Update on lung cancer screening: it works?

Low-dose computed tomographic (CT) screening for lung cancer is a complex and controversial topic. The goal of screening is to detect disease at a stage when it is not causing symptoms and when control or cure is possible. In addition to improving outcome, the screening test must carry low risk, have acceptable levels of sensitivity and specificity, be accessible, and be cost-effective. For cancer screening, disease-specific death (number of cancer deaths relative to number of individuals screened) is considered the ultimate test of screening effectiveness and the only test without bias.1 A number of CT screening trials have been performed, but before the advent of the National Lung Screening Trial (NLST), all were nonrandomized studies that did not deal with mortality rates. One of the more important of these studies was the Early Lung Cancer Action Project (ELCAP) conducted by Henschke and colleagues,2 which began in 1993 and enrolled 1,000 individuals over 60 years of age with at least 10 pack-years of smoking history (median of 45 pack-years). Prevalence data from this single-arm trial confirmed that CT is more sensitive than chest radiography for the detection of lung cancer (2.7% vs 0.7%). However, the number of advanced-stage cancers did not decrease when CT screening results were compared with the chest radiographic screening results of the 1970s. This raised the question of whether the prevalence data represented a true “stage shift” that enabled detection at an earlier stage, or whether these data represented small slow-growing tumors that might not affect overall disease-specific mortality. Single-arm studies have also shown a high rate of nodules and other potentially significant abnormalities that require further evaluation to exclude disease. In 2003, the Mayo Clinic published study results on 1,520 patients who were over the age of 50 and had a smoking history of 20 or more pack-years.3 After 3 years of scanning, 2,832 noncalcified pulmonary nodules were identified in 1,049 (69%) of the participants. Most of these nodules (95%) were less than 8 mm in diameter. In addition, this study made 696 other CT findings that were judged to be of clinical importance, such as adrenal mass and aortic aneurysm. Upon analysis of their data, the Mayo group estimated that patients would have at least 1 false-positive screening CT over their follow-up years. The NLST was designed to answer whether lung-cancer-specific mortality could be reduced with low-dose CT screening. The trial, funded by the National Cancer Institute and the American College of Radiology Imaging Network (ACRIN), was the 1st randomized controlled screening trial for lung cancer. It was a multi-institutional study that was designed to detect a 20% or greater reduction in lung-cancer-specific mortality rates. The study was started in September 2002 and included a baseline CT and an annual CT for 2 more years, with at least 5 years of annual follow-up questionnaires and surveys. In 18 months, there were 53,454 enrolled participants aged 55 to 75 years, with smoking histories of 30 pack-years or more. The study used low-dose multidetector helical CT in the experimental arm and chest radiography in the control arm. In October 2010, the NCI announced that the trial was closed after reaching the designated endpoint: a 20% reduction in the lung-cancer-specific mortality rate. There was also a 6.9% reduction in all-cause mortality, which indicated that death from diseases other than lung cancer was reduced. As with other trials, there was a high rate of positive studies (24% in the NLST), with the majority of these studies not resulting in a lung-cancer diagnosis. Other components of the trial, including cost-effective analysis and quality-of-life evaluations, are evaluated in the recently published NLST results.4 Proving that low-dose CT worked for lung cancer screening was an important and significant accomplishment of the NLST (Fig. 1). While the question of whether screening works has been answered, a host of other questions has arisen. Examples of questions to be considered for screening programs are whether the NLST criteria of age and smoking history are appropriate for generalization, how often screening should be performed, whether 3rd-party payers should fund lung-cancer screening, and what follow-up protocols are appropriate for positive studies and incidental findings. Fig. 1 Computed tomographic image shows a small right-upper-lobe lung cancer (arrow). A cancerous tumor of this size would not be detected on routine chest radiography.