CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohort

Our plain-English summary of CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohort, by A.K. Greenberg, F. Lu, J.D. Goldberg, et al (PloS One, 2012).

The study

• Authors: A.K. Greenberg, F. Lu, J.D. Goldberg, E. Eylers, J.C. Tsay, T.A. Yie, D. Naidich, G. McGuinness, H. Pass, K.M. Tchou-Wong, D. Addrizzo-Harris, A. Chachoua, B. Crawford, W.N. Rom
• Journal: PloS One
• Published: 2012;7(7):e39403
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Low-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.

Methods: We 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).

Results: The 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.

Conclusions: NCNs 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.

In plain English

This New York University study screened 1182 heavy smokers over 50 years of age with low-dose CT scans. Participants were recruited between 2001 and 2010, and some were followed for up to 10 years. Some were referred by a utility workers' union. The authors considered 171 participants (14.5%) to have confirmed asbestos exposure, based on both work history and CT changes such as pleural plaques or asbestosis. The article did not name fiber types. More than half (52.7%) had non-calcified lung nodules over 4 mm, and most nodules stayed stable. Thirty patients were diagnosed with 33 lung cancers. Older age, male gender and emphysema were linked to having nodules. Asbestos exposure was not significantly associated with nodules. The 30 lung cancer patients were compared with 128 people with presumed-benign nodules. The cancer patients had lower lung function, more pack-years of smoking, and more and larger nodules. Asbestos exposure showed no significant association in that comparison. Nine of the 30 cancer patients had significant occupational asbestos exposure. The authors concluded that some screen-detected cancers grow slowly and may contribute to over-diagnosis and lead-time bias.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Longitudinal lung cancer biomarker study with low-dose CT screening, analysed as two case-control comparisons: people with nodules versus no nodules, and lung cancer patients versus people with presumed-benign nodules
• Who was studied: 1182 people over 50 years of age with more than 20 pack-years of smoking, recruited by the NYU Lung Cancer Biomarker Center in New York between March 2001 and June 2010. Recruitment included the utility workers' union of Con Edison (201 referrals).
• Exposure: Cigarette smoking, plus possible asbestos exposure. 171 participants (14.5%) were classed as having confirmed asbestos exposure, based on both employment history and CT changes (pleural plaques, pleural thickening and/or fibrosis consistent with asbestosis). Fiber types were not named.
• Main results:
  • 52.7% of all participants had non-calcified nodules over 4 mm on either their initial or follow-up CT scans.
  • Among nodules with follow-up scans, 84.5% of solid nodules and 54.5% of sub-solid nodules remained stable.
  • 33 lung cancers were diagnosed in 30 patients.
  • In the comparison of people with nodules versus no nodules, increasing age, male gender and emphysema were the only significant predictors of having a nodule.
  • In the same comparison, asbestos exposure was not significantly associated with having nodules.
  • Compared with the 128 people with presumed-benign nodules, the 30 lung cancer patients had significantly lower FVC and FEV1 percent-predicted and significantly higher mean pack-years of smoking.
  • Lung cancer patients had more nodules than people with benign nodules (average total number 5.3 versus 1.7).
  • In the cancer versus benign-nodule comparison, no significant association was found for age, gender, BMI, family cancer history, asbestos exposure or respiratory symptoms.
  • Of the 30 lung cancer patients, 9 had significant occupational asbestos exposure (average 32 years), and 4 had asbestosis and/or pleural plaques on CT.
  • Seven patients had surgery for suspicious nodules that turned out not to be lung cancer. The diagnoses listed included mesothelioma; its site was not stated.
  • In 12 patients (13 cancers), nodules seen on the first CT were stable for a time before growing. All but one of these were stable for more than 3 years before diagnosis.
• The authors' conclusion: The authors concluded that reduced FEV1 and FVC, smoking history and multiple sub-solid nodules were the strongest predictors of lung cancer in people with nodules. They also concluded that some screen-detected cancers are indolent, raising concerns about over-diagnosis and lead-time bias.
• Limitations the authors state:
  • Follow-up was shorter for many of the incident cancer cases.
  • Actual asbestos exposure was difficult to assess, so 'confirmed' exposure was defined as both an occupational history and CT changes.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: CT Scan, Lung Cancer, Low-Dose CT Screening, Biomarker, Discovery, Asbestos Exposure, Adenocarcinoma, FEV1.

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