Department of Woman and Child Health and Public Health-Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.
Università Cattolica del Sacro Cuore, Alta Scuola di Economia e Management dei Sistemi Sanitari (ALTEMS), Roma, Italia.
PLoS One. 2020 Jul 1;15(7):e0235038. doi: 10.1371/journal.pone.0235038. eCollection 2020.
Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the "no testing" strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that "universal testing" versus "no testing" is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy.
林奇综合征（LS）是一种常染色体显性疾病，由错配修复（MMR）基因的致病性变异引起，使个体易患多种恶性肿瘤，如结直肠癌（CRC）和子宫内膜癌。目前的指南建议对新诊断的 CRC 患者进行 LS 检测，以降低亲属的癌症发病率和死亡率。然而，意大利没有支持这种方法的经济评估。我们开发了一种决策分析模型，从意大利国家卫生系统的角度分析 LS 筛查的成本效益。分析了三种测试策略：不进行肿瘤分析而直接对所有 MMR 基因进行测序（策略 1）、进行免疫组化和多重连接探针扩增分析（MS-MLPA）的顺序分析（策略 2）和针对年龄的策略，对 70 岁以上的患者在免疫组化和甲基化特异性 MLPA 之前进行修订后的贝塞斯达标准评估（策略 3），并与“不进行测试”策略进行比较。通过马尔可夫模型估计结肠镜检查后、阿司匹林预防和强化妇科监测后亲属的质量调整生命年（QALY）。假设 CRC 发病率为 0.09%，LS 患者的比例为 2.81%，则在给定年份，根据所采用的测试策略，CRC 病例中检测到的致病性变异数量在 910 到 1167 之间变化。对于整个合格人群（CRC 患者）进行一次性检测的测试策略，总成本在 1753059.93 欧元至 10388000.00 欧元之间。马尔可夫模型的增量成本效益比范围为 941.24 欧元/QALY 至 1681.93 欧元/QALY，这表明“普遍检测”与“不检测”具有成本效益，但与针对年龄的策略相比不一定具有成本效益。这是意大利关于 LS 不同测试策略的首次经济评估。结果可能支持为意大利 LS 筛查引入具有成本效益的建议。
