Lung Cancer Screening Needs to Remain State-of-the-Art

Claudia Henschke, MD, PhD

Director, Early Lung & Cardiac Action Program

Professor of Radiology

Mount Sinai Medical Center

In CT screening for lung cancer, the regimen of screening is a critical factor in diagnosing lung cancer early while limiting unnecessary tests and invasive procedures. This has been clearly demonstrated by comparing the results of two studies, one with and one without a well-defined regimen of screening. The study that used a regimen of screening had a significantly higher proportion of stage I lung cancer, the tumor size was smaller, and the frequency with which the cancer could be removed surgically was higher.¹

As a result, the cure rate was also significantly higher. Screening is increasingly being reimbursed by insurance carriers based on the US Preventive Services Task Force (USPSTF) report in 2013, which recommends annual screening for high-risk smokers aged 55 to 80.² Further, the Centers for Medicare & Medicaid Services recently announced that the agency plans to cover low-dose CT screening

for lung cancer in high-risk Medicare patients. It is increasingly being recognized that to maximize the benefit of screening and minimize potential harms, a regimen of screening must be used, and it requires continuous evaluation and updating to remain state-of-the art, incorporating the latest novel technical innovations and emerging screening data. For this purpose, large databases are needed to provide important information on findings that are identified by screening, particularly in annual rounds of screening where the data have previously been sparse.

Early on in CT screening for lung cancer, data from the Early Lung Cancer Action Project (ELCAP)^3-6 provided guidance that led to the recommendations for workup of nodules identified as a result of the screening. The expanded International Early Lung Cancer Action Program (I-ELCAP), with more than 31,000 participants who had CT screening, provided further information.^7-11

Currently, I-ELCAP has more than 66,000 participants and is using this accumulated evidence to develop the updated guidelines for the workup of findings resulting from CT screening for lung cancer.^12,13 It has been previously shown that the frequency of identifying noncalcified nodules—solid and subsolid—and the frequency of diagnosing lung cancer manifesting in such nodules is very different for the first, baseline round of screening when compared with all subsequent rounds of annual repeat screening.^3,4,14

Using the latest CT scanners, at least one noncalcified nodule is identified in 50% of baseline screenings but much less frequently (about 7%) in annual repeat screenings. Lung cancer is diagnosed much more frequently in the baseline round than in a single round of annual repeat screening. In the baseline round of screening, the probability of diagnosing lung cancer manifesting as a solid nodule is lower than the probability of diagnosing lung cancer manifesting in a sub-solid nodule. But this is reversed in annual repeat rounds where it is more likely to diagnose a cancer manifesting as a new solid nodule than in a new sub-solid nodule. The difference in the relative frequency of different cell-types in baseline and annual rounds of screening has been described.¹⁴

The relative frequency of adenocarcinoma decreases in annual rounds when compared with the baseline round, while it increases for squamous cell and small-cell carcinomas, reflected in the greater aggressiveness of the latter two cell types.

This difference between the baseline and the subsequent annual repeat rounds becomes important when annual rounds of screening are repeated as often as 24 times, according to the USPSTF recommendations for an individual who starts baseline screening at age 55. Unfortunately, these differences were not so apparent in randomized screening trials, such as the National Lung Screening Trial¹⁵ and NELSON,¹⁶ as they had only a few rounds of annual repeat screening, and thus the results are dominated by the baseline round.

In a long-term follow-up of patients in North America who were diagnosed with lung cancer through CT screening and underwent surgical resection of their cancer, 91% had clinical stage I disease and the estimated cure rate was 84% (95% CI, 80%-88%).¹⁷ This report also showed that minimally invasive surgery, as well as sublobar resection, has increased significantly since 2006. Thus, the I-ELCAP regimen provided a high cure rate for those diagnosed with lung cancer and the frequency and extent of surgery for nonmalignant disease was minimized.

In summary, adoption of a regimen that is continuously updated based on emerging technology and data results in a high frequency of diagnosis of early stage lung cancer, and when followed by judicious use of surgery, significantly improves cure rates and limits morbidity. These published results reflect the diagnostic workup and treatment of cases over the past 20 years, but as CT scanners, protocol, and clinician knowledge have improved over these past two decades, the results do not fully reflect what can be achieved today. Clearly, the earlier the cancer is detected, the more likely it is cured, and thus the currently published information provides a lower limit of what can be achieved today.

We believe that the essential and well-accepted requirement of screening programs and clinical practice is to inform the participant in a process of shared decision-making and that data provided by these large databases provide the necessary information.

Unfortunately, the rationale for the follow-up is still not completely known to most physicians, and there is an urgent need for development of consensus on management that does not result in unnecessary diagnostics and surgery.

References

1. Yip R, Henschke CI, Yankelevitz DF, et al. The impact of the regimen of screening on lung cancer cure: a comparison of I-ELCAP and NLST [published online vAugust 2, 2014]. Eur J Cancer Prev. doi:10.1097/ CEJ.0000000000000065.
2. Moyer VA. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(5):330-338.
3. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early lung cancer action project: overall design and findings from baseline screening. Lancet. 1999;354(9173):99-105.
4. Henschke CI, Naidich DP, Yankelevitz DF, et al. Early lung cancer action project: initial findings on repeat screenings. Cancer. 2001;92(1):153-159.
5. Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol. 2002;178(5):1053-1057.
6. Henschke CI, Yankelevitz DF, Naidich DP, et al. CT screening for lung cancer: suspiciousness of nodules according to size on baseline scans. Radiology. 2004;231(1):164-168.
7. Henschke CI, Yankelevitz DF, Miettinen OS, et al. Computed tomographic screening for lung cancer: the relationship of disease stage to tumor size. Arch Intern Med. 2006;166(3):321-325.
8. International Early Lung Cancer Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med. 2006;355(17):1763-1771.
9. New York Early Lung Cancer Action Project Investigators. CT screening for lung cancer: diagnoses resulting from the New York Early Lung Cancer Action Project. Radiology. 2007;243(1):239-249.
10. Henschke CI, Yankelevitz DF, Yip R, et al. Lung cancers diagnosed at annual CT screening: volume doubling times. Radiology. 2012;263(2):578-583.
11. 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. 2013;158(4):246-252.
12. International Early Lung Cancer Action Program Conferences and Consensus Statements. www.IELCAP.org. Accessed October 15, 2014.
13. International Early Lung Cancer Action Program protocol. www.IELCAP.org. Accessed October 15, 2014.
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15. National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395-409.
16. van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009;361(23):2221-2229.
17. Flores R, Bauer T, Aye R, et al. Balancing curability and unnecessary surgery in the context of CT screening for lung cancer. J Thorac Cardiovasc Surg. 2014;147(5):1619-1626.