High-specificity colorectal cancer screening is desirable to triage patients <50 years for colonoscopy; however, most endorsed colorectal cancer screening tests have not been rigorously evaluated in younger populations. This prospective cross-sectional study determined the specificity of the multitarget stool DNA (mt-sDNA) test in an average-risk screening population of 45 to 49 year-olds. Specificity was the primary outcome and was measured in participants without colorectal cancer or advanced precancerous lesions [APL- advanced adenomas (AA), and sessile serrated lesions ≥10 mm], and in the subgroup of participants with negative colonoscopic findings. APL sensitivity was a secondary outcome. The evaluable cohort included those who completed the study without protocol deviations and had a usable mt-sDNA test. Of 983 enrolled participants, 816 formed the evaluable cohort, with a mean age of 47.8 (SD, 1.5) years; 47.7% were women. No participants had colorectal cancer, 49 had APL, 253 had nonadvanced adenomas (NAA), and 514 had negative colonoscopic findings. mt-sDNA test specificity was 95.2% (95% CI, 93.4-96.6) in participants with NAA or negative findings [96.3% (confidence interval (CI), 94.3%-97.8%)] in those with negative findings, and did not differ by sex (P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9-47.5%), with most APL (83.7%) measuring 10-19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64-0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening.

中文翻译：

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多靶点粪便 DNA 检测对 45-49 岁平均风险人群进行大肠癌筛查的特异性：一项横断面研究

对<50岁的患者进行结肠镜检查需要高特异性结直肠癌筛查；然而，大多数认可的结直肠癌筛查测试尚未在年轻人群中进行严格评估。这项前瞻性横断面研究确定了多靶点粪便 DNA (mt-sDNA) 测试在 45 至 49 岁的平均风险筛查人群中的特异性。特异性是主要结果，并在没有结直肠癌或晚期癌前病变[APL-晚期腺瘤 (AA) 和无蒂锯齿状病变 ≥10 mm] 的参与者以及结肠镜检查结果阴性的参与者亚组中进行测量。APL 敏感性是次要结果。可评估的队列包括那些在没有偏离方案的情况下完成研究并进行了可用的 mt-sDNA 测试的人。在 983 名注册参与者中，816 人组成了可评估的队列，平均年龄为 47.8（SD，1.5）岁；47.7% 是女性。没有参与者患有结直肠癌，49 人患有 APL，253 人患有非晚期腺瘤 (NAA)，514 人结肠镜检查结果阴性。在有 NAA 或阴性结果的参与者中，mt-sDNA 检测特异性为 95.2%（95% CI，93.4-96.6）[96.3%（置信区间（CI），94.3%-97.8%）]，在那些有阴性结果的参与者中，没有NAA 或阴性结果的参与者因性别 (P = 0.75) 或种族 (P = 0.36) 而不同。APL 的敏感性为 32.7% (CI, 19.9-47.5%)，大多数 APL (83.7%) 为 10-19 mm，没有高度不典型增生。区分 APL 和较小发现的 ROC 曲线下面积为 0.72 (CI, 0.64-0.81)。mt-sDNA 的高特异性将有助于将这个年龄组不必要的诊断程序的风险降至最低。