Lung Cancer Mortality Suggested to be Significantly Lower with Volume CT

The NELSON trial, published in The New England Journal of Medicine, suggested that in high risk individuals, lung cancer mortality was found to be significantly lower among participants who underwent volume computed tomographic (CT) screening compared to those who underwent no screening. 

“Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary workup procedures), without jeopardizing favorable outcomes,” the authors wrote.

Additionally, the trial data suggested a greater benefit in women than in men, however this was observed within a relatively low subgroup of women. The researchers indicated that these results suggest that further analysis is required in women, as well as in other subgroups.

In the primary analysis, a total of 13,195 men who were current or former smokers between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or undergo no screening. The same methods and patient criteria were studied in a subgroup of 2,594 women. Researchers acquired data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed the cause of death as lung cancer when possible. All participants completed a minimum follow-up of 10 years until December 31, 2015.

At baseline, those in the screening group reported a longer duration of smoking than those in the control group, but the same number of pack-years. Moreover, smoking behavior was indicated to be similar in the 2 groups after 2 years of follow-up. Therefore, bias in screening effect in favor of the screening group was not expected. 

Of the men in the study, the average adherence to CT screening was 90%. On average, 9.2% of the screened participants underwent at least 1 additional CT scan (initially indeterminate) and the overall referral rate for suspicious nodules was 2.1%. At 10-years of follow-up, the incidence of lung cancer was 5.8 cases per 1,000 person-years in the screening group and 4.91 cases per 1,000 person-years in the control group. Furthermore, lung cancer mortality was 2.50 deaths per 1,000 person-years and 3.30 deaths per 1,000 person-years, respectively.

The cumulative rate ratio for death resulting from lung cancer at 10 years was 0.76 (95% CI, 0.61-0.94; P = 0.01) in the screening group compared to the control group, similar to the values observed at years 8 and 9. Among the subgroup of women, the rate ratio was 0.67 (95% CI, 0.38-1.14) at 10 years of follow-up, with values of 0.41 and 0.52 seen in years 7 through 9. 

“The high adherence to CT screening may reflect a high level of conscientiousness among trial participants,” the authors wrote. “In the future, improvement in screening selection (personalized risk-based approach) will probably result in a more favorable trade-off between harms and benefits of CT lung-cancer screening). 

Concerns have previously been discussed about the possibility of overdiagnosis in lung-cancer screening. In this trial, an excess of 40 cases was found among the male participants in the screening group 10 years after randomization (4.5 years after the final screening round), which suggests an excess-incidence overdiagnosis rate of 19.7% (bootstrapped 95% CI, -5.2 to 41.6) for screening-detected cases. However, extending the follow-up to 11 years after randomization (5.5 years after the final screening round) reduced the number of excess cases to 18, yielding an excess-incidence overdiagnosis rate of 8.9% (bootstrapped 95% Ci, -18.2 to 32.4). 

According to the study, only 15% of patients with lung cancer are still alive 5 years after diagnosis, because approximately 70% of patients have advansced disease at the time of diagnosis. However, the US-based National Lung Screening Trial found that a strategy of 3 annual CT screenings resulted in 20% lower mortality from lung cancer than screening with the use of chest radiography. 

Reference:

de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. The New England Journal of Medicine. doi:10.1056/NEJMoa1911793.