Results of the very large, randomized, population-based NELSON trial confirm the value of low-dose computed tomography (CT) screening in people at high risk for developing lung cancer. The protective value of screening was more pronounced in women than in men. These study findings were presented at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer.1 Overall, CT scanning decreased mortality by 26% in high-risk men and up to 61% in high-risk women over a 10-year period.
Harry J. de Koning, MD, PhD
NELSON is the second largest randomised-controlled trial to demonstrate a reduction in lung cancer mortality with CT screening of people at high risk. The National Lung Screening Trial (NLST) previously showed a 20% reduction in lung cancer mortality for annual screening over 3 years with low-dose CT scanning compared with chest radiography. That trial included 53,454 people at high risk, 59% of them men.2 A post hoc analysis suggested a gender difference, with a greater benefit for screening in women.
A major difference in the management of pulmonary nodules between NELSON and NLST was the use of nodule volume and volume doubling time to identify potential cases of early lung cancer.
“The NELSON mortality results are more favorable than the NLST results and provides evidence for gender differences,” explained lead author Harry J. de Koning, MD, PhD, of the Erasmus Medical Center, Rotterdam, the Netherlands. “Volume CT lung cancer screening of high-risk former and current smokers results in low referral rates and a very substantial reduction in lung cancer mortality in both genders.”
The NELSON trial recruited individuals from population-based registries in the Netherlands and Belgium and compared groups offered screening with CT with those not screened. Participants were followed for more than 10 years through national registries and case notes review. The study was powered to detect a reduction in lung cancer mortality of 25% or more at 10 years.
General health questionnaires were sent to about 600,000 men and women between the ages of 50 and 74 with a smoking history of more than 10 cigarettes per day for more than 30 years or more than 15 cigarettes per day for 25 years. From that group, the study enrolled more than 15,000 people: 7,892 in the control group and 7,900 who had CT screening at prespecified intervals. The screen group was assigned chest CT imaging during years 1 and 2 of the trial, followed by screening at 4 and 6.5 years.
The screen and not-screen (control) groups had similar baseline characteristics, including age, gender ratio, smoking history, and smoking cessation. The average age of patients was about 59 years, 84% were men, and about 55% were current smokers. The CT protocol included centralized reading of the images as well as monitoring of lung nodule volume and volume doubling time.
“The uptake of screening was enormous in the beginning [95% at year 1] and leveled off to about two-thirds by year 6.5,” Dr. de Koning said.
A total of 27,000 screens were obtained; of them, 2,503 (9.3%) were “indeterminate”; 598 (2.2%) were positive results, and 243 (0.9%) detected lung cancer. Screening was calculated to have a 41% positive predictive value. Patients with indeterminate results were sent a letter informing them of an abnormality that required a repeat scan within 3 to 4 months.
One of the main benefits of CT screening in this population is identification of lung cancers at an early stage. About 50% of the cancers diagnosed in the screening arm were early stage, and 65% to 70% were stages IA to II; in contrast, about 70% of cancers in the control arm were stage III/IV at diagnosis.
“The finding that at least half of all cancers detected were early stage is new,” Dr. de Koning stated.
At year 10, there were 214 lung cancer deaths in the male control arm and 157 deaths in the screened arm. The lung cancer mortality rate ratio for men in the screened vs unscreened arm was 0.74 (26% reduction, P = .0003). At 10 years, the lung cancer mortality rate ratio in women was 0.61 (39% reduction, P = .0054). “Over time, we saw consistently better results in females,” Dr. de Koning said.
“The key message is that high-risk people should be screened with CT,” he concluded. ■
DISCLOSURE: The NELSON trial was primarily funded by public funds from the Netherlands, notably ZonMw and the Dutch Cancer Society, as well as seven smaller organizaitons. Roche and Perceptronics provided funds for two side studies, and Siemens provided workstations for uniform reading software across the centers.
1. De Koning H, Van Der Aalst C, Ten Haaf K, et al: Effects of volume CT lung cancer screening: Mortality results of the NELSON randomized-controlled population based trial. 2018 World Conference on Lung Cancer. Abstract PL02.05. Presented September 25, 2018.
2. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al: Reduced lung-cancer screening mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.
“This wonderful result joins other landmark studies. The differential effect by gender is extremely important,” said formal discussant of the trial, John K. Field, PhD, FRCP, of the University of Liverpool, UK.
John K. Field, PhD, FRCP
“This study validates the management protocol and...!-->!-->