Parkin D M, Moss S M
The International Agency for Research on Cancer, Lyon, France.
Cancer. 2000 Dec 1;89(11 Suppl):2369-76. doi: 10.1002/1097-0142(20001201)89:11+<2369::aid-cncr10>3.0.co;2-a.
Randomized controlled trials (RCTs) of lung cancer screening consistently show an excess number of cancer cases and longer survival in screened groups, but no difference in mortality between screened and control populations.
The current study reviewed the various types of biases that confuse comparisons based on intermediate endpoints such as stage distribution and survival and the reasons for basing evaluations in RCTs of screening for early cancers on mortality from a specific cancer.
Four RCTs all showed improved stage of disease and survival in screened subjects, but there was no difference in mortality between screened and unscreened populations. The possible explanations for the higher incidence are chance (failed randomization) or "overdiagnosis" (detection of cases by screening that otherwise would never have surfaced). Analysis of the trial results confirmed that chance alone was a very unlikely explanation. Evidence suggests that some overdiagnosis of lung cancer is likely in screened subjects. This is a consistent observation in all other programs of screening for early cancers (breast, prostate, and neuroblastoma).
Overdiagnosis of cancer cases resulting from the screening process itself will give rise to excess cases of disease, and may, at least in part, explain the observations in the randomized trials.
肺癌筛查的随机对照试验(RCT)一致表明,筛查组的癌症病例数量过多且生存期更长,但筛查人群与对照人群的死亡率并无差异。
本研究回顾了各类混淆基于中间终点(如分期分布和生存期)进行比较的偏倚,以及在早期癌症筛查的RCT中以特定癌症死亡率为评估依据的原因。
四项RCT均显示,筛查对象的疾病分期和生存期有所改善,但筛查人群与未筛查人群的死亡率并无差异。发病率较高的可能解释是偶然因素(随机分组失败)或“过度诊断”(通过筛查发现的病例,否则这些病例可能永远不会出现)。对试验结果的分析证实,仅偶然因素不太可能是原因。有证据表明,筛查对象中可能存在一定程度的肺癌过度诊断。这在所有其他早期癌症筛查项目(乳腺癌、前列腺癌和神经母细胞瘤)中都是一致的观察结果。
筛查过程本身导致的癌症病例过度诊断会导致疾病病例过多,并且可能至少部分解释了随机试验中的观察结果。