Cost-effectiveness analysis of genetic diagnostic strategies for Lynch syndrome in Italy.

Roberta Pastorino,Alessia Tognetto,Adriano Grossi,Marco Di Marco,Stefania Boccia,Emanuela Lucci-Cordisco,Franco Scaldaferri,Antonio Federici,Andrea De Censi,Walter Ricciardi,Michele Basile,Maurizio Genuardi,Paolo Villari,Alvaro Galli

doi:10.1371/journal.pone.0235038

Abstract

Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the “no testing” strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that “universal testing” versus “no testing” is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy.

Highlights

Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer death worldwide, accounting for approximately 1,800,000 new cases and 881,000 deaths in 2018 [1, 2]
Lynch syndrome (LS), previously known as hereditary non polyposis colorectal cancer, is an autosomal dominant disorder caused by a pathogenic sequence variant in one of four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2)
We developed a decision analytical model to estimate the quality-adjusted life-year gained (QALYs) and costs financed by the Italian National Health Service for the provision of tests aimed at the identification of LS individuals and the management of their family members

Summary

Introduction

Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer death worldwide, accounting for approximately 1,800,000 new cases and 881,000 deaths in 2018 [1, 2]. Lynch syndrome (LS), previously known as hereditary non polyposis colorectal cancer, is an autosomal dominant disorder caused by a pathogenic sequence variant in one of four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). It accounts for about 3% of newly diagnosed CRC cases [4, 5]. Approximately 10% of sporadic CRCs show loss of MLH1 due to methylation of the MLH1 promoter

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