NEJM Data Show Volume CT Screening Lowers Mortality in High-Risk Lung Cancer

Chandra Belani, MD

Patients with high-risk lung cancer who underwent volume CT screening had a significantly lower lung cancer mortality compared with those who were not screened, according to 10-year follow-up results from the NELSON trial that were published in the New England Journal of Medicine.¹

Findings, which were initially presented at the IASLC World Conference on Lung Cancer in Toronto in 2018, showed that the lung-cancer mortality was 2.50 deaths per 1000 person-years in those who had screening and 3.30 deaths per 1000 person-years in those who did not, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% CI, 0.61-0.94; P = .01) in the screening group compared with the control group. In a smaller subanalysis of female participants (n = 2594), the rate ratio for death was 0.67 (95% CI, 0.38-1.14) at 10 years of follow-up, and the rate ratio for death was 0.41 to 0.52 in years 7 through 9.

"Overall uptake of low-dose CT-screening needs to increase with elevated awareness and educational efforts if we are going to make a further dent in the lung-cancer mortality," Chandra Belani, MD, chief science officer at the International Association for the Study of Lung Cancer, said in a statement. "The most common histology of lung cancer in the screened population is adenocarcinoma. To help stratify the indeterminate nodule on the screening scans, the detection of squamous cell and small cell lung cancer earlier will be of importance. Application of Artificial Intelligence, Machine, and Deep learning will pick up relevant images for further invasive procedures and biomarker studies."

In the United States, current lung cancer screening recommendations are to annually screen people aged 55 to 80 years with a smoking history of ≥30 pack-years, who currently smoke or have quit within the past 15 year.

In the population-based NELSON study, 13,195 men were included in the primary analysis and a subgroup analysis comprised 2594 women; both groups had patients between the ages of 50 and 74. Overall, patients were randomized to undergo CT screening at baseline, and again at 1, 3, and 5.5 years or undergo no screening. There were no significant differences between the screening and control groups. In the primary analysis, the median age was 58 years and the median smoking history was 38.0 pack-years; 44.9% of male participants were former smokers.

A minimum follow-up of 10 years was conducted until December 31, 2015, which was completed by all patients.

The average adherence to CT screening was 90%, with an average of 9.2% of screened participants undergoing ≥1 additional CT scan. The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, lung cancer was found in 5.58 cases per 1000 person-years (341) and 4.91 cases per 1000 person-years (304) in the control group (rate ratio, 1.14; 95% CI, 0.97-1.33).

Fifty-nine percent of all lung cancers in the screening arm were detected on screening, and 12.8% were interval cancers. The lung cancers found on screening were more often diagnosed as stage IA or IB (58.6%); 14.2% and 13.5% of those on the screening and control arms, respectively, with non—screening-detected lung cancers were diagnosed with stage IA or IB lung cancer.

Moreover, stage IV cancer was diagnosed in nearly half of participants with non—screening-detected lung cancers, at 51.8% and 45.7% of the screening and control groups, respectively. However, 9.4% of the screening-detected lung cancers were diagnosed as stage IV disease. In the screening and control groups, 52.0% and 43.8% of screening-detected lung cancers were adenocarcinomas.

Other trials have evaluated the impact of lung cancer screening for early disease detection. In the National Lung Screening Trial, investigators evaluated regular CT screening in patients for early detection of lung cancer.² Patients were underwent low-dose CT (n = 26,722) or single-view posteroanterior chest radiography (n = 26,732).

Results showed that low-dose CT screening reduces mortality from lung cancer, paralleling the NELSON study. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all 3 rounds. Lung cancer was found in 645 cases per 100,000 person-years (1060) in the low-dose CT group and 572 cases per 100,000 person-years (941) in the radiography group (95% CI, 1.03-1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group. Overall, the results showed an approximate 20% reduction in lung cancer mortality with low-dose CT screening (95% CI, 6.8-26.7; P = .004). The rate of death was reduced in the low-dose CT group versus the radiography group by 6.7% (95% CI, 1.2-13.6; P = .02).

References

1. De Koning HJ, Van Der Aalst CM, De Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial [published online February 6, 2020]. N Eng J Med. doi: 10.1056/NEJMoa1911793.
2. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395-409. doi: 10.1056/NEJMoa1102873.