Pd25-08 the bladder tumor microbiome may augment response to bcg in non-muscle invasive bladder cancer

You have accessJournal of UrologyCME1 Apr 2023PD25-08 THE BLADDER TUMOR MICROBIOME MAY AUGMENT RESPONSE TO BCG IN NON-MUSCLE INVASIVE BLADDER CANCER Zaeem Lone, Jacob Knorr, Glenn Werneburg, Ava Adler, Jose Agudelo, Rebecca Campbell, Petar Bajic, Nima Almassi, Christopher Weight, Georges Pascal-Haber, Aaron Miller, and Byron Lee Zaeem LoneZaeem Lone More articles by this author , Jacob KnorrJacob Knorr More articles by this author , Glenn WerneburgGlenn Werneburg More articles by this author , Ava AdlerAva Adler More articles by this author , Jose AgudeloJose Agudelo More articles by this author , Rebecca CampbellRebecca Campbell More articles by this author , Petar BajicPetar Bajic More articles by this author , Nima AlmassiNima Almassi More articles by this author , Christopher WeightChristopher Weight More articles by this author , Georges Pascal-HaberGeorges Pascal-Haber More articles by this author , Aaron MillerAaron Miller More articles by this author , and Byron LeeByron Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003303.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical installation of BCG has been the gold standard for the management of non-muscle invasive bladder cancer (NMIBC). However, approximately 30-40% of patients experience treatment failure and it remains unclear who will benefit from this therapy. One potential modifiable factor in treatment response may be the urinary microbiome. Therefore, we sought to investigate how the urinary microbiome may differ between BCG responders and non-responders and identify any commensal bacteria that might increase the efficacy of this therapy. METHODS: 16S next-generation sequencing (NGS) and shotgun metagenomics were performed on formalin-fixed bladder tumors from patients prior to intravesical BCG therapy for NMIBC. BCG responders was defined as no recurrence two years after induction. Differences in the alpha and beta diversity of the two populations were compared. Subsequently, to validate the NGS data, GFP-tagged BCG was co-cultured with a urothelial carcinoma (UC) cell line (SW780) and candidate bacteria based on the NGS data. A Pearson-Chi Square test was utilized to compare percent internalization. Additionally, fresh tumor samples were collected at the time of transurethral resection of bladder tumor (TURBT) and were cultured in five different media conditions to confirm the viability of the tumor microbiome and quantify the bacterial mass per sample. RESULTS: Forty-seven patients (23 responders, 24 non-responders) were included in the analysis. Overall microbiome composition differed significantly as determined by both NGS (p=0.042) and shotgun metagenomics (p=0.047). Lactobacillus spp were significantly enriched in the BCG responders. Co-culture with increasing concentrations of Lactobacillus crispatus resulted in increased BCG-GFP internalization in UCC (179/1133, 16%) when compared to controls (75/1166, 6%) (p<0.001). Additionally, from ten fresh tumor samples, four samples produced viable bacteria through culture-based approaches and we calculated tumor bacterial density at 1.25×106 colony forming units/gram of tissue. CONCLUSIONS: A compositional difference exists in the tumor microbiome of BCG responders and non-responders. Lactobacillus crispatus was associated with a significant increase in the internalization of BCG. Our findings suggest that an association exists between the tumor microbiome and response to BCG, which may offer new strategies to improve intravesical therapy for NMIBC patients. Source of Funding: Case Comprehensive Cancer Center Summer Medical Student Award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e732 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zaeem Lone More articles by this author Jacob Knorr More articles by this author Glenn Werneburg More articles by this author Ava Adler More articles by this author Jose Agudelo More articles by this author Rebecca Campbell More articles by this author Petar Bajic More articles by this author Nima Almassi More articles by this author Christopher Weight More articles by this author Georges Pascal-Haber More articles by this author Aaron Miller More articles by this author Byron Lee More articles by this author Expand All Advertisement PDF downloadLoading ...