Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
J Gastroenterol Hepatol. 2018 Oct;33(10):1737-1744. doi: 10.1111/jgh.14154. Epub 2018 May 17.
Individuals with Lynch syndrome (LS) are at increased risk of LS-related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost-effectiveness has not been assessed. We aim to determine the cost-effectiveness of screening individuals with CRC for LS at different age-at-diagnosis thresholds.
We developed a decision analysis model to estimate yield and costs of LS screening. Age-specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1-Pathway) or BRAF V600E testing (BRAF-Pathway) if MLH1 expression was lost) for four age-at-diagnosis thresholds-screening < 50, screening < 60, screening < 70, and universal screening.
Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1-Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF-Pathway identified the same number of LS cases for higher costs.
The MLH1-Pathway is more cost-effective than BRAF-Pathway for all age-at-diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.
林奇综合征（LS）患者罹患 LS 相关癌症（包括结直肠癌[CRC]）的风险增加。澳大利亚建议对 CRC 患者进行错配修复（MMR）缺陷检测以筛查 LS，但尚未评估其成本效益。我们旨在确定不同诊断年龄阈值下对 CRC 患者进行 LS 筛查的成本效益。
我们开发了一项决策分析模型，以评估 LS 筛查的效果和成本。基于澳大利亚数据，确定了各年龄组 LS 诊断概率。评估了两种 CRC 肿瘤筛查途径（如果 MLH1 表达缺失，则进行 MMR 免疫组化，随后进行 MLH1 甲基化（MLH1 途径）或 BRAF V600E 检测（BRAF 途径）），用于四个诊断年龄阈值-筛查<50 岁、筛查<60 岁、筛查<70 岁和普遍筛查。
每 1000 例 CRC 病例中，筛查<50 岁可发现 5.2 例 LS 病例，在 MLH1 途径中每发现 1 例 LS 病例的成本为 7041 澳元。筛查<60 岁可增加 1.5 例 LS 病例的检出率，每增加 1 例 LS 病例的额外成本为 25177 澳元。筛查<70 岁可额外检出 1.6 例 LS 病例，每增加 1 例 LS 病例的额外成本为 40278 澳元。与筛查<70 岁相比，普遍筛查并未发现更多的 LS 病例，但额外花费 158724 澳元。BRAF 途径在所有诊断年龄阈值下的成本效益均低于 MLH1 途径。对诊断为 CRC 且年龄<70 岁的个体进行 MMR 免疫组化肿瘤筛查可在合理的成本下提高 LS 病例的检出率。需要进一步研究 CRC 患者≥70 岁的 LS 筛查效果，以确定是否有必要进行普遍筛查。
