{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:17:01Z","timestamp":1788225421422,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for real-time disease monitoring in muscle-invasive bladder cancer (MIBC). This narrative review summarizes current clinical evidence regarding ctDNA across disease stages. Methods: We examine recent translational and clinical findings, incorporating key prospective data from practice-changing trials, as well as insights into minimal residual disease (MRD) detection, treatment escalation and de-escalation strategies, and systemic barriers to adoption. Results: Postoperative ctDNA positivity consistently identifies patients with molecular residual disease (MRD) who face a substantially higher risk of recurrence and mortality, frequently preceding radiographic relapse by several months. Prospective evidence now validates ctDNA as a predictive biomarker to guide adjuvant immunotherapy escalation, while sustained ctDNA negativity correlates with high long-term disease-free survival. Beyond plasma ctDNA, emerging multi-compartment liquid biopsies\u2014integrating urinary tumor DNA (utDNA)\u2014demonstrate enhanced sensitivity, particularly in bladder-sparing and local surveillance settings. Furthermore, integrating genomic ctDNA profiling with novel post-transcriptional layers like epitranscriptomics offers a functional framework to capture tumor adaptation under therapeutic pressure. However, clinical translation remains constrained by a lack of assay harmonization, variable analytical sensitivity, and the need for standardized intervention thresholds. Conclusions: Longitudinal liquid biopsies are rapidly shifting MIBC management from static, stage-based paradigms toward dynamic, molecularly informed precision oncology. While ctDNA-guided strategies show robust clinical utility, prospective interventional validation and technical standardization are required before widespread routine integration.<\/jats:p>","DOI":"10.3390\/cancers18172816","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"2816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Tumor DNA in Bladder Cancer: Current Clinical Evidence and Emerging Multi-Omics Perspectives\u2014A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1586-8676","authenticated-orcid":false,"given":"Mariam Grazia","family":"Polito","sequence":"first","affiliation":[{"name":"UOC Oncologia Territoriale, ASL Latina, CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino, 04100 Latina, Italy"},{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisana","family":"Sisca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Department of Translational Research, Institut Curie, 26 Rue d\u2019Ulm, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Caruso","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale, ASL Latina, CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2636-3198","authenticated-orcid":false,"given":"Antonella","family":"Cosimati","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale, ASL Latina, CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8182-8332","authenticated-orcid":false,"given":"Carla Adriana","family":"Ramirez Reinaga","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale, ASL Latina, CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0903-9421","authenticated-orcid":false,"given":"Etien","family":"Leka","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale, ASL Latina, CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science and Biotechnology, Universit\u00e0 \u201cLa Sapienza\u201d, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-6274","authenticated-orcid":false,"given":"Gian Paolo","family":"Spinelli","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale, ASL Latina, CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41572-023-00475-w","article-title":"Bladder cancer","volume":"9","author":"Hansel","year":"2023","journal-title":"Nat. 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