Experience of the implementation and outcomes of universal testing for Lynch syndrome in the United Kingdom

Abstract

Aim Colorectal cancer (CRC) is diagnosed in approximately 45 000 people annually in the UK, and it is estimated that Lynch syndrome (LS) accounts for 3.1% of these cases. In February 2017, National Institute for Health and Care Excellence (NICE guideline DG27 recommended universal testing of new cases of CRC for mismatch repair (MMR) status. The aim of this study was to implement universal testing for LS in CRC patients in a secondary care setting.Method We prospectively collected data on consecutive newly diagnosed CRC patients at our centre from November 2016 to August 2018, including evidence of MMR status determined by immunohistochemistry. We recorded clinicopathological data including age at diagnosis, stage, tumour site, reported histological findings and MMR tumour status. Statistical analysis was performed using the chi-square test and the twotailed t-test for binary and continuous variables, respectively.Results A cohort of 203 consecutive patients were diagnosed with CRC during this period. Universal MMR testing was performed for the 198 CRC patients in whom a diagnosis of adenocarcinoma was confirmed, with colonoscopic biopsy used as the source material in 68.6% of cases. Twenty-three CRCs (11.6%) were MMR deficient (dMMR). Most dMMR CRCs (21/23) were early stage tumours (Dukes A or B, P = 0.002). In 39 Dukes B CRCs in patients under 70 years of age, the result of MMR testing influenced decision-making about personalized treatment with 5-fluorouracil based chemotherapy.Conclusion Our results demonstrate that universal testing of all new cases of CRC for features suggestive of LS is feasible and effective in the UK. Our data also indicate the importance of genetic testing and personalized oncological care.

Swiss cost-effectiveness analysis of universal screening for Lynch syndrome of patients with colorectal cancer followed by cascade genetic testing of relatives

“…We demonstrate that universal LS screening with cascade testing of relatives results in substantial benefits for the Swiss healthcare system at a reasonable cost. Our findings provide evidence needed to inform policymakers, healthcare providers and insurance companies about the costs and health benefits associated with universal LS screening and cascade testing of relatives as a public health intervention, supporting NICE guidelines 45. The overall cost-effectiveness of this approach depends on the costs of DNA sequencing and the willingness of patients and relatives to be tested.…”

Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)

“…A comprehensive review performed by NICE of the clinical- and cost-effectiveness of universal diagnostic testing for LS was published in 2017 18. We recommend the use of colonoscopic biopsies as the preferred source material for tumour MMR testing 114…”

Compliance with mismatch repair testing in pT1 colorectal cancer diagnosed before the age of 70 years

“…MMR testing has been shown to be cost-effective when performed in all CRCs diagnosed before age of 70 years [18]. In one English hospital the compliance to MMR testing in newly diagnosed CRCs was 100% [15], while in 19 Dutch hospitals compliance to MMR testing was 84% in all newly diagnosed CRCs including stage I to IV and diagnosed from January 2016 to July 2017 [19]. Our study evaluated specifically pT1 CRC.…”

“…To reinforce the detection of Lynch syndrome, MMR testing has been recommended as routine diagnostics in newly diagnosed CRC diagnosed <70 years of age [12,[14][15][16][17]. MMR testing has been shown to be cost-effective when performed in all CRCs diagnosed before age of 70 years [18].…”

“…MMR testing is more conventionally performed on oncological surgical resection specimen, and therefore MMR testing may be forgotten when only local excision has In case of oncological surgical resection of pT1 CRC, MMR status was evaluated in 89% and was known prior to surgery in 51% of the cases. In a single-center UK study, MMR status was evaluated in 69% on diagnostic biopsies prior to surgery [15]. MMR testing should preferably be performed on biopsy material as the concordance of IHC between biopsies and resection specimen is high [15,20,21].…”