The results from the Dutch–Belgian lung cancer screening trial (Nederlands–Leuvens Longkanker Screenings Onderzoek [NELSON]) trial, published on 29 January 2020 in The New England Journal of Medicine (NEJM), show that in this randomised study that involved high-risk persons, lung cancer mortality was significantly lower among those who underwent volume-based, low-dose computed tomographic (CT) screening compared to those without screening. There were low rates of follow-up procedures for results suggestive of lung cancer. More research is required in women, as well as in other subgroups.
Lung cancer is the leading cause of death from cancer worldwide and causes more deaths than breast, colorectal, and cervical cancers combined. Those are three cancer types for which population-based screening programmes exist. Lung cancer prognosis is dismal because approximately 70% of patients have advanced disease at the time of diagnosis. Lung cancer is expected to remain important health problem worldwide for decades.
The authors wrote in the study background that there are limited data from randomised trials regarding whether volume-based, low-dose CT screening can reduce lung cancer mortality among male former and current smokers.
The US-based National Lung Screening Trial (NLST) showed that a strategy of three annual CT screenings resulted in 20.0% lower mortality from lung cancer than screening with the use of chest radiography among participants at high-risk for lung cancer. The US Preventive Services Task Force requested an independent review and a modelling study, which resulted in the recommendation to annually screen persons 55 to 80 years of age with a smoking history of 30 or more pack-years, who currently smoke or quit smoking within the past 15 years.
However, policy decision and implementation are lacking in other countries, despite the NLST results. It is partly due to early publication of inconclusive results of a number of smaller trials in Europe. Since NLST, no other study of lung cancer screening has reported benefits regarding mortality.
The NELSON is a population-based, randomised, controlled trial initiated in 2000, with aim to show a reduction in lung cancer mortality of 25% or more with volume-based, low-dose CT screening in high-risk male participants at 10 years of follow-up. In the latest article published in NEJM, the authors report lung cancer incidence, mortality, and the performance of the four screening rounds among male participants (main analysis) and female participants (subgroup analyses).
A total of 13,195 men and 2594 women between the ages of 50 and 74 were randomly assigned to undergo CT screening at baseline, year 1, year 3, and year 5.5 or no screening. The study team obtained data on cancer diagnosis and the date and cause of death through links with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until 31 December 2015, was completed for all participants.
Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan. The overall referral rate for suspicious nodules was 2.1%.
At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group.
Lung cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; p = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9.
The authors concluded that the NELSON trial showed that volume-based, low-dose CT lung cancer screening resulted in substantially lower lung cancer mortality than no screening among high-risk persons. Furthermore, low-dose CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures), without jeopardising favourable outcomes. The study data suggest greater benefits in women than in men, but in a subgroup with a relatively low number of women. More research is required in women, as well as in other subgroups.
In an accompanied editorial article, the editorialists emphasized that “with the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works: it does. Our job is to identify the target population in which it will be acceptable and cost-effective.”
The study was supported by the Netherlands Organization of Health Research and Development, the Dutch Cancer Society (KWF Kankerbestrijding), the Health Insurance Innovation Foundation (Innovatiefonds Zorgverzekeraars), G.Ph. Verhagen Stichting, the Rotterdam Oncologic Thoracic Study Group, the Erasmus Trust Fund, Stichting tegen Kanker, Vlaamse Liga tegen Kanker, and Lokaal Gezondheids Overleg (LOGO) Leuven. Siemens Germany provided four workstations and software for volume measurements.
de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. NEJM; Published online 29 January 2020. DOI: 10.1056/NEJMoa1911793
Duffy SW, Field JK. Mortality Reduction with Low-Dose CT Screening for Lung Cancer. NEJM; Published online 29 January 2020. DOI: 10.1056/NEJMe1916361