结肠镜、免疫法粪便潜血检测及风险分级筛查策略在结直肠癌筛查中的效果研究:一项多中心随机对照试验

Evaluation of the Effectiveness of Colonoscopy,Fecal Immunochemical Test and Risk-adapted Screening Strategies in Population-based Colorectal Cancer Screening:A Multicenter Randomized Controlled Trial

目的评价结肠镜、免疫法粪便潜血检测(fecal immunochemical test,FIT)及风险分级筛查策略在人群结直肠癌筛查中的可行性和有效性。方法基于2018年5月—2021年5月全国6个中心开展的人群结直肠癌筛查随机对照试验(TARGET-C研究),将符合要求的受试者按照1∶2∶2的比例随机分配至结肠镜组、FIT组、分级筛查组(经风险评估,高风险人群接受结肠镜检查;低风险人群接受FIT检测,FIT阳性者接受结肠镜检查)。3组人群分别接受不同方案的结直肠癌筛查,其中结肠镜组仅接受基线筛查,FIT组与分级筛查组在基线筛查的基础上接受每年1次的随访筛查。主要研究结局为进展期肿瘤(包括结直肠癌和进展期腺瘤)检出率。比较3种筛查方案的人群参与率、进展期肿瘤检出率和结肠镜检查负荷。结果共入选符合纳入与排除标准的受试者19373名,包括男性8082名(41.7%),女性11291名(58.3%);平均年龄(60.5±6.5)岁。其中结肠镜组3883名、FIT组7793名、分级筛查组7697名。FIT组与分级筛查组已完成2轮次随访筛查。FIT组整体人群筛查参与率最高(99.3%),分级筛查组次之(89.2%),结肠镜组最低(42.3%)。意向性分析结果显示,结肠镜组进展期肿瘤检出率高于FIT组(2.76%比2.17%,OR结肠镜组比FIT组=1.30,95%CI:1.01~1.65,P=0.037),结肠镜组与分级筛查组进展期肿瘤检出率无统计学差异(2.76%比2.35%,OR结肠镜组比分级筛查组=1.19,95%CI:0.93~1.51,P=0.156),分级筛查组与FIT组进展期肿瘤检出率亦无统计学差异(2.35%比2.17%,OR分级筛查组比FIT组=1.09,95%CI:0.88~1.34,P=0.440)。以每检出1例进展期肿瘤所需要的结肠镜检查次数作为评价人群筛查时结肠镜检查负荷的指标,结肠镜组的结肠镜检查负荷最高(15.4次),分级筛查组次之(10.2次),FIT组最低(7.8次)。结论基于结直肠癌风险评估的分级筛查策略对于人群结直肠癌的筛查具有可行性和有效性,可作为传统结肠镜检查和FIT筛查方案的有效补充。

Objective To evaluate the feasibility and effectiveness of colonoscopy,fecal immunochemical test(FIT)and risk-adapted screening strategies in population-based colorectal cancer screening.Methods Based on the randomized controlled trial of colorectal cancer screening(TARGET-C)which was carried out in 6 centers of 5 provinces in China from May 2018 to May 2021,the participants who met the inclusion criteria of the study were randomly assigned to one of the following screening intervention groups in a ratio of 1∶2∶2,which were colonoscopy group,FIT group and risk-adapted screening group(participants evaluated to be at high risk were recommended to undertake colonoscopy,those at low risk were recommended to undertake FIT and FIT positive people received colonoscopy).The 3 groups received different schemes of colorectal cancer screening,in which the colonoscopy group only received baseline screening,whereas the FIT group and the risk-adapted screening group received annual follow-up screening on the basis of baseline screening.The main outcome was the detection rate for advanced colorectal neoplasm(including colorectal cancer and advanced adenoma).The participation rate,detection rate for any neoplasm and resource load of colonoscopy among different screening groups were further analyzed.Results A total of 19373 participants meeting the inclusion and exclusion criteria were enrolled,including 8082 males(41.7%)and 11291 females(58.3%),with an average age of(60.5±6.5)years.Among them,3883 were in the colonoscopy group,7793 in the FIT group,and 7697 in the risk-adapted screening group.After 1 or 3 rounds of screening(2 rounds of follow-up screening completed in FIT group and risk-adapted screening group),the overall participation was the highest for the FIT group(99.3%),followed by the risk-adapted screening group(89.2%)and the coloscopy group(42.3%).According to the intention-to-treat analysis,the detection rates of advanced neoplasm in the colonoscopy group was higher than that in the FIT group(2.76%vs.2.17%,ORcolonoscopy vs FIT=1.30,95%CI:1.01-1.65,P=0.037);there were no statistically significant differences regarding the detection rates of advanced neoplasm between the colonoscopy group and the risk-adapted screening group(2.76%vs.2.35%,ORcolonoscopy vs risk-adapted screening=1.19,95%CI:0.93-1.51,P=0.156),and between the risk-adapted screening group and the FIT group(2.35%vs.2.17%,ORrisk-adapted screening vs FIT=1.09,95%CI:0.88-1.34,P=0.440).The number of colonoscopies needed to be performed to detect one advanced neoplasm was used as an indicator to evaluate the resource load of colonoscopy.The number was the highest for the coloscopy group(15.4),followed by the risk-adapted screening group(10.2)and the FIT group(7.8).Conclusions The risk-adapted screening strategy is feasible and effective in population-based colorectal cancer screening,and could serve as an effective supplement to the traditional colonoscopy and FIT-based colorectal cancer screening strategies.