仅接受一次软式乙状结肠镜筛查预防结直肠癌的多中心随机对照试验
2011-06-07 MedSci MedSci原创
背景： 结直肠癌是全球第三大最常见的癌症，死亡率很高。我们假设，55岁至64岁人群仅进行1次软式乙状结肠镜检查可明显降低结直肠癌的发病率和死亡率。 方法： 在英国14个中心进行随机对
背景：
结直肠癌是全球第三大最常见的癌症，死亡率很高。我们假设，55岁至64岁人群仅进行1次软式乙状结肠镜检查可明显降低结直肠癌的发病率和死亡率。
方法：
在英国14个中心进行随机对照试验。170,432名此前接受调查问卷表示愿意进行筛查的男性和女性纳入研究，随机分为干预组（提供软式乙状结肠镜检查）或对照组（不联系）。通过生成连续数字进行随机化，分为12个区组，按照研究中心、医疗实践和家庭类型进行分层。主要终点是结直肠癌的发生率，包括筛查时流行情况，以及结直肠癌的死亡率。以意向治疗针按方案进行分析。试验注册编号ISRCTN28352761。
结果：
对照组113,195人，干预组57,237人，纳入最终分析的分别为112, 939人和57, 099人。 40 674（71％）人接受软式乙状结肠镜检查。在筛选和中位随访11.2年期间（IQR 10.7-11.9），2524名受试者诊断为结直肠癌（对照组1818人，干预组706人），20 543人死亡（13 768 vs 6775; 727例确定是结直肠癌所致[538 vs 189]）。意向性治疗分析发现，干预组结直肠癌发病率降低了23％（危险比0.77，95％CI 0.70-0.84），死亡率降低31％
（0.69，0.59-0.82）。按方案分析，校正干预组自我选择偏差后，筛查组受试者结直肠癌发生率降低了33％（0.67，0.60-0.76），死亡率降低了43％（0.57，0.45-0.72）。远端结直肠癌（直肠和乙状结肠）的发生率减少了50％（0.50，0.42-0.59; 次要结局）。研究结束时，防止一例结直肠癌诊断或死亡需要筛查的人数分别为191名（95％CI 145-277）和489名（343-852）。
释义：
软式乙状结肠镜检查是一种安全实用的检查方式， 55岁至64岁期间仅进行一次软式乙状结肠镜检查可获得显著长期获益。
结直肠癌是全球第三大最常见的癌症，死亡率很高。我们假设，55岁至64岁人群仅进行1次软式乙状结肠镜检查可明显降低结直肠癌的发病率和死亡率。
方法：
在英国14个中心进行随机对照试验。170,432名此前接受调查问卷表示愿意进行筛查的男性和女性纳入研究，随机分为干预组（提供软式乙状结肠镜检查）或对照组（不联系）。通过生成连续数字进行随机化，分为12个区组，按照研究中心、医疗实践和家庭类型进行分层。主要终点是结直肠癌的发生率，包括筛查时流行情况，以及结直肠癌的死亡率。以意向治疗针按方案进行分析。试验注册编号ISRCTN28352761。
结果：
对照组113,195人，干预组57,237人，纳入最终分析的分别为112, 939人和57, 099人。 40 674（71％）人接受软式乙状结肠镜检查。在筛选和中位随访11.2年期间（IQR 10.7-11.9），2524名受试者诊断为结直肠癌（对照组1818人，干预组706人），20 543人死亡（13 768 vs 6775; 727例确定是结直肠癌所致[538 vs 189]）。意向性治疗分析发现，干预组结直肠癌发病率降低了23％（危险比0.77，95％CI 0.70-0.84），死亡率降低31％
（0.69，0.59-0.82）。按方案分析，校正干预组自我选择偏差后，筛查组受试者结直肠癌发生率降低了33％（0.67，0.60-0.76），死亡率降低了43％（0.57，0.45-0.72）。远端结直肠癌（直肠和乙状结肠）的发生率减少了50％（0.50，0.42-0.59; 次要结局）。研究结束时，防止一例结直肠癌诊断或死亡需要筛查的人数分别为191名（95％CI 145-277）和489名（343-852）。
释义：
软式乙状结肠镜检查是一种安全实用的检查方式， 55岁至64岁期间仅进行一次软式乙状结肠镜检查可获得显著长期获益。
BACKGROUND: Colorectal cancer is the third most common cancer worldwide and has a high mortality rate. We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality.
METHODS: This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761.
FINDINGS: 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11.2 years (IQR 10.7-11.9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0.77, 95% CI 0.70-0.84) and mortality by 31% (0.69, 0.59-0.82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0.67, 0.60-0.76) and mortality by 43% (0.57, 0.45-0.72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0.50, 0.42-0.59; secondary outcome). The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 (95% CI 145-277) and 489 (343-852), respectively.
INTERPRETATION: Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit.
评论
1、Colonoscopy is the dominant and preferred screening modality for colorectal cancer (CRC) in the US. Colonoscopy is the gold standard, and while its use for screening in the high-risk population is justifiable, comparative data in the average-risk population are largely absent. The risk of perforation from a colonoscopy is also about twice that of a flexible sigmoidoscopy. In the US, about 2 million colonoscopies at an average cost of about $2500 (sedation costs included) are performed annually.
The direct and indirect costs related to colonoscopy continue to rise, given the increasing use of propofol (which may be administered only by anesthesiologists in the US) and an aging population (hence a rising number of at-risk population for CRC). As a result, the investigation of alternative screening modalities for CRC is compelling in order to reduce worldwide mortality from this preventable condition. Data from this study support the use of flexible sigmoidoscopy for CRC screening especially in an environment of cost containment and limited healthcare resources in most parts of the world.
Dr Wendy Atkin from the Imperial College and colleagues randomized 170,432 participants to either flexible sigmoidoscopy or usual care for a median period of 11 years in a 2:1 ratio. All participants were 'average risk' for CRC with a mean age of 60 years. There were 33% fewer colon cancers and 43% fewer deaths from CRC in the flexible sigmoidoscopy group -- total of 706 patients in the flexible sigmoidoscopy group versus 1818 cancers in the control group (hazard ratio 0.64; 95% confidence interval 0.57-0.72). These results suggest that the number of individuals requiring screening to prevent one CRC is 191 and to prevent CRC-related death the number is 489. The authors concluded that flexible sigmoidoscopy with removal of small polyps during the exam was safe and, when offered only once between ages 55 and 64, conferred a substantial and long-lasting benefit.
Several questions remain. Here, patients underwent a complete colon cleansing and colonoscopies were performed by a small group of experienced operators. The additional time required to complete the colonoscopy and the additional costs of a colonoscopy versus flexible sigmoidoscopy in such circumstances require evaluation. After all, opponents will argue that flexible sigmoidoscopy is unable to examine the right colon, where nearly a third of the cancers arise. Other questions that remain following this study include the age of instituting the test and if once in a lifetime screening is indeed adequate. It is likely that a menu of CRC screening modalities (such as fecal occult blood testing, flexible sigmoidoscopy, virtual colonoscopy, stool DNA testing, etc.) with a step up approach following a comprehensive clinical risk evaluation for CRC and patient preferences may be maximally effective. Trial registration: ISRCTN28352761
Competing interests: No potential interests relevant to this article were reported.
Evaluated by:Bhawna Halwan and Atul Kumar
2、This is the first randomized controlled trial (RCT) to test the effectiveness of any form of endoscopic screening to reduce mortality from colorectal cancer (CRC). The results indicate that flexible sigmoidoscopy reduces cancer incidence and mortality by 23% and 31%, respectively.
Despite widescale adoption of colonoscopy screening to reduce mortality from CRC, no randomized controlled trials exist to support this practice. This study is significant since it is the only study to date that evaluates endoscopic screening in a RCT. The investigators enrolled over 160,000 patients at average risk for CRC through 14 sites in the UK and assigned them to either receive an invitation to undergo flexible sigmoidoscopy or not be contacted. Polypectomies were performed during this procedure and patients were referred to colonoscopy only if there were polyps >1cm diameter, 3 or more adenomas, or lesions harboring villous histology, high-grade dysplasia or cancer. After 11 years of follow-up the investigators report the reduction in CRC incidence and mortality as intention to treat (above); per protocol analysis (i.e. patients who received sigmoidoscopy compared with control patients) improved benefit to a 33% reduction in incidence and a 43% reduction in CRC mortality. Moreover, the incidence of CRC within reach of the sigmoidoscope was reduced by 50%.
Of note, all-cause mortality was not significantly different between groups.
Competing interests: No potential interests relevant to this article were reported.
Evaluated by:John Inadomi
METHODS: This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761.
FINDINGS: 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11.2 years (IQR 10.7-11.9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0.77, 95% CI 0.70-0.84) and mortality by 31% (0.69, 0.59-0.82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0.67, 0.60-0.76) and mortality by 43% (0.57, 0.45-0.72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0.50, 0.42-0.59; secondary outcome). The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 (95% CI 145-277) and 489 (343-852), respectively.
INTERPRETATION: Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit.
评论
1、Colonoscopy is the dominant and preferred screening modality for colorectal cancer (CRC) in the US. Colonoscopy is the gold standard, and while its use for screening in the high-risk population is justifiable, comparative data in the average-risk population are largely absent. The risk of perforation from a colonoscopy is also about twice that of a flexible sigmoidoscopy. In the US, about 2 million colonoscopies at an average cost of about $2500 (sedation costs included) are performed annually.
The direct and indirect costs related to colonoscopy continue to rise, given the increasing use of propofol (which may be administered only by anesthesiologists in the US) and an aging population (hence a rising number of at-risk population for CRC). As a result, the investigation of alternative screening modalities for CRC is compelling in order to reduce worldwide mortality from this preventable condition. Data from this study support the use of flexible sigmoidoscopy for CRC screening especially in an environment of cost containment and limited healthcare resources in most parts of the world.
Dr Wendy Atkin from the Imperial College and colleagues randomized 170,432 participants to either flexible sigmoidoscopy or usual care for a median period of 11 years in a 2:1 ratio. All participants were 'average risk' for CRC with a mean age of 60 years. There were 33% fewer colon cancers and 43% fewer deaths from CRC in the flexible sigmoidoscopy group -- total of 706 patients in the flexible sigmoidoscopy group versus 1818 cancers in the control group (hazard ratio 0.64; 95% confidence interval 0.57-0.72). These results suggest that the number of individuals requiring screening to prevent one CRC is 191 and to prevent CRC-related death the number is 489. The authors concluded that flexible sigmoidoscopy with removal of small polyps during the exam was safe and, when offered only once between ages 55 and 64, conferred a substantial and long-lasting benefit.
Several questions remain. Here, patients underwent a complete colon cleansing and colonoscopies were performed by a small group of experienced operators. The additional time required to complete the colonoscopy and the additional costs of a colonoscopy versus flexible sigmoidoscopy in such circumstances require evaluation. After all, opponents will argue that flexible sigmoidoscopy is unable to examine the right colon, where nearly a third of the cancers arise. Other questions that remain following this study include the age of instituting the test and if once in a lifetime screening is indeed adequate. It is likely that a menu of CRC screening modalities (such as fecal occult blood testing, flexible sigmoidoscopy, virtual colonoscopy, stool DNA testing, etc.) with a step up approach following a comprehensive clinical risk evaluation for CRC and patient preferences may be maximally effective. Trial registration: ISRCTN28352761
Competing interests: No potential interests relevant to this article were reported.
Evaluated by:Bhawna Halwan and Atul Kumar
2、This is the first randomized controlled trial (RCT) to test the effectiveness of any form of endoscopic screening to reduce mortality from colorectal cancer (CRC). The results indicate that flexible sigmoidoscopy reduces cancer incidence and mortality by 23% and 31%, respectively.
Despite widescale adoption of colonoscopy screening to reduce mortality from CRC, no randomized controlled trials exist to support this practice. This study is significant since it is the only study to date that evaluates endoscopic screening in a RCT. The investigators enrolled over 160,000 patients at average risk for CRC through 14 sites in the UK and assigned them to either receive an invitation to undergo flexible sigmoidoscopy or not be contacted. Polypectomies were performed during this procedure and patients were referred to colonoscopy only if there were polyps >1cm diameter, 3 or more adenomas, or lesions harboring villous histology, high-grade dysplasia or cancer. After 11 years of follow-up the investigators report the reduction in CRC incidence and mortality as intention to treat (above); per protocol analysis (i.e. patients who received sigmoidoscopy compared with control patients) improved benefit to a 33% reduction in incidence and a 43% reduction in CRC mortality. Moreover, the incidence of CRC within reach of the sigmoidoscope was reduced by 50%.
Of note, all-cause mortality was not significantly different between groups.
Competing interests: No potential interests relevant to this article were reported.
Evaluated by:John Inadomi
专家评价：
结肠镜检查是美国筛查结直肠癌（CRC）的主要和首选检查方式。结肠镜检查是金标准，用于筛选高危人群是合理的，用于CRC平均风险人群比较数据的报道尚十分少见。结肠镜检查的穿孔风险是软式乙状结肠镜检查的2倍。在美国，每年约进行200万次结肠镜检查，检查成本约为2500美元（包括镇静成本）。
由于异丙酚（在美国只能由麻醉师给药）使用增加和人口老龄化（CRC风险人群不断增加），结肠镜检查的直接和间接费用仍继续上升。因此，研究CRC的替代筛查方式对于减少全球CRC死亡率至关重要。这项研究结果建议使用软质乙状结肠镜进行CRC筛查，尤其是在需要控制医疗成本和医疗资源有限的世界大部分地区。
帝国学院的Wendy Atkin医生和同事将170432名受试者按照2:1的比例随机分为软式乙状结肠镜或常规医疗组，中位随访11年。所有受试者平均年龄60岁，具有 CRC “平均风险”。软式结肠镜组结肠癌的发生减少了33％，因CRC死亡人数减少43％——乙状结肠镜组706例结直肠癌，对照组为1818例（危险比 0.64; 95％可信区间0.57-0.72）。这些结果表明，防止一例结直肠癌需要筛查的人数为191名，防止一例结直肠癌相关性死亡需要筛查的人数是489名。作者结论是，软式乙状结肠镜联合小息肉切除术是安全的，在55岁到64岁之间仅接受一次检查能获得显著长期获益。
但该研究依然存在几个问题。该研究中患者接受了完全结肠清洁，结肠镜检查由一批经验丰富的操作者进行。完成结肠镜所需的额外时间和结肠镜检查相对于软式乙状结肠镜检查的额外费用在这种情况下仍需要评价。毕竟，反对者会认为，软式乙状结肠镜无法检查右半结肠，而近三分之一的肿瘤发生在此部位。其他问题包括接受检查的次数，一生中进行一次筛查是否足够。全面评估结直肠癌风险，根据患者偏好逐步进行结直肠癌筛查（如粪便潜血试验、软式乙状结肠镜、虚拟结肠镜检查、粪便DNA测试等），可能获得最大受益。试验注册：ISRCTN28352761
竞争利益：没有报道与本文相关的潜在利益。
作者:Bhawna Halwan and Atul Kumar
这是首项研究不同内镜检查对于减少结直肠癌（CRC）死亡率有效性的随机对照试验（RCT）。结果表明，乙状结肠镜使结直肠癌的发病率和死亡率分别降低了23％和31％。
尽管目前临床上广泛采用结肠镜筛检以减少CRC死亡率，但尚无随机对照试验支持这一做法。该研究具有重要意义，因为它是目前唯一评估内镜检查方式的RCT 研究。研究人员在英国的14个研究点招募了超过16万具有平均CRC风险的患者，邀请他们接受乙状结肠镜检查或者不予联系。在进行检查的过程中实施息肉切除术，只有息肉直径>1cm、发现3个或以上腺瘤、病变具有绒毛组织学改变、高度异型增生或癌症者接受结肠镜检查。经过11年的随访，研究者报告了意向治疗分析（上文所述）的结果，乙状结肠镜检查降低了结直肠癌的发生率和死亡率；按方案分析（接受乙状结肠镜检查者与对照组相比）发生率降低 33％，CRC死亡率降低43％。此外，接受乙状结肠镜者远端CRC发生率减少了50％。值得注意的是，两组的全因死亡率没有显著差异。
竞争利益：没有报道与本文相关的潜在利益。
作者:John Inadomi
作者：MedSci
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