美国华盛顿大学医学院Erica K. Barnell团队研究了多靶点粪便RNA检测用于结直肠癌筛查的敏感性与特异性。2023年10月23日出版的《美国医学会杂志》发表了这项成果。

结直肠癌癌症筛查的无创检测必须包括对结直肠癌癌症和癌前病变的敏感检测。这些测试必须针对预期使用人群进行验证，其中包括45岁或以上的平均风险人群。该研究旨在与结肠镜检查结果进行比较，评价无创、多靶点粪便RNA检测（ColoSense）的敏感性和特异性。

这项3期临床试验（CRC-PREVENT）是一项双盲、前瞻性、横断面研究，旨在支持III类医疗器械的上市前批准申请。2021年6月至2022年6月，共有8920名参与者通过社交媒体平台在线识别，并通过分散的护士呼叫中心注册。所有参与者都完成了mt sRNA检测，包括商业上可获得的粪便免疫化学测试（FIT）、8种RNA转录物的浓度，以及参与者报告的吸烟状态。参与者在当地内窥镜检查中心完成结肠镜检查之前，收集粪便样本。

将mt sRNA检测结果（阳性或阴性）与结肠镜检查中观察到的指数病变进行比较。在12个月的过程中，45岁及以上的个体使用分散招募策略参与临床试验。参与者来自美国49个州，在3800多个不同的内镜中心进行了结肠镜检查。主要结局包括mt-sRNA检测对结直肠癌癌症和晚期腺瘤的敏感性，以及对结肠镜检查无病变的特异性。

参与者的平均年龄为55岁，其中4%自称亚洲人，11%自称黑人，7%自称西班牙裔。在8920名符合条件的参与者中，36人（0.40%）患有结直肠癌癌症，606人（6.8%）患有晚期腺瘤。mt-sRNA检测结直肠癌癌症的敏感性为94%，检测晚期腺瘤的敏感性为46%，结肠镜检查无病变的特异性为88%。与FIT的结果进行比较，mt-sRNA检测显示对结直肠癌癌症（94%对78%；McNemar P = .01）和晚期腺瘤（46%对29%；McNemar P < .001）的敏感性显著提高。

研究结果表明，在45岁及以上的个体中，mt-sRNA检测显示出对结直肠肿瘤（结直肠癌癌症和晚期腺瘤）的高敏感性，与FIT相比，敏感性显著提高。结肠镜检查无病变的特异性与现有的分子诊断测试相当。

附：英文原文

Title: Multitarget Stool RNA Test for Colorectal Cancer Screening

Author: Erica K. Barnell, Elizabeth M. Wurtzler, Julie La Rocca, Thomas Fitzgerald, Jessica Petrone, Yansheng Hao, Yiming Kang, Faith L. Holmes, David A. Lieberman

Issue&Volume: 2023-10-23

Abstract:

Importance  Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk individuals 45 years or older.

Objective  To evaluate the sensitivity and specificity of a noninvasive, multitarget stool RNA (mt-sRNA) test (ColoSense) test compared with results from a colonoscopy.

Design, Setting, and Participants  This phase 3 clinical trial (CRC-PREVENT) was a blinded, prospective, cross-sectional study to support a premarket approval application for a class III medical device. A total of 8920 participants were identified online using social media platforms and enrolled from June 2021 to June 2022 using a decentralized nurse call center. All participants completed the mt-sRNA test, which incorporated a commercially available fecal immunochemical test (FIT), concentration of 8 RNA transcripts, and participant-reported smoking status. Stool samples were collected prior to participants completing a colonoscopy at their local endoscopy center. The mt-sRNA test results (positive or negative) were compared with index lesions observed on colonoscopy. Over the course of 12 months, individuals 45 years and older were enrolled in the clinical trial using the decentralized recruitment strategy. Participants were enrolled from 49 US states and obtained colonoscopies at more than 3800 different endoscopy centers.

Main Outcomes and Measures  The primary outcomes included the sensitivity of the mt-sRNA test for detecting colorectal cancer and advanced adenomas and the specificity for no lesions on colonoscopy.

Results  The mean (range) age of participants was 55 (45-90) years, with 4% self-identified as Asian, 11% as Black, and 7% as Hispanic. Of the 8920 eligible participants, 36 (0.40%) had colorectal cancer and 606 (6.8%) had advanced adenomas. The mt-sRNA test sensitivity for detecting colorectal cancer was 94%, sensitivity for detecting advanced adenomas was 46%, and specificity for no lesions on colonoscopy was 88%. The mt-sRNA test showed significant improvement in sensitivity for colorectal cancer (94% vs 78%; McNemar P=.01) and advanced adenomas (46% vs 29%; McNemar P<.001) compared with results of the FIT.

Conclusions and Relevance  In individuals 45 years and older, the mt-sRNA test showed high sensitivity for colorectal neoplasia (colorectal cancer and advanced adenoma) with significant improvement in sensitivity relative to the FIT. Specificity for no lesions on colonoscopy was comparable to existing molecular diagnostic tests.

DOI: 10.1001/jama.2023.22231

Source: https://jamanetwork.com/journals/jama/fullarticle/2811133