NCI stops large lung cancer trial early; CT tops x-ray screening
 | |
| Unenhanced chest CT lung window image reveals that lingula, right middle lobe, and both lower lobes show patchy, peripheral, rounded, peribronchial ground-glass opacities with air bronchograms. Image source: American Journal of Roentgenology |
The NLST, a randomized national trial involving more than 53,000 current and former heavy smokers aged 55 to 74, compared the effects of two screening procedures for lung cancer— low-dose helical CT and standard chest X-ray—on lung cancer mortality rates.
The NCI said it made a decision to announce the initial findings from the NLST after the trial’s independent Data and Safety Monitoring Board (DSMB) notified the NCI director that the accumulated data now provide a statistically convincing answer to the study’s primary question and that the trial should therefore be stopped. The investigators said they will inform the participants individually.
Both chest x-rays and CT scans have been used in efforts to find lung cancer early, according to researchers, who said this study examined the consequences of the screening methods on large, randomized populations, using death from lung cancer as the primary endpoint.
“This large and well-designed study used rigorous scientific methods to test ways to prevent death from lung cancer by screening patients at especially high risk,” said Harold Varmus, MD, NCI director. “Lung cancer is the leading cause of cancer mortality in the U.S. and throughout the world, so a validated approach that can reduce lung cancer mortality by even 20 percent has the potential to spare very significant numbers of people from the ravages of this disease. But these findings should in no way distract us from continued efforts to curtail the use of tobacco, which will remain the major causative factor for lung cancer and several other diseases.”
Starting in August 2002, the NLST enrolled about 53,500 men and women at 33 trial sites nationwide over a 20 month period. Participants were required to have a smoking history of at least 30 pack-years and were either current or former smokers without signs, symptoms or history of lung cancer.
Participants were randomly assigned to receive three annual screens with either low-dose helical CT (or spiral CT) or standard chest x-ray.
“Previous efforts to demonstrate that standard chest x-ray exams can reduce lung cancer mortality have been unsuccessful,” the researchers wrote.
The trial participants received their screening tests at enrollment and at the end of their first and second years on the trial. The participants were then followed for up to five years; all deaths were documented, with special attention given to the verification of lung cancer as a cause of death.
At the time the DSMB held its final meeting on Oct. 20, a total of 354 deaths from lung cancer had occurred among participants in the CT arm of the study, whereas a significantly larger 442 lung cancer deaths had occurred among those in the chest X-ray group. The DSMB concluded that this 20.3 percent reduction in lung cancer mortality met the standard for statistical significance and recommended ending the study.
“This is the first time that we have seen clear evidence of a significant reduction in lung cancer mortality with a screening test in a randomized controlled trial. The fact that low-dose helical CT provides a decided benefit is a result that will have implications for the screening and management of lung cancer for many years to come,” said Christine Berg, MD, NLST project officer at NCI.
The researchers also reported that an ancillary finding, which was not the main endpoint of the trial’s design, showed that all-cause mortality was 7 percent lower in those screened with low-dose helical CT than in those screened with chest x-ray. Approximately 25 percent of deaths in the NLST were due to lung cancer, while other deaths were due to factors such as cardiovascular disease. “Further analysis will be required to understand this aspect of the findings more fully,” they wrote.
“The results of this trial provide objective evidence of the benefits of low-dose helical CT screening in an older, high-risk population and suggest that if low-dose helical CT screening is implemented responsibly, and individuals with abnormalities are judiciously followed, we have the potential to save thousands of lives,” said Denise Aberle, MD, NLST national principal investigator for ACRIN.
The researchers added that the “population enrolled in this study, while ethnically representative of the high-risk U.S. population of smokers, was a highly motivated and primarily urban group that was screened at major medical centers. Thus, the results may not accurately predict the effects of recommending low-dose helical CT scanning for other populations.”
Aberle and colleagues plan to release a fuller analysis, with more detailed results, which will be prepared for publication in a peer-reviewed journal within the next few months.