A Quantitative Framework to Study Potential Benefits and Harms of Multi-Cancer Early Detection Testing.
A Quantitative Framework to Study Potential Benefits and Harms of Multi-Cancer Early Detection Testing.
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DOI：
10.1158/1055-9965.epi-21-0380
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Etzioni R
中科院分区：
文献类型：
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作者：
Jiao B;Gulati R;Katki HA;Castle PE;Etzioni R
多种癌症测试可以通过一次抽血来筛查多种癌症，但对潜在的人群影响知之甚少。我们制定了数学表达式的预期人数暴露于不必要的确认测试（EUC），癌症检测（CD），并挽救了生命（LS）的测试性能，疾病发病率和死亡率，以及死亡率降低。我们将结直肠癌、肝癌、肺癌、卵巢癌和胰腺癌加入到乳腺癌的检测中，使用未来5年的发病率来估计50岁、60岁或70岁的患病率，并使用监测、流行病学和最终结果登记处15年内癌症死亡的相应概率来估计死亡率。EUC主要由特异性决定。对于特定的特异性，EUC/CD对高患病率的癌症最有利。在99%的特异性和敏感性下，50岁时乳腺+肺的EUC/CD为1.1，而乳腺+肝的EUC/CD为1.3。在与筛查相关的常见死亡率降低下，当检测包括死亡率较高的癌症时，EUC/CD最有利（例如，50岁时乳腺癌+肺癌为19.9，乳腺癌+肝癌为30.4，假设死亡率降低10%）。已公布的多种癌症检测结果表明，EUC与CD之间存在有利的权衡，然而，不必要的确认的全部负担将取决于检测后的检查方案。如果测试优先考虑存在治愈性治疗的更普遍和/或致命的癌症，则将改善危害-效益权衡。多癌检测对人群的影响不仅取决于检测结果，还取决于疾病特征和早期治疗的效果。
Multi-cancer tests offer screening for multiple cancers with one blood draw, but the potential population impact is poorly understood. We formulate mathematical expressions for expected numbers of individuals exposed to unnecessary confirmation tests (EUC), cancers detected (CD), and lives saved (LS) given test performance, disease incidence and mortality, and mortality reduction. We add colorectal, liver, lung, ovary, and pancreatic cancer to a test for breast cancer, approximating prevalence at ages 50, 60, or 70 using incidence over the next 5 years and mortality using corresponding probabilities of cancer death over 15 years in the Surveillance, Epidemiology, and End Results registry. EUC is overwhelmingly determined by specificity. For a given specificity, EUC/CD is most favorable for higher-prevalence cancers. Under 99% specificity and sensitivities as published for a 50-cancer test, EUC/CD is 1.1 for breast+lung versus 1.3 for breast+liver at age 50. Under a common mortality reduction associated with screening, EUC/CD is most favorable when the test includes higher-mortality cancers (e.g., 19.9 for breast+lung versus 30.4 for breast+liver at age 50 assuming a common 10% mortality reduction). Published multi-cancer test performance suggests a favorable tradeoff of EUC to CD, yet the full burden of unnecessary confirmations will depend on the post-test work-up protocol. Harm-benefit tradeoffs will be improved if tests prioritize more prevalent and/or lethal cancers for which curative treatments exist. The population impact of multi-cancer testing will depend not only on test performance but also on disease characteristics and efficacy of early treatment.