SINGLE SIGMOIDOSCOPY SCREENING IN PREVENTION OF BOWEL CANCER(The UK Flexible Sigmoidoscopy Screening Trial; UKFSST)

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Datasets: + NDRS Cancer Consolidated Data Set; + NDRS Cancer Registrations

Objective for processing

The UK Flexible Sigmoidoscopy Screening Trial (UKFSST) is a randomised controlled trial examining the long-term effect of a single flexible sigmoidoscopy (FS) screen on colorectal cancer (CRC) incidence and mortality in the United Kingdom. It is now in long-term follow-up. Results published after 10 and 17 years showed that a single FS examination resulted in a substantial reduction in CRC incidence and mortality. The Cancer Screening and Prevention Research Group (CSPRG) now wish to see if this reduction in CRC incidence remains over a longer period or if it begins to diminish. Imperial College London requires access to NHS England data for the purpose of the following research project: Single Sigmoidoscopy Screening in Prevention of Bowel Cancer : The UK Flexible Sigmoidoscopy Screening Trial (UKFSST) The CSPRG at Imperial College London, are responsible for the long-term follow-up of the study participants, combining demographic data, mortality data and cancer type / site data from NHS Digital with cancer staging data (from cancer registries in England, Wales and Scotland), clinical data directly from participating hospitals and screening data from the Bowel Cancer Screening Programme (England). The following is a summary of the aims of the research project provided Imperial College London: The UK Flexible Sigmoidoscopy Screening Trial (UKFSST) was initiated to investigate whether a single flexible sigmoidoscopy (FS) screening could significantly reduce the incidence and mortality of colorectal cancer (CRC) in individuals aged 55–64. Conducted across 14 UK centres between 1994 and 1999, the trial recruited over 170,000 participants and randomised them into control and intervention groups. The intervention group received a one-time FS screening, with follow-up colonoscopy for those with high-risk polyps. Early results published after 10, 17, and 21 years demonstrated substantial reductions in CRC incidence and mortality among screened individuals. These findings supported the inclusion of FS in the English Bowel Cancer Screening Programme (BCSP) from 2013 until its withdrawal in 2021. Imperial College London, through its Cancer Screening and Prevention Research Group (CSPRG), continues to lead the long-term follow-up of the UKFSST cohort. The current phase of the project, funded by the NIHR Health Technology Assessment programme, aims to extend follow-up until 2027, when all participants will be at least 80 years old. This Data Sharing Agreement is crucial for evaluating whether the protective effects of FS persist into older age, the period of highest CRC risk. The study integrates data from NHS England, cancer registries, and participating hospitals to assess outcomes such as cancer incidence, staging, and mortality. [1 paragraph unchanged] - To quantify the reduction in incidence and mortality from CRC resulting from [6 words unchanged] 55-64 years with colonoscopy surveillance for those found to have high-risk polyps. Secondary Aims: Secondary aims of the project are: 1. - To examine efficacy of FS screening in each of the specific age bands 55-59 years and 60-64 years. 2. - To quantify the reduction in incidence and mortality from distal CRC (rectum, sigmoid colon) resulting from a single FS screen at age 55-64 years. 3. - To quantify the reduction in incidence and mortality from proximal colon cancer [15 words unchanged] to those found at the screening FS to have high risk polyps. 4. - To determine the duration of efficacy of a single FS. 5. - To determine the optimum age for a FS screening examination. 6. - To undertake an on-going evaluation of health service research issues to permit [5 words unchanged] end of the trial about its long-term suitability within national screening programmes. In addition to the original study objectives listed above, the UKFSST study [24 words unchanged] the CSPRG medical statistician(s) or PhD students and published in peer reviewed journals. journals: • - The quality of FS screening on screening outcomes and CRC incidence/mortality • - Patient and procedural factors affecting performance of FS screening • - The safety and acceptability of once-only FS • - The effect of family history of CRC on the incidence of CRC after screening • - The use of advanced stage at diagnosis of incident cancers as a surrogate for CRC mortality • - The efficacy of colonoscopy surveillance for higher-risk adenomas found at screening • - The incidence of proximal colon cancer after FS, by the number and type of polyp detected at FS • - The incidence of CRC according to smoking history • - The potential contamination of UKFSST by Faecal Occult Blood Tests (FOBTs) given as part of the Bowel Cancer Screening Programme (BCSP) • - Medications in relation to risk of adenomas and CRC • - The effect of prior FS on participation and outcomes of FOBTs as part of the BCSP The UKFSST Protocol has been previously amended to add one more study objective (to investigate the effect of diet and lifestyle factors on the development of polyps, and colorectal cancer by subsite) and to include the use of UKFSST data to validate findings of the Intermediate Adenomas study. The following NHS England Data will be accessed: In addition, the study team has been awarded additional funding from the National Institute for Health Research-Health Technology Assessment (NIHR-HTA) to continue to follow-up the UKFSST cohort for a further 10 years to March 2027, until all the participants have reached the age of 80 years old. - Civil Registrations of Death - Necessary because it enables accurate tracking of mortality outcomes, which is essential for evaluating the long-term impact of flexible sigmoidoscopy screening on colorectal cancer-related deaths. Mortality data which is held by the study from 1994 to 2012 was originally disseminated by the Office of National Statistics (ONS). NHS Digital are now Data Controllers for that data and so this Agreement covers the retention of that data period also. - Cancer Registration Data - Necessary because it provides detailed information on cancer diagnoses, including site, type, and staging, required to assess the effectiveness of screening in reducing cancer incidence and severity. GDPR Legal Basis for Processing: - Demographics - Necessary because demographic details are required to correctly identify and link individuals across datasets, ensuring the integrity and accuracy of longitudinal analyses. The GDPR legal bases relied upon for data processing for the purposes described in this Agreement are Article 6(1)(e) (processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller) and Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). - NDRS Cancer Consolidated Data Set - Necessary because the inclusion is required to provide updates to staging data that we already hold and was previously updated with data received from Public Health England. This data is required to address one of the key aims of the study, which is the use of advanced stage at diagnosis of incident cancers as a surrogate for Colorectal Cancer mortality. The CSPRG processes special category personal health data for the UKFSST study under these two articles. Under Article 6(1)e, processing is necessary for the performance of a task carried out in the public interest, They Iin this case, the use of this special category personal data to examine the long-term effectiveness of a once-only flexible sigmoidoscopy. Effectiveness, in this case, refers to reduced incidence of CRC, and a reduced chance of CRC induced mortality. The level of the Data will be: To determine this effectiveness, they need to process special category personal data relating to cancer incidence and mortality for participants enrolled in the trial. The special category personal data used in this study is crucial to the success of this project, and the public good generally with processing therefore necessary for archiving purposes in the public interest and for scientific purposes under Article 9(2)(j). Identifiable – necessary for accurately linking individual UKFSST participant records held by Imperial College London with NHS England datasets, ensuring reliable long-term follow-up and outcome analysis. It enables consistent tracking and correct attribution of health outcomes over time. Data Subjects: The Data will be minimised as follows: The UKFSST was undertaken in 14 UK centres (11 in England, 2 in Wales, 1 in Scotland). Study recruitment commenced in November 1994 and ended in March 1999. Eligible participants (55-64 years old belonging to participating general practices) were sent an invitation questionnaire asking whether they would be interested in participating. Those who responded indicating a potential interest were randomised. In total, 170,432 participants were randomised in a 2:1 ratio to control (113,178) or the intervention, a single FS screening exam (57,254). - Limited to a study cohort comprising 157,513 individuals recruited between 1994 and 1999. Data Summary: Imperial College London is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. The study requires identifying data. As described, participants’ randomisation dates within the trial are spread over a period of approximately 4.5 years, meaning that the maximum follow-up time of observation in the trial can vary by as much as 4.5 years between participants. Thus, it is important that Imperial College London receive individual- level data on deaths and cancers, in order to accurately estimate the follow-up time for each participant and be able to accurately estimate the CRC incidence and mortality rates for the cohort members. This is essential for achieving the primary aim of the trial. The trial was conducted in 14 centres geographically spread across the UK to provide generalisability of the results to the population of the UK. In the future, Imperial College London plan to request data on events until 2024, when all cohort members will be at least 80 years old, as current funding was given to allow the study to determine if the effect of FS continues to last over the period of highest CRC incidence in a person’s life. There are no less intrusive methods by which the study could achieve the trial aims and for this purpose, the study will also need to retain access to the data already held for this cohort. This allows us to perform long-term analysis of the outcomes of CRC incidence and mortality within the cohort and it is essential to retain previous data extracts in order to be able to exactly reproduce already published analyses in line with our funding agreement and Imperial College’s data retention policy. The lawful basis for processing personal data under the UK GDPR is: Data Minimisation: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; Imperial College London have minimised the request for data to only the data items required to carry out our ongoing analyses as discussed above, which is being requested as single a data refresh (in 2023) to further minimise the data received. The lawful basis for processing special category data under the UK GDPR is: Imperial College London is the sole Data Controller under this Agreement who also process the data. No other organisations have any access to the data or have any involvement in deciding how the data is processed. Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care. The funding comes from multiple sources. Current funders include: - Cancer Research UK. - National Institute for Health Research – Health Technology Assessment (NIHR-HTA) – Funding is in place until until March 2027. The funders will have no ability to suppress or otherwise limit the publication of findings. Data will be accessed by: - PhD students enrolled with Imperial College London. The individuals have completed mandatory data protection and confidentiality training and is subject to Imperial College London’s policies on data protection and confidentiality. The individuals accessing the data will do so under the supervision of a substantive employee of Imperial College London. Imperial College London would be responsible and liable for any work carried out by the individuals. The PhD students would only work on the data for the purposes described in this Data Sharing Agreement (DSA). Members of the public and patients have played a meaningful role in shaping the UKFSST, particularly in ensuring that the proposed use of data aligns with public benefit and ethical standards. A patient representative is actively involved in the Trial Steering Committee (TSC), which provides strategic oversight and guidance. This inclusion ensures that patient perspectives are considered in decisions about study design, data use, and dissemination of findings. The TSC also includes external experts in colorectal cancer screening, further strengthening the study’s governance and relevance to public health. In addition to formal representation, the study team has engaged with patient support organisations such as Maggie’s Centre at Charing Cross Hospital. These partnerships help disseminate research findings to the wider public and ensure that diverse views are considered in interpreting and communicating results. The team also shares updates and outputs through accessible platforms like the CSPRG website and social media channels, promoting transparency and encouraging public engagement with the research. This approach supports the ethical use of data and reinforces the study’s commitment to delivering public benefit.

Processing activities

On receipt of the data already disseminated by NHS England on the UKFSST study cohort, Imperial College London formatted it in accordance with existing UKFSST database schema before uploading it to the UKFSST study database. Imperial College London will transfer data to NHS England. With the new data in the database, and after basic data cleaning, Imperial College London matched the cancers and deaths to the trial participants. This tells Imperial College London which new cancers or deaths have occurred since the last data extract was received. It also tells Imperial College London which, if any, deaths or cancers were incorrectly reported in the previous excerpt. The data was then pseudonymised and given to CSPRG statisticians for analysis and to give the required outputs for reporting and publication in accordance with Imperial College London grants. The data will consist of identifying details (specifically NHS Number, Date of Birth, and a unique person ID) for the cohort to be linked with NHS England data. Data already held: NHS England will provide the relevant records from the Civil Registrations of Death, Cancer Registration Data, Demographics and NDRS Cancer Consolidated datasets to Imperial College London. CSPRG have a number of secondary analyses planned, which will use the existing data. These secondary analyses are covered within the purpose section of this agreement. Any additional analyses / research questions Imperial College London identify will be defined and approval sought through the amendment process. The Data will contain directly identifying data items including Names, NHS Number, Date of Birth, Postcode, and Gender which are required to link the Data at record level with data already held by the Imperial College London. In 2019 and 2021, CSPRG requested a refresh of the same data items as previously provided, using the existing flagged study cohort. In 2023 CSPRG intend to continue to request a further refresh of these same data items. This new data will be combined with the existing UKFSST database and updated data from each of the data providers listed under the ‘purpose’ section and illustrated in the data flow diagram. The Data will not be transferred to any other location. CSPRG has been approached by external parties to collaborate on additional research questions using the combined UKFSST study database. Data has been requested in an anonymised, aggregated format. Any requests for pseudonymised record-level data will be subject to an amendment request to NHS England prior to release. The Data will be stored on servers at Imperial College London. All CSPRG staff members who have access to the data are substantive employees of Imperial College London or PhD students. As PhD students at Imperial College London are not held to the same contractual clauses as staff, the CSPRG have implemented a ‘student data access agreement’ which they must complete to indicate their obligations for processing personal data. Data will not be accessed or processed by any other third parties not mentioned in this agreement. The Data will be accessed by authorised personnel via remote access. In order to validate the Intermediate Adenomas (IA) study and All Adenomas (AA) study findings, the CSPRG used a subset of the UKFSST data on its own, and in combination with data obtained from external sources (English data from the UK Faecal Occult Blood test (FOBT) pilot and Kaiser Permanente dataset). No attempt was made to individually match UKFSST patients to those on the IA study. The Controller must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract. This analysis will investigate if the subgroup of intermediate-risk patients who may be eligible for less frequent surveillance identified in the IA study, are also at lower risk in the UKFSST dataset. For remote access: - Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA; - Access controls granting users the minimum level of access required are in place; - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; - Multifactor authentication (MFA) is required for re - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; - All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy. The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose). Remote processing will be from secure locations within England and Wales. The data will not leave England and Wales at any time. Access is restricted to individuals within the Cancer Screening and Prevention Research Group of Imperial College London who have authorisation from the Principal Investigator. All such individuals are substantive employees of Imperial College London. PhD students within the Cancer Screening and Prevention Research Group are permitted to access the data.. Students must complete mandatory data protection and confidentiality training and operate under supervision of substantive employees of Imperial College London. All personnel accessing the Data have been appropriately trained in data protection and confidentiality. The Data will be linked at person record level with dataset(s)] obtained from the UKFSST participant records held by Imperial College London. The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset. Analysts/researchers from the Cancer Screening and Prevention Research Group of Imperial College London will process/analyse the Data for the purposes described above.

Expected output

Imperial College London anticipate a number of publications from the continuation of the UKFSST study, in line with the analyses listed in the ‘objective for processing’ section. All outputs will only contain data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. The expected outputs of the processing will be: Updates to the main UKFSST paper on the effect of FS on CRC incidence and mortality (Lancet 2010 and Lancet 2017) will be written periodically and at the end of the study, in line with available funding. - A report of findings to the TSC. Updates are provided periodically, with the last report delivered in April 2024 and another planned at the end of the study. Imperial College London have recently published two additional papers on the UKFSST, listed below. - Submissions to peer-reviewed journals – ongoing and planned analyses will result in multiple publications. A major update on long-term effects after approximately 26 years of follow-up is expected to be submitted in 2026. All additional manuscripts will be submitted to high impact, peer-reviewed journals; for example, The Lancet, Lancet Oncology or leading gastroenterology journals such as Gut. In addition, Imperial College London aim to make publications available through ‘open access’. The results from this study will be presented at national and international scientific and clinical meetings as appropriate, such as the British Society of Gastroenterology meeting in the U.K. and the Digestive Disease Week conference in the United States. - Presentations to national and international stakeholders, including policy makers and clinical audiences, to inform colorectal cancer screening strategies. Outputs published to date: - Presentations at appropriate conferences such as the British Society of Gastroenterology and Digestive Disease Week (USA), as well as other academic and public health forums. 1. Brown JP, Wooldrage K, Kralj-Hans I, Wright S, Cross AJ, Atkin WS. Effect of once-only flexible sigmoidoscopy screening on the outcomes of subsequent faecal occult blood test screening. J Med Screen. 2018 Oct 3:969141318785654. - Publication of summaries and dashboards on the CSPRG website: www.csprg.org.uk/ukfsst, and dissemination via social media platforms (Twitter/X, Facebook, LinkedIn, Bluesky). 2. Pinsky PF, Loberg M, Senore C, Wooldrage K, Atkin W, Bretthauer M, Cross AJ, Hoff G, Holme O, Kalager M, Segnan N, Schoen RE. Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening. Gastroenterology. 2018 Jun 20. Pii: S0016-5085(18)34667-5. - A database to be utilised as a resource for health research. The UKFSST dataset will continue to support secondary analyses and collaborative research, with data shared in anonymised, aggregated formats. 3. Atkin W, Wooldrage K, Parkin DM, Kralj-Hans I, MacRae E, Shah U, Duffy S, Cross AJ. Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial. Lancet. 2017 Apr 1; The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived. 4. Atkin WS, Edwards R, Kralj-Hans I, Wooldrage K, Hart AR, Northover JM, Parkin DM, Wardle J, Duffy SW, Cuzick J. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010; The outputs will be communicated to relevant recipients through the following dissemination channels: 5. Kralj-Hans I, Wooldrage K, Moss S, Patnick J, Duffy S, Atkin W. The UK Flexible Sigmoidoscopy Screening Trial: Uptake and Outcomes of First Round Faecal Occult Blood Testing in the English NHS Bowel Cancer Screening Programme. Gastroenterology, Vol. 144, Issue 5, S-45. Published in issue: May 2013. - Journals 6. Robbins EC, Wooldrage K, Saunders BP, Duffy SW, Cross AJ. Impact of adenoma detection rates at flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality. Gut. 2021;70:A53. - Workshops involving academic and clinical stakeholders to discuss implications for colorectal cancer screening policy. 7. Robbins EC, Wooldrage K, Stenson I, Pack K, Duffy S, Weller D, Levin T, Conell C, Wright S, Nickerson C, Martin J, Cross AJ. Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study. Endoscopy. 2021 Apr;53(4):402-410. - Webinars open to researchers, clinicians, and public health professionals hosted by Imperial College London and CSPRG. 8. Cross AJ, Robbins EC, Saunders BP, Duffy SW, Wooldrage K. Higher Adenoma Detection Rates at Screening Associated With Lower Long-Term Colorectal Cancer Incidence and Mortality. Clin Gastroenterol Hepatol. 2022 Feb;20(2):e148-e167. - Social media Talks given at external meetings referencing published UKFSST data: - Public reports 1. Cross AJ. Colorectal cancer screening and early detection. National Cancer Research Institute: Screening, Prevention and Early Diagnosis (SPED) strategy meeting. London, U.K. Apr 2018. - Presentations at appropriate conferences including British Society of Gastroenterology and Digestive Disease Week. 2. Cross AJ. Colorectal Cancer Screening Programmes: UK Experience. 2nd Combined Gulf Cancer Conference. King Faisal Specialist Hospital and Research Centre, Riyadh. Mar 27th-29th 2018. - Public promotion of the research through patient support groups such as Maggie’s Centre and public-facing events. 3. Cross AJ. Colorectal Cancer Screening in the UK. Saudi-International Colorectal Diseases forum. Four Seasons Hotel, Riyadh. Mar 25th-27th 2018. - Participant newsletters to keep trial participants informed of progress and findings. 4. Cross AJ. Early detection of colorectal cancer. Dining with the Stars, Cancer Research UK fundraiser, London, U.K. Mar 2018. - Reports aimed at patients and the public, summarising key outcomes and public health relevance. 5. Cross AJ. Targeted endoscopy: Who, what, when? Difficult questions in colorectal cancer research workshop. International Agency for Research on Cancer and the U.S. National Cancer Institute. Lyon, France. Nov 2017. The UKFSST study's first output is expected by April 2026, with annual updates planned throughout the agreement period, ending in April 2028. These outputs will include peer-reviewed publications, updates to previous findings, and dissemination through the CSPRG website, social media, and conference presentations. 6. Harewood R. Are all bowel cancers created equal? CRUK’s Fundraising & Mass Directorate Immersion Day: from Bench to Bedside, Sir Alexander Fleming Building, London. Jul 2018. 7. Harewood R. Early diagnosis of colorectal cancer. CRUK's Policy and Information Department Away Day, Francs Crick Institute, London. Nov 2018. 8. Harewood R & Disney R. 100 Roles to Beat Cancer. Cancer Research UK Stand at the Great Exhibition Road Festival, London. Jun 29th 2019. 9. Cross AJ. Colorectal cancer: prevention requires shared responsibility. 11th International Cancer Conference 2019, Trinity Translational Medicine Institute, St. James's Hospital, Dublin. Sep 24th 2019. 10. Cross AJ. Preventing and detecting colorectal cancer. Imperial College London Academic Health Science Centre Seminar Series. The Royal Marsden NHS Foundation Trust. Nov 20th 2019. 11. Cross AJ. Progress in cancer research. CRUK's Annual Evening of Christmas Music. St Mary's Church, Wyndham Place London. Dec 18th 2019. 12. Cross AJ. Colorectal cancer screening and surveillance. COLO-SPEED meeting, Laing Art Gallery, Newcastle. Dec 10th 2019. 13. Robbins EC. Impact of variable adenoma detection rates at screening flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality. The Institute of Global Health Innovation and Division of Surgery Research Afternoon, Imperial College London. Dec 12th 2019. 14. Cross AJ. Colorectal cancer screening. Oslo Group Conference. Lillehammer, Norway. Feb 12th-14th 2020. 15. Robbins EC. Colorectal cancer screening in a COVID-19 era: outreach & increasing participation in population-based programs. World Endoscopy Organisation Colorectal Cancer Screening Committee: Virtual Meeting. Via video conference. Oct 9th 2020. 16. Cross AJ. Global challenges in cancer prevention research: opportunities for a collaborative approach. Launch event for the new ICL and Institute of Cancer Research Cancer Epidemiology and Prevention Research Unit. Via video conference. Nov 2nd 2020. 17. Harewood R. Risk factors for proximal colon cancer: how informative are polyp findings in determining future risk?. 2020 BSG Virtual Campus. Via video conference. Jan 26th 2021. 18. Robbins EC. Impact of adenoma detection rates at flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality. 2020 BSG Virtual Campus. Via video conference. Jan 26th 2021. Planned analyses / publications & corresponding timescales: 1. Juul FE, Cross AJ, Schoen RE, Senore C, Pinsky P, Miller E, Segnan N, Wooldrage K, Wieszczy-Szczepanik P, Armaroli P, Garborg KK, Adami HO, Hoff G, Kalager M, Bretthauer M, Løberg M, Holme O. 15-Year Benefits of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality: A Pooled Analysis of Randomized Trials. Revisions requested and re-submitted to Annals Internal Medicine. 2. Long term effects of once-only flexible sigmoidoscopy screening after ~22 years of follow-up, analysis complete, paper being drafted for submission in 2023. 3. Long term effects of once-only flexible sigmoidoscopy screening after ~26 years of follow-up, submission 2026 In addition, CSPRG are planning other secondary data analyses as part of PhD studentships funded until the end of June 2023 addressing: • The quality of flexible sigmoidoscopy (FS) screening on outcomes and colorectal cancer (CRC) incidence/mortality • Patient and procedural factors affecting performance of FS screening • The safety and acceptability of once-only FS • The effect of family history of CRC on the incidence of CRC after screening • The efficacy of colonoscopy surveillance for higher-risk adenomas found at screening • The incidence of proximal CRC after FS, by the number and type of polyp detected at FS • The incidence of CRC according to smoking history • Medications in relation to risk of adenomas and CRC • The effect of diet and lifestyle factors on the development of polyps, and CRC by subsite Furthermore, this cutting edge research on the benefits of screening will be disseminated to patient groups through contacts of the patient representative for this study, as well as existing relations with support groups such as Maggie’s centre at Charing Cross hospital (https://www.maggiescentres.org/). It will also be summarised on the CSPRG website (http://www.csprg.org.uk/ukfsst/) and disseminated via twitter (@csprg_imperial). All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

Expected measurable benefits

The results of the long-term follow-up of the UKFSST in 2022 and 2026 will be made available to inform policy makers via publications and presentations at national and international meetings. The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study. Colorectal cancer (CRC) is a common malignancy that is very treatable when diagnosed at an early stage. However, late-stage diagnoses have a poor prognosis and are more costly to treat. The use of FS as a screening tool can not only identify cancers at an earlier stage but can also remove precursor lesions potentially leading to long-term protection. The study has already demonstrated a significant benefit to participants who received a single FS screen compared to those who did not in preventing CRC incidence and mortality after 10 years of follow up, and the study team have published extensively on the uptake, acceptability and impact of a FS screening examination. The use of the data could: The UKFSST has been instrumental in providing data to support the use of FS in the National BCSP in England, which began offering FS at age 55 years in 2013: however, there is no data on the long term benefits of this procedure. If the protective effect on CRC incidence and mortality is sustained over the long term, the health economic benefits of FS would be even larger than expected. - Help the system better understand the health and care needs of populations at risk of colorectal cancer, particularly older adults. This research will build on existing knowledge on the impact of FS and will provide evidence to the National BCSP on the long term effectiveness of a single FS examination on the reduction in incidence and mortality from CRC over a period of more than 25 years. This data can then be used to directly inform estimations of patient and economic benefits over a 25-year period. - Lead to the identification and improvement of preventative interventions, such as flexible sigmoidoscopy screening, to reduce cancer incidence and mortality. Examining long term follow up is important because the participants will be approaching the highest incidence age group for CRC. In addition, as the participants age, the outcomes of surgery are not as good, so it is imperative to prevent cancer in these individuals. Finally, the average life expectancy for those aged 75 years is currently 13 years for women and 11 for men, therefore, quality of life in these older age groups is important. - Advance understanding of regional and national trends in colorectal cancer outcomes and screening uptake. The past and future contribution of the UKFSST continues to be acknowledged by the Trial Steering Committee (TSC) for the study. The TSC, which is comprised of external experts in the field and a patient representative, concluded that the UKFSST is a unique resource able to provide vital information to National screening committees on the efficiency of FS, the duration of effect, the number needed to screen to prevent one CRC diagnosis (important for cost effectiveness analyses) and whether the effect is evident in subgroup analysis by gender, age and sub-site. In addition, the UKFSST forms the basis for many value added prospective analyses. The TSC strongly supported the continued follow up of the study cohort to investigate the duration of the effect of a single FS examination. The last data update was provided to the TSC in September 2022. - Inform planning of health services and programmes, ensuring more equitable access to effective screening and early detection strategies. - Support decisions on funding allocation by demonstrating the long-term cost-effectiveness of single-screen interventions. - Provide a mechanism for checking the quality of care, identifying areas of good practice in cancer prevention and areas needing improvement. - Support exploratory research and innovation, contributing to the development of future screening models and public health strategies. The UKFSST study is expected to deliver direct benefits to patients by improving early detection and prevention of colorectal cancer through evidence supporting flexible sigmoidoscopy screening. This could lead to reduced cancer incidence and mortality, particularly among older adults who are at higher risk. Patients will benefit from more informed clinical decisions, enhanced care pathways, and improved outcomes. The findings may also support more equitable access to screening programmes and empower patients with clearer guidance on preventative options, ultimately improving their overall experience and quality of care. It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients. Clients will need to take action based on the findings of the study to realise the potential improvement opportunities. For example, NHS screening programme leads may decide to adjust the recommended age for flexible sigmoidoscopy screening based on evidence showing long-term benefits in older populations. This could involve updating clinical guidelines, reallocating resources to support expanded screening access, and training healthcare professionals to implement the revised protocols. Without such action, the insights gained from the data may not translate into improved patient outcomes or more effective cancer prevention strategies. To optimise the potential public benefits from the use of the UKFSST study, several actions are planned to ensure wide dissemination and impact. The study findings will be shared through peer-reviewed publications, open-access platforms, and presentations at national and international conferences, such as the British Society of Gastroenterology and Digestive Disease Week. Additionally, results will be promoted via the CSPRG website and social media channels (Twitter/X, Facebook, Bluesky, LinkedIn). Importantly, findings will be communicated to patient groups through the study’s patient representative and existing relationships with support organisations like Maggie’s Centre at Charing Cross Hospital. These efforts aim to ensure that the insights gained reach clinicians, policy-makers, and the public, enabling informed decisions and improvements in colorectal cancer screening and prevention.

Benefits reported

Imperial College London have already demonstrated a significant benefit to participants who [6 words unchanged] to those who did not in preventing CRC incidence and mortality after 17 21 years of follow-up, and have published extensively on the uptake, acceptability, and impact of a FS screening examination. The study has been instrumental in providing data to support the use [5 words unchanged] in England, which began offering a FS at age 55 years in 2013; 2013 and it was subsequently withdrawn in 2021; however, there is no data on the long-term benefits of this procedure. [16 words unchanged] health economic benefits of the test would be even larger than anticipated. [1 paragraph unchanged] The study gave rise to two three very significant publications in The Lancet in 2010 and 2010, 2017 in 2017 2024 on the long-term effects of FS screening. In addition, Imperial College London published two several additional manuscripts in 2018, one in 2022 since 2018 and several talks were given referencing published UKFSST data (see outputs section). CSPRG PhD research supported by the study includes analyses of: [9 paragraphs unchanged]

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: − MRIS - Cause of Death Report; − MRIS - Cohort Event Notification Report; − MRIS - Flagging Current Status Report; − MRIS - Members and Postings Report

Objective for processing

The UK Flexible Sigmoidoscopy Screening Trial (UKFSST) is a randomised controlled trial [38 words unchanged] single FS examination resulted in a substantial reduction in CRC incidence and mortality (Atkin WS, et al. Lancet. 2010; 375: 1624–33; Atkin WS, et al. Lancet. 2017; 389: 1299–1311). mortality. The Cancer Screening and Prevention Research Group (CSPRG) now wish to see [5 words unchanged] incidence remains over a longer period or if it begins to diminish. The CSPRG, CSPRG at Imperial College London, are responsible for the long-term follow-up of the study [31 words unchanged] participating hospitals and screening data from the Bowel Cancer Screening Programme (England). [9 paragraphs unchanged] In addition to the original study objectives listed above, the UKFSST study team identified the following potential questions to be addressed by further analysis of the UKFSST dataset. These [9 words unchanged] CSPRG medical statistician(s) or PhD students and published in peer reviewed journals. [11 paragraphs unchanged] The UKFSST Protocol has been previously amended to add one more study [23 words unchanged] the use of UKFSST data to validate findings of the Intermediate Adenomas study and All Adenomas studies (DARS-NIC-147827-NC2TC). study. In addition, the study team has been awarded additional funding from the National Institute for Health Research-Health [16 words unchanged] March 2027, until all the participants have reached the age of 80 years. years old. Mortality data which is held by the study from 1994 to 2012 was originally disseminated by the Office of National Statistics (ONS). NHS Digital are now Data Controllers for that data and so this Agreement covers the retention of that data period also. GDPR Legal Basis for Processing: [1 paragraph unchanged] The CSPRG processes special category personal health data for the UKFSST study under these two articles. Under Article 6(1)e, processing is necessary for the performance of a task carried out in the public interest, They Iin this case, the use of this special category personal data to examine the long-term effectiveness of a once-only flexible sigmoidoscopy. Effectiveness, in this case, refers to reduced incidence of CRC, and a reduced chance of CRC induced mortality. To determine this effectiveness, they need to process special category personal data relating to cancer incidence and mortality for participants enrolled in the trial. The special category personal data used in this study is crucial to the success of this project, and the public good generally with processing therefore necessary for archiving purposes in the public interest and for scientific purposes under Article 9(2)(j). Data Subjects: The UKFSST was undertaken in 14 UK centres (11 in England, 2 in Wales, 1 in Scotland). Study recruitment commenced in November 1994 and ended in March 1999. Eligible participants (55-64 years old belonging to participating general practices) were sent an invitation questionnaire asking whether they would be interested in participating. Those who responded indicating a potential interest were randomised. In total, 170,432 participants were randomised in a 2:1 ratio to control (113,178) or the intervention, a single FS screening exam (57,254). Data Summary: The study requires identifying data. As described, participants’ randomisation dates within the trial are spread over a period of approximately 4.5 years, meaning that the maximum follow-up time of observation in the trial can vary by as much as 4.5 years between participants. Thus, it is important that Imperial College London receive individual- level data on deaths and cancers, in order to accurately estimate the follow-up time for each participant and be able to accurately estimate the CRC incidence and mortality rates for the cohort members. This is essential for achieving the primary aim of the trial. The trial was conducted in 14 centres geographically spread across the UK to provide generalisability of the results to the population of the UK. In the future, Imperial College London plan to request data on events until 2024, when all cohort members will be at least 80 years old, as current funding was given to allow the study to determine if the effect of FS continues to last over the period of highest CRC incidence in a person’s life. There are no less intrusive methods by which the study could achieve the trial aims and for this purpose, the study will also need to retain access to the data already held for this cohort. This allows us to perform long-term analysis of the outcomes of CRC incidence and mortality within the cohort and it is essential to retain previous data extracts in order to be able to exactly reproduce already published analyses in line with our funding agreement and Imperial College’s data retention policy. Data Minimisation: Imperial College London have minimised the request for data to only the data items required to carry out our ongoing analyses as discussed above, which is being requested as single a data refresh (in 2023) to further minimise the data received. [1 paragraph unchanged]

Processing activities

On receipt of the data already disseminated by NHS Digital England on the UKFSST study cohort, Imperial College London formatted it in accordance with existing UKFSST database schema before uploading it to the UKFSST study database. [2 paragraphs unchanged] CSPRG have a number of secondary analyses planned, which will use the existing data. These secondary analyses are covered within the purpose section of this application. agreement. Any additional analyses / research questions Imperial College London identify will be defined and approval sought through the amendment process. In 2019 and 2021 2021, CSPRG will request requested a refresh of the same data items as previously provided, using the existing flagged study cohort. In 2023 CSPRG intend to continue to request a further refresh of these same data items. This new data will be combined with the existing UKFSST database and [8 words unchanged] listed under the ‘purpose’ section and illustrated in the data flow diagram. CSPRG has been approached by external parties to collaborate on additional research [19 words unchanged] pseudonymised record-level data will be subject to an amendment request to NHS Digital England prior to release. All outputs contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data). [1 paragraph unchanged] 2019 Amendment In order to validate the Intermediate Adenomas (IA) study and All Adenomas (AA) study findings, the CSPRG used a subset of the UKFSST data on its own, and in combination with data obtained from external sources (English data from the UK Faecal Occult Blood test (FOBT) pilot and Kaiser Permanente dataset). No attempt was made to individually match UKFSST patients to those on the IA study. In order to validate the Intermediate Adenomas (IA) study (Atkin W, et al. Lancet Oncol 2017; 18: 823–34) and All Adenomas (AA) study findings, the CSPRG will use a subset of the UKFSST data on its own, and in combination with data obtained from external sources (English data from the UK Faecal Occult Blood test (FOBT) pilot and Kaiser Permanente dataset). No attempt will be made to individually match UKFSST patients to those on the IA/AA studies. This analysis will investigate if the subgroup of intermediate-risk patients who may be eligible for less frequent surveillance identified in the IA study, are also at lower risk in the UKFSST dataset. This analysis will investigate if the subgroup of intermediate-risk patients who may be eligible for less frequent surveillance identified in the IA study, are also at lower risk in the UKFSST dataset. Once the AA study analysis is complete, any new subgroups identified in the low- and high-risk patients will be examined in the same way to determine whether their risk is similar in the UKFSST to that observed in the IA study.

Expected output

Imperial College London anticipate a number of publications from the continuation of [6 words unchanged] the analyses listed in the ‘objective for processing’ section. All outputs will only contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. [2 paragraphs unchanged] All additional manuscripts will be submitted to high impact, peer-reviewed journals; for example example, The Lancet, Lancet Oncology or leading gastroenterology journals such as Gut. In [39 words unchanged] the U.K. and the Digestive Disease Week conference in the United States. [1 paragraph unchanged] 1. Brown JP, Wooldrage K, Kralj-Hans I, Wright S, Cross AJ, Atkin [11 words unchanged] subsequent faecal occult blood test screening. J Med Screen. 2018 Oct 3:969141318785654. Doi: 10.1177/0969141318785654. [Epub ahead of print] PMID: 30282520. 2. Pinsky PF, Loberg M, Senore C, Wooldrage K, Atkin W, Bretthauer [22 words unchanged] Randomized Trials of Flexible Sigmoidoscopy Screening. Gastroenterology. 2018 Jun 20. Pii: S0016-5085(18)34667-5. Doi: 10.1053/j.gastro.2018.06.040. [Epub ahead of print] PMID: 29935150. [2 paragraphs unchanged] 5. Kralj-Hans I, Wooldrage K, Moss S, Patnick J, Duffy S, Atkin [24 words unchanged] Programme. Gastroenterology, Vol. 144, Issue 5, S-45. Published in issue: May 2013. DOI: https://doi.org/10.1016/S0016-5085(13)60159-6 Planned analyses / publications & corresponding timescales: 6. Robbins EC, Wooldrage K, Saunders BP, Duffy SW, Cross AJ. Impact of adenoma detection rates at flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality. Gut. 2021;70:A53. 1. Effect of variation in adenoma detection rates at screening FS on CRC incidence (17 year follow-up data); submission 2019 7. Robbins EC, Wooldrage K, Stenson I, Pack K, Duffy S, Weller D, Levin T, Conell C, Wright S, Nickerson C, Martin J, Cross AJ. Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study. Endoscopy. 2021 Apr;53(4):402-410. 2. Flexible sigmoidoscopy screening in colorectal cancer: a pooled analysis of four randomised controlled trials; analyses to be conducted in 2019 8. Cross AJ, Robbins EC, Saunders BP, Duffy SW, Wooldrage K. Higher Adenoma Detection Rates at Screening Associated With Lower Long-Term Colorectal Cancer Incidence and Mortality. Clin Gastroenterol Hepatol. 2022 Feb;20(2):e148-e167. 3. Validation of the Intermediate Adenomas study findings, submission 2019 4. Validation of the All Adenomas study findings, submission 2020 5. Long term effects of once-only flexible sigmoidoscopy screening after ~22 years of follow-up, submission 2022 5. Long term effects of once-only flexible sigmoidoscopy screening after ~26 years of follow-up, submission 2026 In addition, CSPRG are planning other secondary data analyses as part of PhD studentships funded until the end of 2022 addressing: • The quality of flexible sigmoidoscopy (FS) screening on outcomes and colorectal cancer (CRC) incidence/mortality • Patient and procedural factors affecting performance of FS screening • The safety and acceptability of once-only FS • The effect of family history of CRC on the incidence of CRC after screening • The use of advanced stage at diagnosis of incident cancers as a surrogate for CRC mortality • The efficacy of colonoscopy surveillance for higher-risk adenomas found at screening • The incidence of proximal CRC after FS, by the number and type of polyp detected at FS • The incidence of CRC according to smoking history • Medications in relation to risk of adenomas and CRC • The effect of diet and lifestyle factors on the development of polyps, and CRC by subsite [6 paragraphs unchanged] 6. Harewood R. Are all bowel cancers created equal? CRUK’s Fundraising & Mass Directorate Immersion Day: from Bench to Bedside, Sir Alexander Fleming Building, London. Jul 2018. 7. Harewood R. Early diagnosis of colorectal cancer. CRUK's Policy and Information Department Away Day, Francs Crick Institute, London. Nov 2018. 8. Harewood R & Disney R. 100 Roles to Beat Cancer. Cancer Research UK Stand at the Great Exhibition Road Festival, London. Jun 29th 2019. 9. Cross AJ. Colorectal cancer: prevention requires shared responsibility. 11th International Cancer Conference 2019, Trinity Translational Medicine Institute, St. James's Hospital, Dublin. Sep 24th 2019. 10. Cross AJ. Preventing and detecting colorectal cancer. Imperial College London Academic Health Science Centre Seminar Series. The Royal Marsden NHS Foundation Trust. Nov 20th 2019. 11. Cross AJ. Progress in cancer research. CRUK's Annual Evening of Christmas Music. St Mary's Church, Wyndham Place London. Dec 18th 2019. 12. Cross AJ. Colorectal cancer screening and surveillance. COLO-SPEED meeting, Laing Art Gallery, Newcastle. Dec 10th 2019. 13. Robbins EC. Impact of variable adenoma detection rates at screening flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality. The Institute of Global Health Innovation and Division of Surgery Research Afternoon, Imperial College London. Dec 12th 2019. 14. Cross AJ. Colorectal cancer screening. Oslo Group Conference. Lillehammer, Norway. Feb 12th-14th 2020. 15. Robbins EC. Colorectal cancer screening in a COVID-19 era: outreach & increasing participation in population-based programs. World Endoscopy Organisation Colorectal Cancer Screening Committee: Virtual Meeting. Via video conference. Oct 9th 2020. 16. Cross AJ. Global challenges in cancer prevention research: opportunities for a collaborative approach. Launch event for the new ICL and Institute of Cancer Research Cancer Epidemiology and Prevention Research Unit. Via video conference. Nov 2nd 2020. 17. Harewood R. Risk factors for proximal colon cancer: how informative are polyp findings in determining future risk?. 2020 BSG Virtual Campus. Via video conference. Jan 26th 2021. 18. Robbins EC. Impact of adenoma detection rates at flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality. 2020 BSG Virtual Campus. Via video conference. Jan 26th 2021. Planned analyses / publications & corresponding timescales: 1. Juul FE, Cross AJ, Schoen RE, Senore C, Pinsky P, Miller E, Segnan N, Wooldrage K, Wieszczy-Szczepanik P, Armaroli P, Garborg KK, Adami HO, Hoff G, Kalager M, Bretthauer M, Løberg M, Holme O. 15-Year Benefits of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality: A Pooled Analysis of Randomized Trials. Revisions requested and re-submitted to Annals Internal Medicine. 2. Long term effects of once-only flexible sigmoidoscopy screening after ~22 years of follow-up, analysis complete, paper being drafted for submission in 2023. 3. Long term effects of once-only flexible sigmoidoscopy screening after ~26 years of follow-up, submission 2026 In addition, CSPRG are planning other secondary data analyses as part of PhD studentships funded until the end of June 2023 addressing: • The quality of flexible sigmoidoscopy (FS) screening on outcomes and colorectal cancer (CRC) incidence/mortality • Patient and procedural factors affecting performance of FS screening • The safety and acceptability of once-only FS • The effect of family history of CRC on the incidence of CRC after screening • The efficacy of colonoscopy surveillance for higher-risk adenomas found at screening • The incidence of proximal CRC after FS, by the number and type of polyp detected at FS • The incidence of CRC according to smoking history • Medications in relation to risk of adenomas and CRC • The effect of diet and lifestyle factors on the development of polyps, and CRC by subsite [2 paragraphs unchanged]

Expected measurable benefits

The results of the long-term follow-up of the UKFSST in 2022 and 2026, as well as the additional secondary analyses up to 2022, 2026 will be made available to inform policy makers via publications and presentations at national and international meetings. Colorectal cancer (CRC) is a very common malignancy that is very treatable when diagnosed at an early stage. However, late stage late-stage diagnoses have a very poor prognosis and are more costly to treat. The use of FS [14 words unchanged] can also remove precursor lesions potentially leading to long-term protection. The study have has already demonstrated a significant benefit to participants who received a single FS [8 words unchanged] preventing CRC incidence and mortality after 10 years of follow up, and the study team have published extensively on the positive uptake, acceptability and impact of a FS screening examination. The UKFSST has been instrumental in providing data to support the use [5 words unchanged] BCSP in England, which began offering FS at age 55 years in 2011: 2013: however, there is no data on the long term benefits of this [16 words unchanged] the health economic benefits of FS would be even larger than expected. This research will build on existing knowledge on the impact of FS [19 words unchanged] the reduction in incidence and mortality from CRC over a period of up to more than 25 years. This data can then be used to directly inform estimations of patient and economic benefits over a 25 years 25-year period. Examining long term follow up is important because the participants will be [9 words unchanged] addition, as the participants age, the outcomes of surgery are not as good good, so it is imperative to prevent cancer in these individuals. Finally, the [6 words unchanged] 75 years is currently 13 years for women and 11 for men, therefore , therefore, quality of life in these older age groups is important. The past and future contribution of the UKFSST was continues to be acknowledged at by the most recent Trial Steering Committee (TSC) meeting for the study in April 2016. study. The TSC, which is comprised of external experts in the field, field and a patient representative, concluded that the UKFSST is a unique resource able to provide vital [68 words unchanged] to investigate the duration of the effect of a single FS examination. The last data update was provided to the TSC in September 2022.

Benefits reported

Imperial College London have already demonstrated a significant benefit to participants who received a single flexible sigmoidoscopy (FS) FS screen compared to those who did not in preventing colorectal cancer (CRC) CRC incidence and mortality after 17 years of follow-up, and have published extensively on the positive uptake, acceptability acceptability, and impact of a FS screening examination. The study gave rise to two very significant publications in The Lancet in 2010 and in 2017 on the long-term effects of FS screening. In addition, Imperial College London published two additional manuscripts in 2018 and several talks were given referencing published UKFSST data (see outputs section). The study has been instrumental in providing data to support the use of FS in the BCSP in England, which began offering a FS at age 55 years in 2013; however, there is no data on the long-term benefits of this procedure. If the protective effect of a FS on preventing CRC is sustained over the long-term, the health economic benefits of the test would be even larger than anticipated. This research builds on existing knowledge on the impact of FS and will provide evidence to the BCSP on the long-term effectiveness of a FS examination on reducing the number of people being diagnosed and dying from CRC over a period of more than 25 years. It will also provide a rich dataset that can be used to address additional questions about FS and the answers will provide important information that can inform future healthcare policies. The study gave rise to two very significant publications in The Lancet in 2010 and in 2017 on the long-term effects of FS screening. In addition, Imperial College London published two additional manuscripts in 2018, one in 2022 and several talks were given referencing published UKFSST data (see outputs section). CSPRG PhD research supported by the study includes analyses of: • The quality of FS screening on outcomes and CRC incidence/mortality • Patient and procedural factors affecting performance of FS screening • The safety and acceptability of once-only FS • The effect of family history of CRC on the incidence of CRC after screening • The efficacy of colonoscopy surveillance for higher-risk adenomas found at screening • The incidence of proximal CRC after FS, by the number and type of polyp detected at FS • The incidence of CRC according to smoking history • Medications in relation to risk of adenomas and CRC • The effect of diet and lifestyle factors on the development of polyps, and CRC by subsite

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

[23 paragraphs unchanged] 2019 Amendment The UKFSST Protocol has been previously amended to add one more study objective (to investigate the effect of diet and lifestyle factors on the development of polyps, and colorectal cancer by subsite) and to include the use of UKFSST data to validate findings of the Intermediate Adenomas study and All Adenomas studies (DARS-NIC-147827-NC2TC). The UKFSST Protocol has been amended to add one more study objective (to investigate the effect of diet and lifestyle factors on the development of polyps, and colorectal cancer by subsite) and to include the use of UKFSST data to validate findings of the Intermediate Adenomas study and All Adenomas studies (DARS-NIC-147827-NC2TC). In addition, the study has been awarded additional funding from the National Institute for Health Research-Health Technology Assessment (NIHR-HTA) to continue to follow-up the UKFSST cohort for a further 10 years to March 2027, until all the participants have reached the age of 80 years. In addition, the study have now been awarded additional funding from the National Institute for Health Research-Health Technology Assessment (NIHR-HTA) to continue to follow-up the UKFSST cohort for a further 10 years to March 2027, until all the participants have reached the age of 80 years. [1 paragraph unchanged] The GDPR legal bases relied upon for data processing for the purposes described in this Agreement are Article 6(1)(e) (processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller) and Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). Imperial College London is the sole Data Controller under this Agreement who also process the data. No other organisations have any access to the data or have any involvement in deciding how the data is processed.

Unchanged: Processing activities, Expected output, Expected measurable benefits, Benefits reported.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: + Cancer Registration Data; + Civil Registrations of Death; + Demographics

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits, Benefits reported.