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

Abstract

Purpose: Lynch syndrome (LS) screening can significantly reduce cancer morbidity and mortality in mutation carriers. Our aim was to identify cost-effective LS screening programs that can be implemented in the "real world."Methods: We performed a systematic review of full economic evaluations of genetic screening for LS in different target populations; health outcomes were estimated in life-years gained or quality-adjusted life-years.Results: Overall, 20 studies were included in the systematic review. Based on the study populations, we identified six categories of LS screening program: colorectal cancer (CRC)-based, endometrial cancer-based, general population-based, LS family registry-based, cascade testing-based, and genetics clinic-based screening programs. We performed an in-depth analysis of CRC-based LS programs, classifying them into three additional subcategories: universal, age-targeted, and selective. In five studies, universal programs based on immunohistochemistry, either alone or in combination with the BRAF test, were cost-effective compared with no screening, while in two studies age-targeted programs with a cutoff of 70 years were cost-effective when compared with agetargeted programs with lower age thresholds.Conclusion: Universal or o70 years-age-targeted CRC-based LS screening programs are cost-effective and should be implemented in the "real world." Genet Med advance online publication 4 January 2018Key Words: colorectal cancer; cost-effectiveness; Lynch syndrome; screening program; systematic review INTRODUCTIONLynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC), accounting for about 3% of newly diagnosed cases, and results from a mutation in one of the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). As LS is associated with an increased risk of colorectal, endometrial, and other cancers, it is important to identify both the probands and their family members. 1 In 2009, the Evaluation of Genomic Applications in Practice and Prevention Working Group recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. 2 The working group declared that there is a moderate certainty that this would provide moderate population benefit, but it did not recommend a specific genetic testing strategy among the several examined, nor did it deal with implementation issues. 2 Thereafter the US Department of Health and Human Services adopted the following as a Healthy People 2020 developmental objective: 3 "Increase the proportion of persons with newly diagnosed colorectal cancer who receive genetic testing to identify Lynch syndrome (or familial colorectal cancer syndromes)."Although genomic information has the potential to improve the delivery of patient-centered care through tailored preventive, diagnostic, and treatment strategies, there is a considerable gap between discoveries in genomics research and the translation of these findings into genetic services that benefit patients. 4,5 A previous study highl...

Genomics knowledge and attitudes among European public health professionals: Results of a cross-sectional survey

“…In this regard, a high proportion of respondents agreed with the idea that evidence on effectiveness and cost-effectiveness should guide the decision of whether to introduce genetic and genomic applications into clinical and PH practice. Such evidence is already robust for some genetic tests of chronic clinical conditions, such as hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolemia [31][32][33][34]. However, according to the responses recorded in our survey, many PH professionals are not fully aware of this: 26% for hereditary breast/ovarian cancer, 44% for Lynch Syndrome and 50% for familial hypercholesterolemia Table 3.…”

Attitudes toward the right to autonomous decision‐making in psychiatric genetic testing: Controversial and context‐dependent

“…Testing the burden of the cumulative effects of common risk variants is in principle possible and already marketed (e.g., https://staging.geneplaza.com/app-store/68/preview; Plomin & von Stumm, ), albeit not recommended yet for clinical use (International Society of Psychiatric Genetics, ; https://ispg.net/genetic-testing-statement). The effective translation of the abovementioned findings in clinical practice will require a full evaluation, which includes several requirements (Haddow & Palomaki, ; International Society of Psychiatric Genetics, ; Marzuillo, De Vito, D'Andrea, Rosso, & Villari, ); today, evaluation frameworks of genetic testing mainly focus on analytic and clinical validity, clinical utility, and even economic aspects, but less on ethical, legal, and social implications (ELSI), the context of implementation, and viewpoints of consumers (D'Andrea et al, ; D'Andrea, Marzuillo, Pelone, De Vito, & Villari, ; Di Marco et al, ; Pitini et al, ). This is likely due to concerns about systematic ethical examination in ELSI research (Walker & Morrissey, ).…”

Endometrial cancer: modern concepts of screening

“…Значительно повышен риск РЭ у больных раком молочной железы, получающих адъювантную терапию тамоксифеном [15,16], пациенток с синдромом Линча [12,20] В конце 1970-х годов было предложено измерять толщину эндометрия при помощи трансвагинального ультразвукового исследования (УЗИ) и производить забор материала из полости матки с последующим цитологическим исследованием в качестве возможного алгоритма исследования состояния эндометрия [35].…”

“…Гинекологический скрининг должен проводится с 35-летнего возраста и включать ежегодную биопсию эндометрия для выявления заболевания на ранних стадиях [26,29]. Нет данных об эффективности и необходимости скрининга РЭ у женщин, страдающих ненаследственными формами колоректального рака [12,43].…”