Uptake of germline testing for Lynch Syndrome in patients with deficient mismatch repair/ microsatellite-high colorectal cancer in the public hospital system in South Australia
Background: Lynch syndrome (LS) accounts for up to 6% of all colorectal cancer (CRC) cases and is caused by inherited pathogenic variants in one of the mismatch repair(MMR) genes: MLH1, MSH2, MSH6, or PMS2. Australian national guidelines recommend universal screening for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) in all patients with colorectal adenocarcinoma, with subsequent germline testing and referral to an Adult Genetics Unit (AGU) when indicated. However, uptake in clinical practice remains inconsistent. This study aims to determine the rates of MMR screening, germline testing, and AGU referrals across 2 major public hospitals in South Australia.
Methods: Data of 1,775 patients discussed at colorectal multidisciplinary team (MDT) meetings at the Royal Adelaide Hospital and Queen Elizabeth Hospital between Jan'21 and Dec' 23 were analyzed. The study assessed whether patients underwent testing for MMR/MSI, BRAF V600E and MLH1 methylation when applicable, and if eligible patients were referred to AGU for germline testing.
Results: Of 1,129 CRC patients, 93.2% (1052/1129) underwent MMR/MSI testing of whom 12.5% (131/1052) had dMMR. Of these, 37% (49/131) were eligible for AGU referral. 73.5% (36/49) were referred, 43% (21/49) underwent germline testing.LS was confirmed in 12 patients (9% of all dMMR), and Lynch-like syndrome in 3 patients (2.3%).
Conclusion: The critical gaps identified in this study include the absence of reflex testing for MMR status and BRAF V600E mutation, missed referral opportunities due to inadequate follow-up, and patient refusal of germline testing for undocumented reasons. These findings underscore the urgent need for genomic education and targeted interventions among healthcare professionals and the wider population to improve adherence to national guidelines and optimise patient outcomes.