{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:05:47Z","timestamp":1793286347778,"version":"4.5.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Exposures<\/jats:title><jats:p>Participants were required to complete a screening colonoscopy after blood collection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median age of participants in the evaluable cohort (n\u2009=\u200927\u202f010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57\/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22\u202f306\/24\u202f371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22\u202f306\/24\u202f567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378\/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321\/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04369053\">NCT04369053<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2025.7515","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T16:30:21Z","timestamp":1748881821000},"page":"56","source":"Crossref","is-referenced-by-count":73,"title":["Clinical Validation of a Circulating Tumor DNA\u2013Based Blood Test to Screen for Colorectal Cancer"],"prefix":"10.1001","volume":"334","author":[{"given":"Aasma","family":"Shaukat","sequence":"first","affiliation":[{"name":"NYU Grossman School of Medicine, New York, New York"},{"name":"University of Minnesota Twin Cities, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Chan","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Grady","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Seattle, Washington"},{"name":"University of Washington School of Medicine, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryson W.","family":"Katona","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Ladabaum","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Liang","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Morehouse School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Putcha","sequence":"additional","affiliation":[{"name":"Freenome Holdings Inc, Brisbane, California"},{"name":"Now with Precision Medicine and Diagnostics, Los Altos Hills, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Hanover, New Hampshire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Schoen","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Epidemiology, University of Pittsburgh and the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Meng","sequence":"additional","affiliation":[{"name":"Freenome Holdings Inc, Brisbane, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Piscitello","sequence":"additional","affiliation":[{"name":"Freenome Holdings Inc, Brisbane, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"Freenome Holdings Inc, Brisbane, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanbo","family":"Xu","sequence":"additional","affiliation":[{"name":"Freenome Holdings Inc, Brisbane, California"},{"name":"Now with CBX Consulting LLC, San Jose, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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