Lung Cancer Screening, Radiation, Risks, Benefits, and Uncertainty

Abstract

COMPUTED TOMOGRAPHY (CT) SCANNING, WHICH WAS introduced for imaging the head in 1972 and became widely available for imaging the rest of the body by the early 1980s, has revolutionized the practice of medicine and surgery. This technology, for which the Nobel Prize was awarded in 1979, has been used to diagnose and guide the management of diseases affecting every part of the body, improving quality of life and saving countless lives. Two articles in this issue of JAMA, however, point out the complexities involved in deciding whether to extend the use of CT scanning from diagnosis to screening and in determining whether the current use of CT scanning is appropriate or excessive. As the value of CT scanning as a diagnostic tool became clear, it was natural to consider a potential role for this technology to screen for subclinical disease amenable to early intervention. The potential benefits of such screening must, of course, be weighed against the risks and costs. The risk that the ionizing radiation exposure from medical diagnostic tests will cause cancer appears to be small but not zero. Ionizing radiation causes DNA double-strand breaks that are repaired imperfectly, potentially leading to mutations and consequent cancers. An analysis of data from 15 countries has led to the estimate that from 0.6% to 3.2% of cancer diagnosed to age 75 years may be attributable to diagnostic x-rays, including CT scans, although these calculations involved assumptions subject to considerable uncertainty. Another risk of screening is the occurrence of falsepositive findings that may lead to adverse psychological effects on patients as well as physical harm caused by diagnostic procedures undertaken to investigate the findings. Moreover, CT scans are expensive, as are the diagnostic procedures performed to evaluate abnormalities detected. In this issue of JAMA, Bach and colleagues report the results of their systematic review of randomized clinical trials (RCTs) and cohort studies addressing the benefits and risks of screening for early-stage lung cancer using low-dose CT (LDCT) scans. The authors focus on lung cancer–specific and all-cause mortality outcomes in RCTs, avoiding the mistaken inferences that can result from lead-time bias, lengthbiased sampling, and overdiagnosis with other outcomes and designs. Their review yielded only 3 RCTs from which valid inferences can be drawn concerning the effect of LDCT screening for lung cancer among current or former smokers aged 50 years or older. Of these 3 studies, the National Cancer Institute’s National Lung Screening Trial (NLST) was by far the largest and most persuasive, driving the authors’ conclusion that lung cancer mortality is reduced by LDCT screening of adults meeting the NLST entry criteria: age 55 to 74 years, current or former smokers, 30 or more pack-years, and still smoking or having done so within the past 15 years. The good news of a mortality benefit is tempered by some of the specifics. In the NLST, the number needed to screen to prevent 1 lung cancer death was 320 persons undergoing 3 annual LDCTs. Across all studies reviewed, the average rate of detecting nodules per round of screening was 20%, and more than 90% of these nodules turned out to be benign, leading to substantial follow-up testing including invasive procedures. Combining screening and follow-up diagnostic scans, the estimated mean 3-year radiation exposure of NLST participants in the screening group was 8 mSv, which Bach et al estimate would cause 1 cancer death per 2500 persons screened, although this death would likely occur many years later. The heterogeneity in nodule detection rate both among NLST sites and among the other studies reviewed by Bach et al, and the inconsistent mortality results of the 2 smaller RCTs, add a measure of uncertainty to the estimated benefit that would be obtained from broad application of LDCT screening. Nevertheless, the estimates of the benefits and risks of LDCT screening for lung cancer derived from the NLST are the best information currently available. The American College of Chest Physicians, the American Society of Clinical Oncology, and the American Thoracic Society have endorsed an evidence-based practice guideline, included as an online appendix to the article by Bach et al, rec-