The Daffodil Centre, The University of Sydney, A Joint Venture With Cancer Council NSW, Sydney, New South Wales, Australia.
The Daffodil Centre, The University of Sydney, A Joint Venture With Cancer Council NSW, Sydney, New South Wales, Australia.
Genet Med. 2022 Sep;24(9):1831-1846. doi: 10.1016/j.gim.2022.05.016. Epub 2022 Jul 9.
Lynch syndrome-related colorectal cancer (CRC) risk substantially varies by mismatch repair (MMR) gene. We evaluated the health impact and cost-effectiveness of MMR gene-tailored colonoscopic surveillance.
We first estimated sex- and MMR gene-specific cumulative lifetime risk of first CRC without colonoscopic surveillance using an optimization algorithm. Next, we harnessed these risk estimates in a microsimulation model, "Policy1-Lynch," and compared 126 colonoscopic surveillance strategies against no surveillance.
The most cost-effective strategy was 3-yearly surveillance from age 25 to 70 years (pathogenic variants [path_] in MLH1 [path_MLH1], path_MSH2) with delayed surveillance for path_MSH6 (age 30-70 years) and path_PMS2 (age 35-70 years) heterozygotes (incremental cost-effectiveness ratio = Australian dollars (A) $8,833/life-year saved). This strategy averted 60 CRC deaths (153 colonoscopies per death averted) over the lifetime of 1000 confirmed patients with Lynch syndrome (vs no surveillance). This also reduced colonoscopies by 5% without substantial change in health outcomes (vs nontailored 3-yearly surveillance from 25-70 years). Generally, starting surveillance at age 25 (vs 20) years was more cost-effective with minimal effect on life-years saved and starting 5 to 10 years later for path_MSH6 and path_PMS2 heterozygotes (vs path_MLH1 and path_MSH2) further improved cost-effectiveness. Surveillance end age (70/75/80 years) had a minor effect. Three-yearly surveillance strategies were more cost-effective (vs 1 or 2-yearly) but prevented 3 fewer CRC deaths.
MMR gene-specific colonoscopic surveillance would be effective and cost-effective.
林奇综合征相关结直肠癌（CRC）的风险在很大程度上因错配修复（MMR）基因而异。我们评估了 MMR 基因定制结肠镜监测的健康影响和成本效益。
我们首先使用优化算法估计了在没有结肠镜监测的情况下，按性别和 MMR 基因特异性计算的首次 CRC 的终生累积风险。接下来，我们利用这些风险估计值在一个微模拟模型“Policy1-Lynch”中，比较了 126 种结肠镜监测策略与无监测策略。
最具成本效益的策略是从 25 岁到 70 岁每 3 年进行一次监测（MLH1 中的致病性变异[path_MLH1]、path_MSH2），对 path_MSH6（30-70 岁）和 path_PMS2（35-70 岁）杂合子进行延迟监测（增量成本效益比为澳大利亚元（A）$8833/生命年节省）。这种策略在 1000 名确诊为林奇综合征的患者的一生中避免了 60 例 CRC 死亡（每例死亡避免 153 次结肠镜检查）。与无监测相比，这也减少了 5%的结肠镜检查，而对健康结果没有实质性改变（与 25-70 岁的非定制 3 年一次的监测相比）。一般来说，与 20 岁相比，从 25 岁开始进行监测更具成本效益，对节省生命年的影响最小，而对于 path_MSH6 和 path_PMS2 杂合子（与 path_MLH1 和 path_MSH2 相比）晚 5-10 年开始监测进一步提高了成本效益。监测结束年龄（70/75/80 岁）的影响较小。每 3 年进行一次的监测策略更具成本效益（与每年 1 次或 2 次相比），但可预防 3 例 CRC 死亡。
MMR 基因特异性结肠镜监测将是有效和具有成本效益的。
