The National Lung Screening Trial (NLST), a randomized, national trial involving 53,000 current and former heavy smokers, compared the effects of 2 screening procedures for lung cancer—low-dose helical computed tomography (CT) and standard chest x-ray— on lung cancer mortality. In November, the study authors reported 20% fewer lung cancer deaths among trial participants screened with CT scans.
In its wake, patient advocate groups are calling for swift implementation of national screening guidelines, while researchers are pursuing follow-on studies that will both refine testing protocols and expand the scope of the study.
The results were particularly striking because there are no early-screening protocols in place for lung cancer, and, in their absence, few of these tests are now performed. The disease kills nearly 80% of the approximately 200,000 people treated for it each year—more than any other cancer—in large part, researchers say, because the majority of lung cancers are detected at later stages. Participants in the trial were asymptomatic.
“Effective screening changes the nature of the disease,” noted Bruce E. Johnson, MD, director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute and a professor at Harvard Medical School, Boston, Massachusetts. “We take care of many lung cancer patients too often after the horse is out of the barn. Most people we see end up dying.”
“If we can change outcomes for 40,000 people a year, that would be almost the numbers of deaths from pancreatic and head and neck cancer combined,” said Mary E. Reid, PhD, an oncology professor and director of collaborative research for the Department of Medicine at Roswell Park Cancer Institute, Buffalo, New York. NCCN Guideline Changes Are Under Consideration
Indeed, the results are so compelling that cancer experts, while noting that the study awaits peer review, are acting on them nonetheless.
“The control group in this study got chest x-rays, while the control in the real world gets nothing, so this may underestimate the true benefit,” said Douglas E. Wood, MD, a professor and chief of general thoracic surgery at the University of Washington School of Medicine in Seattle. Wood, who is chairman of the lung cancer screening committee for the National Comprehensive Cancer Network (NCCN), says the screening panel will likely release its guidelines by late spring.
“We have decided that we don’t need to wait for publication of the NLST results to publish our guidelines. A lot of people depend on the NCCN for guidance and our goal is to get the best data to physicians and patients as soon as possible,” he said. “It is no problem for us to refine our information as it becomes available. And we expect there will be new information coming that we will work in—better and more information.”
Wood declined comment on the guidelines, which will address both whom to screen and how best to screen, but noted that the NLST “gave us better data to talk about” and “a stronger validation of screening than any study that exists to date.”
He called publication and peer review important steps, while adding, “We’re enthusiastic and look to see details in forthcoming publications that validate the study results. And so, presuming that this follows as expected, this is an enormous, radical, major sea change in lung cancer detection and management—the largest in our lifetime.”
While cautioning that the NLST results apply only to the group studied, current or former heavy smokers who are 55 to 74 years old, Christine Berg, MD, chief of the NCI’s Early Detection Research Group and project officer for the study, said recently that individuals within that population “should have a conversation with their physicians about their options.”
Research studies that build on the NLST findings—some long underway and others still in the proposal stage—will refine its results by better defining the population of high-risk patients who would benefit most from screening and, following that, more invasive testing if nodules are discovered.
NCI points to studies indicating that 20% to 60% of screening CT scans of current and former smokers will show abnormalities, such as scars from smoking, areas of inflammation, and other noncancerous conditions. Most abnormalities are not lung cancer, the agency notes, and biopsies can cause partial lung collapse, among other complications. More major chest surgery to remove larger amounts of tissue poses even greater risks for patients with heart or lung conditions.
“The number of false positives is not trivial and so the clinical screening guidelines will have to be refined in the future,” said Reid.Looking to Biomarkers for Clues
The hunt for valid biomarkers to identify patients most likely to develop cancer is central to much of this research.