A micro-costing study of screening for Lynch syndrome-associated pathogenic variants in an unselected endometrial cancer population: cheap as NGS chips?

Background: Lynch syndrome is the most common inherited cause of endometrial cancer. Identifying individuals affected by Lynch syndrome enables risk-reducing interventions including colorectal surveillance, and cascade testing of relatives.

Methods: We conducted a micro-costing study of screening all women with endometrial cancer for Lynch syndrome using one of four diagnostic strategies combining tumour microsatellite instability testing (MSI), immunohistochemistry (IHC) and/or MLH1 methylation testing, and germline next generation sequencing (NGS). Resource use (consumables, capital equipment, and staff) was identified through direct observation and laboratory protocols. Published sources were used to identify unit costs to calculate a per-patient cost (£; 2017) of each testing strategy, assuming a National Health Service (NHS) perspective.

Results: Tumour triage with MSI and reflex MLH1 methylation testing followed by germline NGS of women with likely Lynch syndrome was the cheapest strategy at £42.01 per case. Tumour triage with IHC and reflex MLH1 methylation testing of MLH1 protein-deficient cancers followed by NGS of women with likely Lynch syndrome cost £45.68. Tumour triage with MSI followed by NGS of all women found to have tumour microsatellite instability cost £78.95. Immediate germline NGS of all women with endometrial cancer cost £176.24. The cost of NGS was affected by the skills and time needed to interpret results (£44.55/patient).

Conclusion: This study identified the cost of reflex screening of all women with endometrial cancer for Lynch syndrome, which can be used in a model-based cost-effectiveness analysis to understand the added value of introducing reflex screening into clinical practice.