CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

Alissa K Greenberg,Ellen Eylers,Jun-Chieh Tsay,Georgeann Mcguinness,Kam-Meng Tchou-Wong,Ting-An Yie,Judith D Goldberg,William N Rom,Doreen Addrizzo-Harris,David Naidich,Bernard Crawford,Feng Lu,Abraham Chachoua,Harvey Pass,Juan P De Torres

doi:10.1371/journal.pone.0039403

Abstract

BackgroundLow-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant.MethodsWe performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128).ResultsThe NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas.ConclusionsNCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.

Highlights

Over 94 million current and former smokers are at increased risk for lung cancer, and might benefit from an effective screening test for early detection. [1,2] The challenge is to develop a screening strategy that will identify a small lung nodule, and specify whether the nodule is malignant before micro-metastasis occurs [3,4]
We review the demographic, clinical, and radiographic characteristics of individuals with nodules on their initial computed tomography (CT) compared to individuals with no nodules, and of our patients diagnosed with lung cancer compared to subjects with presumed-benign non-calcified nodules (NCNs)
To identify risk factors associated with increased risk of malignancy in patients found to have NCN on screening CT, we compared cases, defined as patients diagnosed with lung cancer, to controls, defined as individuals with presumed-benign NCNs which either resolved or remained stable for more than 3 years

Summary

Introduction

Over 94 million current and former smokers are at increased risk for lung cancer, and might benefit from an effective screening test for early detection. [1,2] The challenge is to develop a screening strategy that will identify a small lung nodule, and specify whether the nodule is malignant before micro-metastasis occurs [3,4]. Over 94 million current and former smokers are at increased risk for lung cancer, and might benefit from an effective screening test for early detection. The evidence from chest computed tomography (CT) screening studies conducted since the 1990’s show that the scans can detect early lung cancer, but at the cost of false-positive nodules in more than 25% of those screened [8,9,10,11,12]. Over 24% of screens were positive for non-calcified nodules (NCNs); more than 96% of these were found to be false-positive results on follow-up. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant

Methods

Results

Conclusion