van Klaveren Rob J, van't Westeinde Susan C, de Hoop Bart-Jan, Hoogsteden Henk C
Department of Pulmonology, Erasmus MC-Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands.
Clin Cancer Res. 2009 Apr 1;15(7):2215-8. doi: 10.1158/1078-0432.CCR-08-1920. Epub 2009 Mar 17.
Lung cancer is not simply a single disease, but a collection of several phenotypically very diverse and regionally distinct neoplasias. Its natural history is complex and not yet fully understood. Stem cells and the complex interaction with the microenvironment of the tumor and the immune system play an important role in tumor progression and metastasizing capacity. This finding explains why lung cancer does not always follow the multistep carcinogenetic and exponential growth model and why small lesions do not always equate to early-stage disease. Despite the fact that volume doubling times are increasingly used as surrogate markers for the natural history of lung cancer and as estimates for the proportion of overdiagnosed cases, it is only a momentary impression. At baseline screening especially, screen-detected lung cancer cases are preferably detected when they are in the indolent phase of their growth curve (length-biased sampling), from which it can by no means be concluded that they may not progress or metastasize at a later stage. Because the natural history of lung cancer is only partly elucidated, conclusions on the impact of overdiagnosis in lung cancer screening are premature.
肺癌并非单一疾病，而是多种表型差异极大且区域特征各异的肿瘤的集合。其自然病程复杂，尚未完全明晰。干细胞以及肿瘤与免疫系统微环境之间的复杂相互作用在肿瘤进展和转移能力方面起着重要作用。这一发现解释了为何肺癌并不总是遵循多步骤致癌和指数增长模式，以及为何小病灶并不总是等同于早期疾病。尽管体积倍增时间越来越多地被用作肺癌自然病程的替代标志物以及过度诊断病例比例的估计指标，但这只是一种暂时的现象。尤其是在基线筛查时，筛查发现的肺癌病例最好是在其生长曲线的惰性阶段（长度偏倚抽样）被检测到，由此绝不能得出它们在后期不会进展或转移的结论。由于肺癌的自然病程仅部分得到阐明，因此关于肺癌筛查中过度诊断影响的结论还为时过早。
