Title: Randomised controlled trial of contrast enhanced colonoscopy in the reduction of right sided bowel cancer. (The CONSCOP 2 study)
Funder: Health and Care Research Wales (Welsh Government)

Abstract: There is a need to reduce deaths from Cancer in the Upper Bowel._x000D_ A colonoscopy (bowel camera examination) is offered to all persons who test positive on a Bowel Cancer Screening Stool Test. About half of those then examined by camera have within their bowel cancers or polyps (small abnormal growths that might lead to cancer in the future). Currently polyp removal is reducing death from cancer in the lower bowel. However, in the upper bowel the types of polyps often present are more obscure and are difficult to visually detect by camera examination making them a higher risk. About 1:5 Bowel Cancers may have developed from these upper bowel polyps. Deaths from cancer in the upper bowel are not reducing._x000D_ The need to increase the accuracy of surveillance colonoscopy phasing. Further colonoscopies are scheduled for persons who have polyps present on the initial examination. Currently it is difficult to accurately set the frequency of surveillance colonoscopies for those who require monitoring_x000D_ _x000D_ AIM OF THIS RESEARCH_x000D_ To detect more polyps by use of a dye assisted camera examination._x000D_ A traditional colonoscopy uses a camera lens for polyp detection. We will seek further improvements in polyp detection by spraying blue dye into the bowel prior to the camera examination. The dye assisted examination makes polyps easier to visually detect. This procedure is known as a chromocolonoscopy. A previous study has shown that the revised procedure is safe, relatively low in additional cost, takes about 6 minutes longer per examination and does not cause any more discomfort for the patient. By comparing the traditional colonoscopy with the dye assisted chromocolonoscopy we will be able to find out if: _x000D_ a) it improves the number of high risk polyps found _x000D_ b) removing these additional high risk polyps leads to less others being present in 3 years _x000D_ c) Chromocolonoscopy in the longer term prevents Cancers in the large Upper Bowel _x000D_ d) if the revised procedure is cost effective in the NHS._x000D_ To personalise surveillance colonoscopy frequency more accurately according to a Patient's individual risk factors._x000D_ We will use the data collected over the 3-year period of the study to assist in setting the frequency of further bowel examinations for individual patients._x000D_ _x000D_ THE STUDY ACTIVITY- WHAT WILL BE DONE_x000D_ Stage 1 - We will test whether chromocolonoscopy improves the number of high-risk polyps found at the initial procedure by randomly assigning consenting trial participants to either have a standard colonoscopy or a chromocolonoscopy (the dye use) for their initial assessment. _x000D_ Stage 2 - We will use routinely collected patient data to find out if those having chromocolonoscopy have fewer high-risk polyps and cancers in the next 3 years. We will also make recommendations regarding personalised surveillance frequencies and this will allow us to assess the cost effectiveness of the programme._x000D_ PATIENT AND PUBLIC INVOLVEMENT _x000D_ A research partner, a co-applicant and is amongst other patient representatives._x000D_ BENEFIT TO PATIENTS _x000D_ If chromocolonoscopy is better than current practice then it will lead to more high-risk polyps being found, more accurate phasing of colonoscopy surveillance and fewer bowel cancers in the longer term.

Lay abstract: Research question_x000D_ Does chromocolonoscopy lead to an increased proximal significant serrated lesion detection rate compared to standard (high definition white light) colonoscopy in participants of the UK bowel screening programmes who had a positive FIT and are eligible for colonoscopy?_x000D_ _x000D_ Background_x000D_ Screening has been shown to reduce colorectal cancer (CRC) incidence and mortality. This benefit is substantial in the reduction of distal CRCs, but modest for proximal colon cancers. Proximal CRCs have worse survival outcomes and often develop from serrated lesions that are more difficult to detect at colonoscopy. Some evidence suggests that detection of significant serrated polyps may be improved with chromocolonoscopy (colonoscopy using blue dye). There is also evidence to suggest that the current guidelines for allocating patients to different surveillance frequencies may be causing unnecessary colonoscopies._x000D_ _x000D_ Aims and objectives_x000D_ Primary aim: Establish whether or not chromocolonoscopy should be used instead of standard HD white light for index colonoscopies within the UK bowel cancer screening programmes._x000D_ We will compare significant proximal serrated lesion detection rates (and other lesion detection rates) for chromocolonoscopy and standard colonoscopy, assess the impact of FIT thresholds, and evaluate the longer-term economic impact of chromocolonoscopy within the screening setting, and model cancer detection and death rates for the two arms._x000D_ _x000D_ Secondary aim: To understand the impact of demographic and lifestyle facts on polyp incidence and development in order to make recommendations about beneficial demographic and lifestyle factor changes and personalising and stratifying surveillance frequency. We will assess the association between demographic and lifestyle factors. We will also assess the association between demographic, lifestyle factors, polyps detected at index and polyps detected at surveillance colonoscopies._x000D_ _x000D_ Methods_x000D_ We will conduct a multicentre, open-label, individually randomised controlled trial of standard versus chromocolonoscopy. We will recruit 2652 patients from 20 centres in England, Wales and Scotland and follow them up through routinely collected data systems. We will collect all proximal polyps removed at the index procedures for central review to ensure accurate assessment of the primary endpoint._x000D_ Timelines for delivery. In stage 1 we aim to open the first site to recruitment in 6 months, recruit over 2 years, collect data on index colonoscopies and associated repeats and analyse the primary endpoint by the end of year 4. In stage 2 we aim to finish the follow up of all patients up to 3 years post index colonoscopy then analyse and report the secondary endpoints before the end of year 6._x000D_ _x000D_ _x000D_ Anticipated impact and dissemination_x000D_ If successful we anticipate that chromocolonoscopy will be adopted into routine use in the UK screening programmes resulting in a reduction in the incidence of bowel cancer (reducing cancer incidence by 1% could save the NHS in England £10million per year). It could also prevent the need for unnecessarily frequent surveillance colonoscopies by personalising recommendations (reducing the number of surveillance colonoscopies at 1 year from 13% to 10% would save the NHS in England ~£640,000 per year) and increase awareness of factors that are associated with significant polyp development. Dissemination will be through academic papers, guidelines, charities, and public health bodies.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL