A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients
Background: Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. Methods: A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. Results: All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh the health benefits of testing, resulting in overall QALY loss. Conclusions: Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is predicted to be a cost-effective use of limited financial resources in England and Wales. Research is recommended into the cost-effectiveness of reflex testing for Lynch syndrome in other associated cancers and into the impact of prophylactic H-BSO on HRQoL.
Citation
@article{t.2015,
author = {Snowsill, T. and Huxley, N. and Hoyle, M. and Jones-Hughes,
T. and Coelho, H. and Cooper, C. and Frayling, I. and Hyde, C.},
title = {A Model-Based Assessment of the Cost-Utility of Strategies to
Identify {Lynch} Syndrome in Early-Onset Colorectal Cancer Patients},
journal = {BMC Cancer},
volume = {15},
pages = {313},
date = {2015-01-01},
url = {https://tristansnowsill.co.uk/a-model-based-assessment-of-the-cost-utility-of-strategies.html},
doi = {10.1186/s12885-015-1254-5},
langid = {en},
abstract = {Background: Lynch syndrome is an autosomal dominant cancer
predisposition syndrome caused by mutations in the DNA mismatch
repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch
syndrome have an increased risk of colorectal cancer, endometrial
cancer, ovarian and other cancers. Lynch syndrome remains
underdiagnosed in the UK. Reflex testing for Lynch syndrome in
early-onset colorectal cancer patients is proposed as a method to
identify more families affected by Lynch syndrome and offer
surveillance to reduce cancer risks, although cost-effectiveness is
viewed as a barrier to implementation. The objective of this project
was to estimate the cost-utility of strategies to identify Lynch
syndrome in individuals with early-onset colorectal cancer in the
NHS. Methods: A decision analytic model was developed which
simulated diagnostic and long-term outcomes over a lifetime horizon
for colorectal cancer patients with and without Lynch syndrome and
for relatives of those patients. Nine diagnostic strategies were
modelled which included microsatellite instability (MSI) testing,
immunohistochemistry (IHC), BRAF mutation testing (methylation
testing in a scenario analysis), diagnostic mutation testing and
Amsterdam II criteria. Biennial colonoscopic surveillance was
included for individuals diagnosed with Lynch syndrome and accepting
surveillance. Prophylactic hysterectomy with bilateral
salpingo-oophorectomy (H-BSO) was similarly included for women
diagnosed with Lynch syndrome. Costs from NHS and Personal Social
Services perspective and quality-adjusted life years (QALYs) were
estimated and discounted at 3.5\% per annum. Results: All strategies
included for the identification of Lynch syndrome were
cost-effective versus no testing. The strategy with the greatest net
health benefit was MSI followed by BRAF followed by diagnostic
genetic testing, costing £5,491 per QALY gained over no testing. The
effect of prophylactic H-BSO on health-related quality of life
(HRQoL) is uncertain and could outweigh the health benefits of
testing, resulting in overall QALY loss. Conclusions: Reflex testing
for Lynch syndrome in early-onset colorectal cancer patients is
predicted to be a cost-effective use of limited financial resources
in England and Wales. Research is recommended into the
cost-effectiveness of reflex testing for Lynch syndrome in other
associated cancers and into the impact of prophylactic H-BSO on
HRQoL.}
}