Title: Retrospective cohort study to examine the long-term colorectal cancer risk and surveillance requirements following diagnosis of adenomas (The All Adenomas Study)
Funder: Department of Health and Social Care

Abstract: DESIGN An efficient study design, exploiting an existing retrospective cohort, to review the long-term risk of colorectal cancer (CRC) and surveillance requirements in all adenoma risk groups. SETTING Routinely reported clinical data from 17 UK NHS hospitals, on all colonoscopies for 253,798 patients, including 30,259 with adenomas (collected for NIHR study HTA 04/33/01). In this cohort, 86% of all colonoscopies were performed after 2000. Additional data will be collected to extend the median follow-up time to 10 years, and to obtain data on CRC incidence, staging and pathology, as well as deaths, via data providers such as NHS Digital and Public Health England Office for Data Release (PHE-ODR). EXISTING LITERATURE The current UK Adenoma Surveillance Guideline (UK-ASG) is based on risk of advanced adenomas (AA) at follow-up colonoscopy as a surrogate for long-term CRC risk, even though it is not known how long AAs take to develop into cancer and whether they are a valid surrogate measure. The guideline has not changed since first publication in 2002 due to lack of high quality evidence, and of evidence on long-term CRC risk: numerous studies have documented AA incidence at surveillance, but very few have documented CRC outcomes. Since 2002, interval cancers after colonoscopy have reduced by 30%, due to national initiatives to improve colonoscopy standards. Therefore, surveillance needs should be reassessed based on more recent data that not only considers improvements in colonoscopy quality, but also long-term risk of CRC rather than AA. TARGET POPULATION Consecutive NHS patients diagnosed with adenomas at colonoscopy from 17 UK hospitals. INCLUSION/EXCLUSION CRITERIA Patients with medical conditions that increase their risk of CRC, and those missing information needed for risk categorisation will be excluded. HEALTH TECHNOLOGIES BEING ASSESSED Colonoscopic surveillance in adenoma patients. MEASUREMENTS OF COSTS AND OUTCOMES Primary Outcome: CRC incidence. Costs: The economic impact of different surveillance strategies will be determined by estimating costs per person, per CRC diagnosed, and per life year/quality-adjusted life year gained. SAMPLE SIZE Our database holds routinely reported clinical data on all colonoscopies for 30,259 consecutive patients with 359 CRCs diagnosed during a median follow-up time of 6 years (interquartile range (IQR): 3.8-9.0). Additional data collection through 2016 will increase the median follow-up time to 10 years with an estimated 195 additional CRCs. Sample size calculations reveal that 60 CRCs are required in each risk group to provide sufficient precision for estimation of the CRC rate; an expected accrual of over 550 CRCs will provide sufficient precision. PROJECT TIMETABLE The study will be conducted over 27 months (Q1-9): 6 months (Q1-2) to obtain all necessary updated approvals - completed; 6 months in parallel (Q1-2) to collect additional hospital data - completed; 12 months (Q3-6) to receive updated data from external data providers (NHS Digital, NHS Scotland); 15 months (Q3-7) to obtain approval to receive staging and pathology data from PHE-ODR for the health economic (HE) analysis; 9 months for statistical and HE analysis (Q7-9), and 3 months to write up the results (Q9). EXPERTISE IN TEAM Epidemiology, colorectal cancer screening and prevention, clinical gastrointestinal endoscopy, health economics, statistics, data collection and management, clinical informatics, scientific writing, patient experience.

Lay abstract: Bowel cancer (also known as colorectal cancer or CRC) is the second most frequent cause of cancer death in the UK, and costs the NHS over £1 billion each year. CRC frequently develops from common bowel growths or polyps called adenomas; therefore, removing adenomas during colonoscopy, which is an endoscopic examination of the bowel using a camera on a flexible tube passed through the anus, can protect against future CRC. Because adenomas tend to reappear, NHS guidelines recommend that people with adenomas are followed-up with regular ‘surveillance’ colonoscopies to remove any missed or reappearing adenomas, to prevent future cancer. Patients are classified as low, intermediate, or high risk depending mainly on the size and quantity of their initial adenomas. The amount and frequency of follow-up that is recommended to a given patient depends on their risk classification. Our study aims to determine whether the current NHS guidelines recommending follow-up colonoscopies to minimize cancer developing in patients with previously found adenomas, could be updated to avoid unnecessary colonoscopies to patients and costs to the NHS. A review of the NHS adenoma surveillance guidelines is now warranted for the following reasons: 1. The guidelines have not changed since 2002 due to the lack of new research. 2. With roll-out of the National Bowel Cancer Screening Programme, more adenomas are being detected and more patients are recommended surveillance. The increasing demand for NHS colonoscopy resources is unsustainable. Colonoscopies are also invasive and carry some risk of complications; therefore, any new evidence that justifies fewer surveillance colonoscopies would benefit both patients and the NHS. 3. The guidelines estimate a patient’s risk, not on whether they are likely to get cancer, but on finding a potentially pre-cancerous ‘advanced’ adenoma at follow-up. This is due to a lack of studies linking adenoma features to future cancer risk. This is important for surveillance guidelines because not all adenomas develop into cancer. We can now study this using our unique dataset. The risk of getting cancer is more important for patients and doctors in deciding an appropriate follow-up routine, and could prevent unnecessary colonoscopies. 4. Nowadays, colonoscopies are better quality and are likely to be more thorough in removing adenomas with potentially longer-lasting effects; therefore, fewer surveillance colonoscopies may be required. DESIGN AND METHODS: We have generated a database holding colonoscopy and cancer information on 30,259 NHS patients with adenomas from 17 UK NHS hospitals. We recently used this database for a study looking at the effect of surveillance on cancer risk in patients with intermediate-risk adenomas. We found that this group may indeed need less surveillance than recommended in the guidelines. This analysis can now be efficiently extended to all patients with adenomas, with minimal effort, as a large amount of the data has already been collected and organised, and analyses methods have been tried and tested. We have collected opinions from patient representatives about the acceptability of surveillance as well as specific comments on this proposed study plan. The results of this study will be reported in a freely available HTA report, in scientific literature and conference presentations.

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