Screening of People at High-Risk for Lung Cancer With Low Dose CT Scans Significantly Reduces Lung Cancer Deaths

The National Cancer Institute (NCI) released initial results from a large-scale clinical trial evaluating whether lung cancer screening with low-dose helical computed tomography (CT) or standard chest X-rays saves lives.

Lung cancer, most frequently caused by cigarette smoking, is the leading cause of cancer-related deaths in the United States. It is expected to claim 157,300 lives in 2010. There are more than 94 million current and former smokers in the United States, many of whom are at high risk of lung cancer. 

The American College of Radiology Imaging Network (ACRIN) and the Lung Screening Study group enrolled more than 53,000 current and former heavy smokers ages 55 to 74 into the National Lung Screening Trial (NLST) at 33 sites across the United States. The NLST, a randomized clinical trial, compared the effects of lung cancer screening with CT and X-ray on lung cancer mortality and found 20 percent fewer lung cancer deaths among trial participants screened with low-dose helical CT.  The NLST was sponsored by NCI, a part of the National Institutes of Health and is the largest randomized study of lung cancer screening in a high-risk population to date.

“Everyone who participated in this trial has played an important role in providing hard evidence of a mortality benefit from CT screening for lung cancer as well as a road map for public policy development in the future," states Denise R. Aberle, MD, the national principal investigator for NLST ACRIN, site co-principal investigator for the UCLA NLST team and a deputy chair of ACRIN. Aberle, a member of the UCLA Jonsson Comprehensive Cancer Center, professor of Radiology and Bioengineering and vice chair for Research in Radiology at UCLA, also emphasizes “Given the high association between lung cancer and cigarette smoking, the single best way to prevent lung cancer deaths is to never start smoking, and if already smoking, to quit permanently.” 

Starting in August 2002, participants were enrolled over a 20-month period and randomly assigned to receive three annual screens with either low-dose helical CT (often referred to as spiral CT) or a standard chest X-ray.  Helical CT uses X-rays to obtain a multiple-image scan of the entire chest compared to a standard chest X-ray that produces a single image of the whole chest in which anatomic structures overlie one another.

(For images go to www.acrin.org)

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 another five years; all deaths were documented, with special attention given to the verification of lung cancer as a cause of death.  The NCI’s decision to announce the initial findings from the NLST was made after the trial’s independent Data and Safety Monitoring Board (DSMB) notified the NCI director Harold Varmus, MD, that the accumulated data now provide a statistically convincing answer to the study’s primary question and that the trial should therefore be stopped.  At the time of the DSMB’s final meeting on October 20, 2010, 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.

An ancillary finding showed that all-cause mortality (deaths due to any factor, including lung cancer) 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.

“Many, many people across the country dedicated years of their lives to bring this study to its successful conclusion. They should take pride in the results of their efforts announced today. The main conclusion on the reduction of mortality due to lung cancer and the reduction of overall mortality constitute powerful evidence about the effectiveness of screening with helical CT,” says Constantine Gatsonis, PhD, the director of the ACRIN Biostatistics and Data Management Center, and professor of medical science and director of the Center for Statistical Sciences at Brown University.

In addition to collecting detailed information about the imaging screens and other clinical information, 15 NLST ACRIN sites collected and banked specimens of blood, sputum, and urine.  Tissue of trial participants’ lung cancer was also collected across most sites.  These specimens will provide a rich resource to validate molecular markers that may compliment imaging to detect early lung cancer.  "The NLST ACRIN biospecimens were collected at the time of each of the three screening exams.  There is major potential from these specimens to identify panels of genetic, protein and other molecular biomarkers of early lung cancer that can ultimately be translated into clinical practice,” says Aberle.

The NLST results reported today are initial mortality findings and many more analyses will be completed in the coming months. Research topics include medical resource utilization for CT and chest X-ray screening, overall cost effectiveness of CT lung cancer screening, the affect of screening on an individual’s quality of life and what early biomarkers can be validated in the biospecimen archive.

“Trial results of the importance of NLST can only be accomplished through a strong collaboration of a diverse team of investigators across the country generously contributing their time and effort.  Through everyone’s hard work, extensive trial data have been amassed and a biospecimen archive developed.  These resources will be instrumental for gaining additional insight about lung cancer and the most beneficial screening practices,” says Mitchell D. Schnall, M.D., Ph.D, ACRIN’s network chair and the Matthew J. Wilson Professor of Research Radiology at the University of Pennsylvania.

The possible disadvantages of helical CT include the cumulative effects of radiation from multiple CT scans; however, low dose CT, as employed in the study, uses approximately twenty percent of the dose of a conventional CT scan.  Also, surgical and medical complications are possible in patients who prove not to have lung cancer but who need additional testing to make that determination; and risks from additional diagnostic work-up for findings unrelated to potential lung cancer, such as liver or kidney disease. In addition, the screening process itself can generate suspicious findings that turn out not to be cancer in the vast majority of cases, producing significant anxiety and expense.   These problems must, of course, be weighed against the advantage of a significant reduction in lung cancer mortality.   

A fuller analysis, with more detailed results, will be prepared for publication in a peer-reviewed journal within the next few months.

A paper describing the design and protocol of the NLST, “The National Lung Screening Trial: Overview and Study Design” by the NLST research team, was published yesterday by the journal Radiology and is openly available at http://radiology.rsna.org/cgi/content/abstract/radiol.10091808.

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CT and X-ray images are available at www.acrin.org .

For a Q&A on the NLST, please go to http://www.cancer.gov/newscenter/qa/2002/nlstqaQA.  

For a Fact Sheet on the NLST, please go to http://www.cancer.gov/newscenter/pressreleases/NLSTFastFacts.

For more information on lung cancer and screening, please go to http://www.cancer.gov/cancertopics/types/lung.

“The National Lung Screening Trial: Overview and Study Design" has been published by Radiology. This paper is openly available at http://radiology.rsna.org/cgi/content/abstract/radiol.10091808.

ACRIN is an NCI-sponsored clinical trials cooperative group made up of investigators from over 100 academic and community-based facilities in the United States and abroad.  ACRIN’s oncology mission is to develop information through clinical trials of medical imaging that increase the length and quality of life of cancer patients.  ACRIN is administered by the American College of Radiology and is headquartered at the ACR Clinical Research Center in Philadelphia, PA. The ACRIN Biostatistics Center is located at Brown University in Providence, RI.