False-positive screens and lung cancer risk in the National Lung Screening Trial: Implications for shared decision-making

Abstract

Objectives Low-dose computed tomography lung cancer screening has been shown to reduce lung cancer mortality but has a high false-positive rate. The precision medicine approach to low-dose computed tomography screening assesses subjects' benefits versus harms based on their personal lung cancer risk, where harms include false-positive screens and resultant invasive procedures. We assess the relationship between lung cancer risk and the rate of false-positive LDCT screens. Methods The National Lung Screening Trial randomized high-risk subjects to three annual screens with low-dose computed tomography or chest radiographs. Following the completion of National Lung Screening Trial, the Lung CT Screening Reporting and Data System (Lung-RADS) classification system was developed and retrospectively applied to National Lung Screening Trial low-dose computed tomography findings. The rate of false-positive screens (by Lung-RADS) and the resultant invasive procedures were examined as a function of lung cancer risk estimated by a model. Results Of 26,722 subjects randomized to the low-dose computed tomography arm, 26,309 received a baseline screen and were included in the analysis. The proportion with any false positive over three screening rounds increased from 12.9% to 25.9% from lowest to highest risk decile, and the proportion with an invasive procedure following a false positive also significantly increased from 0.7% to 2.0% from lowest to highest risk decile. Conclusion These findings indicate a need for personalized low-dose computed tomography lung cancer screening decision aids to accurately convey the benefits to harm trade-off.

Primary care providers’ views on a future lung cancer screening program

“…Screening Trial Pilot in the United Kingdom (3) suggested that screening with low dose CT scans (LDCT) significantly reduces mortality from lung cancer among high risk individuals aged 55 to 74 years as compared to chest x-rays. In the NLST, there were potential harms associated with LDCT screening (4).…”

Circulating ensembles of tumor‐associated cells: A redoubtable new systemic hallmark of cancer

“…However, the probability of a future clinical presentation of cancer in these 392 asymptomatic individuals (with C‐ETAC positivity) cannot be presently predicted, nor can the “clinical false‐positive” fraction, that is, those individuals among the 392 in whom cancer will not manifest clinically in their lifetimes. Hypothesizing that the cancer will not clinically manifest in any of the 392 individuals among the total 10,625 yields a hypothetical‐maximum false‐positive rate of 3.7% which is yet significantly and unambiguously lower than the false positives observed for LDCT (12.9–25.9%), mammography (7–12% at first mammogram and 50–60% after 10 yearly mammograms) and CA markers (e.g., 66% for PSA, 29% for CA‐125, 10–60% for CA19‐9) which are routinely used in early detection screening. Radiological scans such as LDCT and mammography not only have high false positive rates, but are also nonconfirmatory, that is, necessitate an invasive biopsy for histopathological confirmation of suspected malignancy, as well as being associated with radiation exposure risks .…”

Risk prediction models versus simplified selection criteria to determine eligibility for lung cancer screening: an analysis of German federal-wide survey and incidence data

“…False-positive screen tests can cause major harm especially when they lead to further, invasive medical investigations. An analysis of NLST trial data showed that, even within the limits of NLST eligibility criteria, the ratio of true-positive lung cancer diagnoses over invasive diagnostic work-up (bronchoscopic or surgical biopsies) triggered by a false-positive screen-test can still vary substantially according to individuals' 5-year lung cancer risk, from about 1.35 in the lowest risk deciles of the PLCO M2012 risk score (i.e., 5-year risk < 1.0%) to about 5.0 in the highest decile (5-year risk ≥ 6.5%) [36]. These findings indicate that the balance between expected benefit of screening (life years gained through mortality reduction, for expected true test positives) versus the risk of undergoing invasive diagnostic investigations following a false-positive screen test will depend not only on an individual's number of screening participations, but also on a person's actual lung cancer risk.…”