• Daniel C Chung, Darrell M Gray, Harminder Singh, Rachel B Issaka, Victoria M Raymond, Craig Eagle, Sylvia Hu, Darya I Chudova, AmirAli Talasaz, Joel K Greenson, Frank A Sinicrope, Samir Gupta, and William M Grady.
• From the Division of Gastroenterology and Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston (D.C.C.); Gray Area Strategies, Owings Mills, MD (D.M.G.); the Association of Black Gastroenterologists and Hepatologists, New York (D.M.G.); the Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba and Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, Canada (H.S.); the Divisions of Public Health Sciences (R.B.I., W.M.G.), Clinical Research (R.B.I.), and Translational Science and Therapeutics (W.M.G.), Fred Hutchinson Cancer Center, and the Division of Gastroenterology, University of Washington School of Medicine (R.B.I., W.M.G.) - both in Seattle; Guardant Health, Palo Alto (V.M.R., C.E., S.H., D.I.C., A.T.), and the University of California, San Diego, La Jolla (S.G.) - both in California; the Department of Pathology, Michigan Medicine, Ann Arbor (J.K.G.); and the Divisions of Oncology, Gastroenterology, and Hepatology, Mayo Clinic, Mayo Comprehensive Cancer Center and Mayo Alix School of Medicine, Rochester, MN (F.A.S.).
• N. Engl. J. Med. 2024 Mar 14; 390 (11): 973983973-983.

BackgroundColorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality.MethodsWe assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.ResultsThe clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).ConclusionsIn an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).Copyright © 2024 Massachusetts Medical Society.

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