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

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD42)1 Sep 2021PD42-04 TUMOR MICROBIOME ASSOCIATED WITH BCG RESPONSE IN NON-MUSCLE INVASIVE BLADDER CANCER Jacob Knorr, Ava Adler, Jose Agudelo, Kyle Ericson, Prithvi Murthy, Rebecca Campbell, Petar Bajic, Nima Almassi, Christopher Weight, Georges-Pascal Haber, Aaron Miller, and Byron Lee Jacob KnorrJacob Knorr More articles by this author , Ava AdlerAva Adler More articles by this author , Jose AgudeloJose Agudelo More articles by this author , Kyle EricsonKyle Ericson More articles by this author , Prithvi MurthyPrithvi Murthy 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.0000000000002056.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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 formalin-fixed 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 non-responder 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 non-responders after therapy suggests BCG can persist and may have implications for immune tolerance in the setting of non-response. Source of Funding: CWRU CCCC © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e725-e726 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jacob Knorr More articles by this author Ava Adler More articles by this author Jose Agudelo More articles by this author Kyle Ericson More articles by this author Prithvi Murthy 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 Loading ...