多癌早期检测（MCED）试验的积极结果需要确认性诊断工作。在诊断过程中，包括初始确认性测试未能提供确定性诊断的情况下，残留癌症风险（RR）被建模。采用决策树框架来建模患者通过确认性诊断选项和结果的条件性风险。在假设癌症信号检测（即阳性MCED测试结果）已经导致从筛查转变为诊断，并从阳性结果开始的情况下进行诊断旅程，初始化阳性预测值（PPV）。首先评估最可能（顶部）预测的癌症信号来源（CSO），然后是第二可能预测的CSO。在假设顶部和第二个预测的CSO都各自被定向确认性测试后，为每个后续场景估计了RR。对于具有典型性能特征建模的初始MCED测试结果（PPV，40％；顶部预测的CSO准确性，90％），在负面初始确认性测试（敏感性，70％，90％或100％）后，RR范围从6％至20％。在第二次确认性测试后（准确性为50％），第二预测的CSO仍然与国家卫生和社会保险理事会建议的对症状个体进行调查的癌症风险阈值（3％）相比，仍然提供了显著的RR（3％至18％）。在MCED测试的40％PPV和确认性测试的90％特异性的情况下，完成一或两次确认性测试后的偶然发现风险分别为6％和12％。这些结果可以说明阳性MCED测试对后续决策的影响。 © 2023年作者。 Wiley Periodicals LLC出版的《癌症》代表美国癌症协会。

Positive results of a multi-cancer early detection (MCED) test require confirmatory diagnostic workup. Here, residual current cancer risk (RR) during the process of diagnostic resolution, including situations where the initial confirmatory test does not provide resolution, was modeled.A decision-tree framework was used to model conditional risk in a patient's journey through confirmatory diagnostic options and outcomes. The diagnostic journey assumed that cancer signal detection (a positive MCED test result) had already led to a transition from screening to diagnosis and began with an initial positive predictive value (PPV) from the positive result. Evaluation of a most probable (top) predicted cancer signal origin (CSO) and then a second-most probable predicted CSO followed. Under the assumption that the top- and second-predicted CSOs were each followed by a targeted confirmatory test, the RR was estimated for each subsequent scenario.For an initial MCED test result with typical performance characteristics modeled (PPV, 40%; top-predicted CSO accuracy, 90%), after a negative initial confirmatory test (sensitivity, 70%, 90%, or 100%) the RR ranged from 6% to 20%. A second-predicted CSO (accuracy, 50%), after a negative second confirmatory test, still provided a significant RR (3%-18%) in comparison with the National Institute for Health and Care Excellence-recommended cancer risk threshold warranting investigation in symptomatic individuals (3%). With a 40% PPV for an MCED test and 90% specificity for a confirmatory test, the risk of incidental findings after one or two confirmatory tests was 6% and 12%, respectively.These results may illustrate the impact of a positive MCED test on follow-up decision-making.© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.