Two large RCTs reported findings in 2011 regarding the utility of lung cancer screening. The Prostate, Lung, Colorectal and Ovarian Randomized Trial (PLCO) randomized 154,901 adults (52% current or former smokers) between the ages of 55 and 74 years to receive either no screening or annual posterior-anterior chest radiographs for 4 consecutive years. The investigators monitored the participants after screening for an average of 12 years. Results showed no mortality benefit from four annual chest radiographs either in the whole cohort or in a subset of heavy smokers who met the entry criteria for the other major trial, the National Lung Screening Trial (NLST). The NLST enrolled 53,454 current or former smokers (minimum 30-pack year exposure history) between the ages of 55 and 74 years who were randomly assigned to one of two screening modalities: three annual posterior-anterior chest radiographs or three annual low-dose chest CT scans. They were monitored for an additional 6.5 years after screening. Compared with chest radiography, low-dose chest CT detected more early-stage lung cancers and fewer advanced-stage lung cancers, indicating that CT screening systematically shifted the time of diagnosis to earlier stages, thereby providing more persons the opportunity for effective treatment. Furthermore, compared with chest radiographs, the cohort that received three annual CT scans had a statistically significant mortality benefit, with reductions in both lung cancer deaths (20.0%) and all-cause mortality (6.7%). This was the first evidence from an RCT demonstrating that lung cancer screening reduced all-cause mortality.
Additional information from PLCO, the NLST, and multiple other ongoing randomized trials is available. Trials in the Netherlands and Belgium (NELSON), Germany (LUSI), Denmark (DLCST), the United Kingdom (UKLS), and Italy (MILD) have been completed. These have revealed variable findings depending on the risk profile of the included patients, but the broad results are that screening is most likely to be effective if performed at short intervals in a high-risk population, as was done in NLST.
Salient issues that temper enthusiasm for widespread screening at this time include the following: (1) Generalizability to community practice: NLST-participating institutions demonstrated a high level of expertise in imaging interpretation and diagnostic evaluation. Ninety-six percent of findings on CT were false positives but the vast majority of patients were monitored with serial imaging. Invasive diagnostic evaluations were uncommon and were associated with a low complication rate (1.4%). (2) Duration of screening: The rate of detection of new lung cancers did not fall with each subsequent annual screening over 3 years. Since new lung cancers become detectable during each year-long screening interval, the optimal number of annual CT scans is unknown as is the optimal screening interval. (3) Overdiagnosis: After 6.4 years of post-screening observation, there were more lung cancers in the NLST CT cohort than the chest radiography cohort (1089 and 969, respectively). Since the groups were randomized and well matched, lung cancer incidence should have been identical. Therefore, 18.5% of the lung cancers detected by CT remained clinically silent and invisible on chest radiograph for 6.4 years. Many, perhaps most, of these lung cancers would never cause clinical disease and represent overdiagnosis. (4) Cost effectiveness: The number needed to screen with three annual chest CT scans to prevent one death from lung cancer was 320.
Given the level of evidence from US studies showing benefit, the US Preventive Services Task Force has been recommending screening with low-dose chest CT in high-risk individuals since late 2013. There is no evidence of benefit in a mixed population screened with chest radiography.
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