ArticlesSingle flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised triala
Introduction
A randomised controlled trial is in progress to examine the hypothesis1 that a flexible sigmoidoscopy screening offered on a single occasion at around age 60 years is a cost-effective and acceptable means of reducing the incidence and mortality of colorectal cancer. According to the latest estimates, there are more than 34 000 new cases of colorectal cancer diagnosed each year in the UK and around 16 000 deaths, incurring annual expenditure of more than £300 million in surgical, adjuvant, and palliative treatment. With an ageing population, these costs are set to increase. The low survival characteristic of this disease is the result of the advanced stage at which most cases are diagnosed; when the disease is early, localised, and in most cases symptomless, cure rates exceed 90%. Colorectal cancer is potentially preventable by population screening, since most malignant tumours develop from adenomatous polyps. The development of cancer from an adenoma is generally a slow process, taking 10 years on average; thus there is sufficient time for adenoma detection and removal by screening during the preinvasive phase of the disease.
Two methods of screening for colorectal cancer are under consideration in the UK for implementation in a national programme: faecal occult-blood testing and flexible sigmoidoscopy. Three randomised trials2, 3, 4 have shown that faecal occult-blood testing lowers mortality rates of colorectal cancer by around 15–20% if testing is offered every 2 years, mainly through the detection of early colorectal cancer. Faecal occult-blood testing is currently being evaluated in England and Scotland in a pilot study. Endoscopic screening is more sensitive for the detection of adenomatous polyps and in epidemiological studies has been associated with greater reductions in incidence rates.5, 6
In the UK, flexible sigmoidoscopy is judged a more suitable tool for population screening than colonoscopy (advocated in the USA7), because it is safer,8, 9 cheaper, quicker, and more convenient, and uptake rates are much higher.10, 11 Two thirds of adenomas and cancers are located in the rectum and sigmoid colon, which is within reach of the flexible sigmoidoscope,1, and the procedure takes only 5 min, requiring no sedation and only a self-administered enema to clear the bowel.12
A single screening by flexible sigmoidoscopy in the sixth decade of life might be a cost-effective way to lower incidence rates, because the rate of detection of distal adenomas increases with age until the late fifties and then appears to level off.1 This pattern suggests that most people destined to develop distal colorectal cancer will have developed a distal adenoma by this age. The trial aims to identify the optimum age for the screening by including people in the age-range 55–64 years. Screening at older ages will give greater protection against subsequent cancer but will miss cancers diagnosed before the age of screening (4% of colorectal cancers are diagnosed between ages 50 and 54 years; 7% between 55 and 59 years1). In our proposed screening regimen, small polyps are removed during sigmoidoscopic screening, and colonoscopy (plus surveillance) is undertaken only when polyps with characteristics known to be associated with a high risk of advanced proximal lesions are detected. These features include large size (1 cm or greater in diameter), villous histology, severe dysplasia, and multiple small adenomas (three or more). We have suggested that the risks of colonoscopy may outweigh the benefits in individuals with only low-risk adenomas.13 We shall be able to examine this hypothesis as part of the trial by comparing the incidence of colorectal cancer in the no-polyp and low-risk-polyp groups. We will also assess whether this targeted approach is more cost-effective than the screening strategy currently recommended in the USA,7 which involves screening from age 50 by one or a combination of the following tests: annual faecal occult-blood testing, flexible sigmoidoscopy screening every 5 years with colonoscopy for any adenomatous polyp, or colonoscopy every 10 years.
The design and rationale for the trial have been described elsewhere.14 This randomised trial has a no-screening control group, because this is usual care in the UK. To increase compliance rates, and thereby the statistical power of the trial, potentially eligible individuals were enrolled in the trial and randomised only if they responded positively to a questionnaire asking whether they would be likely to accept the offer of screening. We initially undertook two pilot studies15 to refine the protocol and to confirm the assumptions on which our sample-size calculations were based. The results of these studies suggested that the screening regimen was likely to be acceptable in terms of attendance rates, adverse events, and psychological morbidity, and that the workload was achievable.15, 16, 17, 18 The main randomised trial started in 1996. A parallel study, using the UK protocol, has been undertaken in six centres in Italy19 and the results will be reported shortly.
The recruitment and screening phases of the UK trial are now complete and the cohort will be followed up for 15 years by use of the records held at the Office of National Statistics. The data collected so far provide an opportunity to examine the neoplasia detection rates, acceptability, safety, and feasibility of this method of screening.
Section snippets
Participants
The study took place in 14 geographical centres, located throughout the UK, with at least one centre in each Regional Health Authority in England, two in Wales, and one in Scotland. Approval by the local research ethics committee was obtained for each of the centres. Flexible sigmoidoscopy screening was carried out in endoscopy units able to undertake the estimated 3000 examinations within 2 years. Additional equipment was purchased for use in the trial. A local trial coordinator, a
Results
Recruitment for the main study took place between October 1996 and March 1999, following immediately from pilot studies that started in September 1994. The last baseline flexible sigmoidoscopy took place in July 1999. 574 general practices were invited to take part in the study, and 505 (88%) agreed, with a total of 2102 general practitioners. Local Health Authorities identified 375 744 men and women who were aged between 55 and 64 years at the time of the request for data and were registered
Discussion
The main aim of the trial is to assess the efficacy of a single flexible sigmoidoscopy screening in reducing incidence and mortality of colorectal cancer. Evidence already exists from case-control studies that a single exposure to sigmoidoscopy reduces the risk of fatal distal colorectal cancer by about 60% over the following 10 years5 and the risk of developing colon cancer by 44% over the following 6 years.6 In addition, the wider use of screening flexible sigmoidoscopy and removal of
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