{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:54:22Z","timestamp":1794002062095,"version":"4.8.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"8","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["U01CA230691"],"award-info":[{"award-number":["U01CA230691"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["RA37CA230400"],"award-info":[{"award-number":["RA37CA230400"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R21NS113016"],"award-info":[{"award-number":["R21NS113016"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006352","name":"Virginia and D.K. Ludwig Fund for Cancer Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100006352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HT9425-25-1-0489"],"award-info":[{"award-number":["HT9425-25-1-0489"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,24]]},"abstract":"<jats:p>\n                    We previously reported initial results from a clinical trial testing a strategy in which patients with muscle-invasive bladder cancer (MIBC) achieving a clinical complete response after cystoscopic resection of the bladder tumor plus systemic therapy could forgo removal of their entire bladder (cystectomy). While the results were highly promising, a subset of patients omitting initial cystectomy developed recurrence highlighting the need for biomarkers to refine selection of patients for this approach. We here report long-term follow-up of these patients and investigate whether tumor DNA in the plasma (ctDNA) or urine (utDNA) could inform prognosis and the need for cystectomy. Three-year bladder-intact survival among patients with a complete clinical response following four rounds of systemic therapy was 69%. Metastatic risk was significantly higher for patients with detectable versus undetectable ctDNA presystemic therapy (HR 4.68; 95% CI 1.10-43.35; log-rank\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    <\/jats:italic>\n                    = 0.036). Only 4.5% (1 of 22) of patients with undetectable baseline ctDNA developed metastatic disease. Undetectable ctDNA before or after systemic therapy was associated with extremely low metastatic risk. Urine utDNA was more sensitive than plasma ctDNA at detecting residual disease within the bladder, and detectable urine utDNA in patients with a complete clinical response was associated with shorter bladder-intact survival (HR 6.47, 95% CI 1.34-31.31; log-rank\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.008). These findings establish the conceptual and experimental foundation for incorporating ctDNA and utDNA assays into the management of patients with MIBC, particularly with respect to the need for cystectomy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2533449123","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T18:52:59Z","timestamp":1771440779000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Monitoring of plasma and urine tumor-derived DNA to inform bladder-sparing approaches for patients with muscle-invasive bladder cancer"],"prefix":"10.1073","volume":"123","author":[{"given":"Matthew D.","family":"Galsky","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai","place":["New York"]},{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai","place":["New 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Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Douville","sequence":"additional","affiliation":[{"name":"Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine","place":["Baltimore"]},{"name":"Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Popoli","sequence":"additional","affiliation":[{"name":"Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine","place":["Baltimore"]},{"name":"Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Ptak","sequence":"additional","affiliation":[{"name":"Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of 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Chase"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin G.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Urology, City of Hope Comprehensive Cancer Center","place":["Duarte"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya B.","family":"Dorff","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center","place":["Duarte"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P.","family":"Cetnar","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Oregon Health and Science University","place":["Portland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brock","family":"O\u2019Neil","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Utah","place":["Salt Lake 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detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy","volume":"7","author":"Springer S. U.","year":"2018","unstructured":"S. U. Springer , Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. Elife 7, 1\u201327 (2018).","journal-title":"Elife"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","unstructured":"D. Benjamin Calling somatic SNVs and indels with Mutect2. bioRxiv [Preprint] (2019). https:\/\/doi.org\/10.1101\/861054 (Accessed 17 November 2025).","DOI":"10.1101\/861054"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/80.1.27"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2001.00114.x"},{"key":"e_1_3_4_29_2","unstructured":"M. Galsky Extended follow-up of a response-guided bladder-sparing treatment approach for muscle-invasive bladder cancer and monitoring of plasma and urine tumor DNA. EGA. https:\/\/ega-archive.org\/studies\/EGAS00001008004. Deposited 17 November 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2533449123","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2533449123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T15:52:50Z","timestamp":1777996370000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2533449123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":29,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,2,24]]}},"alternative-id":["10.1073\/pnas.2533449123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2533449123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"2025-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2533449123"}}