1 Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA.
2 Program in Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Stat Methods Med Res. 2019 Apr;28(4):1261-1271. doi: 10.1177/0962280217754232. Epub 2018 Feb 5.
Cancer screening can detect cancer that would not have been detected in a patient's lifetime without screening. Standard methods for analyzing screening data do not explicitly account for the possibility that a fraction of tumors may remain latent indefinitely. We extend these methods by representing cancers as a mixture of those that progress to symptoms (progressive) and those that remain latent (indolent). Given sensitivity of the screening test, we derive likelihood expressions to simultaneously estimate (1) the rate of onset of preclinical cancer, (2) the average preclinical duration of progressive cancers, and (3) the fraction of preclinical cancers that are indolent. Simulations demonstrate satisfactory performance of the estimation approach to identify model parameters subject to precise specifications of input parameters and adequate numbers of interval cancers. In application to four breast cancer screening trials, the estimated indolent fraction among preclinical cancers varies between 2% and 35% when assuming 80% test sensitivity and varying specifications for the earliest time that participants could plausibly have developed cancer. We conclude that standard methods for analyzing screening data can be extended to allow some indolent cancers, but accurate estimation depends on correctly specifying key inputs that may be difficult to determine precisely in practice.
癌症筛查可以检测到在没有筛查的情况下患者一生中都无法检测到的癌症。分析筛查数据的标准方法并没有明确考虑到一部分肿瘤可能无限期潜伏的可能性。我们通过将癌症表示为进展到症状（进行性）和潜伏（惰性）的肿瘤的混合物来扩展这些方法。考虑到筛查测试的敏感性，我们推导出似然表达式，以同时估计（1）临床前癌症的发病速度，（2）进行性癌症的平均临床前持续时间，以及（3）潜伏的临床前癌症的比例。模拟表明，该估计方法在识别模型参数方面具有令人满意的性能，这些参数受到输入参数的精确规范和足够数量的间隔性癌症的限制。在对四项乳腺癌筛查试验的应用中，当假设 80%的测试敏感性和参与者可能最早发生癌症的不同规范时，临床前癌症中的惰性比例在 2%到 35%之间变化。我们得出的结论是，分析筛查数据的标准方法可以扩展到允许一些惰性癌症，但准确的估计取决于正确指定关键输入，这些输入在实践中可能难以准确确定。
