Strauss Gary M
Division of Hematology-Oncology, Roger Williams Medical Center, Providence, RI 02908, USA.
J Clin Oncol. 2002 Apr 15;20(8):1973-83. doi: 10.1200/JCO.2002.08.074.
The Mayo Lung Project has been interpreted as negative because it failed to demonstrate a significant mortality reduction among those randomized to chest x-ray and cytology. In contrast, survival suggests that screening is highly effective. This report was undertaken to analyze the trial as a closed cohort study, in an effort to identify predictors of lung cancer incidence and mortality, and to determine whether survival or mortality was unbiased.
The Mayo Lung Cohort comprised all 9,192 randomized individuals. Cox proportional hazards regression was used both to determine predictors of incidence and mortality in the population and to identify predictors of mortality among cases. Survival analyses using intent-to-treat principles and measuring survival from randomization were used to evaluate length bias and lead-time bias. Multivariate Cox regression was used to investigate the extent to which the data are consistent with overdiagnosis.
Cox regression demonstrates that, in addition to age and smoking, randomization to screening predicted increased lung cancer incidence (hazard ratio, 1.30; 95% confidence interval [CI], 1.06 to 1.60). Predictors of mortality were similar, except randomization to screening was not significant (hazard ratio, 1.06; 95% CI, 0.83 to 1.37). Among cases, survival was significantly superior in the experimental population. Higher incidence in the experimental group accounts for the mortality/survival discrepancy. Both lead-time and length biases can be excluded, because survival from randomization was superior in the experimental population. Overdiagnosis is eliminated because resection was the only significant multivariate predictor of survival. Overall, 50% of resected and 0% of unresected cases were cured.
Survival was superior in the screened population, and this advantage was not attributable to lead-time bias, length bias, or overdiagnosis bias. Mortality was biased, because incidence differences confounded the ability of mortality to reflect the true effect of screening. Indeed, survival provided an unbiased surrogate for cure in the Mayo Lung Cohort.
梅奥肺癌项目被认为是阴性结果，因为它未能证明随机接受胸部X线检查和细胞学检查的人群死亡率有显著降低。相比之下，生存率表明筛查是非常有效的。本报告旨在将该试验作为一项封闭队列研究进行分析，以确定肺癌发病率和死亡率的预测因素，并确定生存率或死亡率是否无偏差。
梅奥肺癌队列包括所有9192名随机分组的个体。使用Cox比例风险回归来确定人群中发病率和死亡率的预测因素，并识别病例中的死亡率预测因素。采用意向性分析原则并从随机分组开始测量生存率的生存分析，用于评估长度偏倚和领先时间偏倚。使用多变量Cox回归来研究数据与过度诊断的一致程度。
Cox回归表明，除了年龄和吸烟外，随机接受筛查预测肺癌发病率增加（风险比，1.30；95%置信区间[CI]，1.06至1.60）。死亡率的预测因素相似，但随机接受筛查不显著（风险比，1.06；95%CI，0.83至1.37）。在病例中，试验人群的生存率显著更高。试验组中较高的发病率解释了死亡率/生存率差异。领先时间偏倚和长度偏倚均可排除，因为试验人群从随机分组开始的生存率更高。由于切除是生存的唯一显著多变量预测因素，因此消除了过度诊断。总体而言，50%的切除病例和0%的未切除病例被治愈。
筛查人群的生存率更高，且这一优势并非归因于领先时间偏倚、长度偏倚或过度诊断偏倚。死亡率存在偏差，因为发病率差异混淆了死亡率反映筛查真实效果的能力。事实上，在梅奥肺癌队列中，生存率为治愈提供了无偏差的替代指标。
