A retrospective analysis of the National Lung Screening Trial (NLST) by Pinsky et al, summarized in the April 25, 2022, issue of The ASCO Post, found high rates of incidental respiratory abnormalities on low-dose computed tomography (CT) examinations.1 Specifically, the findings of emphysema and reticular pattern were associated with an increased respiratory disease mortality, even when controlling for a history of emphysema or chronic obstructive pulmonary disease (COPD).
With a rise in lung cancer screening, even during the COVID-19 pandemic,2 providers will be faced with challenges in the management of incidental respiratory disease findings on low-dose CT examinations. These challenges include an opportunity to act early on evaluating incidental findings and provide health-care recommendations to potentially affect health outcomes.
Incidental Respiratory Findings on Low-Dose CT Examinations
The authors analyzed data from 25,002 subjects in the NLST cohort who received a baseline and at least one subsequent low-dose CT examination; 23,574 received all three screenings within the trial. Subject demographics, smoking history, and medical history (including respiratory disease history) were captured in a baseline questionnaire.
Ryan Nguyen, DO
Lawrence E. Feldman, MD
Mary M. Pasquinelli, DNP, FNP-BC
Prior to screening, emphysema, chronic bronchitis, or COPD was reported by 17.3% of subjects on the baseline questionnaire, with emphysema or COPD reported by 10.6%. Findings of emphysema and reticular opacities on low-dose CT were reported in 44% and 37% of subjects, respectively. Other incidental findings included pleural thickening or effusion in 6% of subjects and adenopathy, atelectasis, and consolidation inup to 3%. Only a small fraction (about 20%) of subjects with emphysema observed on low-dose CT scanning self-reported a prior emphysema diagnosis.
Respiratory Disease Mortality Associated With Incidental Findings
Among subjects with no history of COPD or emphysema, 10-year respiratory disease mortality ranged from 4% for those with emphysema and/or reticular opacities on low-dose CT to 1.1% for those with neither condition on imaging. For those with COPD or emphysema, 10-year respiratory disease mortality ranged from 17% with either emphysema or reticular opacities on imaging to 3.7% for those with neither.
Emphysema on low-dose CT was associated with a significantly increased risk of respiratory disease mortality (hazard ratio [HR] = 2.27, 95% confidence interval [CI] = 1.92–2.7), as were reticular opacities (HR = 1.39, 95% CI = 1.19–1.62). The effects of emphysema and reticular opacities seemed to have an additive impact, with both findings having the highest respiratory disease mortality risk. Demographic factors found to be associated with an increased risk of respiratory disease mortality were older age, male sex, current smoking, more than 50 pack-year history, history of pneumonia, and history of asthma.
Challenges With Interventions for Incidental Findings
As reported by the authors of the NLST analysis, two necessary conditions for a substantial benefit of reporting incidental findings follow:
- The finding must be relatively common and associated with an increased risk of a negative outcome.
- Early detection should lead to improved outcomes.
Although these data suggest that the first condition is true, the second condition is less certain in a disease such as emphysema, for which there is no specific treatment. However, reporting the diagnosis may support a decision to quit smoking as well as motivate treatment for COPD.3,4
The study was not designed to determine whether subjects with abnormal respiratory imaging had diagnostic or therapeutic interventions. However, the authors concluded that findings were often regarded as not clinically significant, and follow-up could be assumed to have not been intensive.
Incidental Findings Are Common in Low-Dose CT Examinations
This study adds to the literature on incidental findings during lung cancer screening. Due to the various approaches in the reporting of screening incidental findings, rates of incidental findings span a wide range. Two studies of lung cancer screening programs in the United States reported incidental finding rates of 41% to 94%, although just 2% to 13% of patients required further evaluation.5,6
“There is currently no consensus among professional organizations on the detection, reporting, or management of incidental findings at CT screening for lung cancer.”— Ryan Nguyen, DO, Lawrence E. Feldman, MD, and Mary M. Pasquinelli, DNP, FNP-BC
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Coronary artery calcification and emphysema remain the most reported incidental findings, and they have been argued to represent opportunistic findings due to their representation as smoking-related diseases.7 There is currently no consensus among professional organizations on the detection, reporting, or management of incidental findings at CT screening for lung cancer.
Low-Dose CT as an Opportunity to Improve Respiratory Health
The findings of Pinsky et al reinforce the notion that patients who are candidates for low-dose CT are at high risk for respiratory disease and associated mortality, regardless of whether a lung cancer diagnosis is made. A key question that arises from this study is: “Should screening for COPD be undertaken in the setting of low-dose CT to alert clinicians and participants to the presence of early lung disease?”
In addition to the NLST showing a 20% reduction in lung cancer mortality, it also showed an overall mortality reduction of 6.7%,8 pointing to the importance of incidental findings on low-dose CT scans and to potential opportunities to improve upon this mortality reduction. Smoking cessation rates have been found to be strongly associated with the amount of abnormality detected on low-dose CT scans, including scans negative for lung cancer with other clinically significant abnormalities.9 With standardized reporting of incidental findings such as emphysema on low-dose CT scans, and proper messaging regarding results, lung screening can serve as a “teachable moment” to improve lung health outcomes. A tailored approach and interventions that focus on smoking cessation and potentially other preventive measures such as annual influenza vaccinations, pneumococcal vaccination, increased physical activity, and possible medications could offer such individuals an opportunity to prevent decline in their lung health and quality of life.
“With standardized reporting of incidental findings … on low-dose CT scans, and proper messaging regarding results, lung screening can serve as a ‘teachable moment’ to improve lung health outcomes.”— Ryan Nguyen, DO, Lawrence E. Feldman, MD, and Mary M. Pasquinelli, DNP, FNP-BC
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“As lung screening programs are initiated and expanded across the United States, more research regarding incidental findings, interventions, and outcomes is needed.”— Ryan Nguyen, DO, Lawrence E. Feldman, MD, and Mary M. Pasquinelli, DNP, FNP-BC
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The U.S. Preventive Services Task Force and the Centers for Medicare & Medicaid Services lung cancer screening guidelines were recently revised, decreasing the starting age criteria to 50 years and the smoking history to 20 pack-years. As lung screening programs are initiated and expanded across the United States, more research regarding incidental findings, interventions, and outcomes is needed.
DISCLOSURE: Dr. Nguyen, Dr. Feldman, and Dr. Pasquinelli reported no conflicts of interest.
REFERENCES
1. Pinsky PF, Lynch DA, Gierada DS: Incidental findings on low-dose CT lung cancer screenings and deaths from respiratory diseases. Chest 161:1092-1100, 2022.
2. Fedewa SA, Bandi P, Smith RA, et al: Lung cancer screening rates during the COVID-19 pandemic. Chest 161:586-589, 2022.
3. Lindsay HG, Wamboldt FS, Holm KE, et al: Impact of a medical diagnosis on decision to stop smoking and successful smoking cessation. Chronic Obstr Pulm Dis 8:360-370, 2021.
4. Steiger D, Siddiqi MF, Yip R, et al: The importance of low-dose CT screening to identify emphysema in asymptomatic participants with and without a prior diagnosis of COPD. Clin Imaging 78:136-141, 2021.
5. Kinsinger LS, Anderson C, Kim J, et al: Implementation of lung cancer screening in the Veterans Health Administration. JAMA Intern Med 177:399-406, 2017.
6. Morgan L, Choi H, Reid M, et al: Frequency of incidental findings and subsequent evaluation in low-dose computed tomographic scans for lung cancer screening. Ann Am Thorac Soc 14:1450-1456, 2017.
7. Tsai EB, Chiles C, Carter BW, et al: Incidental findings on lung cancer screening: Significance and management. Semin Ultrasound CT MR 39:273-281, 2018.
8. Aberle DR, Berg CD, Black WC, et al: The National Lung Screening Trial: Overview and study design. Radiology 258:243-253, 2011.
9. Tammemägi MC, Berg CD, Riley TL, et al: Impact of lung cancer screening results on smoking cessation. J Natl Cancer Inst 106:dju0842014, 2014.
Dr. Nguyen is Chief Fellow in Hematology/Oncology at the University of Illinois, Chicago. Dr. Feldman is Professor in the Division of Hematology/Oncology at the University of Illinois Chicago and the Jessie Brown VA Medical Center.Dr. Pasquinelli is a nurse practitioner and Doctor of Nursing Practice specializing in lung cancer screening in the Division of Pulmonary, Critical Care, Sleep, and Allergy at the University of Illinois, Chicago.
