Ito Satoko, Xicola Rosa M, Sra Manraj, Potnis Kunal C, Singh Vinit, Gershkovich Peter, Stites Edward, Gibson Joanna, Krumholz Harlan M, Llor Xavier, Goshua George
Section of Medical Oncology and Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut.
Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
Clin Gastroenterol Hepatol. 2025 Apr 30. doi: 10.1016/j.cgh.2025.03.006.
BACKGROUND & AIMS: Testing all colorectal cancers (CRCs) for mismatch repair status to evaluate for Lynch syndrome (LS) has been recommended for years. Owing to attrition in the multistep diagnostic testing pathway, most qualifying patients still do not receive genetic testing for LS. This leads to missed diagnoses and preventable cancer incidence. To tackle this, we previously reported a systems approach that resulted in a dramatic increase in the identification of patients with LS. We aim to evaluate the cost-effectiveness of this intervention compared with both real-world pre-intervention experience and with upfront germline testing of all CRC probands.
We employed data from the Prospective Lynch Syndrome Database, the National Cancer Institute Surveillance, Epidemiology, and End Results program, and pre-/post-intervention cohort studies to build lifetime Markov cohorts of CRC probands, testing 3 strategies: (1) current standard-of-care; (2) optimized standard-of-care; and (3) upfront germline testing. The primary outcome was the incremental cost-effectiveness ratio (ICER) in $ per quality-adjusted life-year (QALY) from the United States health system perspective.
Strategies #1 to #3 accrued 11.97, 11.98, and 11.99 discounted QALYs at discounted costs of $100,610, $100,980, and $102,290, respectively. The pairwise ICERs on the frontier were $34,500/QALY (95% credible interval [CI], $28,400-$44,200) and $98,500/QALY (95% CI, $73,700-$216,000), respectively. The cost-effectiveness of #3 vs #1 was $70,300/QALY (95% CI, $54,600-$92,500). Current standard-of-care was favored in 0.0% of 10,000 Monte Carlo iterations.
Current clinical practice is cost-ineffective. Prospective intervention to dramatically increase LS testing (ie, to reach a threshold of >75%) or, if this level cannot be reached, upfront germline testing are cost-effective interventions that improve quality-adjusted life expectancy.
多年来一直建议对所有结直肠癌（CRC）进行错配修复状态检测，以评估林奇综合征（LS）。由于多步骤诊断检测流程中的损耗，大多数符合条件的患者仍未接受LS的基因检测。这导致诊断遗漏和可预防的癌症发病率上升。为了解决这个问题，我们之前报告了一种系统方法，该方法显著增加了LS患者的识别率。我们旨在评估这种干预措施与实际干预前经验以及对所有CRC先证者进行 upfront 种系检测相比的成本效益。
我们使用了前瞻性林奇综合征数据库、美国国立癌症研究所监测、流行病学和最终结果计划以及干预前后队列研究的数据，构建了CRC先证者的终生马尔可夫队列，测试了3种策略：（1）当前的标准治疗；（2）优化的标准治疗；（3） upfront 种系检测。主要结局是从美国卫生系统角度计算的每质量调整生命年（QALY）的增量成本效益比（ICER）。
策略1至3分别产生了11.97、11.98和11.99个贴现QALY，贴现成本分别为100,610美元、100,980美元和102,290美元。前沿上的两两ICER分别为34,500美元/QALY（95%可信区间[CI]，28,400 - 44,200美元）和98,500美元/QALY（95%CI，73,700 - 216,000美元）。策略3与策略1相比的成本效益为70,300美元/QALY（95%CI，54,600 - 92,500美元）。在10,000次蒙特卡洛迭代中，0.0%的结果支持当前的标准治疗。
当前的临床实践成本效益不佳。大幅增加LS检测的前瞻性干预措施（即达到>75%的阈值），或者如果无法达到该水平，则进行 upfront 种系检测，是具有成本效益的干预措施，可提高质量调整后的预期寿命。
