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Guidelines for the Management of Hereditary Colorectal Cancer

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Guidelines for the Management of Hereditary Colorectal Cancer Guidelines Guidelines for the management of hereditary Gut: first published as 10.1136/gutjnl-2019-319915 on 28 November 2019. Downloaded from colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/ United Kingdom Cancer Genetics Group (UKCGG) Kevin J Monahan ,1,2 Nicola Bradshaw,3 Sunil Dolwani,4 Bianca Desouza,5 Malcolm G Dunlop,6 James E East,7,8 Mohammad Ilyas,9 Asha Kaur,10 Fiona Lalloo,11 Andrew Latchford,12 Matthew D Rutter ,13,14 Ian Tomlinson ,15,16 Huw J W Thomas,1,2 James Hill,11 Hereditary CRC guidelines eDelphi consensus group ► Additional material is ABSTRact having a family history of a first-degree relative published online only. To view Heritable factors account for approximately 35% of (FDR) or second degree relative (SDR) with CRC.2 please visit the journal online (http:// dx. doi. org/ 10. 1136/ colorectal cancer (CRC) risk, and almost 30% of the While highly penetrant syndromes such as Lynch gutjnl- 2019- 319915). population in the UK have a family history of CRC. syndrome (LS), familial adenomatous polyposis (FAP) The quantification of an individual’s lifetime risk of and other polyposis syndromes account for account For numbered affiliations see end of article. gastrointestinal cancer may incorporate clinical and for only 5–10% of all CRC diagnoses, advances molecular data, and depends on accurate phenotypic in genetic diagnosis, improvements in endoscopic Correspondence to assessment and genetic diagnosis. In turn this may surgical control, and medical and lifestyle interven- Dr Kevin J Monahan, Family facilitate targeted risk-reducing interventions, including tions provide opportunities for CRC prevention and Cancer Clinic, St Mark’s endoscopic surveillance, preventative surgery and effective treatment in susceptible individuals. Hospital, London, HA1 3UJ, UK; chemoprophylaxis, which provide opportunities for The purpose of this guideline is to provide an k. monahan@ imperial. ac. uk cancer prevention. This guideline is an update from the evidence- based framework for the optimal manage- Received 20 September 2019 2010 British Society of Gastroenterology/Association of ment of hereditary CRC for clinicians involved in Revised 25 October 2019 Coloproctology of Great Britain and Ireland (BSG/ACPGBI) their management, including gastroenterologists, Accepted 5 November 2019 guidelines for colorectal screening and surveillance in nurse practitioners, physicians, colorectal surgeons, moderate and high-risk groups; however, this guideline clinical geneticists, genetic counsellors and pathol- http://gut.bmj.com/ is concerned specifically with people who have increased ogists. This guideline was commissioned by the lifetime risk of CRC due to hereditary factors, including Clinical Services and Standards Committee (CSSC) those with Lynch syndrome, polyposis or a family history of of the British Society of Gastroenterology (BSG), CRC. On this occasion we invited the UK Cancer Genetics via the colorectal section, and a guideline chair Group (UKCGG), a subgroup within the British Society selected. It is an update of the previous iteration of Genetic Medicine (BSGM), as a partner to BSG and of the BSG/Association of Coloproctology of Great on September 30, 2021 by guest. Protected copyright. ACPGBI in the multidisciplinary guideline development Britain and Ireland (ACPGBI) guideline published process. We also invited external review through the in 2010 and developed in accordance with the BSG Delphi process by members of the public as well as National Institute for Health and Care Excellence the steering committees of the European Hereditary (NICE)-compliant guideline process. Tumour Group (EHTG) and the European Society of The Guideline Development Group (GDG), Gastrointestinal Endoscopy (ESGE). A systematic review which included gastroenterologists from the BSG, of 10 189 publications was undertaken to develop 67 clinical geneticists from United Kingdom Cancer evidence and expert opinion-based recommendations Genetics Group (UKCGG), colorectal surgeons for the management of hereditary CRC risk. Ten research from the ACPGBI, a pathologist, a genetic coun- recommendations are also prioritised to inform clinical sellor and a patient representative, was selected to management of people at hereditary CRC risk. ensure wide-ranging expertise across all relevant © Author(s) (or their disciplines. Members of the GDG, and participants employer(s)) 2019. Re- use in the eDelphi process, completed a Declaration permitted under CC BY- NC. No OBJECTIVE of Conflict of Interests (COI) form which was commercial re- use. See rights reviewed and vetted by the BSG. and permissions. Published To provide a clear strategy for the management of by BMJ. people at hereditary risk of colorectal cancer (CRC), A scoping meeting was held on 13 October 2017, which includes diagnosis, endoscopic management, and in advance of this meeting the GDG was asked To cite: Monahan KJ, prevention and surgical care. to develop key priorities and questions. Bradshaw N, Dolwani S, et al. Gut Epub ahead of print: The GDG determined that the primary measure [please include Day Month AIMS AND METHODS of effectiveness of any intervention was a reduc- Year]. doi:10.1136/ An estimated 35% of CRC is due to heritable factors,1 tion of the lifetime risk of CRC, and the following gutjnl-2019-319915 with approximately 29% of the UK population secondary outcome measures: Monahan KJ, et al. Gut 2019;0:1–34. doi:10.1136/gutjnl-2019-319915 1 Guidelines i. Reduction in the incidence of advanced adenomas at were also scrutinised. After each round of Delphi, and before the colonoscopy guideline was finalised, the search was repeated and any important Gut: first published as 10.1136/gutjnl-2019-319915 on 28 November 2019. Downloaded from ii. Prevention of CRC studies published since the initial evidence search were incorporated. iii. Reduced morbidity related to CRC, or morbidity secondary A modified electronic Delphi process6 was used to develop and to complications of surveillance and treatment refine statements. Initial draft statements formulated by the writing iv. Improved identification of hereditary CRC syndromes committee were reviewed by the GDG to allow for modification v. Improved pathways from diagnosis to treatment in suscep- and to identify additional references. After a preliminary discus- tible populations. sion, formal anonymous voting rounds were undertaken using We sought a consistent approach in our assessment of the rela- SurveyMonkey. Each statement was scored by each member of the tive effectiveness of interventions. In principle we agreed that GDG using a five-point scale. We also invited key national and surveillance should only be offered to individuals who remain international opinion leaders from the UKCGG steering group, at higher risk of developing CRC than the general population. ACPGBI, BSG, the European Hereditary Tumour Group (EHTG) As CRC risk is not always clearly defined, as a surrogate we and the European Society of Gastrointestinal Endoscopy (ESGE) accepted that advanced adenoma yield on surveillance should be to participate in the modified Delphi process. We included addi- approximately double that in susceptible populations compared tional patient and public involvement in the Delphi process by with the average risk population. inviting participants through the national charities Bowel Cancer A relative threshold for genetic testing was agreed for people UK and Lynch Syndrome UK. Consensus required at least 80% with a 10% or greater probability of having a germline patho- agreement, and consensus of over 70% was accepted if the GDG genic variant in a cancer susceptibility gene in accordance with felt a statement was required for clinical practice. Where consensus 3 4 previous UK guidelines. However the GDG agreed that the was not reached, feedback from the GDG members was dissemi- arbitrary nature of this threshold meant that it could be modified nated after each round to allow members to reconsider their orig- in cases where objective risk assessment was difficult to attain, inal position.7 Where appropriate, revisions to statements were and clinicians had sufficient clinical suspicion of risk. made and a further voting round was undertaken in second and Key questions we sought to cover included the following: third rounds. A final (fourth) round of voting for statements where 1. Which aspects of the previous guidelines require updating? consensus had not been reached for 11 statements was performed 2. What is the lifetime CRC risk and optimal surveillance for within the GDG only. those with a family history of CRC (where LS and polyposis Surveillance and molecular testing recommendations are syndromes have been excluded)? summarised in table 1 and table 2 respectively. The GDG also 3. What is the diagnostic yield of genetic testing and/or sur- developed 10 research recommendations (online supplementary veillance for high-risk populations? file 1) which were prioritised by electronic voting. 4. What is the optimal gastrointestinal (GI) surveillance for pa- The GRADE (Grading of Recommendations, Assessment, tients at hereditary risk GI cancer? Development and Evaluations) tool8 was used to evaluate the 5. What is the impact of high-qual ity endoscopy in patients strength of evidence and the strength of recommendations made with known or suspected hereditary cancer syndromes? (see executive summary). The GRADE system specifically sepa- 6. Should we
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