Lung Cancer Screening with Chest CT: Efficacy Confirmed

Take-Away Points

• ■ Major Focus: The Dutch-Belgian Lung Cancer Screening Trial (NELSON) is the second largest randomized controlled trial with a primary endpoint of lung cancer mortality designed to evaluate CT screening versus no screening in male current and former smokers.

• ■ Key Result: Participants in the CT screening group had an increased incidence of lung cancer, 24% reduction in lung cancer mortality over a 10-year period, and approximately 40% of lung cancers in the screened group were early stage (stage I).

• ■ Impact: These results corroborate results from the National Lung Screening Trial, supporting the benefits of CT screening for lung cancer and furthering population-based CT screening for high-risk patients.

The United States Preventative Services Task Force recommends annual low-dose chest CT for lung cancer screening in high-risk current and former smokers. This recommendation, released in 2015, was based largely on results of the National Lung Screening Trial (NLST), which demonstrated a 20% relative reduction in lung cancer mortality with low-dose chest CT screening versus chest radiography. Since the publication of the NLST, a number of European studies evaluating lung cancer screening have been underway. The largest, and only sufficiently powered, of these is the Dutch-Belgian Lung Cancer Screening Trial (NELSON), recently published by de Koning et al. NELSON enrolled 13 195 men between the ages of 50 and 74 years. Participants were randomly assigned to CT screening (at baseline and subsequently at years 1, 3, and 5.5) or no screening. CT-detected pulmonary nodules were analyzed via volume measurement. The primary study endpoint was lung cancer mortality, and participants were followed for a minimum of 10 years. More lung cancers were detected in the CT screening group compared with the control group (rate ratio 1.14; 95% confidence interval [CI]: 0.97, 1.33). There was a 24% reduction in lung cancer mortality with CT screening (rate ratio 0.76; 95% CI: 0.61, 0.94). The benefit of CT screening in a smaller subset of women (n = 2594) was suggested to be greater, with a mortality reduction of 33% (rate ratio 0.67; 95% CI: 0.38, 1.14). Approximately 40% of cancers detected in the screening group were stage IA–B, while more than 70% of lung cancers in the control group were stage IIIA or higher. Overall, after analysis of nodule volumes, including doubling time determination via repeat CT for indeterminate nodules, the percentage of participants with a positive test was 2.1%, and the positive predictive value was 43.5%. There were no adverse events. Overdiagnosis calculated at 10 years was similar to that of the NLST.

The NELSON trial furthers high-quality evidence for CT to reduce lung cancer mortality in high-risk individuals. In conjunction with the NLST, the NELSON trial confirms a benefit of CT for early lung cancer detection. Moving forward, it is incumbent that efforts be focused toward effective clinical translation, including improved identification of the most high-risk individuals, effective management of screen-detected abnormalities, and improved tumor phenotyping to further reduce overdiagnosis. This is necessary to ensure that the mortality benefit observed in the clinical trial setting be translated to lives saved in everyday clinical practice.

Highlighted Article

de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. New Engl J Med 2020;382:503–513. doi: 10.1056/NEJMoa1911793