Denise R. Aberle, MD
Skepticism about the use of low-dose helical computed tomography (LDCT) for early screening of lung cancer has abated in light of recent findings from the National Lung Screening Trial (NLST), which revealed that participants who received these scans had a 20% lower risk of dying from lung cancer than participants who received standard chest x-rays. Now that the data are in, healthcare institutions are considering early computed tomography (CT) screening programs for at-risk patients. This will necessitate the development of recommended standards for the use of these programs.
Denise R. Aberle, MD, one of the principal investigators in the trial, summarized key points from the NLST in August at the 12th International Lung Cancer Congress. In this exclusive interview, Aberle, vice chair of research and professor of both Radiological Science and Bioengineering at UCLA, addressed the challenging issues that need to be considered now that these pivotal data have been released.
Discuss some of the skepticism that you encountered—both prior to and during the NLST trial— regarding the relationship between CT screening and improved mortality.
Randomized trials were conducted in the 1970s using chest x-ray (CXR) and sputum to determine whether screening would reduce lung cancer mortality. A primary observation was that CXR/sputum screening resulted in a significant increase in the diagnosis of early-stage lung cancers, but no decrease in the detection of late-stage cancers and no reduction in lung cancer mortality. Many have attributed these results to overdiagnosis, meaning that screening identified very indolent lung cancers that would not result in death, while failing to detect cancers at an early stage that would otherwise have progressed to advanced stage and death.
Similar concerns have been raised with CT screening and the NLST. The skepticism regarding the NLST was based on the concern that screening would result in overdiagnosis and would subject individuals with positive screens to unnecessary and potentially harmful additional procedures (eg, radiation, biopsies, surgery, emotional distress), while not achieving a reduction in lung cancer mortality.
I believe that scientific skepticism is what keeps medical research honest. In fact, it was because of skepticism that this randomized trial was so necessary.
Can you describe your specific involvement in the NLST?
The NLST was sponsored by the National Cancer Institute (NCI) and represents the union of two research teams: a grant to the American College of Radiology Imaging Network (ACRIN) sponsored by the Cancer Imaging Program, Division of Cancer Treatment and Diagnosis; and a contract called the Lung Screening Study administered through the Division of Cancer Prevention. I was the PI for the ACRIN group and was responsible for 23 of the 33 sites that participated in the NLST. Christine Berg, MD, chief of the Early Detection Research Group, was the project officer for the NLST Lung Screening Study.
The primary objective of the NLST—to determine whether LDCT reduced lung cancer mortality relative to CXR in high-risk individuals—was harmonized across all 33 NLST sites. However, beyond this fundamental epidemiologic question, ACRIN addressed a host of companion questions that examine the following issues: (1) the effects of screening—and of positive screening results—on patients’ quality of life and anxiety levels; (2) a formal cost-effectiveness analysis of the NLST; (3) the creation of a biospecimen archive for purposes of validating biomarkers of risk and of early lung cancer; and (4) the effects of screening on smoking behaviors and beliefs.
As the ACRIN PI, I was centrally involved in the coordination of all substudies. I helped to determine the hundreds of data elements to be captured, developed the case report forms, and established all ACRIN study procedures. I worked with ACRIN’s regulatory team to develop site auditing and monitoring procedures and participated in some of the audits. I ran several monthly ACRIN NLST calls with site investigators, study coordinators, our NCI sponsor, and the various executive committees; assembled specific committees to ensure optimal operations and procedures (ie, the medical physics committee and the protocol and operations committee); ran the biannual NLST Working Group meetings where we discussed progress, problems, and procedures; represented ACRIN in our biannual meetings of the Data and Safety Monitoring Board and our NLST Oversight Committee; cajoled individual investigators and collaborators and functioned as cheerleader for the team; and helped to conduct the NLST at my own site at UCLA.