The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer

Abstract

Purpose:To estimate the cost-effectiveness of genetic testing strategies to identify Lynch syndrome among newly diagnosed patients with colorectal cancer and to offer targeted testing to relatives of patients with Lynch syndrome. Methods: We calculated incremental costs per life-year saved for universal testing relative to no testing and age-targeted testing for strategies that use preliminary genetic tests (immunohistochemistry or microsatellite instability) of tumors followed by sequencing of mismatch repair genes. We also calculated incremental cost-effectiveness ratios for pairs of testing strategies. Results: Strategies to test for Lynch syndrome in newly diagnosed colorectal tumors using preliminary tests before gene sequencing have incremental cost-effectiveness ratios of Յ$45,000 per life-year saved compared with no testing and Յ$75,000 per life-year saved compared with testing restricted to patients younger than 50 years. The lowest cost testing strategies, using immunohistochemistry as a preliminary test, cost Յ$25,000 per life-year saved relative to no testing and Յ$40,000 per life-year saved relative to testing only patients younger than 50 years. Other testing strategies have incremental cost-effectiveness ratios Ն$700,000 per life-year saved relative to the lowest cost strategies. Increasing the number of relatives tested would improve cost-effectiveness. Conclusion: Laboratory-based strategies using preliminary tests seem costeffective from the US health care system perspective. Universal testing detects nearly twice as many cases of Lynch syndrome as targeting younger patients and has an incremental cost-effectiveness ratio comparable with other preventive services. This finding provides support for a recent US recommendation to offer testing for Lynch syndrome to all newly diagnosed patients with colorectal cancer. Genet Med 2010:12(2):93-104.Key Words: cost-effectiveness analysis, genetic testing, Lynch syndrome, HNPCC, cancer, genomics, economic evaluation L ynch syndrome is a genetic predisposition to colorectal cancer (CRC) and certain other malignancies as a result of a germline mismatch repair (MMR) gene mutation. In this article, we present an economic evaluation of genetic testing protocols to identify Lynch syndrome among newly diagnosed cases of CRC in order to identify and test blood relatives for the presence of Lynch syndrome. The benefit of identifying an asymptomatic individual with Lynch syndrome is that it allows for early and intensive surveillance to detect colon polyps, which can prevent malignancies and reduce the risk of premature death.The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) commissioned evidence reviews 1,2 of testing strategies for Lynch syndrome and in January 2009 published a recommendation to offer laboratory testing to all newly diagnosed patients with CRC, regardless of age or family history. 3 The primary research question was whether the EWG recommendation of universal testing to identify mutations for which...

Which Lynch syndrome screening programs could be implemented in the “real world”? A systematic review of economic evaluations

“…[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] The health-care system perspective was adopted as the viewpoint of analysis in most studies. 25,[27][28][29][30][35][36][37]40,41,43,44 Four studies declared a societal perspective, but none of these included social costs. 26,31,32,39 Most economic models used were based on a decision analysis, [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]…”

“…29,35,37,[40][41][42]44 Although to different degrees, most studies gave details of the modeling and parameters used. [26][27][28][30][31][32][33][34][35][36][37][38][39]42,43 The time horizon of the analysis was not always clearly defined, although it could be deduced from the model. 29,31,40,41,44 Sensitivity analysis was performed in all economic evaluations: [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] six studies used only univariate analysis, 25,28,31,...…”

“…26,27,33,34,36,38,40,42,43 Furthermore, most studies reported the range over which variables varied. [25][26][27][28][29][30][33][34][35][37][38][39][40][41][42][43][44] All economic evaluations provided an incremental analysis. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Influential parameters and basic assumptions…”

“…43 Several studies reported percentages greater than 99% for both sensitivity and specificity of MMR genes sequencing 30,[38][39][40]43,44 (Supplementary Table S5), but a lower sensitivity was assumed by Ramsey (87%), 26,27 Dinh (90%), 31 and Snowsill (90%). 37 The sensitivity ranges of microsatellite instability (MSI) and immunohistochemistry (IHC) tests were respectively 76-91% 26,27,30,33,34,[37][38][39]42 and 77-92%, [30][31][32][33][34][37][38][39][40]42,43 whereas specificity ranges were 79-93% for MSI [26][27][28]30,33,34,[37][38][39]42 tests and 70-91% for IHC tests. [30][31][32][33][34][37]…”

“…37 The sensitivity ranges of microsatellite instability (MSI) and immunohistochemistry (IHC) tests were respectively 76-91% 26,27,30,33,34,[37][38][39]42 and 77-92%, [30][31][32][33][34][37][38][39][40]42,43 whereas specificity ranges were 79-93% for MSI [26][27][28]30,33,34,[37][38][39]42 tests and 70-91% for IHC tests. [30][31][32][33][34][37][38][39][40]42,43 Being context-specific, cost assumptions (Supplementary Table S6) are not directly comparable; single-gene sequencing costs ranged from 600 to 1,200 dollars in American studies, [30][31][32][33][34]39,…”