Perception, paradox, paradigm - Alice in the Wonderland of lung cancer prevention and early detection

BACKGROUND. In less than a century, lung cancer has progressed from a medic al curiosity to the most deadly of all malignant diseases on our planet. Be cause cigarette smoking is responsible for the existing global lung cancer epidemic, policy initiatives have focused almost exclusively on primary pre vention. There is no question that smoking prevention is the most effective method of reducing future lung cancer mortality rates among children, adol escents, and young adults. However, smoking cessation has limited effective ness as a lung cancer prevention strategy among long term smokers, particul arly in the short term. PERCEPTION. Conventional wisdom maintains that screening for lung cancer is ineffective. This is because no randomized trial has demonstrated a signif icant reduction in lung cancer mortality Indeed, mortality was higher in tw o of four randomized trials focusing on chest X-ray (CXR) screening for lun g cancer. Accordingly, the recommendation against CXR screening is believed to be based upon powerful and direct evidence hom randomized trials that C XR screening is ineffective. PARADOX. Because lung cancer is almost uniformly fatal, a plausible explana tion for the ineffectiveness of lung cancer screening, at least with CXR, i s readily apparent Coventional widsom maintains that in lung cancer, the as ymptomatic preclinical interval is so short that apparently localized cance rs are already metastatic when they are detected at an apparently localized stage. Accordingly, "early" lesions are not truly amenable to cure through surgical resection. The problem with this interpretation, however, is that it pays no heed to what the data actually show. While mortality reductions have not been observed, significant stage and long term survival advantage s have consistently been demonstrated in populations randomized to screenin g. Interpretation of existing trials within the strict constraints of our a ccepted paradigm lends support to the hypothesis that CXR screening detects and labels as cancer a substantial number of early stage lesions that are clinically unimportant in that they would never have become clinically evid ent during the life of the patient. The paradox is that this hypothesis, kn own as overdiagnosis, is biologically implausible and is not supported by a ny epidemiologic or clinical evidence. PARADIGM. Based upon our accepted paradigm, a reduction in cause specific m ortality in a population-based randomized trial is accepted without questio n as an unbiased and definitive measure of screening effectiveness. The mor tality paradigm is dependent upon true assumptions, which relate first, to the randomization process, and second, to the confounding influence of scre ening biases on other endpoints. The fundamental problem, however, is that these assumptions, which should always have been the focus of investigation rather than supposition, are invalid. Reconsideration of our assumptions i s imperative to a proper understanding of the effect of interventions in po pulation-based research. Indeed, reexamination of our paradigm is key to re ducing the global burden of lung cancer mortality. Cancer 2000;89:2422-31. (C) 2000 American Cancer Society.