Cancer Research Division, Cancer Council New South Wales, Sydney, NSW.
Institute of Medical Genetics, University Hospital of Wales, Cardiff, United Kingdom.
Med J Aust. 2020 Feb;212(2):72-81. doi: 10.5694/mja2.50356. Epub 2019 Oct 8.
To evaluate the health impact and cost-effectiveness of systematic testing for Lynch syndrome (LS) in people with incident colorectal cancer (CRC) in Australia.
DESIGN, SETTING, PARTICIPANTS: We investigated the impact of LS testing strategies in a micro-simulation model (Policy1-Lynch), explicitly modelling the cost of testing all patients diagnosed with incident CRC during 2017, with detailed modelling of outcomes for patients identified as LS carriers (probands) and their at-risk relatives throughout their lifetimes. For people with confirmed LS, we modelled ongoing colonoscopic surveillance.
Cost-effectiveness of six universal tumour testing strategies (testing for DNA mismatch repair deficiencies) and of universal germline gene panel testing of patients with incident CRC; impact on cost-effectiveness of restricting testing by age at CRC diagnosis (all ages, under 50/60/70 years) and of colonoscopic surveillance interval (one, two years).
The cost-effectiveness ratio of universal tumour testing strategies (annual colonoscopic surveillance, no testing age limit) compared with no testing ranged from $28 915 to $31 904/life-year saved (LYS) (indicative willingness-to-pay threshold: $30 000-$50 000/LYS). These strategies could avert 184-189 CRC deaths with an additional 30 597-31 084 colonoscopies over the lifetimes of 1000 patients with incident CRC with LS and 1420 confirmed LS carrier relatives (164-166 additional colonoscopies/death averted). The most cost-effective strategy was immunohistochemistry and BRAF V600E testing (incremental cost-effectiveness ratio [ICER], $28 915/LYS). Universal germline gene panel testing was not cost-effective compared with universal tumour testing strategies (ICER, $2.4 million/LYS). Immunohistochemistry and BRAF V600E testing was cost-effective at all age limits when paired with 2-yearly colonoscopic surveillance (ICER, $11 525-$32 153/LYS), and required 4778-15 860 additional colonoscopies to avert 46-181 CRC deaths (88-103 additional colonoscopies/death averted).
Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective.
评估在澳大利亚对新发结直肠癌（CRC）患者进行林奇综合征（LS）系统检测的健康影响和成本效益。
设计、地点、参与者：我们在一个微观模拟模型（Policy1-Lynch）中研究了 LS 检测策略的影响，该模型明确地对 2017 年所有新发 CRC 患者的检测成本进行建模，对确定为 LS 携带者（先证者）及其高危亲属的患者的终生结局进行详细建模。对于确诊为 LS 的患者，我们对持续的结肠镜监测进行了建模。
六种通用肿瘤检测策略（检测 DNA 错配修复缺陷）和对新发 CRC 患者进行通用种系基因谱检测的成本效益；通过 CRC 诊断时的年龄（所有年龄、<50/60/70 岁）和结肠镜监测间隔（1 年、2 年）限制检测对成本效益的影响。
与不检测相比，通用肿瘤检测策略（每年结肠镜监测，无检测年龄限制）的成本效益比为 28915 美元至 31904 美元/生命年（LYS）（表示意愿支付阈值：30000 美元至 50000 美元/ LYS）。这些策略可以在 1000 名患有 LS 和 1420 名确诊 LS 携带者亲属的新发 CRC 患者的一生中避免 184-189 例 CRC 死亡，并增加 30597-31084 次结肠镜检查（每例额外 164-166 次结肠镜检查/避免死亡）。最具成本效益的策略是免疫组织化学和 BRAF V600E 检测（增量成本效益比 [ICER]，28915 美元/ LYS）。与通用肿瘤检测策略相比，通用种系基因谱检测不具有成本效益（ICER，240 万美元/ LYS）。当与 2 年一次的结肠镜监测相结合时，免疫组织化学和 BRAF V600E 检测在所有年龄限制下均具有成本效益（ICER，11525 美元至 32153 美元/ LYS），需要进行 4778-15860 次额外的结肠镜检查，以避免 46-181 例 CRC 死亡（88-103 例额外结肠镜检查/避免死亡）。
与不检测相比，澳大利亚对新发 CRC 患者进行 LS 指导种系基因检测的通用肿瘤检测策略可能具有成本效益。通用种系基因谱检测目前不具有成本效益。
