Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
Lancet Gastroenterol Hepatol. 2024 Sep;9(9):811-824. doi: 10.1016/S2468-1253(24)00190-0. Epub 2024 Jul 20.
Flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality; however, uncertainty exists about the duration of protection and differences by sex and age. We assessed effects of once-only flexible sigmoidoscopy screening after 21 years' follow-up.
The UK Flexible Sigmoidoscopy Screening Trial is a multicentre randomised controlled trial that recruited men and women aged 55-64 years from general practices serving 14 hospitals. Among participants indicating that they would attend flexible sigmoidoscopy screening if invited, randomisation (2:1) to the control (no further contact) or intervention (invited to once-only flexible sigmoidoscopy screening) group was performed centrally in blocks of 12, stratified by centre, general practice, and household type. Masking of intervention was infeasible. Primary outcomes were colorectal cancer incidence and mortality. The Kaplan-Meier method estimated cumulative incidence. Primary analyses estimated intention-to-treat hazard ratios (HRs) and risk differences, overall and stratified by subsite, sex, and age. The trial is registered with ISRCTN, number 28352761.
Among participants recruited between Nov 14, 1994, and March 30, 1999, 170 432 were eligible and 113 195 were randomly assigned to the control group and 57 237 were randomly assigned to the intervention group. 406 participants were excluded from analyses (268 in the control group and 138 in the intervention group), leaving 112 927 participants in the control group (55 336 [49%] men and 57 591 [51%] women) and 57 099 in the intervention group (27 966 [49%] men and 29 103 [51%] women). Of participants who were invited to be screened, 40 624 (71%) attended screening. Median follow-up was 21·3 years (IQR 18·0-22·2). In the invited-to-screening group, colorectal cancer incidence was reduced compared with the control group (1631 vs 4201 cases; cumulative incidence at 21 years was 3·18% [95% CI 3·03 to 3·34] vs 4·16% [4·04 to 4·29]; HR 0·76 [95% CI 0·72 to 0·81]) with 47 fewer cases per 100 000 person-years (95% CI -56 to -37). Colorectal cancer mortality was also reduced in the invited-to-screening group compared with the control group (502 vs 1329 deaths; cumulative incidence at 21 years was 0·97% [0·88 to 1·06] vs 1·33% [1·26 to 1·40]; HR 0·75 [0·67 to 0·83]) with 16 fewer deaths per 100 000 person-years (-21 to -11). Effects were particularly evident in the distal colorectum (726 incident cancer cases in the invited-to-screening group vs 2434 cases in the control group; HR 0·59 [0·54 to 0·64]; 47 fewer cases per 100 000 person-years [-54 to -41]; 196 cancer deaths in the invited-to-screening group vs 708 deaths in the control group; HR 0·55 [0·47 to 0·64]; 15 fewer deaths per 100 000 person-years [-19 to -12]) and not the proximal colon (871 incident cancer cases in the invited-to-screening group vs 1749 cases in the control group; HR 0·98 [0·91 to 1·07]; one fewer case per 100 000 person-years [-8 to 5]; 277 cancer deaths in the invited-to-screening group vs 547 deaths in the control group; HR 1·00 [0·86 to 1·15]; zero fewer deaths per 100 000 person-years [-4 to 4]). The HR for colorectal cancer incidence was lower in men (0·70 [0·65-0·76]) than women (0·86 [0·79 to 0·93]; p=0·0007) but there was no difference by age.
We show that once-only flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality for two decades and provide important data to inform colorectal cancer screening guidelines.
National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council.
柔性乙状结肠镜筛查可降低结直肠癌的发病率和死亡率；然而，关于保护期的长短以及性别和年龄的差异仍存在不确定性。我们评估了在 21 年的随访后进行一次性柔性乙状结肠镜筛查的效果。
英国柔性乙状结肠镜筛查试验是一项多中心随机对照试验，从为 14 家医院服务的 14 家医院的普通诊所招募了 55-64 岁的男性和女性。在表示如果受邀，他们将参加柔性乙状结肠镜筛查的参与者中，通过中心、普通诊所和家庭类型进行分层，以 2:1 的比例随机分配到对照组（不再进一步联系）或干预组（受邀进行一次性柔性乙状结肠镜筛查）。干预组的盲法不可行。主要结局是结直肠癌的发病率和死亡率。Kaplan-Meier 法估计累积发病率。主要分析估计了意向治疗的危险比（HR）和风险差异，总体和按结直肠亚部位、性别和年龄分层。该试验在 ISRCTN 注册，编号为 28352761。
在 1994 年 11 月 14 日至 1999 年 3 月 30 日期间招募的参与者中，有 170432 人符合条件，113195 人被随机分配到对照组，57237 人被随机分配到干预组。406 名参与者被排除在分析之外（对照组 268 人，干预组 138 人），留下 112927 名对照组参与者（55336 名男性[49%]和 57591 名女性[51%]）和 57099 名干预组参与者（27966 名男性[49%]和 29103 名女性[51%]）。在受邀进行筛查的参与者中，有 40624 人（71%）接受了筛查。中位随访时间为 21.3 年（IQR 18.0-22.2）。在受邀筛查组中，与对照组相比，结直肠癌的发病率降低（1631 例与 4201 例；21 年累积发病率为 3.18%[95%CI 3.03-3.34]与 4.16%[4.04-4.29]；HR 0.76[95%CI 0.72-0.81]），每 100000 人年减少 47 例（95%CI-56 至-37）。与对照组相比，受邀筛查组的结直肠癌死亡率也降低（502 例与 1329 例死亡；21 年累积发病率为 0.97%[0.88-1.06]与 1.33%[1.26-1.40]；HR 0.75[0.67-0.83]），每 100000 人年减少 16 例死亡（95%CI-21 至-11）。这些效果在远端结直肠尤其明显（受邀筛查组有 726 例新发癌症病例，对照组有 2434 例；HR 0.59[0.54-0.64]；每 100000 人年减少 47 例[-54 至-41]；受邀筛查组有 196 例癌症死亡，对照组有 708 例死亡；HR 0.55[0.47-0.64]；每 100000 人年减少 15 例死亡[-19 至-12]），而近端结肠则不然（受邀筛查组有 871 例新发癌症病例，对照组有 1749 例；HR 0.98[0.91-1.07]；每 100000 人年减少 1 例[-8 至 5]；受邀筛查组有 277 例癌症死亡，对照组有 547 例死亡；HR 1.00[0.86-1.15]；每 100000 人年减少 0 例死亡[-4 至 4]）。男性（0.70[0.65-0.76]）的结直肠癌发病率 HR 低于女性（0.86[0.79-0.93]；p=0.0007），但与年龄无关。
我们表明，一次性柔性乙状结肠镜筛查可降低 20 年的结直肠癌发病率和死亡率，并为结直肠癌筛查指南提供了重要数据。
英国国家卫生与保健优化研究所卫生技术评估计划和医学研究理事会。
