NCI-Funded Study Finds Low-Dose CT Scans Better than X-Rays in Reducing Lung Cancer Mortality

The NCI has released the results of the almost 10-year National Lung Screening Trial (NLST), which compared two lung cancer-detecting techniques: low dose computed tomography (CT), known as spiral CT, and standard chest X-ray.  While both techniques are widely used, this is the first study to directly compare the efficacy of each. The NCI had released interim results in November 2010 after the trial’s independent Data and Safety Monitoring Board notified the NCI that the data provided enough statistically sound evidence that had fully addressed the trial’s primary question.  Christine Berg, MD, an NLST project officer for the study had stated that “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.”

Spiral CT depiction. Rotation of image aquisition apparatus (Tube and sensor array) around the patient. Source: Nevit Dilmen, Wikimedia Commons

354 deaths from lung cancer had occurred in the spiral CT arm compared to 442 lung cancer deaths in the X-ray arm by October of 2010. These results correspond to a 20% decrease in lung cancer mortality, a statistically significant result. In total, the rate of positive screening tests was 6.9% in the X-ray arm compared to 24.2% in the spiral CT arm. The results are published online in the New England Journal of Medicine (DOI:10.1056/nejmoa1102873) on June 29, 2011.

Overall, the rate of positive results was three-fold higher with CT scans compared to X-rays. CT scans were associated with a higher rate of false positives but the large majority of false positives were likely due to benign intrapulmonary lymph nodes or noncalcified granulomas, according to the study authors. These false positives were subsequently confirmed by subsequent CT scans. Complications arising from invasive diagnostic techniques were not common.

“Today’s publication gives researchers, policy makers, and the public full access to primary findings from the NLST to guide the use of low-dose helical CT scanning by current and former smokers,” said Harold Varmus, MD, the director of the NCI.  “The NCI marshaled the scientific and financial resources required for this expansive study, because only trials such as this allow us to say which methods of screening are effective, and how effective, in defined populations. Having a validated screening test that provides significant, but partial, protection against death from lung cancer complements – but should not be seen as replacing – ongoing efforts to control use of tobacco and to find other ways to prevent and treat lung cancer.”

The Trial Design and Caveats
A total of 53,454 current or former heavy smokers from 33 centers in the U.S. were enrolled throughout twenty months starting in August of 2002. All trial participants had smoked at least 30 pack-years and did not have either symptoms or signs of lung cancer. Participants were assigned randomly and received three annual screenings with either spiral CT or X-rays. Screenings were scheduled at enrollment, end of year 1 and year 2 of the trial, with final follow-up after another 5 years. If lung cancer was the cause of death, verification of lung cancer was confirmed. 

As discussed by the authors, the NLST trial results may be partly confounded by the “healthy volunteer” affect and may not fully reflect results seen in the real world. Additionally, since currently used scanners have evolved since this study and are likely better at detection, early screening with scanners today may result in an even larger reduction in deaths from lung cancer, with more false positive detected as well. As this study was conducted at medical institutions with radiology expertise, results seen here may not fully translate in a community setting where screening programs and medical care may not be as readily available due to cost, reimbursement, and other factors. Lastly, only three screenings were undertaken per patient. The reduction in rate of death from lung cancer may be even greater with ongoing spiral CT programs.