Is Universal Genetic Testing Cost-Effective to Detect and Manage Lynch Syndrome in Singapore?

OBJECTIVES: Universal genetic testing in colorectal cancer (CRC) patients coupled with cascade testing among family members has been proposed as a public health strategy to reduce LS-related cancer burden in a cost-effective manner. However, it has never been validated in Singapore’s context. Therefore, the current study aims to investigate whether universal genetic testing plus cascade testing is cost-effective to detect and manage LS in incident CRC patients and their first-degree relatives (FDRs).

METHODS: This model-based economic evaluation adopted a healthcare system perspective to compare universal genetic testing with universal tumor-based testing strategies (standard of care) and no testing. A decision tree along with Markov models was constructed to simulate the lifetimes of CRC patients and their FDRs (siblings and children), estimating the outcomes of the diagnostic strategies, LS-associated cancer surveillance, and/or prophylactic surgery. We assumed 100% acceptance of tests and compliance with recommended surveillance programs in all strategies. Costs and quality-adjusted life years (QALYs) were calculated for each strategy and discounted at 3.5% annually. Costs were in SGD, May 2024.

RESULTS: In the base-case analysis with ~3 FDRs per patient, the universal genetic testing strategy dominated the comparators, yielding 148 QALYs (9.44 QALYs for patients and 138.56 QALYs for FDRs) at a total cost of SGD 51,928 per family. This resulted in a cost-savings of SGD 1,685 and a QALY gain of 0.004 per family compared to the next best strategy (immunohistochemistry followed by genetic testing) and a cost-savings of SGD 392 and QALY gain of 0.09 compared to no testing.

CONCLUSIONS: In Singapore, universal genetic testing appears to be a cost-effective strategy to detect and manage LS cases in CRC patients and their FDRs compared to currently used strategies. This finding has significant policy implications, supporting the consideration of universal genetic testing as a routine strategy and subsidy allocation.