Projecting Benefits and Harms of Novel Cancer Screening Biomarkers: A Study of PCA3 and Prostate Cancer.
Projecting Benefits and Harms of Novel Cancer Screening Biomarkers: A Study of PCA3 and Prostate Cancer.
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DOI：
10.1158/1055-9965.epi-14-1224
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发表时间：
2015-04
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影响因子：
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通讯作者：
Etzioni R
中科院分区：
文献类型：
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作者：
Birnbaum JK;Feng Z;Gulati R;Fan J;Lotan Y;Wei JT;Etzioni R
用于癌症早期检测的新生物标记物必须经过几个发展阶段。早期阶段提供了关于诊断特性的信息，但没有提供关于总体益处和危害的信息。前列腺癌抗原3(PCA3)是一种很有前途的前列腺癌生物标志物，但仍处于早期开发阶段。我们使用模拟模型来预测PCA3加入前列腺特异性抗原(PSA)筛查对美国前列腺癌检测和死亡率的影响。我们使用了最近一项关于PCA3在男性前列腺活检中的研究数据，以扩展现有的PSA增长、疾病进展和生存的模拟模型。我们指定了几种PSA-PCA3策略，旨在提高特异性和减少过度诊断。使用这些策略对年龄在50岁到74岁之间的男性进行两年一次的筛查，我们预测与基于PSA的策略相比，真阳性和假阳性测试、过度诊断和挽救的生命相比，活组织检查转诊的临界值为4.0 ng/ml。我们确定了几种PSA-PCA3策略，这些策略大大减少了假阳性检测和过度诊断，同时保留了大多数获救的生命。对于PSA在4.0到10.0 ng/ml之间的男性，PCA3>；35用于活检转诊保留了85%的生命，同时将假阳性减少了大约一半，并将过度诊断减少了25%。将PCA3添加到PSA筛查可以显著减少不良筛查结果。与基于PSA的筛查相比，可以确定保存大部分获救生命的策略。模拟模型提供了对新的筛查生物标志物的群体结果的提前预测，并可能有助于指导早期检测研究。
New biomarkers for early detection of cancer must pass through several phases of development. Early phases provide information on diagnostic properties but not on population benefits and harms. Prostate cancer antigen 3 (PCA3) is a promising prostate cancer biomarker still in early development. We use simulation modeling to project the impact of adding PCA3 to prostate-specific antigen (PSA) screening on prostate cancer detection and mortality in the United States. We used data from a recent study of PCA3 in men referred for prostate biopsy to extend an existing simulation model of PSA growth, disease progression and survival. We specified several PSA-PCA3 strategies designed to improve specificity and reduce overdiagnosis. Using these strategies to screen a cohort of men biennially between ages 50 and 74, we projected true and false positive tests, overdiagnoses, and lives saved relative to a PSA-based strategy with a cutoff of 4.0 ng/ml for biopsy referral. We identified several PSA-PCA3 strategies that substantially reduced false positive tests and overdiagnoses while preserving the majority of lives saved. PCA3>35 for biopsy referral in men with PSA between 4.0 and 10.0 ng/ml retained 85% of lives saved while approximately halving false positives and reducing overdiagnoses by 25%. Adding PCA3 to PSA screening can significantly reduce adverse screening outcomes. Strategies can be identified that preserve most of the lives saved relative to PSA-based screening. Simulation modeling provides advance projections of population outcomes of new screening biomarkers and may help guide early detection research.