Cumulative risk for a false-positive test using low-dose computed tomography in lung cancer screening

Abstract

CRA1502 Background: Screening with low-dose computed tomography (LDCT) has been promoted as the best hope for curing lung cancer. However, cumulative false-positive (FP) rates have never been formally reported. We quantified the cumulative risk of receiving ≥1 FP test for individuals in a lung cancer screening program with 2 annual screens. Methods: Prior to the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial of LDCT versus single-view chest xray (CXR), a randomized controlled feasibility trial was conducted at six NLST centers. Participants (55–74 years at entry, current or former smokers, and ≥ 30 pack/year smoking history) were offered a baseline LDCT (N = 1,610) or CXR (N = 1,580), and one repeat annual screen, and were followed for 1 year after their final screen. Participants who received at least one screening exam were eligible for this analysis. Exclusion criteria included chest CT in the past 24 months or history of lung cancer. A positive screen was any noncalcified nodule ≥ 4mm or other radiographic finding deemed suspicious for cancer. A FP was a positive screen with: 1) a completed negative work-up, or 2) ≥ 12 months follow-up with no cancer diagnosis. Results: Using a Kaplan-Meier analysis, an individual's cumulative probability of ≥ 1 FP LDCT was 21% (95% CI, 19%–23%) after one screen and 33% (95% CI, 30%–35%) after two. The cumulative probability of ≥ 1 FP CXR was 9% (95% CI, 8%–11%) and 15% (95% CI, 13%–16%) after one and two screens, respectively. On multivariable analysis, higher odds of FP for LDCT were associated with increased participant age (>64 years) (OR 1.34, 95% CI, 1.04–1.73); current versus former smoker status trended toward higher FP odds (OR 1.22, 95% CI, 0.95–1.56). 6.6% of participants with a FP LDCT underwent an invasive diagnostic follow-up procedure; 1.6% had major surgery. 4.2% of participants with a FP CXR underwent an invasive diagnostic follow-up procedure; 1.9% had major surgery. Conclusions: Risks of LDCT FP are substantial after only two annual examinations; the potential resulting economic, psychosocial, and physical burdens of this modality warrant investigation. No significant financial relationships to disclose.