P621: The health economics of Lynch syndrome screening in colorectal cancer: When genetic testing is cost-saving in a middle-income country

Introduction: Lynch syndrome (LS) was estimated to be 3-5% of all colorectal cancer (CRC.)Molecular diagnosis of LS helps guide CRC surveillance and treatment.Tumor mismatch repair protein immunohistochemistry has been used to "universally" screen for LS since the late 2000s.This has been a logistical challenge with only half of all the patients screened.Prior studies evaluating direct genetics screening (DGS) as an alternative approach have never shown costeffectiveness acceptability.Notably, these health economics analyses were performed only in the high-income country settings.The drop in cost of sequencing has pondered our team whether DGS approach may compliment LS screening uptake at an acceptable cost in a middle-income country setting.The study pilots health economics analysis of DGS for Lynch syndrome in high-risk CRC patients (defined by National Comprehensive Cancer Network guidelines version 1.2020) in a middle-income country setting, Thailand.Methods: Hybrid decision tree and Markov model were utilized to assess health outcomes and costs using a lifetime horizon from a societal perspective.The model took into consideration the colorectal and endometrial cancer risk differences between genders.Local, real-world data were prioritized at each transitional probability.Multigene panel testing (covering MLH1, MSH2, MSH6, PMS2 and EPCAM with next-generation sequencing and MLPA) in the proband ($555 per unit cost) was utilized in DGS approach.Targeted testing was exploited in the family members ($69 per unit cost.)CRC surveillance, referenced from NCCN guidelines, includes the starting age of Colonoscopy at 20-year-old and 2-year interval.56 endometrial cancer patients were interviewed to address missing relevant costs and quality of life using the EQ-5D-5L questionnaire.One-way sensitivity analysis, and Monte Carlo simulation were performed to estimate outcome under Thailand's Universal Health Coverage scheme.The study was approved under Siriraj Hospital IRB and COA approval number 205/ 2022.Currency is in US Dollars.Results: Addition of DGS compared to no-testing in high-risk CRC proband was estimated to increment -$214 in cost, and 2.2 quality-adjusted life years (QALY) gained.In the family member of proband with pathogenic/likely pathogenic variants in LS, familial cascade testing increment -$202 in cost and 2.8 QALY gained in comparison to no-testing.These led to the incremental cost-effectiveness ratio of DGS in high-risk CRC and their family member being costsaving (at -$97/QALY and -$73/QALY.)Subgroup analysis suggested that DGS high-risk female was more cost-saving than in high-risk male patients (-$363/ QALY and $167/QALY respectively.)Cost-saving aspect was still observed upon extrapolation of the model into average-risk CRC group.Direct medical cost of endometrial cancer treatment was at the top of proband and family members' Tornado diagrams.Second adjustable costs in the Tornado diagram costs were "cost of multigene panel" in the proband and "cost of colonoscopy" in the family member.Implementing DGS approach had a 100% probability of being costeffective both in proband and family members.Conclusion: Genetic testing has been perceived to be costly, limiting its broad implication in patient care.The lifesaving and cost-saving aspect of direct genetic testing strongly support healthcare stakeholders in the endorsement of DGS in high-risk CRC patients and their family member across all health care benefits in Thailand to overcome health care inequities.Expansion to average-risk CRC should be considered, however without investment in genomic infrastructure, a sequencing bottleneck might impede the workflow.Future drop in the cost of sequencing and modification of colonoscopy strategy based on molecular status (less stringent in MSH6, PMS2) may further save the cost of DGS implementation.Different health care systems may observe different health economics outcomes and should be broadly discussed.The health economic analysis of other common hereditary conditions in middle-income countries should be further explored.