BETHESDA, MD—The announcement from the National Cancer Institute of a 20% reduction in lung cancer mortality among older current or former smokers screened with low-dose helical (spiral) computed tomography is good news and has implications for public health and medical practice.
If further analysis of the $250 million, NCI-funded National Lung Screening Trial (NLST) bears out the initial results, the screening technique could potentially save tens of thousands of lives, since lung cancer is the leading cause of cancer deaths in the United States and globally.
NLST is the first randomized, controlled trial to show clear evidence of a significant reduction in lung cancer deaths from a screening test. Still, it is too early to make any recommendations based on these initial, unpublished results, emphasized NCI Director Harold Varmus, MD, and US cancer groups. “We're making no recommendations at this point,” he said.
NLST's initial results were released in a telebriefing held by the NCI here. The randomized clinical trial involved more than 53,000 current and former male and female heavy smokers aged 55 to 74 who had a smoking history of at least 30 pack years and were asymptomatic of lung cancer at the time of screening.
Trial participants at 33 US sites received three annual screens with either low-dose helical CT or with a standard chest x-ray; they were followed for at least five years.
The trial was carried out by the American College of Radiology Imaging Network (ACRIN) and the Lung Screening Study group. A paper on NLST's design and protocol from NLST's researchers was published online on Nov. 3 in the journal Radiology.
Applicable Only to High-Risk Population Subset in the Study
In announcing the results, Dr. Varmus emphasized that while the data from NLST are very encouraging and have important implications for public health strategies to cut down on lung cancer deaths, the data should in no way be interpreted to mean that screening prevents lung cancer or that smoking is any safer.
“Not smoking and quitting smoking remain important public health goals,” he said. He also stressed that these initial trial results are applicable only to the high-risk population subset studied, not to the general population of smokers or to younger smokers.
Asked by OT why the initial results showed a marked reduction in mortality in the helical CT screened group, Dr. Varmus said the assumption is that this screening technique detected smaller lung cancers that would have proved lethal earlier, tumors which were then surgically removed. He noted that some of the smaller tumors would probably never have proved lethal, but that the strength of the NLST study was using lung cancer mortality as the endpoint.
‘A Really Big Deal, and Really Good News’
OT Editorial Board Chairman Robert C. Young, MD, who is Chair of NLST's Oversight Committee, said of the announcement of initial trial results, “It is a really big deal, and it is really good news....trials in the past have been negative. I was very pleased.”
Dr. Young noted that he has been involved with NLST for some time; he sat on NCI's Board of Scientific Advisors when the trial was proposed. The board “had some concerns,” he said in a telephone interview. These concerns primarily revolved around the expense of the trial and whether patients would want to enroll. Enrollment started in August 2002.
“Lung cancer is not my field; I was a neutral figure,” said Dr. Young. He said he became a forceful advocate for NLST because he reasoned that if low-dose helical screening in this high-risk population turned out to have benefit, “it would be a huge advance, and one that we should pursue.” If, on the other hand, the screening procedure turned out to have no benefit, people should be informed that they should not be spending their money on a test that did not work.
Medicare and insurance companies currently do not pay for low-dose helical CT screening for lung cancer, Dr. Varmus noted. But he said that Donald Berwick, MD, Administrator of the Centers for Medicare and Medicaid Services (CMS), has expressed an interest in reviewing the published results of NLST when more of the trial data have been analyzed.
Dr. Young predicted that the encouraging results of NLST, when published in a peer-reviewed journal, will lead CMS to cover low-dose helical CT for the subset of high-risk, older, heavy smokers whose profile is similar to those participating in NLST. Dr. Young also noted that health insurers tend to follow CMS's lead when deciding whether to cover a medical test or procedure.
The American Cancer Society does not have a formal recommendation at this time based on the initial results of NLST, but its officials said that the organization might issue a statement in the future as more information from NLST becomes available.
In a statement, ACS Chief Medical Officer Otis W. Brawley, MD, said that the findings are important, but “as with any study of screening, there are also potential harms to be considered, such as potential overdiagnosis and needless surgeries. We have learned from the long-term analysis of other screening tests, such as mammography, that it is important to consider both benefit and harms associated with the test.
“That this finding occurs in a well designed prospective randomized trial is important, because it is most likely to give the correct answer,” he continued. “The NLST is an example of how to do good, responsible science. But we've also learned that promising initial results, even in large trials, are not always a sure bet. This study is strengthened by the fact that it showed the screening group had lower mortality from all causes, but we still must be cautious in interpreting the results before a full analysis is done.”
Dr. Brawley also emphasized that the finding should not weaken efforts to reduce and eliminate tobacco use, the number one cause of lung cancer, and that even if detecting lung cancer early reduces mortality, by far the best way to reduce deaths is by doing whatever is possible to prevent the disease.
He also noted the possible harms associated with CT scans: “the effects of radiation from multiple scans; complications in patients who go through additional testing only to find they did not have lung cancer; and the possibility that patients will go through additional procedures that are actually not related to a potential finding of lung cancer.”
Dr. Brawley said that it should also be noted that the study population, “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.”
The American Society of Clinical Oncology said it will be up to the medical community to decide how to translate NLST's findings into practice. “What has happened here is that the technology shows you can cut down on lung cancer deaths, the leading cause of cancer mortality, and save nearly as many lives as the number of people who die from breast cancer per year,” Bruce E. Johnson, MD, Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in a statement about the Society's perspective.
“We as a medical community now need to figure out how to do this in a way that the cost is acceptable to the public.”
NCI officials said a low-dose spiral CT scan costs several hundred dollars. Dr. Varmus cautioned that at this point the optimal frequency of such screening is not known, should screening eventually be offered. “We don't know the ideal way yet to do this screening,” he said.
Dr. Young said one of the major concerns when the NLST trial was being discussed was whether low-dose helical CT screening would pick up non-cancerous small nodules and lead to unnecessary invasive follow-up for patients. “I was concerned that there would be a lot of surgeries and that the risk would be substantial,” he said.
But, he said, the trial's Data Safety and Monitoring Board concluded that this risk was acceptable and not unreasonable. The false-positive rate in the helical CT screening group in NLST was 25%. Dr. Young noted that built into the trial's protocol was a structured way of managing small lesions with follow-up CT scans, so that there would be reasonable consistency in the way they were approached and treated. This structured protocol for management, he said, reassured him that there would not be an excessive amount of unnecessary thoracic surgical intervention.
NCI officials noted that potential disadvantages of helical CT screening include the cumulative effects of radiation from multiple CT scans; surgical and medical complications in patients who prove not to have lung cancer but undergo additional testing such as biopsies to find that out; and the expense and anxiety caused by follow-up testing for suspicious findings that turn out not to be cancer in the vast majority of cases.
Coming Next Issue - and Now Online
* Commentary about the study from James Jett, MD, Editor of the Journal of Thoracic Oncology and a long-time leader in lung cancer screening.
* News article by Lola Butcher about how some diagnostic imaging centers started preying on peopl's cancer fears within 72 hours of the announcement of the study's results.