Ilana Gareen

Ph.D., M.P.H.

Brown University

Associate Professor

NLST (Learn more about this study)

NLST-308

May 10, 2017

Outcomes associated with significant incidental findings in lung cancer screening

The National Lung Screening Trial (NLST) was designed to detect a difference in lung cancer mortality between patients screened with low-dose CT (LDCT) and those screened using chest X-ray (CXR). In 2011, the NLST reported a 20% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality for participants screened with LDCT as opposed to CXR. Based largely on these findings, LDCT screening is now a covered service for most individuals at high-risk of lung cancer.
In the course of LDCT screening, potentially significant abnormalities unrelated to lung cancer, commonly referred to as significant incidental findings (SIFs), are often detected. As lung screening becomes widely adopted, the high prevalence of these SIFs is a major concern. In the NLST, SIFs were detected in 10% of participants at the first screen and an average of 6% at each of the two incidence screens. Detection of a SIF frequently leads to additional diagnostic interventions, which increases the costs of screening as well as the risks associated with screening. Yet the impact of these LDCT-detected SIFs on patient morbidity and mortality remains unclear. Although there is evidence from smaller studies that SIFs are associated with the diagnosis of extrapulmonary cancers and with the detection of markers for cardiovascular disease, there are no similar data available from large multi-center trials. More importantly, there is no evidence linking the early detection of these abnormalities with a reduction in morbidity or mortality. In addition, no publications from large, multi-center, randomized trials of LDCT screening have reported information on complications associated with SIF detection. Further complicating the issue is that the outcomes associated with SIF detection are likely to be heterogeneous, differing according to the nature of the SIF and organ location. Research is needed to determine whether this early detection is associated with the reported reduction in all-cause mortality observed in the LDCT arm of the NLST, and to identify which SIF findings are likely to result in a cancer diagnosis, as well as those SIF findings most likely to be associated with complications during the post-screening period.
The NLST is the only large, multi-center, clinical trial with extended follow-up data available and provides a rich resource to evaluate the association between SIF detection and patient morbidity and mortality. This information is of vital importance, because as lung screening disseminates, identifying the SIFs for which follow-up enhances patient health, as opposed to the SIFs for which follow-up is likely unnecessary, is crucial to the success of lung screening programs. This project seeks to elucidate the potential health and mortality impacts associated with a SIF finding on LDCT. We will use data from the NLST to investigate the unintended downstream consequences of implementing LDCT screening. By describing and quantifying these consequences in the NLST population, we can anticipate the impact of screening implementation in the general population and provide information for the development of practice guidelines designed to maximize the health impact of LDCT lung screening and minimize any negative consequences.