Chest X‐ray screening for lung cancer: Overdiagnosis, endpoints, and randomized population trials

Abstract

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.

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“…One of the major reasons for this poor prognosis is the lack of effective lung cancer screening or early diagnostic methods . Several studies have evaluated lung cancer screening methods such as X‐ray, sputum cytology, and chest computed tomography (CT); however, such methods yield low sensitivity or specificity and thus are not adequate to diagnose NSCLC at an early stage.…”

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“…As randomized controlled trials (RCT) have shown no reduction in lung cancer mortality compared to control groups it has been concluded by most investigators that screening with chest radiography is ineffective [1] . This view has been repeatedly challenged: most RCT have shown a survival advantage for screened individuals because of a stage shift in diagnosed cancers [4,5] . Because RCT are prone to selection bias (selection of highly motivated individuals and problem of generating two comparable groups) population based cohort studies may give a more realistic view of the situation in medical care [5,6] .…”

“…This view has been repeatedly challenged: most RCT have shown a survival advantage for screened individuals because of a stage shift in diagnosed cancers [4,5] . Because RCT are prone to selection bias (selection of highly motivated individuals and problem of generating two comparable groups) population based cohort studies may give a more realistic view of the situation in medical care [5,6] . Recently, a group of Italian investigators presented their follow-up data of a large population based cohort study [7] .…”