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):973-983. doi: 10.1056/NEJMoa2304714.
Colorectal 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.
We 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.
The 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).
In 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.).
在美国，结直肠癌是成年人中第三大常见的癌症。早期发现可以预防 90%以上的结直肠癌相关死亡，但尽管有多种可用的检测方法，仍有超过三分之一的筛查合格人群没有进行筛查。血液检测有可能提高筛查的依从性，更早地发现结直肠癌，并降低结直肠癌相关死亡率。
我们评估了一种基于细胞游离 DNA (cfDNA) 的血液检测在有结直肠癌筛查资格的人群中的性能特征。主要结局是与筛查结肠镜检查相比，cfDNA 检测对结直肠癌和高级肿瘤（结直肠癌或高级癌前病变）的敏感性和特异性。次要结局是检测高级癌前病变的敏感性。
临床验证队列纳入了 10258 人，其中 7861 人符合入组条件且可进行评估。结肠镜检查发现的结直肠癌患者中，有 83.1%的 cfDNA 检测呈阳性，16.9%的 cfDNA 检测呈阴性，这表明 cfDNA 检测对结直肠癌的敏感性为 83.1%（95%置信区间[CI]，72.2%至 90.3%）。I 期、II 期或 III 期结直肠癌的敏感性为 87.5%（95%CI，75.3%至 94.1%），高级癌前病变的敏感性为 13.2%（95%CI，11.3%至 15.3%）。结肠镜检查未发现任何高级结直肠肿瘤（结直肠癌或高级癌前病变）的参与者中，有 89.6%的 cfDNA 血液检测呈阴性，而有 10.4%的 cfDNA 血液检测呈阳性，这表明任何高级肿瘤的特异性为 89.6%（95%CI，88.8%至 90.3%）。阴性结肠镜检查（无结直肠癌、高级癌前病变或非高级癌前病变）的特异性为 89.9%（95%CI，89.0%至 90.7%）。
在一般风险的筛查人群中，这种基于 cfDNA 的血液检测对结直肠癌的敏感性为 83%，对高级肿瘤的特异性为 90%，对高级癌前病变的敏感性为 13%。（由 Guardant Health 资助；ECLIPSE ClinicalTrials.gov 编号，NCT04136002。）
