SCREENING FOR LUNG-CANCER - ANOTHER LOOK - A DIFFERENT VIEW

Purpose: There is widespread acceptance that screening for lung cancer is not indicated, to our knowledge, because no randomized trial has d emonstrated a reduction in mortality as a result of screening. The obj ectives of this work are to review prospective studies on lung cancer screening and to analyze the extent to which known biases may have inf luenced observed results. Background: Four randomized controlled trial s have been conducted. The Memorial-Sloan Kettering and Johns Hopkins Lung Projects compared annual chest radiographs (CXRs) in a control gr oup with CXRs and sputum cytologic findings in an experimental group. Although both studies failed to demonstrate any difference in outcome by the addition of cytologic study to CXR, long-term survival in both studies was approximately three times that predicted by other data. Ac cordingly, these results are at least consistent with the hypothesis t hat the screening CXRs may have improved survival. Two randomized tria ls, the Mayo Lung Project and the Czechoslovak study, compared regular and frequent rescreening CXRs in an experimental group with sporadic and/or infrequent rescreening in a control group. Results: Both the Ma yo and Czech studies demonstrated a striking advantage for screening w ith respect to stage distribution, resectability, survival, and fatali ty. Nevertheless, mortality was somewhat higher in the screened groups in both studies. Survival and fatality comparisons in randomized tria ls can be confounded by overdiagnosis bias, Iced-time bias, and length bias, while mortality is not subject to these biases. Accordingly, it is believed that a mortality reduction represents the strongest evide nce for screening efficacy. Mortality is directly proportional to cumu lative incidence. In both the Mayo and Czech studies, incidence of lun g cancer was higher in the screened group. The higher cumulative incid ence (which in the Mayo Lung Project was statistically significant) ma de possible the discordant findings of superior survival/fatality and inferior mortality in the screened populations. Overdiagnosis has been widely accepted to account for the ''missing cases'' in the control p opulations in the Mayo and Czech studies. However, epidemiologic and a utopsy evidence as well as an outcome analysis of unresected early-sta ge screen-detected lung cancer demonstrates that screening does not le ad to the overdiagnosis of lung cancer. Similarly, lead-time bias and length bias cannot account for the outcome differences in the Mayo Lun g Project or Czech study. If survival and fatality comparisons (which suggest a striking benefit from screening) are not biased, then mortal ity comparisons (which suggest no benefit) cannot accurately reflect l ung cancer death rates in these trials. Population heterogeneity may p rovide an explanation for how outcome differences-may have been misrep resented by mortality comparisons in these two trials, as well as othe r large population-based randomized studies. Conclusions: Periodic scr eening CXRs lead to clinically meaningful improvements in stage distri bution, resectability, survival, and fatality in lung cancer. Mortalit y reductions have not been demonstrated, but mortality did not accurat ely reflect lung cancer death rates in the Mayo Lung Project and Czech oslovak study. Accordingly, reconsideration of the desirability of per iodic CXR screening may be appropriate for individuals at high risk of lung cancer.