Evolving Issues in Low-dose CT Lung Cancer Screening 

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Ongoing focus on quality control and continuous process improvement are essential, as for all high-quality cancer screening services.

—James L. Mulshine, MD, and Jeffrey Schneider, MD

Over a decade has passed since the start of the National Lung Cancer Screening Trial and more than 2 years since the first report indicating that this randomized study had demonstrated a significant reduction in lung cancer mortality with low-dose computed tomography (CT) screening.1 That favorable result has been reinforced with follow-up data,2 which have been complemented by other reports showing that this service can be delivered with more efficient management approaches (defined after the start of the National Lung Screening Trial).3,4 Moreover, techniques have evolved so that radiation exposures associated with low-dose CT screening can be comparable to routine mammography.

Broad Adoption

Following the lead of the National Comprehensive Cancer Network (NCCN), a number of professional organizations have endorsed low-dose CT screening in the high-risk group studied in the National Lung Screening Trial.5-9 A number of centers are collaborating to implement screening by adopting a disciplined approach incorporating best screening practices.10

In contemplating the broad adoption of low-dose CT screening, the medical community has been concerned with the information conveyed to potential screening candidates. Several observations are relevant in this regard.

First, a measure of screening benefit is the number of individuals needed to screen in order to prevent a lung cancer death. This measure of benefit is important since it relates to the absolute screening benefit, incorporating both relative risk reduction and absolute risk. For the National Lung Screening Trial, low-dose CT was associated with a number of individuals needed to screen of 320. By comparison, in the 50- to 59-year-old age group in which screening mammography has been universally recommended and reduces breast cancer mortality by 14%, the number of individuals needed to screen to prevent a breast cancer death is 1,339.11

The National Lung Screening Trial was designed to determine whether low-dose CT could reduce lung cancer mortality by 20%. A recent report suggested the benefit of low-dose CT could exceed this, if a more precise study entry tool were employed.12

Cost and Manageability

Moving beyond the question of low-dose CT efficacy, the most frequently discussed concern arises over the issue of the cost and manageability of population-based low-dose CT, particularly in relation to the high rate of so-called false-positive scans attributable to small pulmonary nodules. In 2002, the National Lung Screening Trial applied a nodule size criterion of just 4 mm to define a positive scan. A recent report reviewing the diagnostic workup efficiency in over 21, 000 prospective screening subjects from the International Early Lung Cancer Action Program (I-ELCAP) suggested that moving the invasive diagnostic workup threshold from 4 mm to nodules greater than 8 mm would have reduced diagnostic workups by 75%, while not significantly eroding curability.13

With regard to the issue of lung cancer screening cost, a detailed actuarial analysis showed that screening of all individuals at risk by National Lung Screening Trial criteria (while including the provision for smoking cessation counseling at screening) can be provided at a cost that is lower than that of mammographic screening.14 Major payers have begun to cover low-dose CT screening.

In light of the critical recommendation of the U.S. Preventive Services Task Force regarding coverage for this service as stipulated by the Affordable Care Act, it is worth noting that the National Lung Screening Trial found that low-dose CT was associated with a significant all-cause mortality reduction of 6.7%. This is a critical parameter for prevention trials and a benchmark that no previous cancer screening approach has ever achieved.


With continued improvement of CT imaging, tailored surgical approaches, refined screening eligibility criteria, and fuller integration of tailored smoking cessations efforts, the full benefit of lung cancer screening could continue to improve. However, ongoing focus on quality control and continuous process improvement are essential, as for all high-quality cancer screening services. ■

Dr. Mulshine is Professor, Internal Medicine, and Vice President of Research at Rush Medical College, Rush University, Chicago, and Dr. Schneider is Director of the Thoracic Oncology Program and Associate Professor of Medicine at SUNY Health Sciences Center at Stony Brook and Winthrop-University Hospital, New York.

Disclosure: Drs. Mulshine and Schneider reported no potential conflicts of interest.


1. Aberle DR, Adams AM, Berg CD, et al: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.

2. The National Lung Screening Trial Research Team: Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 368:1980-1991, 2013.

3. van Klaveren R, Oudkerk M, Prokop M, et al: Management of lung nodules detected by volume CT scanning. N Engl J Med 361:2221-2229, 2009.

4. Wagnetz U, Menezes RJ, Boerner S, et al: CT screening for lung cancer: Implication of lung biopsy recommendations. Am J Roentgenol 198:351-358, 2012.

5. Wood DE, Eapen GA, Ettinger DS, et al: Lung cancer screening. J Natl Compr Canc Netw 10:240-265, 2012.

6. Wender R, Fontham ET, Barrera E Jr, et al: American Cancer Society lung cancer screening guidelines. CA Cancer J Clin 63:107-117, 2013.

7. Jaklitsch MT, Jacobson FL, Austin JH, et al: The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thorac Cardiovasc Surg 144:33-38, 2012.

8. Bach PB, Mirkin JN, Oliver TK, et al: Benefits and harms of CT screening for lung cancer: A systematic review. JAMA 307:2418-2429, 2012.

9. Travis WD, Brambilla E, Noguchi M, et al: International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:244-285, 2011.

10. Lung Cancer Alliance: National framework for excellence in lung cancer screening and continuum of care. Available at http://www.lungcanceralliance.org/assets/docs/am-i-at-risk/NationalFramework.pdf. Accessed July 11, 2013.

11. Warner E: Breast cancer screening. N Engl J Med 365:1025-1032, 2011.

12. Tammemägi MC, Katki HA, Hocking WG, et al: Selection criteria for lung-cancer screening. N Engl J Med 368:728-736, 2013.

13. Henschke CI, Yip R, Yankelevitz DF, et al: Definition of a positive test result in computed tomography screening for lung cancer: A cohort study. Ann Intern Med 158:246-252, 2013.

14. Pyenson B, Sander M, Jiang Y, et al: An actuarial analysis shows that offering lung cancer screening as an insurance benefit would save lives at relatively low cost. Health Aff (Millwood) 31:770-779, 2012.

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