Shaukat Aasma, Burke Carol A, Chan Andrew T, Grady William M, Gupta Samir, Katona Bryson W, Ladabaum Uri, Liang Peter S, Liu Julia J, Putcha Girish, Robertson Douglas J, Schoen Robert E, Meng Zhen, Piscitello Andrew, Sun Chung-Kai, Xu Chuanbo, Lin C Jimmy, Lee Lilian C, Baldo Lance, Levin Theodore R
NYU Grossman School of Medicine, New York, New York.
University of Minnesota Twin Cities, Minneapolis.
JAMA. 2025 Jun 2. doi: 10.1001/jama.2025.7515.
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.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
Participants were required to complete a screening colonoscopy after blood collection.
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.
The median age of participants in the evaluable cohort (n = 27 010) 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% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 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.
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.
ClinicalTrials.gov Identifier: NCT04369053.
结直肠癌筛查虽被广泛推荐，但实际应用不足。与内镜检查或粪便检测相比，基于血液的筛查具有更高的依从性潜力，但必须首先在筛查人群中进行临床验证。
以结肠镜检查及组织病理学为参考方法，评估一种用于平均风险人群结直肠癌检测的基于血液的循环肿瘤DNA试验的临床性能。
设计、地点和参与者：前瞻性、多中心、横断面观察性研究，纳入2020年5月至2022年4月期间无症状的45至85岁成年参与者，这些参与者患结直肠癌的风险平均，且愿意接受标准的结肠镜筛查。参与者、工作人员和病理学家对血液检测结果不知情，实验室检测对结肠镜检查结果不知情。该研究在美国49个州和阿拉伯联合酋长国的201个中心进行。采用现场和移动采血方式采集血液。
参与者在采血后需完成一次筛查结肠镜检查。
主要终点为结直肠癌的敏感性、晚期结直肠肿瘤（结直肠癌或晚期癌前病变）的特异性、晚期结直肠肿瘤的阴性预测值以及晚期结直肠肿瘤的阳性预测值。次要终点为晚期癌前病变的敏感性。
可评估队列（n = 27010）中参与者的中位年龄为57.0岁，55.8%为女性。结直肠癌的敏感性为79.2%（57/72；95%CI，68.4%-86.9%），晚期结直肠肿瘤的特异性为91.5%（22306/24371；95%CI，91.2%-91.9%）。晚期结直肠肿瘤的阴性预测值为90.8%（22306/24567；95%CI，90.7%-90.9%），晚期结直肠肿瘤的阳性预测值为15.5%（378/2443；95%CI，14.2%-16.8%）。所有主要终点均符合预先设定的接受标准。晚期癌前病变的敏感性为12.5%（321/2567；95%CI，11.3%-13.8%），未达到预先设定的接受标准。
在平均风险的结直肠癌筛查人群中，一种基于血液的检测方法在结直肠癌检测方面显示出可接受的准确性，但检测晚期癌前病变仍然是一项挑战，需要持续努力提高检测敏感性。
ClinicalTrials.gov标识符：NCT04369053。
