Cost-effectiveness of population screening for Lynch syndrome and hereditary breast and ovarian cancer syndrome in Singapore.

Hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS) are the most prevalent hereditary cancer syndromes. Population-based germline genetic testing (GT) has been proposed to improve carrier detection beyond family history (FH)-guided approaches, but economic evidence from Asian settings is lacking. We evaluated the cost-effectiveness of population-based GT strategies for HBOC and LS diagnosis in Singapore. We conducted cost-utility analyses from Singapore's healthcare system perspective with a lifetime horizon using decision trees and Markov models. For HBOC diagnosis, we compared population-based GT for , FH-guided GT, and no testing in cancer-unaffected women aged 30 years. For LS diagnosis, we compared population-based GT for , , and ; FH-guided GT, and no testing in cancer-unaffected individuals aged 30 years. Both models included cascade testing of first-degree relatives. Confirmed carriers received syndrome-specific enhanced surveillance and risk-reducing interventions. The willingness-to-pay threshold was S$75,000 per quality-adjusted life-year (QALY). Deterministic, probabilistic, and scenario analyses assessed uncertainty. Budget impact analyses estimated the five-year costs of the optimal strategy. Population-based testing was the optimal strategy with an ICER of S$50,541/QALY relative to FH-guided testing with 99.93% probability of cost-effectiveness and averted one additional cancer per 1,000 women tested. Implementation of population-based testing requires an additional annual investment of S$1.69 million and identifies 182 additional carriers per annual cohort. For LS diagnosis, population-based GT was not cost-effective (ICER: S$179,564/QALY relative to FH-guided GT). FH-guided GT for LS had an ICER of S$75,210/QALY versus no testing but exhibited substantial decision uncertainty (45.44% vs 54.50% probability of cost-effectiveness), which resolved when cascade testing was extended to second-degree relatives (ICER: S$63,809/QALY). Cost-effectiveness outcomes were highly sensitive to surveillance adherence, cascade testing uptake, and LS prevalence. Population-based GT is cost-effective for but not for LS. FH-guided GT for LS approaches cost-effectiveness, particularly when cascade testing is extended to second-degree relatives. Future analyses should evaluate the integration of LS-associated genes into multigene hereditary cancer panels alongside to leverage shared infrastructure.

Duke Scholars

Author David Bruce Matchar Medicine, General Internal Medicine