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

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.

背景
林奇综合征（Lynch syndrome）是一类由DNA错配修复（DNA mismatch repair, MMR）系统胚系致病变异引发的遗传性癌症综合征，会提升结直肠癌、子宫内膜癌及其他癌症的发病风险。本研究旨在明确针对子宫内膜癌女性患者开展林奇综合征筛查的各类策略的增量成本与结局。

方法
本研究从英国国民保健服务（National Health Service, NHS）视角出发，以终身随访为时限，构建决策分析模型，用于评估针对子宫内膜癌女性患者开展林奇综合征筛查的反射式检测策略的相对成本效用。模型输入参数源自各类已发表文献。结局采用质量调整生命年（quality-adjusted life years, QALYs）进行衡量，本次研究采用的成本效用阈值为20000英镑每质量调整生命年。

结果
相较于未开展筛查的策略，采用DNA错配修复免疫组化及MLH1甲基化检测的林奇综合征反射式筛查具备成本效用，每获得1个质量调整生命年的成本为14200英镑。本研究存在因参数不精确性带来的不确定性：相较于未筛查策略，该策略不具备成本效用的概率约为42%。年龄对成本效用具有显著影响，65岁及以上患者群体的筛查策略未被预测具备成本效用。

结论
针对子宫内膜癌年轻女性患者，采用DNA错配修复免疫组化及MLH1甲基化检测开展林奇综合征筛查或具备成本效用。年龄界值的设定或引发争议，并对筛查的实施产生不利影响。