Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals

Abstract

Background: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states.

Methods: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals.

Results: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients).

Conclusions: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

Keywords: Bottleneck; Gap; Genetics services referral; Heterogeneity in practice; Lynch syndrome; Medical records; Mismatch repair; Tumour testing.

Fig. 1

LS tumour testing and referral to genetics services at seven Australian hospitals in 2017–2018. The percentages in each box are calculated relative to the number of patients in the previous testing step. The numbers of patients with (i) MSH2 or MSH6 loss, or (ii) PMS2 loss only, together account for < 10 patients per hospital and are not shown separately to protect patient confidentiality. * test used for at least some patients

Fig. 2

dMMR/MSI test results and referral to genetics services by patient age group. a dMMR/MSI tumours were more common in older patients (Wilcoxon p = 3.7 × 10^− 13 for difference in ages of patients with and without dMMR/MSI). b Older patients with tumour test results complete and indicating high LS risk were less likely to be referred to genetics services (Wilcoxon p = 9.8 × 10^− 5 for difference in ages of patients with and without referral record)