Clinical utility and cost-effectiveness of universal tumor screening to identify Lynch syndrome in patients with stage II/III colorectal cancer: a prospective observational study in Japan.

BACKGROUND: Universal tumor screening (UTS) for Lynch syndrome (LS) is cost-effective in Western countries; however, cost-effectiveness varies based on the frequency of hereditary diseases and testing costs. This study aimed to clarify the clinical utility and cost-effectiveness of UTS in identifying LS in patients with stage II/III colorectal cancer (CRC) in Japan.

METHODS: This single-center, prospective cohort study evaluated 591 consecutive patients who underwent surgical resection for Stage II/III colorectal adenocarcinoma between 2016 and 2018. Immunohistochemistry (IHC) was used to evaluate mismatch repair (MMR) proteins. In patients with MMR deficiency, BRAF V600E mutational testing and genetic counseling/testing were performed to identify LS based on MMR deficiency patterns. Genetic counseling/testing was also conducted for blood relatives upon request. The cost-effectiveness of implementing UTS was evaluated from the perspective of healthcare payers using a Markov state-transition model, with the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained as the reference value.

RESULTS: A total of 40 cases (6.8%) exhibited MMR deficiency; 12 cases (2.0%) had LS, of whom 2 (16.7%) did not meet Amsterdam criteria II or any criteria of the revised Bethesda guidelines. Eleven relatives of five LS probands underwent genetic testing, and six (54.5%) were diagnosed with LS. The ICER for UTS was JPY 0.6 million per QALY gained, substantially below the Japanese threshold of JPY 5.0-6.0 million per QALY.

CONCLUSIONS: The UTS of LS in patients with stage II/III CRC is a useful and cost-effective tool in Japan.