From the Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, and Regenstrief Institute, Indianapolis (T.F.I.); Exact Sciences, Madison, WI (K.P., J.Z., Z.D.G., M.C.O., S.S., J.G., P.J.L.); Boston Biostatistics Research Foundation, Framingham, MA (P.T.L.); Louisiana Research Center, Shreveport (H.A.); Great Lakes Gastroenterology Research, Mentor, OH (D.B.); Southwest Gastroenterology, Oak Lawn, IL (C.B.); and the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (J.B.K.).
N Engl J Med. 2024 Mar 14;390(11):984-993. doi: 10.1056/NEJMoa2310336.
BACKGROUND: A next-generation multitarget stool DNA test, including assessments of DNA molecular markers and hemoglobin level, was developed to improve the performance of colorectal cancer screening, primarily with regard to specificity. METHODS: In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The primary outcomes were sensitivity of the test for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions). Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. Secondary objectives included the quantification of sensitivity for advanced precancerous lesions and specificity for nonneoplastic findings or negative colonoscopy and comparison of sensitivities for colorectal cancer and advanced precancerous lesions between the multitarget stool DNA test and a commercially available fecal immunochemical test (FIT). RESULTS: Of 20,176 participants, 98 had colorectal cancer, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy. With the next-generation test, sensitivity for colorectal cancer was 93.9% (95% confidence interval [CI], 87.1 to 97.7), and specificity for advanced neoplasia was 90.6% (95% CI, 90.1 to 91.0). Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3 to 45.6), and specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2 to 93.1). With the FIT, sensitivity was 67.3% (95% CI, 57.1 to 76.5) for colorectal cancer and 23.3% (95% CI, 21.5 to 25.2) for advanced precancerous lesions; specificity was 94.8% (95% CI, 94.4 to 95.1) for advanced neoplasia and 95.7% (95% CI, 95.3 to 96.1) for nonneoplastic findings or negative colonoscopy. As compared with FIT, the next-generation test had superior sensitivity for colorectal cancer (P<0.001) and for advanced precancerous lesions (P<0.001) but had lower specificity for advanced neoplasia (P<0.001). No adverse events occurred. CONCLUSIONS: The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. (Funded by Exact Sciences; BLUE-C ClinicalTrials.gov number, NCT04144738.).
背景：开发了一种下一代多靶点粪便 DNA 检测方法，包括评估 DNA 分子标志物和血红蛋白水平，以提高结直肠癌筛查的性能，主要是提高特异性。
方法：在一项前瞻性研究中，我们评估了一种用于 40 岁或以上无症状成年人筛查结肠镜检查的下一代多靶点粪便 DNA 检测方法。主要结果是该检测方法对结直肠癌的敏感性和对高级肿瘤（结直肠癌或高级癌前病变）的特异性。高级癌前病变包括一个或多个长度至少 1 厘米的腺瘤或无蒂锯齿状病变、具有绒毛组织学特征的病变和高级别异型增生。次要目标包括定量检测高级癌前病变的敏感性和非肿瘤性发现或阴性结肠镜检查的特异性，并比较多靶点粪便 DNA 检测和商业上可用的粪便免疫化学检测（FIT）对结直肠癌和高级癌前病变的敏感性。
结果：在 20176 名参与者中，98 人患有结直肠癌，2144 人患有高级癌前病变，6973 人患有非高级腺瘤，10961 人患有非肿瘤性发现或阴性结肠镜检查。下一代检测方法对结直肠癌的敏感性为 93.9%（95%可信区间[CI]，87.1 至 97.7），对高级肿瘤的特异性为 90.6%（95%CI，90.1 至 91.0）。对高级癌前病变的敏感性为 43.4%（95%CI，41.3 至 45.6），对非肿瘤性发现或阴性结肠镜检查的特异性为 92.7%（95%CI，92.2 至 93.1）。使用 FIT，结直肠癌的敏感性为 67.3%（95%CI，57.1 至 76.5），高级癌前病变的敏感性为 23.3%（95%CI，21.5 至 25.2）；高级肿瘤的特异性为 94.8%（95%CI，94.4 至 95.1），非肿瘤性发现或阴性结肠镜检查的特异性为 95.7%（95%CI，95.3 至 96.1）。与 FIT 相比，下一代检测方法对结直肠癌（P<0.001）和高级癌前病变（P<0.001）的敏感性更高，但对高级肿瘤的特异性更低（P<0.001）。未发生不良事件。
结论：下一代多靶点粪便 DNA 检测方法对结直肠癌和高级癌前病变的敏感性高于 FIT，但特异性较低。（由 Exact Sciences 资助；BLUE-C 临床试验.gov 编号，NCT04144738）。
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