CT Screening Reduces Lung Cancer Deaths

Findings of a US lung cancer-screening trial reported a 20% reduction in lung cancer deaths among study participants who were screened with low-dose helical computed tomography (CT) versus those screened with chest X-ray.

Conducted by the American College of Radiology Imaging Network (ACRIN; Philadelphia, PA, USA) and the US National Cancer Institute’s Lung Screening Study Group, the National Lung Screening Trial (NLST) enrolled 53,000 current and former heavy smokers aged 55 to 74 at 33 sites across the United States. The NLST published online in the June 30, 2011, in the New England Journal of Medicine.

Most lung cancers are detected when they cause symptoms, by which time the disease is more likely to be advanced and less curable. “The trial results provide hard evidence of the mortality benefit from low-dose helical CT screening for lung cancer in an older and heavy smoker population. These findings, and the vast amount of additional data generated by the NLST that are still being studied, offer a rich resource of information that will inform the development of clinical guidelines and policy recommendations,” stated Denise R. Aberle, MD, the national principal investigator for NLST ACRIN, a deputy co-chair of ACRIN, professor of radiology and bioengineering and vice chair for research in Radiological Sciences at the University of California, Los Angeles (UCLA).

The nearly decade old trial, sponsored by the US National Cancer Institute (Bethesda, MD, USA), a part of the National Institutes of Health, enrolled participants, over a 20-month period, who were randomly assigned to receive three yearly screening examinations with either low-dose helical CT or standard chest X-ray.

The article provides important details about the number of screens that identified abnormalities potentially related to lung cancer and how many abnormalities were ultimately found to be cancer. The authors reported, “During the screening phase of the trial, 39.1% of participants in the low-dose helical CT arm and 16.0% of those in the chest X-ray arm had a positive screening result. Across all three screening examination rounds, when a positive result was found, 96.4% of the low-dose helical CT and 94.5% of the chest X-ray examinations were false-positive.”

William C. Black, MD, chair of the ACRIN Outcomes and Economics Committee and NLST site principal investigator at Dartmouth-Hitchcock Medical Center (Hanover, NH, USA) commented, “The follow-up for positive screening examinations most frequently involved further imaging tests and the data show that follow-up with invasive procedures was uncommon. We also found that lower rates of follow-up resulting from a positive scan occurred at later screening rounds.”

The vast majority of false-positive results was probably due to the detection of normal lymph nodes or inflamed tissues. Adverse events (damages resulting from the actual screening examinations) were few and relatively minor in the NLST. The rate of complications among participants who underwent a diagnostic evaluation prompted by a positive screening was under 2% for either type of screening.

“Although the NLST provides definitive evidence about the effectiveness of low-dose helical CT screening for lung cancer, significant further work is required to answer questions critical for the development of public policy recommendations,” stated Constantine Gatsonis, PhD, the director of the ACRIN Biostatistics and Data Management Center, and chair of biostatistics in the public health program of the Warren Alpert Medical School of Brown University (Providence, RI).

Additional studies based on NLST data--to include the use of statistical modeling--will determine significant data about which patient risk profiles, screening regimens and positive screen criteria result in the greatest screening benefit. As Dr. Gatsonis emphasized, “Given the considerable costs associated with low-dose helical CT screening, a cost-effectiveness analysis using the NLST data are underway that will guide decisions about the best use of finite health care resources.”

The NLST also provided a unique opportunity to further investigation of molecular biomarkers for the early detection of lung cancer. Specimens of blood, sputum, and urine collected at ACRIN sites are banked in the NLST-ACRIN Biorepository, as are specimens of early-stage lung cancer, all obtained with consent from NLST participants. This resource is available to the larger research community. “These specimens provide a rich resource to validate molecular markers that may complement imaging to detect early lung cancer,” noted Dr. Aberle. “By coupling biospecimen collection with imaging-based screening, the NLST-ACRIN Biorepository is relatively enriched for early clinical-stage lung cancers and associated biospecimens, and provides a unique resource of extremely well-characterized biospecimens with longitudinal data.”

“The knowledge that low-dose CT is a viable screening tool for detecting lung cancers at a curable stage is a tremendous first step for better understanding its implications for clinical care. Working with the Eastern Cooperative Oncology Group through the recently announced alliance, will allow us to extend these significant results to answer future questions critical for translating [these] findings into clinical practice,” said Mitchell D. Schnall, MD, PhD, ACRIN’s network chair and the Matthew J. Wilson professor of research radiology at the University of Pennsylvania (Philadelphia, USA). “Furthermore, ACRIN is engaged in a research project with Boston University [MA, USA] funded by the United States Department of Defense to investigate the role of blood and sputum-based laboratory tests to better define patient populations who would most benefit from lung cancer screening and, thereby, reducing false-positive screenings.”

Related Links:
American College of Radiology Imaging Network
US National Cancer Institute