience disease recurrence after BCG immunotherapy showed more abundant levels of Firmicutes in the urine, in particular Lactobacillales (P = .049). Cytokine concentrations were measured among a subset of 13 patients, including six patients who had disease recurrence. Changes in urinary IFN-gamma and TNF-alpha levels after 6 weekly doses of BCG were calculated. There were no significant differences observed between patients with and without disease recurrence.
Sweis admitted that the results are limited by the study’s single-institution nature. He says the number of patients enrolled in the study is 50 and that his group is in the process of expanding this into a national, multi-institutional trial.
He told the audience at the SITC Annual Meeting that other studies are ongoing to determine the temporal variation in the urine microbiome after BCG therapy.
“Detection of specific urinary microbes could serve as a potential predictive biomarker for BCG therapy and possibly uncover new mechanisms of resistance that could be therapeutically targeted,” he concluded. – by Drew Amorosi
Reference:
Sweis R, et al. Abstract O67. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 7-10, 2019; National Harbor, Md.
Disclosures: Sweis reports consulting roles with AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, Janssen Biotech, Mirati Therapeutics and Puma Biotechnology; honoraria/speaking fees from AstraZeneca, Bristol-Myers Squibb, Exelixis and Medscape; travel fees from AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis and Janssen Biotech; and grant/research support from AbbVie, Bayer, Bristol-Myers Squibb, CytomX, Eisai, EpiVax Oncology, Genentech and Merck.