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In this review, we summarize evidence that microbiome\u2010related pathways influence urothelial carcinoma (UC) and renal cell carcinoma (RCC) across the continuum from tumor initiation to immunotherapy outcome. We highlight recent preclinical studies showing that gut microbial environments can causally modify urothelial carcinogenesis through carcinogen metabolism, inflammatory priming, and diet\u2010microbiome interactions in N\u2010butyl\u2010N\u2010(4\u2010hydroxybutyl) nitrosamine\u2010based mouse models, including a newly established upper tract urothelial carcinoma mouse model, as well as emerging clinical data indicating that circulating extracellular vesicle (EV)\u2010associated bacterial DNA is associated with tumor immune phenotypes and ICI outcomes in UC and RCC. Because blood is a low\u2010biomass matrix, we use the term \u201ccirculating microbial signals\u201d rather than \u201cblood microbiome\u201d and emphasize the need for contamination\u2010aware analysis, careful EV characterization, and external validation. Current evidence supports a framework in which microbiome\u2010related signals connect intestinal ecology, systemic immune tone, tumor immune contexture, and treatment response, while indicating that circulating EV\u2010associated bacterial DNA remains an exploratory biomarker platform.<\/jats:p>","DOI":"10.1111\/cas.70448","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:54:01Z","timestamp":1782197641000},"page":"2357-2365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microbiome\u2013Driven Carcinogenesis and Circulating Microbial Signals in Genitourinary Cancers"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9369-4264","authenticated-orcid":false,"given":"Atsunari","family":"Kawashima","sequence":"first","affiliation":[{"name":"Department of Urology, Graduate School of Medicine The University of Osaka  Osaka 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