Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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]; pinteraction=0·0007) but there was no difference by age.
CONCLUSIONS: 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.
BACKGROUND: National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council.
METHODS: 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.
RESULTS: 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]; pinteraction=0·0007) but there was no difference by age.
CONCLUSIONS: 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.
BACKGROUND: National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council.
摘要：
背景：软式乙状结肠镜检查可降低结直肠癌的发病率和死亡率；然而，保护的持续时间以及性别和年龄的差异存在不确定性。我们评估了21年随访后一次性软式乙状结肠镜筛查的效果。
方法：英国柔性乙状结肠镜检查筛查试验是一项多中心随机对照试验，招募了来自14家医院的全科医生的55-64岁男性和女性。在参与者中，如果被邀请，他们将参加柔性乙状结肠镜检查，随机分组(2:1)至对照组(无进一步接触)或干预组(被邀请参加一次性软式乙状结肠镜检查),在12个组集中进行,按中心分层,一般实践，和家庭类型。掩盖干预是不可行的。主要结果是结直肠癌的发病率和死亡率。Kaplan-Meier方法估计累积发生率。初步分析估计的意向治疗风险比(HR)和风险差异，整体和按子站点分层，性别,和年龄。该试验已在ISRCTN注册，编号28352761.
结果：在1994年11月14日至1999年3月30日招募的参与者中，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名，干预组138名)，对照组为112927名参与者（55336名[49%]男性和57591名[51%]女性），干预组为57099名（27966名[49%]男性和29103名[51%]女性）。在被邀请接受筛查的参与者中，40624（71％）参加了筛查。中位随访时间为21·3年（IQR18·0-22·2）。在受邀筛选小组中，与对照组相比,结直肠癌发病率降低(1631例vs4201例;21年累积发病率为3·18%[95%CI3·03~3·34]vs4·16%[4·04~4·29];HR0·76[95%CI0·72~0·81]),每10万人年病例减少47例(95%CI-56~-37).与对照组相比，邀请筛查组的大肠癌死亡率也降低了（502例死亡vs1329例死亡；21年的累积发病率为0·97％[0·88至1·06]vs1·33％[1·26至1·40]；HR0·75[0·67至0·83]），每10万人年的死亡人数减少了16例（-21至-11）。效果在结肠直肠远端尤其明显（邀请筛查组726例癌症事件病例比对照组的2434例少；HR0·59[0·54至0·64]；每100000人年减少47例[-54至-41]；邀请筛查组的196例癌症死亡比对照组的708例死亡少，每100例[100例]17例癌症死亡比100例17例]少。男性大肠癌发病率的HR（0·70[0·65-0·76]）低于女性（0·86[0·79至0·93]；pinteraction=0·0007），但年龄差异无统计学意义。
结论：我们表明，仅一次软式乙状结肠镜筛查可在二十年内降低结直肠癌的发病率和死亡率，并为结直肠癌筛查指南提供重要数据。
背景：国家卫生和护理研究所卫生技术评估计划和医学研究委员会。
方法：英国柔性乙状结肠镜检查筛查试验是一项多中心随机对照试验，招募了来自14家医院的全科医生的55-64岁男性和女性。在参与者中，如果被邀请，他们将参加柔性乙状结肠镜检查，随机分组(2:1)至对照组(无进一步接触)或干预组(被邀请参加一次性软式乙状结肠镜检查),在12个组集中进行,按中心分层,一般实践，和家庭类型。掩盖干预是不可行的。主要结果是结直肠癌的发病率和死亡率。Kaplan-Meier方法估计累积发生率。初步分析估计的意向治疗风险比(HR)和风险差异，整体和按子站点分层，性别,和年龄。该试验已在ISRCTN注册，编号28352761.
结果：在1994年11月14日至1999年3月30日招募的参与者中，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名，干预组138名)，对照组为112927名参与者（55336名[49%]男性和57591名[51%]女性），干预组为57099名（27966名[49%]男性和29103名[51%]女性）。在被邀请接受筛查的参与者中，40624（71％）参加了筛查。中位随访时间为21·3年（IQR18·0-22·2）。在受邀筛选小组中，与对照组相比,结直肠癌发病率降低(1631例vs4201例;21年累积发病率为3·18%[95%CI3·03~3·34]vs4·16%[4·04~4·29];HR0·76[95%CI0·72~0·81]),每10万人年病例减少47例(95%CI-56~-37).与对照组相比，邀请筛查组的大肠癌死亡率也降低了（502例死亡vs1329例死亡；21年的累积发病率为0·97％[0·88至1·06]vs1·33％[1·26至1·40]；HR0·75[0·67至0·83]），每10万人年的死亡人数减少了16例（-21至-11）。效果在结肠直肠远端尤其明显（邀请筛查组726例癌症事件病例比对照组的2434例少；HR0·59[0·54至0·64]；每100000人年减少47例[-54至-41]；邀请筛查组的196例癌症死亡比对照组的708例死亡少，每100例[100例]17例癌症死亡比100例17例]少。男性大肠癌发病率的HR（0·70[0·65-0·76]）低于女性（0·86[0·79至0·93]；pinteraction=0·0007），但年龄差异无统计学意义。
结论：我们表明，仅一次软式乙状结肠镜筛查可在二十年内降低结直肠癌的发病率和死亡率，并为结直肠癌筛查指南提供重要数据。
背景：国家卫生和护理研究所卫生技术评估计划和医学研究委员会。
