Economic evaluation of genetic screening for Lynch syndrome in Germany

Purpose: Lynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown. Methods: We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically. Results: On average, detected mutation carriers gained 0.52 lifeyears (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was (Sic)77,268, (Sic)253,258, and (Sic)4,188,036 per life-year gained, respectively. Conclusion: The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.