Background: Multi-cancer tests offer screening for multiple cancers with one blood draw, but the potential population impact is poorly understood. Methods: We formulate mathematical expressions for expected numbers of: (i) individuals exposed to unnecessary confirmation tests (EUC), (ii) cancers detected (CD), and (iii) 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. Results: 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/LS> is most favorable when the test includes higher mortality cancers (e.g., 19.9 for breast + lung vs. 30.4 for breast + liver at age 50 assuming a common 10% mortality reduction). Conclusions: Published multi-cancer test performance suggests a favorable tradeoff of EUC to CD, yet the full burden of unnecessary confirmations will depend on the posttest work-up protocol. Harm–benefit tradeoffs will be improved if tests prioritize more prevalent and/or lethal cancers for which curative treatments exist. Impact: The population impact of multi-cancer testing will depend not only on test performance but also on disease characteristics and efficacy of early treatment. See related commentary by Duffy and Sasieni, [p. 3][1] [1]: /lookup/volpage/31/3?iss=1

中文翻译：

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研究多癌早期检测潜在益处和危害的定量框架

背景：多癌症检测通过一次抽血即可筛查多种癌症，但人们对潜在的人群影响知之甚少。方法：我们制定了预期数量的数学表达式：(i) 暴露于不必要的确认测试 (EUC) 的个体，(ii) 检测到的癌症 (CD)，以及 (iii) 鉴于测试性能、疾病发病率和死亡率而挽救的生命 (LS) ，并降低死亡率。我们将结直肠癌、肝癌、肺癌、卵巢癌和胰腺癌添加到乳腺癌检测中，使用未来 5 年的发病率和死亡率使用 15 年内相应的癌症死亡概率来估算 50、60 或 70 岁时的患病率。监测、流行病学和最终结果登记。结果：EUC 绝大多数是由特异性决定的。对于给定的特异性，EUC/CD 最有利于高患病率的癌症。在 50 岁癌症检测公布的 99% 特异性和敏感性下，50 岁时，EUC/CD 对乳腺 + 肺为 1.1，而对乳腺 + 肝为 1.3。根据与筛查相关的常见死亡率降低，EUC/LS> 是最有利的当测试包括死亡率较高的癌症时（例如，在 50 岁时，乳腺癌 + 肺癌为 19.9，而乳腺癌 + 肝癌为 30.4，假设死亡率普遍降低 10%）。结论：已发表的多癌检测性能表明 EUC 与 CD 的折衷是有利的，但不必要的确认的全部负担将取决于后测工作协议。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，则危害利益权衡将得到改善。影响：多癌检测对人群的影响不仅取决于检测性能，还取决于疾病特征和早期治疗的疗效。见 Duffy 和 Sasieni 的相关评论，[p. 3][1][1]：/lookup/volpage/31/3?iss=1