• Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (DSG); Division of Cancer Prevention, National Cancer Institute, Bethesda, MD (PP); University of Alabama at Birmingham, Birmingham, AL (HN); Wake Forest University Health Science Center, Winston-Salem, NC (CC); Center for Statistical Sciences and Department of Biostatistics, Brown University School of Public Health, Providence, RI (FD); Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA (DRA). gieradad@wustl.edu.
• Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (DSG); Division of Cancer Prevention, National Cancer Institute, Bethesda, MD (PP); University of Alabama at Birmingham, Birmingham, AL (HN); Wake Forest University Health Science Center, Winston-Salem, NC (CC); Center for Statistical Sciences and Department of Biostatistics, Brown University School of Public Health, Providence, RI (FD); Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA (DRA).

BACKGROUND: Computed tomography (CT) screening for lung cancer has been associated with a high frequency of false positive results because of the high prevalence of indeterminate but usually benign small pulmonary nodules. The acceptability of reducing false-positive rates and diagnostic evaluations by increasing the nodule size threshold for a positive screen depends on the projected balance between benefits and risks.

METHODS: We examined data from the National Lung Screening Trial (NLST) to estimate screening CT performance and outcomes for scans with nodules above the 4mm NLST threshold used to classify a CT screen as positive. Outcomes assessed included screening results, subsequent diagnostic tests performed, lung cancer histology and stage distribution, and lung cancer mortality. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the different nodule size thresholds. All statistical tests were two-sided.

RESULTS: In 64% of positive screens (11598/18141), the largest nodule was 7 mm or less in greatest transverse diameter. By increasing the threshold, the percentages of lung cancer diagnoses that would have been missed or delayed and false positives that would have been avoided progressively increased, for example from 1.0% and 15.8% at a 5 mm threshold to 10.5% and 65.8% at an 8 mm threshold, respectively. The projected reductions in postscreening follow-up CT scans and invasive procedures also increased as the threshold was raised. Differences across nodules sizes for lung cancer histology and stage distribution were small but statistically significant. There were no differences across nodule sizes in survival or mortality.

CONCLUSION: Raising the nodule size threshold for a positive screen would substantially reduce false-positive CT screenings and medical resource utilization with a variable impact on screening outcomes.