Low-dose computed tomography screening for lung cancer prevents the greatest number of deaths if it is reserved for smokers at highest risk of dying from the disease within 5 years, and it prevents very few deaths among those at lowest risk, according to a report published online July 18 in the New England Journal of Medicine.
When smokers were stratified into quintiles based on 5-year risk of death, 161 patients in the highest-risk quintile would need to be screened using low-dose CT to prevent 1 lung cancer death. In contrast, among the smokers in the lowest-risk quintile, 5,276 would need to be screened to prevent 1 lung cancer death, said Stephanie A. Kovalchik, Ph.D., of the National Cancer Institute and her associates.
These findings provide the empirical evidence that the medical community has been seeking to identify patients who would reap the most benefit from targeted screening – a benefit that would clearly outweigh the harm of the relatively frequent false-positive results with low-dose CT screening.
At present, screening guidelines all recommend low-dose CT screening for patients who meet the NLST (National Lung Screening Trial) entry criteria, but some experts argue that further refinement of screening criteria would be appropriate. The observations in this study "argue for the use of individualized risk assessment of lung cancer death instead of the NLST entry criteria, to increase the efficiency of low-dose CT screening," the investigators said.
Dr. Kovalchik and her colleagues examined whether the benefits and harms of low-dose CT scanning in the NLST differed according to the study subjects’ prescreening risk of lung cancer death, which was determined at enrollment using a validated prediction model. Risk factors included in this model were age, body mass index, family history of lung cancer, pack-years of smoking, years since smoking cessation (among patients who had quit), presence or absence of emphysema, sex, and race.
The NLST was a large randomized clinical trial that compared the efficacy of this screening technique against that of chest radiography in 53,454 smokers aged 55-74 years who had a minimum of 30 pack-years of smoking.
For their study, Dr. Kovalchik and her associates assessed outcomes in 26,604 NLST participants who had undergone three annual CT scans and 26,554 who had undergone three annual radiographs in the trial’s intention-to-treat population.
The primary end point was the rate of death from lung cancer during a median of 5.5 years of follow-up. This end point was reached by 354 subjects in the CT group, compared with 442 in the radiography group.
The rate of lung cancer deaths was 24.6 per 10,000 person-years among subjects screened by CT, compared with 30.9 per 10,000 person-years among those screened by radiography. This reflects a 20% relative reduction in lung cancer deaths with low-dose CT screening, the investigators reported (N. Engl. J. Med. 2013 July 18 [doi: 10.1056/NEJMoa1301851]).
The researchers developed an absolute risk-prediction model for lung-cancer mortality that accounted for a participant’s specific risk characteristics and life expectancy by incorporating Cox proportional-hazards models of death from lung cancer and competing causes of death. Predictors of lung-cancer death were selected from a set of previously identified demographic and clinical risk factors for lung cancer (including smoking history) using Lasso regression. The prediction model was externally validated with outcome data from 15,114 NLST-eligible and 22,649 NLST-ineligible smokers aged 55-74 years who were enrolled in the radiography group of the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial. The participants were stratified into five quintiles for the predicted 5-year risk of death from lung cancer.
"Participants at highest risk for lung cancer death accounted for a disproportionate share of the benefits of low-dose CT screening. For example, 77 of 88 CT-prevented lung cancer deaths (88%) occurred among the 60% of participants with a 5-year risk of lung-cancer death of 0.85% or more, whereas only 1% of prevented lung-cancer deaths occurred among the 20% of participants at lowest risk," the researchers said.
Restricting screening to the 60% of participants at highest risk for death from lung cancer within 5 years (more than 0.85%), as compared with the entire CT group, captured 88% of CT-preventable lung-cancer deaths, reduced the number of participants who would need to be screened to prevent one lung-cancer death from 302 to 161, and reduced the number of false-positive results per CT-prevented lung cancer death from 108 to 65. In contrast, the 20% of participants at lowest risk for lung cancer death accounted for almost none of the CT-prevented lung cancer deaths, the researchers said.