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

陈宏达, 廖先珍, 杜灵彬, 董栋, 魏东华, 高屹, 郑卫方, 陈静君, 卢明, 张愉涵, 陆斌, 骆晨雨, 李娜, 周月阳, 骆家辉, 蔡洁, 石菊芳, 代敏

陈宏达, 廖先珍, 杜灵彬, 董栋, 魏东华, 高屹, 郑卫方, 陈静君, 卢明, 张愉涵, 陆斌, 骆晨雨, 李娜, 周月阳, 骆家辉, 蔡洁, 石菊芳, 代敏. 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[J]. 协和医学杂志, 2023, 14(1): 114-123. DOI: 10.12290/xhyxzz.2022-0537
引用本文: 陈宏达, 廖先珍, 杜灵彬, 董栋, 魏东华, 高屹, 郑卫方, 陈静君, 卢明, 张愉涵, 陆斌, 骆晨雨, 李娜, 周月阳, 骆家辉, 蔡洁, 石菊芳, 代敏. 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[J]. 协和医学杂志, 2023, 14(1): 114-123. DOI: 10.12290/xhyxzz.2022-0537
CHEN Hongda, LIAO Xianzhen, DU Lingbin, DONG Dong, WEI Donghua, GAO Yi, ZHENG Weifang, CHEN Jingjun, LU Ming, ZHANG Yuhan, LU Bin, LUO Chenyu, LI Na, ZHOU Yueyang, LUO Jiahui, CAI Jie, SHI Jufang, DAI Min. 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[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(1): 114-123. DOI: 10.12290/xhyxzz.2022-0537
Citation: CHEN Hongda, LIAO Xianzhen, DU Lingbin, DONG Dong, WEI Donghua, GAO Yi, ZHENG Weifang, CHEN Jingjun, LU Ming, ZHANG Yuhan, LU Bin, LUO Chenyu, LI Na, ZHOU Yueyang, LUO Jiahui, CAI Jie, SHI Jufang, DAI Min. 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[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(1): 114-123. DOI: 10.12290/xhyxzz.2022-0537

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

基金项目: 

国家自然科学基金 82173606

国家自然科学基金 82273726

北京市科技新星计划 Z191100001119065

北京市自然科学基金 7202169

中国医学科学院医学与健康科技创新工程 2017-I2M-1-006

中国医学科学院医学与健康科技创新工程 2022-I2M-1-003

详细信息
    通讯作者:

    代敏, E-mail:daimin2002@hotmail.com

  • 中图分类号: R1; R73

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

Funds: 

National Natural Science Foundation of China 82173606

National Natural Science Foundation of China 82273726

Beijing Nova Program of Science and Technology Z191100001119065

Natural Science Foundation of Beijing Municipality 7202169

CAMS Innovation Fund for Medical Sciences 2017-I2M-1-006

CAMS Innovation Fund for Medical Sciences 2022-I2M-1-003

More Information
  • 摘要:
      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19 373名,包括男性8082名(41.7%),女性11 291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。
    Abstract:
      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 19 373 participants meeting the inclusion and exclusion criteria were enrolled, including 8082 males(41.7%) and 11 291 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.
  • 经过一天烈日的炙烤,住院部外面的地表温度已经高达40 ℃,进进出出需要加强监护的患者还在不断增加,面对监护室内堆积如山的病患,大家的心情已经烦躁不安。高速周转的病房似乎又经历了一波“大洗牌”,病床上躺着不同的面孔,交班正仔细且有序地进行着。“号外……又有新病人要从急诊科转入,目前鼻导管10 L/min吸氧中,呼吸困难,需要重新评估插管指征......”值班护士小罗一边接听着电话,一边冲大家喊道。此刻空气仿佛凝住了一般,最尴尬的事情莫过如此——在交班时要来病人。“大家先交班,速战速决,准备收病人......”作为今天当值的高年资主治医师,我立刻说道。

    伴随着转运车的声音,病人送来了,大家立刻围了上去,按照平时标准动作过床、吸氧、完成心电监护连接。我走到病床边,那是一位白发苍苍、胸前皮下还隐约有一枚“勋章”的爷爷,一看心电监护,我本能地反应那枚东西应该是心脏永久起搏器。为了判断病人意识及症状,我拍了拍老人肩膀,问道:“爷爷,您知道这是在哪儿吗?”老人没有回答,但是眼睛在不停地转动,嘴巴似乎要表达什么,带着一点儿北方口音,但听得不太清楚。我瞬时像明白了什么,于是俯下身去对着他的耳朵大声喊道:“爷爷,您知道这是在哪儿吗?您是不是听得不太清楚?”老人摇了摇头,又点了点头。

    此时,我身旁一位经验丰富的“老医生”冲我扬了扬手中的听诊器听筒,我第一反应是她要听诊,于是连忙说道:“我来吧。”但她却直接把听头给爷爷戴上了,并对着听筒大声说道:“老爷子,这样能听清吗?”老人喃喃地回答:“听清了,听清了……”慢慢地,他紧崩的神情似乎也逐渐舒展开来。经过一系列问诊和针对性的处理后,爷爷慢慢睡着了。

    病人急性呼吸窘迫的病因尚未完全明确,依然有病情随时加重的危险,依照惯例,我们立即联系家属了解老人的病史并进行谈话签字。通过与家属充分沟通,我们了解到了爷爷的慢性病史以及本次发病的诱因,还得知爷爷听力不好,这几天辗转各大医院,一直没休息好,病情也越来越重了。好在经过我们悉心的治疗和照顾,两周后爷爷终于出院了!

    门诊复诊时,我看到爷爷耳朵上多了一副助听器,便打趣道:“爷爷,现在声音清楚多了吧?”爷爷笑着回答:“这玩意儿还是没有你们给我戴的东西听得清楚。”我和家属听完都哈哈大笑起来……

    后记

    听诊器的发明已有近200年的历史,其除了可以帮助医生完成重要的听诊检查外,在某些情况下还可以成为与病人沟通的桥梁。从法国医生雷奈克为了诊治患者,第一次提出“听诊器”的概念,到吴孟超院士在冬天查房时先用双手捂热听诊器再为患者听诊,再到为了能让患者听清楚,发现听诊器的新用途……不同听诊器的故事中,有不同的主人公以及不同的场景,但伴随的都是那份来自医生的爱,那份给予患者温暖的爱。病人与医生之间的第一步,是沟通,是了解,但病人在任何时候和任何状态下,都一定是需要帮助的那个人。任何人在面对身体的病痛时,或是因为没有足够专业的知识,或是因为疾病带来的切肤之痛,无论是酸胀、麻木、疼痛、无力,还是其他任何一种异样的感觉,都会让其内心产生对于异常表现的无限猜测以及随之而来的焦虑、恐慌。初入医学院时的我,心里想的只是如何掌握高精尖的各种医学技术,如何把病看好。进入医院工作多年以后,特别是在经历新型冠状病毒感染疫情后,我深切地体会到,不管医生的技术有多精湛,医疗水平有多高超,医生的关怀和援助永远都是病人最坚实的情感堡垒。治病一定是依靠科学,但让病人感觉到舒服却更需要医生对于患者那颗帮助的心。从医和患这层关系构建起来的那一刻起,他们就不该是对立的,而是共生的,更是共情的,感同身受、同气连枝才是医治疾病的起点,更是每一个合格医生毕生追求的终点。

    临床医生正如其名字一样,需要站在床边仔细观察病人。观察的目的除正确诊断病情外,更重要的是察觉病人最需要的帮助是什么。故事中的老人一直处于听不清周围声音的状态,这时候病人可能会感到恐惧与烦躁,甚至会导致病情恶化,而一次仔细的观察就能够使问题迎刃而解。一个小小的听诊器,以及听诊器带来的这份“逆向思维”,彰显的不仅是一种临床采集病史的技巧,更是医生把心打开,试图去侧耳倾听病人诉说的耐心,以及尽其所能去关爱病人的慈悲。

    因此,听诊器的故事,讲述的不是一种疾病的诊断,更不是一个病例的转归,听诊器联通的亦非症状与诊断,心跳与鼓膜,而是受伤的心和呵护的手,告诉我你哪里不舒服,我一定会想办法听到你的诉说,也一定会陪着你直到疾病消散。把痛苦告诉我,把希望传给你,这才是听诊器的真正意义所在,才是医生和病人最正确的相处方式。一如美国医生特鲁多对医生这个职业的经典描述——有时是治愈,常常是帮助,总是去安慰!

    作者贡献:陈宏达负责研究方案设计、实施和论文撰写;廖先珍、杜灵彬、董栋、魏东华、高屹、郑卫方、陈静君、石菊芳负责各中心研究实施、数据收集;卢明、张愉涵、陆斌、骆晨雨、李娜、周月阳、骆家辉、蔡洁负责数据整理与核查;代敏负责总体研究设计、论文修订;所有作者均参与论文审校。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1   研究对象入组流程图

    FIT:免疫法粪便潜血检测

    图  2   3组筛查方案的人群参与率

    FIT:同图 1

    表  1   19 373名受试者基线资料比较[n(%)]

    指标 结肠镜组(n=3883) FIT组(n=7793) 分级筛查组(n=7697) P
    性别0.172 0.172
      男性 1617(41.6) 3310(42.5) 3155(41.0)
      女性 2266(58.4) 4483(57.5) 4542(59.0)
    年龄(岁) 0.545
      50~54 906(23.3) 1825(23.4) 1836(23.9)
      55~59 830(21.4) 1603(20.6) 1574(20.4)
      60~64 992(25.5) 1924(24.7) 1886(24.5)
      65~69 807(20.8) 1729(22.2) 1658(21.5)
      70~74 348(9.0) 712(9.1) 743(9.7)
    教育背景* 0.614
      初中及以下 2701(73.4) 5605(72.2) 5595(72.9)
      高中 696(18.9) 1542(19.9) 1495(19.5)
      大学及以上 281(7.6) 621(8.0) 582(7.6)
    体质量指数(kg/m2)* 0.614
      <23 1395(37.9) 2872(37.0) 2860(37.3)
      ≥23 2283(62.1) 4896(63.0) 4812(62.7)
    吸烟* 0.646
      非吸烟 2978(81.0) 6269(80.7) 6154(80.2)
      戒烟 572(15.6) 1217(15.7) 1212(15.8)
      吸烟 128(3.5) 282(3.6) 306(4.0)
    饮酒* 0.168
      从不 2659(72.3) 5722(73.7) 5649(73.6)
      偶尔 491(13.3) 1047(13.5) 983(12.8)
      规律 528(14.4) 999(12.9) 1040(13.6)
    一级亲属结直肠癌家族史* <0.001
      是 160(4.4) 335(4.3) 473(6.2)
      否 3427(93.2) 7277(93.7) 7038(91.7)
      不清楚 91(2.5) 156(2.0) 161(2.1)
    FIT:同图 1*结肠镜组、FIT组和分级筛查组中分别有205名、25名、25名受试者信息缺失
    下载: 导出CSV

    表  2   3次筛查中FIT组与分级筛查组FIT阳性率以及结肠镜检查顺应率比较

    筛查方案 基线筛查 第1次随访筛查 第2次随访筛查
    FIT阳性率
    [%,(N阳性/N受检)]
    结肠镜检查顺应率
    [%,(N接受/N阳性)]
    FIT阳性率
    [%,(N阳性/N受检)]
    结肠镜检查顺应率
    [%,(N接受/N阳性)]
    FIT阳性率
    [%,(N阳性/N受检)]
    结肠镜检查顺应率
    [%,(N接受/N阳性)]
    FIT组 13.7(1071/7793) 76.3(817/1071) 5.6(341/6048) 75.7(258/341) 5.5(339/6113) 71.7(243/339)
    分级筛查组(低风险人群) 10.2(782/7697) 76.9(601/782) 3.8(244/6352) 74.6(182/244) 2.7(163/6131) 60.1(98/163)
    FIT: 同图 1
    下载: 导出CSV

    表  3   结肠镜组、FIT组和分级筛查组3次筛查中进展期肿瘤检出率比较

    筛查阶段 进展期肿瘤(%,95% CI) 结肠镜组比FIT组
    结肠镜组 FIT组 分级筛查组 OR(95% CI) P
    基线筛查
      总体 2.76(2.29~3.32) 1.15(0.94~1.42) 1.65(1.39~1.96) 2.45(1.84~3.26) <0.001
        近端结肠* 1.36(1.05~1.78) 0.53(0.39~0.71) 0.62(0.47~0.83) 2.62(1.74~3.97) <0.001
        远端结肠和直肠# 1.73(1.36~2.19) 0.80(0.62~1.02) 1.17(0.95~1.43) 2.19(1.54~3.12) <0.001
        基线筛查+第1次随访筛查
      总体 2.76(2.29~3.32) 1.67(1.41~1.98) 1.91(1.63~2.24) 1.68(1.29~2.18) <0.001
        近端结肠* 1.36(1.05~1.78) 0.72(0.55~0.93) 0.73(0.56~0.94) 1.91(1.30~2.79) 0.001
        远端结肠和直肠# 1.73(1.36~2.19) 1.15(0.94~1.42) 1.35(1.12~1.63) 1.50(1.08~2.06) 0.014
    基线筛查+第1次随访筛查+第2次随访筛查
      总体 2.76(2.29~3.32) 2.17(1.87~2.52) 2.35(2.04~2.71) 1.30(1.01~1.65) 0.037
        近端结肠* 1.36(1.05~1.78) 0.96(0.77~1.20) 0.90(0.71~1.13) 1.46(1.03~2.05) 0.031
        远端结肠和直肠# 1.73(1.36~2.19) 1.48(1.23~1.77) 1.65(1.39~1.96) 1.19(0.88~1.61) 0.244
    筛查阶段 结肠镜组比分级筛查组 分级筛查组比FIT组
    OR(95% CI) P OR(95% CI) P
    基线筛查
      总体 1.69(1.29~2.20) <0.001 1.45(1.11~1.92) 0.008
        近端结肠* 2.21(1.49~3.28) <0.001 1.19(0.79~1.82) 0.409
        远端结肠和直肠# 1.46(1.06~2.02) 0.021 1.49(1.08~2.08) 0.017
    基线筛查+第1次随访筛查
      总体 1.45(1.12~1.87) 0.004 1.15(0.91~1.47) 0.245
        近端结肠* 1.89(1.29~2.76) 0.001 1.01(0.70~1.47) 0.941
        远端结肠和直肠# 1.26(0.92~1.72) 0.148 1.18(0.88~1.57) 0.266
    基线筛查+第1次随访筛查+第2次随访筛查
      总体 1.19(0.93~1.51) 0.156 1.09(0.88~1.34) 0.440
        近端结肠* 1.56(1.10~2.20) 0.012 0.94(0.68~1.29) 0.681
        远端结肠和直肠# 1.06(0.79~1.42) 0.680 1.12(0.87~1.44) 0.384
    FIT:同图 1*包括病变检出部位仅为近端结肠或近端与远端结肠/直肠同时存在的病例;#包括病变检出部位仅为远端结肠/直肠或近端与远端结肠/直肠同时存在的病例;Logistics回归分析校正年龄、性别和研究中心后,各筛查方案对进展期肿瘤检出风险的OR值和95% CI
    下载: 导出CSV

    表  4   结肠镜组、FIT组和分级筛查组3次筛查中结肠镜检查负荷比较

    筛查阶段 进展期肿瘤(n, 95% CI) 任意结直肠肿瘤(n, 95% CI)
    结肠镜组 FIT组 分级筛查组 结肠镜组 FIT组 分级筛查组
    基线筛查
      总体 15.4(12.8~18.5) 9.1(7.5~11.1) 10.3(8.8~12.2) 4.1(3.8~4.5) 3.2(2.9~3.5) 3.5(3.2~3.8)
        男性 10.7(8.5~13.5) 6.5(5.2~8.3) 8.0(6.7~9.5) 3.0(2.7~3.4) 2.5(2.2~2.8) 2.8(2.6~3.1)
        女性 22.9(17.0~30.9) 14.7(10.4~21.1) 22.4(14.9~34.0) 5.6(4.9~6.4) 4.5(3.8~5.4) 5.9(4.9~7.3)
    基线筛查+第1次随访筛查
      总体 15.4(12.8~18.5) 8.3(7.1~9.7) 10.5(9.0~12.2) 4.1(3.8~4.5) 3.1(2.9~3.4) 3.4(3.2~3.7)
        男性 10.7(8.5~13.5) 6.2(5.1~7.5) 8.2(6.9~9.8) 3.0(2.7~3.4) 2.5(2.3~2.8) 2.9(2.6~3.1)
        女性 22.9(17.0~30.9) 12.5(9.4~16.7) 18.6(13.4~26.1) 5.6(4.9~6.4) 4.2(3.6~4.9) 5.1(4.3~6.0)
    基线筛查+第1次随访筛查+第2次随访筛查
      总体 15.4(12.8~18.5) 7.8(6.8~9.0) 10.2(8.9~11.8) 4.1(3.8~4.5) 3.0(2.8~3.3) 3.5(3.2~3.7)
        男性 10.7(8.5~13.5) 5.9(5.0~7.0) 8.3(7.1~9.8) 3.0(2.7~3.4) 2.5(2.3~2.7) 2.9(2.7~3.1)
        女性 22.9(17.0~30.9) 11.4(8.9~14.5) 15.3(11.8~20.1) 5.6(4.9~6.4) 3.9(3.5~4.5) 4.9(4.3~5.6)
    FIT: 同图 1
    下载: 导出CSV
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  • 收稿日期:  2022-09-25
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