Randomized population trials and screening for lung cancer - Breaking firecure barrier

BACKGROUND. At the current time, there is nearly universal agreement that s creening for the early detection of lung carcinoma is not justified. This i s based on the fact that, to the author's knowledge, no randomized populati on trial (RPT) to date has demonstrated a significant reduction in lung car cinoma mortality as a result of any screening intervention. METHODS. To date, four RPTs, which have included a total of 37,724 male cig arette smokers, have been conducted. Studies at Memorial Sloan-Kettering Ca ncer Center and Johns Hopkins demonstrate no incremental effect by the addi tion of sputum cytology to annual chest X-ray (CXR) screening alone. Howeve r, CXR screening in all participants likely was responsible for stage and l ong term survival rates that were two-to three-fold higher than predicted b ased on contemporary statistics. Studies at the Mayo Clinic and in Czechosl ovakia demonstrated significantly superior stage distribution and survival, but slightly inferior mortality in experimental populations that underwent periodic CXR screening. Such contradictory findings were made possible by a higher cumulative incidence rate of lung carcinoma in experimental popula tions. The constellation of improved survival, higher rate of incidence, an d similar mortality led to the hypothesis that CXR screening leads to the o verdiagnosis of lung carcinoma. RESULTS. Abundant evidence based on epidemiologic, pathologic, and clinical considerations conclusively demonstrate that CXR screening does not lead t o the significant overdiagnosis of lung carcinoma. Moreover, overdiagnosis is the only way to reconcile the results of existing RPTs with the conclusi on that CXR screening is ineffective. The alternative conclusion is that si gnificant stage, resectability, and long term survival advantages reflected the ability of CXR screening to improve cure rates. Population heterogenei ty accounts for the failure of mortality to reflect screening efficacy accu rately in these trials. There is direct evidence that population heterogene ity tvas responsible for the trend toward increased lung carcinoma mortalit y in the Czech study. Moreover, review of all RPTs demonstrates a consisten t pattern in which population heterogeneity confounds the ability of mortal ity to represent an accurate measure of screening effectiveness. CONCLUSIONS. Systematic analysis of RPTs supports two major conclusions: 1) an improvement in the cure rate rather than a reduction is cause specific mortality is the proper measure of screening effectiveness in the RPT setti ng and 2) CXR screening is associated with a two- to three-fold improvement in lung carcinoma cure rates. A paradigm shift is mandatory for the proper evaluation of conventional and newer screening modalities. Indeed, hundred s of thousands of lives would be saved annually on a global basis if CXR sc reening were offered to individuals at high risk for lung carcinoma. Cancer 2000;89:2399-421. (C) 2000 American Cancer Society.