Risk-stratified FIT for urgent colonoscopy in Lynch Syndrome: A clinical service throughout the COVID-19 pandemic

ABSTRACT

IntroductionLynch syndrome (LS) is an autosomal dominant inherited disorder characterised by pathogenic variants within the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, PMS2, and a variant in EPCAM, which regulates MSH2 expression and results in an increased risk of several cancers, particularly colorectal cancer with an annual incidence rate of 3-5%.The faecal immunochemical test (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy. We report preliminary results from an NHS England endorsed clinical service implemented during the COVID-19 pandemic (June-December 2020) which used FIT to prioritise colonoscopy in the highest risk LS patients in response to limited colonoscopy capacity throughout the pandemic.MethodsRegional genetic and endoscopy services across England were invited to participate, with the support of the British Society of Gastroenterology (BSG). Patient eligibility was determined by 1) Diagnosis of Lynch Syndrome 2) Planned colonoscopic surveillance between 1 March 2020 and 31 December 2020. Requests for FIT testing from participating NHS Trusts were sent to the NHS Bowel Cancer Screening South of England Hub in Guildford. The Hub sent patients a FIT kit (OC-Sensor™ (Eiken, Japan)), instructions for use, a questionnaire, and a pre-paid return envelope. Laboratory reports with faecal haemoglobin (f-Hb) results were returned electronically for clinical action. LS patients were risk-stratified for colonoscopy based upon the following f-Hb thresholds (1) f-Hb ≥ 10µg Hb/g faeces triaged for colonoscopy via the two-week wait (2WW) pathway, (2) f-Hb ≤10µg Hb/g faeces schedule patients for colonoscopy within 6-12 weeks, where local endoscopy service availability permits.ResultsFourteen centres across England participated in the clinical service evaluation from 9th June 2020 to 1st December 2020. An uptake rate of 63% was observed from this cohort (269/428 invites). Of the 269 patients who returned their FIT devices, 20% (n=55) had f-Hb ≥ 10µg Hb/g faeces and met criteria for urgent colonoscopy triage via the 2WW pathway. 29% (n=77) of patients had a f-Hb that was greater than the limit of detection of the assay (6µg Hb/g faeces) yet below 10µg Hb/g faeces. 22 patients (8%) had f-Hb between 6 and 9.9µg Hb/g faeces. In a subgroup analysis of 67 patients from St Mark’s Hospital, the adenoma detection rate was 42.4%, and 9/67 proceeded to priority colonoscopy based on their FIT findings.ConclusionsImplementation of this clinical service during the COVID-19 pandemic has demonstrated clinical value for LS patients requiring routine surveillance. Further investigation on the efficacy of this novel intervention is warranted, namely as it pertains to additional data analysis to include endoscopy findings for participating LS patients to discern FIT sensitivity and specificity, which will be further explored under the auspices of a multi-centre prospective research study which is presently in development.