The National Lung Screening Trial showed that a regular
screening program using CT scans can reduce lung
cancer deaths by as much as 20 percent. (Photo
courtesy National Cancer Institute. Daniel Sone,
The NLST had announced the initial results of the $250 milliontrial last fall showing that low-dose CT scans reduced lung-cancer and deaths from any cause overall compared to x-ray screening. The full report appears today in the New England Journal of Medicine but it won’t be the final report as the researchers will be undertaking further analyses to determine if the substantially higher costs of CT scans are worth it.
Co-author Dr. Constantine Gatsonis is the director of the American College of Radiology Imaging Network (ACRIN), which is a member of the National Cancer Institute Clinical Trials Cooperative Group that conducted the study. He says more work is needed before screening guidelines can be developed.
"Although the NLST provides definitive evidence about the effectiveness of low-dose helical CT screening for lung cancer, significant further work is required to answer questions critical for the development of public policy recommendations," said Gatsonis, who is also chair of biostatistics in the Public Health Program at the Medical School of Brown University. "Given the considerable costs associated with low-dose helical CT screening, a cost-effectiveness analysis using the NLST data is underway that will guide decisions about the best use of finite health care resources."
Overall there were a total of 1,060 lung cancers (645 per 100,000 person-years) diagnosed in the low-dose CT group, as compared with 941 (572 per 100,000 person-years) in the x-ray group.
A total of 356 lung cancer deaths occurred in the CT scan group compared to 443 lung cancer deaths in the x-ray group. This works out to 247 deaths per 100,000 person years in the CT scan group compared to 309 deaths per 100,000 person years in the x-ray group. That represents a 20 percent relative reduction in deaths for the CT screening group
There were 1,877 deaths from any cause in the low-dose CT group, as compared with 2,000 all-cause deaths in the radiography group. This represents a significant 6.7 percent reduction in deaths from all causes with low-dose CT screening compared to x-ray screening.
Dr. Ilana Gareen, epidemiologist for the ACRIN center and a co-author of the study told The Hub by e-mail that the reduced mortality rate resulting from screening this high-risk population needs to be weighed against the probability across three rounds of screening that 39.1 percent of the participants in the CT arm had at least one positive screening test, 24 percent of tests were positive, and 23 percent of those tests were false positive.
“The mortality benefits of screening for this high-risk population cannot be considered in a vacuum. The emotional and physical costs, as well as the potential complications must be considered,” said Gareen who is assistant professor of Epidemiology at Brown University. “In addition, the costs of screening and associated diagnostic work-up must be considered.”
Overall, she says more information is needed before CT screening is implemented on a widespread basis. Analyses are currently underway to address questions of the impact of screening on emotional and physical health, the cost-effectiveness of screening, and the medical-care utilization associated with screening.
Gareen said the cost comparison used in the study pegs a CT scan at $300, which is what Medicare pays. They did not compare that to x-rays because they have already been shown ineffective for preventing lung cancer deaths by the Prostate, Lung , Ovarian, and Colon Cancer screening study. The actual cost of a chest CT scan, however ranges widely from an average low of $1,050 in Arkansas to an average high of $7,400 in Ketchikan, Alaska. The national average ranges between $1,500 and $1,700 according to New Choice Health, a medical cost comparison website.
Last fall, after the initial review, the Data and Safety Monitoring Board (DSMB) for the study concluded that the 20 percent reduction in lung cancer mortality met the standard for providing a statistically convincing answer to the study’s primary question and recommended ending the study.
In the final results reported today, a total of 53,454 smokers were screened between Aug. 2002 and Sept. 2007. Participants were followed for events that occurred through Dec. 31, 2009. Eligible participants were between 55 and 74 years of age at the time they were enrolled, and had a history of cigarette smoking of at least 30 pack-years, or the equivalent of smoking two packs a day for 15 years. More than half of them were former smokers who had quit within the previous 15 years. A total of 26,722 were randomly assigned to screening with low-dose CT scans and 26,732 to screening with chest x-rays.
Participants were invited to undergo three screenings at one-year intervals, with the first screening performed soon after enrolling. The participants were followed for a median of 6.5 years, with a maximum duration of 7.4 years in each group.
In all three rounds there was a substantially higher rate of positive screening tests in the low-dose CT group than in the x-ray group. During the screening phase of the trial, 39.1 percent of the participants in the low-dose CT group and 16.0 percent of those in the x-ray group had at least one positive screening result. A total of 7.5 percent of the CT screening tests identified a clinically significant abnormality other than an abnormality suspicious for lung cancer compared to 2.1 percent for the x-ray group.
Of the total number of low-dose CT screening tests in the three rounds, 24.2 percent were classified as positive and 23.3 percent had false positive results. That compared to 6.9 percent of the total x-ray screens classified as positive and 6.5 percent classified as false positive in the three x-ray rounds. Across the three rounds of screening, 96.4 percent of the positive results in the low-dose CT group and 94.5 percent of those in the x-ray group were false positive results.
In addition, Gareen says statistical modeling efforts are underway using NLST data to address questions related to applying screening to other risk groups and to address the issue of optimal screening schedules.