Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Aug 30;14(8):e0221419.
doi: 10.1371/journal.pone.0221419. eCollection 2019.

Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting

Tristan M Snowsill  1 , Neil A J Ryan  2   3 , Emma J Crosbie  2   4 , Ian M Frayling  5 , D Gareth Evans  3   6 , Chris J Hyde  7
Affiliations

Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting

Tristan M Snowsill et al. PLoS One. .

Abstract

Background: Lynch syndrome is a hereditary cancer syndrome caused by constitutional pathogenic variants in the DNA mismatch repair (MMR) system, leading to increased risk of colorectal, endometrial and other cancers. The study aimed to identify the incremental costs and consequences of strategies to identify Lynch syndrome in women with endometrial cancer.

Methods: A decision-analytic model was developed to evaluate the relative cost-effectiveness of reflex testing strategies for identifying Lynch syndrome in women with endometrial cancer taking the NHS perspective and a lifetime horizon. Model input parameters were sourced from various published sources. Consequences were measured using quality-adjusted life years (QALYs). A cost-effectiveness threshold of £20 000/QALY was used.

Results: Reflex testing for Lynch syndrome using MMR immunohistochemistry and MLH1 methylation testing was cost-effective versus no testing, costing £14 200 per QALY gained. There was uncertainty due to parameter imprecision, with an estimated 42% chance this strategy is not cost-effective compared with no testing. Age had a significant impact on cost-effectiveness, with testing not predicted to be cost-effective in patients aged 65 years and over.

Conclusions: Testing for Lynch syndrome in younger women with endometrial cancer using MMR immunohistochemistry and MLH1 methylation testing may be cost-effective. Age cut-offs may be controversial and adversely affect implementation.

PubMed Disclaimer

Conflict of interest statement

IMF is an Honorary Medical Advisor to Lynch Syndrome UK and reports support from St Vincent’s University Hospital (Dublin), Impact Genetics (Bowmanville, Ontario, Canada), and Ambry Genetics (Aliso Viejo, CA, USA), for travel, outside the submitted work. Other authors declare no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Conceptual decision tree for probands.
Key: FH, family history; LS, Lynch syndrome; PLS, putative Lynch syndrome.
Fig 2
Fig 2. Simplified model diagram for long-term outcomes.
Key: CRC, colorectal cancer. Future EC incidence was not included because all probands have already had EC and the vast majority have had a hysterectomy. Female relatives with LS are at risk of EC, but as a simplifying assumption this was not included.
Fig 3
Fig 3. Cost-effectiveness acceptability curve from probabilistic sensitivity analysis.
Key: IHC, immunohistochemistry; MSI, microsatellite instability (testing); QALY, quality-adjusted life year.
Fig 4
Fig 4. Tornado diagram of one-way sensitivity analysis.
Key: IHC, immunohistochemistry; INMB, incremental net monetary benefit (presented per proband); QALY, quality-adjusted life years; WTP, willingness-to-pay; S5 Appendix gives details of all parameter abbreviations. Notes: Only includes parameters with INMB range ≥ 1% of maximum INMB range.
See this image and copyright information in PMC

References

    1. Vasen HF, Blanco I, Aktan-Collan K, Gopie JP, Alonso A, Aretz S, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013;62(6):812–23. Epub 2013/02/15. 10.1136/gutjnl-2012-304356 - DOI - PMC - PubMed
    1. Hampel H, de la Chapelle A. The search for unaffected individuals with Lynch syndrome: do the ends justify the means? Cancer Prev Res (Phila). 2011;4(1):1–5. Epub 2011/01/06. 10.1158/1940-6207.CAPR-10-0345 - DOI - PMC - PubMed
    1. Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, et al. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev. 2017;26(3):404–12. Epub 2016/11/02. 10.1158/1055-9965.EPI-16-0693 - DOI - PMC - PubMed
    1. Snowsill T, Coelho H, Huxley N, Jones-Hughes T, Briscoe S, Frayling IM, et al. Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation. Health Technol Assess. 2017;21(51):1–238. Epub 2017/09/13. 10.3310/hta21510 - DOI - PMC - PubMed
    1. Snowsill T, Huxley N, Hoyle M, Jones-Hughes T, Coelho H, Cooper C, et al. A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome. Health Technol Assess. 2014;18(58):1–406. Epub 2014/09/23. 10.3310/hta18580 - DOI - PMC - PubMed

Publication types

MeSH terms