Title: Multicentre randomised controlled trial of 'once only' flexible sigmoidoscopy in prevention of bowel cancer morbidity and mortality (Study Short Title: The UK Flexible Sigmoidoscopy Screening Trial (UKFSST))
Funder: Department of Health and Social Care

Abstract: Design: The UKFSST is a multicentre randomised controlled trial examining the long-term effect of a single flexible sigmoidoscopy (FS) screen on colorectal cancer (CRC) incidence and mortality. It is now in long -term follow-up. Results published after 10 years showed that FS resulted in a substantial reduction in CRC incidence and mortality, and there has been no attenuation of effect after a median of 17 years’ follow-up. A further 10 years’ of follow-up will determine if the effect of FS lasts to age 80 years. In April 2016, the Trial Steering Committee strongly recommended continuation of the study, recognising the national importance of this rich dataset. In 2017, further funding was acquired to follow the UKFSST study cohort for a further 10 years to the end of March 2027. Setting: The UKFSST randomised 170,034 individuals from 505 general practices to be screened in 14 UK centres with existing endoscopy units between 1994 and 1999. The intervention group (n=57,098) was offered FS with polypectomy for small polyps and referral for colonoscopy if high-risk polyps (3 or more adenomas, size >=1cm, tubulovillous or villous histology or severe dysplasia) were found; the control group (n=112,936) was not contacted. Target Population: Men and women aged between 55-64 years registered with participating general practices across England, Scotland and Wales. Exclusion Criteria: Individuals unable to provide informed consent; with a history of CRC, adenomas, or inflammatory bowel disease; severe or terminal disease; or FS or colonoscopy in the previous 3 years. Health Technologies being assessed: A single FS screen. FS is an endoscopic procedure that directly inspects the rectum and sigmoid colon where 54% of CRCs and adenomas are located. It is quicker, cheaper and easier on the patients than colonoscopy but is more sensitive than a faecal occult blood test. Measurement of costs and outcomes: Participants are linked to routinely collected data from NHS Digital (including ONS data) and cancer registries for the primary outcome of CRC incidence and mortality. It is vital that the long -term effects of FS are examined to determine the longevity of the protection from CRC. We plan to follow all participants for up to an additional 10 years, when all participants will be aged at least 80 years. Sample Size: The sample size was estimated to give 90% power to detect a 20% difference in incidence of CRC at 10 years, and mortality at 15 years after randomisation. We estimate the study will have 89% power to detect 25% attenuation and 99% power to detect 50% or more attenuation over the next 10 years. Project Timetable: We will obtain data updates every two to three years to monitor the effect of FS on CRC incidence and mortality. We will examine the degree of attenuation of effect after 5 years of additional follow-up and, using carefully considered stopping guidelines, determine whether follow-up should continue. Expertise in Team: The study was led by Professor Wendy Atkin, a leader in CRC screening and prevention, until August 2018, with assistance from Dr Amanda Cross, an experienced CRC epidemiologist. Since August 2018, Dr Cross has taken over Chief Investigator responsibilities for the UKFSST. Katherine (Kate) Wooldrage, senior medical statistician, has more than 10 years’ experience working on the UKFSST data. Emma Robbins, epidemiologist, is responsible for analysing data and drafting manuscripts. Iain Stenson, analyst/developer, and Sam Ellis, junior analyst/developer manage the UKFSST database. Paula Kirby is an experienced Project Manager, responsible for research governance and financial oversight. Elizabeth (Liz) Coles, provides research support. Professor Stephen Duffy will provide clinical and statistical oversight and Dr Christian Von Wagner will provide guidance on patient and public involvement. Lindy Berkman is the patient representative and has personal experience with CRC and research.

Lay abstract: Aims of the Research: The aim of the UK Flexible Sigmoidoscopy Screening Trial (UKFSST) is to determine whether having just one examination of the lower bowel, by ‘flexible sigmoidoscopy’ (also known as bowel scope), at around 60 years of age can prevent future bowel cancer and reduce the number of deaths from this disease. The trial also aims to determine how long any benefit lasts, and what is the best age to do this screening examination. Men and women in the UKFSST were recruited between 1994 and 1999; one third were offered bowel scope screening and the others were not. In 2010, we published results which showed that 10 years after screening people who had the bowel scope screening were: • less likely to get bowel cancer – it prevented about one in three new cases of bowel cancer; • less likely to die from the disease – it prevented four in every 10 deaths from bowel cancer. Since then we have found that the benefits of this one screening examination are still not wearing off even after 17 years. We are continuing to follow-up these participants for a further 10 years to see if the protective effect of the screening lasts until people are at least 80 years old. Background to the research: Bowel cancer is the fourth most commonly diagnosed cancer in the UK. Bowel cancers usually develop slowly from common bowel growths or polyps called adenomas, so removing them can help prevent cancer from starting. Bowel scope screening involves inserting a thin flexible tube with a tiny video camera on the end into the bowel to examine the inner surface. Small bowel polyps can be removed during screening. Design and methods used: The UKFSST is a randomised controlled trial; this means that participants were allocated to receive either a bowel scope screening examination, or no screening (which was the usual care offered at the time of the trial). This allows us to compare the effects for those who have had bowel scope screening with those who have not had screening. Well-designed randomised controlled studies such as this are considered to provide the best evidence for whether a new procedure works effectively. Patient and Public Involvement: Since 2010, a patient representative has been an active member of the Trial Steering Committee, which provides guidance to the study team on the way the study is run and understanding the results. Communication of the results: We published the findings on the bowel scope screening examination in 2002. We then published the effects of screening on the development of bowel cancer up to 10 years after the examination in 2010 in the medical journal ‘The Lancet’. In 2017, we reported that the protective effect of bowel scope screening was still evident 17 years later, also in 'The Lancet'. We will repeat the analysis every two to three years and update the publications approximately every 5 years. A summary of the results will also be available on the CSPRG website http://www.csprg.org.uk/ukfsst/ and reported to bowel cancer charities and patient groups.

Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS