Chest X-ray screening for lung cancer: overdiagnosis, endpoints, and randomized population trials

Publication of the National Lung Screening Trial (NLST) generated excitement by concluding that CT screening reduces lung cancer mortality when compared to chest X-ray (CXR) screening. In contrast, CXR screening has long been considered to be ineffective. This is because randomized population trials (RPTs) have failed to demonstrate significant mortality reductions in populations randomized to CXR screening. While these studies demonstrate that CXR screening is associated with significant survival advantages, these advantages have been widely interpreted as spurious, due to the inference that CXR screening leads to substantial lung cancer overdiagnosis. Indeed, the reality of the overdiagnosis hypothesis is the only alternative to the conclusion that CXR screening was effective in these trials and that survival more accurately reflected the benefit of CXR screening than mortality. Mortality comparisons would be biased if randomization fails to create comparison groups with an equal probability of mortality from the target cancer. The objective of this manuscript is to review existing RPTs on CXR screening for lung cancer, and to analyze which endpoint most accurately reflects screening efficacy. We conclude that the evidence supports that CXR screening is superior to no screening, and the magnitude of overdiagnosis is minimal in the context of CXR screening.