Reference: N Engl J Med. 2020 Feb 6;382(6):503-513
In 2011, the National Lung Cancer Screening Trial (NLST) revolutionized lung cancer screening, demonstrating that three low-dose annual chest CTs could reduce both lung cancer and all-cause mortality over a median 6.5-year follow-up. That trial of 53,000 participants (41% women) was so convincing that most experts now recommend some form of CT-based lung cancer screening for high-risk asymptomatic patients who might be expected to benefit. Now along comes the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial, a 10-year study of over 13,000 men and 2,500 women using slightly different methods.
Like the NLST trial, the NELSON trial randomized high-risk middle-aged smokers and participants who quit within the previous 15 years to scheduled low-dose CT scans looking for early-stage lung cancer. Compared to the NLST trial, which had three CTs in three years and a control group with annual chest xrays, the Nelson Trial had four CTs in 5.5 years, and control patients did not receive an intervention. The NELSON trial included 16% women, compared to 41% in the NLST study, and it also looked at patients between the ages of 50 and 55. The NELSON trial used a volume-based protocol for deciding which nodules were positive, while the NLST used a diameter-based protocol.
Changing to a volume-based protocol resulted in a lower false positive rate and a better positive predictive value for the CTs. The NLST trial in 2011 found 24% of patients had a positive screen, and only 3.6% of these patients had lung cancer. With the NELSON trial, only 2.1% of patients had a positive screen, but 43.5% of these ended up with a lung cancer diagnosis. Changing the interpretation of the CT did not seem to result in missed diagnoses that were clinically significant. During at least ten years follow-up, 210 men who were not screened and 160 men who were screened died of lung cancer. The rate ratio for death from lung cancer was 0.76 (95% CI 0.62-0.94, number needed to screen 134). On the other hand, this study failed to find a significant difference between the rate of all-cause mortality between the two groups, which the authors ascribe to sample size.
The study revealed mixed results. For example, subgroup analysis did not demonstrate benefit for men aged 50-55 years. Additionally, the authors noted potential differences between women and men requiring further investigation. In the NLST study, screening with CT discovered clinically significant findings that were not lung cancer in 7.5% of patients and demonstrated a reduction in all-cause mortality beyond the reduction in mortality ascribed to lung cancer. These numbers are not reported in the NELSON trial. On the other hand, the volume-based protocol used by NELSON seems to result in fewer false positive results with no corresponding false negative bump. Overall, this study provides supporting evidence that low-dose lung CT screening reduces death from lung cancer when applied to the right population. As we wrestle with the problem of who to screen, when to screen, and how to interpret the results, it’s apparent the best approach may require fine tuning.
For more information, see the topic Lung Cancer Screening in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.