Assessing the Efficacy of Lung Cancer Screening

Abstract

Jerome M. Reich, MD, FCCP Lung cancerwould seem, apriori, to be an ideal screening candidate: It is the most common lethal neoplasm in the United States; it is often detectable in a preclinical phase; radiographs are noninvasive and readily acceptable; individuals at highest risk—older current and former smokers—are readily identifiable; when it is detected at an early stage, the “5-year cure” rate is approximately 70%; and it is highly lethal when unresectable (1). Although survival is substantially higher in patients with screening-identified disease than in patients in whom disease was identified by other means, screening is not recommended by recognized authorities because results of two large randomized controlled trials demonstrated that although 5-year survival was far higher in the screened than in the unscreened cohort, lung cancer and all-cause mortality were higher as well (1). This controversy has been reignited by the development of low-dose computed tomography (CT), a far more sensitive method than conventional radiography for identifying resectable lung cancers (1). Screening advocates assert that improvement in lung cancer survival, predicated on stage at diagnosis, suffices to demonstrate efficacy (2,3). Others have pointed out that causespecific survival is an invalid metric of screening efficacy because it discounts other causes of mortality and it introduces biases—lead-time bias, length-biased sampling, and overdiagnosis—that generate a spurious improvement (4). The purpose of this communication is to delineate the limitations of outcome metrics used to assess lung cancer screening efficacy. Definitive evidence of efficacy requires the demonstration of a reduction in lung cancer and all-cause mortality in prospective controlled trials.