Risk-Adapted Screening Shows Superior Diagnostic Efficacy than Fecal Immunochemical Test in Colorectal Cancer Screening: Baseline Results of a Multi-Center Randomized Controlled Trial (TARGET-C)

Background: In colorectal cancer (CRC) screening, implementing risk-adapted screening might be more effective than traditional screening strategies. We aimed to compare the effectiveness of a risk-adapted screening strategy with colonoscopy and fecal immunochemical test (FIT) in CRC screening. Methods: A randomized controlled trial was conducted in 6 centers in China since May, 2018. 19,546 eligible participants aged 50-74 years were recruited and randomly allocated into one of the 3 screening groups in a 1:2:2 ratio: 1) one-time colonoscopy (n=3916); 2) annual FIT (n=7854); 3) annual risk-adapted screening (n=7776). Based on the risk-stratification score, high-risk subjects were referred for colonoscopy, and low-risk ones were referred for FIT. All Subjects with positive FIT were referred for diagnostic colonoscopy. The detection rate of advanced neoplasm was the primary outcome. Findings: For baselines screening, the participation rates of the colonoscopy, FIT, and risk-adapted screening groups were 42·5% (1665/3916), 94·0% (7386/7854), and 85·2% (6628/7776), respectively. For the intention-to-screen analysis, the detection rates for advanced neoplasm were 2·40% (94/3916), 1·13% (89/7854) and 1·66% (129/7776), with ORs (95% CIs) of 2·16 (1·61-2·90; P<0.001) for colonoscopy vs. FIT, 1·45 (1·10-1·90; P <0.001) for colonoscopy vs. risk-adapted screening, and 1·49 (1·13-1·97; P <0.001) for risk-adapted screening vs. FIT, respectively. The numbers of subjects who required colonoscopy examination to detect 1 advanced neoplasm were 18 in the colonoscopy group, 10 in the FIT group, and 11 in the risk-adapted screening group. Interpretation: For baseline screening, the risk-adapted screening approach showed a remarkably high participation rate, and its diagnostic yield was superior to FIT at a similarly low resource load of colonoscopy. Trial Registration: The study is registered with the China Clinical Trial Registry (www.chictr.org.cn Identifier: ChiCTR1800015506). Funding Statement: This work was supported by the CAMS Innovation Fund for Medical Sciences (2017-I2M-1-006, 2019-I2M-2-002), the National Natural Science Foundation of China (81703309), and National Key Research and Development Plan Program (2016YFC1302702). Declaration of Interests: The authors stated: None. Ethics Approval Statement: This study was approved by Ethics Committee of the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences and Peking Union Medical College (approved number: 18-013/1615). All participants provided written informed consent.