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

ABSTRACT

Background: Lynch syndrome (LS) is an inherited disorder characterized by pathogenic variants within mismatch repair genes resulting in an increased risk of colorectal cancer (CRC). In England, the fecal immunochemical test for Haemoglobin (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy. Herein, we report results from a national emergency clinical service implemented during the COVID-19 pandemic which used FIT to prioritize colonoscopy in LS patients while endoscopy services were limited. Methods: Regional genetic and endoscopy services across England were invited to participate. Patient eligibility was determined by 1) Diagnosis of Lynch Syndrome 2) Planned colonoscopic surveillance between 1 March 2020 and 31 March 2021. Requests for FIT testing from participating NHS Trusts were sent to the NHS Bowel Cancer Screening South of England Hub's Research Laboratory in Surrey. The Hub sent patients a FIT kit (OC-Sensor? (Eiken, Japan)), instructions for use, a questionnaire, and a pre-paid return envelope. Lab reports with feecal 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 ≥10mg of Haemoglobin (Hb)/g (mg/g) faeces triaged for colonoscopy via an urgent two-week wait (2WW) pathway, (2) f-Hb ≤10mg/g schedule patients for colonoscopy within 6-12 weeks, where local endoscopy service availability permits. Results: Fifteen centers across England participated in the clinical service from 9th June 2020 to 31st March 2021. An uptake rate of 64% was observed from this cohort (375/588 invites), though 21 cases were removed from analysis due to repeat FITs, insufficient sample, missing clinical data, or FIT completed after colonoscopy. Of the remaining 354 patients analyzed, 269 patients (76%) had a f-Hb of <6mg/g. 6% (n=23) of patients had a f-Hb that was at or between greater than the limit of detection of the assay (≥6mg/g) yet below 10mg/g.18% (n=62) had FIT results of ≥10mg/g and met criteria for urgent colonoscopy triage via the 2WW pathway. Of the 62 urgently triaged patients, 22 had detectable adenomas, 6 had advanced adenomas (AAs), and 4 were diagnosed with CRC (table). Conclusions: The utility of FIT during the pandemic has demonstrated clinical value for LS patients requiring CRC surveillance. Further longitudinal investigation on the efficacy of FIT in people with LS is warranted and will be examined as part of the multi-center prospective research study “FIT for Lynch Syndrome” (ISRCTN15740250) which is presently recruiting patients in the UK.