Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer

Abstract

IntroductionIntravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.MethodsPatients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated.ResultsAcross the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort.ConclusionIVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

Clinical relevance of expanded quantitative urine culture in health and disease

“…Cumulative studies have suggested that dysbiosis of urobiome influences the microenvironments of the urinary tract and thereby contributing to the onset and progression of the bladder cancer and prostate cancer ( Alfano et al., 2016 ; Annels et al., 2020 ; Chipollini et al., 2020 ; Cai et al., 2021 ; James et al., 2023 ). Urobiome dysbiosis has also been found to affect the treatment response to the bladder cancer ( Annels et al., 2020 ).…”

Microbial Communities in Gynecological Cancers and Their Association with Tumor Somatic Variation

“…Some of the genera most informative for HGSC in the lasso multivariate analysis and in the correlation with significant genomic SNVs, Escherichia/Shigella , Pantoea , and Ralstonia , have been associated with other types of cancer, including bladder, pancreatic, cholangiocarcinoma, colorectal, breast, and oral malignancies [ 42 , 43 , 44 , 45 , 46 ]. Likewise, variants of the dynein axonemal heavy chain ( DNAH ) family have been previously associated with breast and ovarian cancer [ 47 ].…”

The Urinary Microbiome in Health and Disease: Relevance for Bladder Cancer

“…An investigation involving patients with NMIBC has found that non-recurrence patients tend to exhibit higher levels of Escherichia/Shigella and Ureaplasma, while patients experiencing a relapse after BCG or intravesical therapy tend to exhibit higher levels of Aerococcus, thus being predictive of a poor cancer response [177].…”