Lung Cancer Screening: Actionable Evidence 


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This recent paper in The New England Journal of Medicine outlines the details of the clinical outcomes with two incidence screens that were conducted as part of the National Lung Screening Trial (NLST).1 In the wake of the positive review of the U.S. Preventive Services Task Force (USPSTF) draft recommendation, the results of this current report are being subjected to much greater scrutiny as the nation contemplates implementation of the new screening service. What emerges from this analysis is decidedly reassuring.

Key Findings

As outlined in the discussion in this issue of The ASCO Post, the NLST investigators found a 2.7-fold increase in the detection of lung cancers over the two intervals of screening in the spiral CT arm compared to the chest x-ray arm of the trial, and this finding resulted in a corresponding threefold decrease in the rate of screen-negative (ie, missed) lung cancers. In addition, the efficiency of the screening process improved, reflected in the ratio of suspected cancers to detected cancers, which went from 2.4% of 27.9% to 5.2% of 16.8% across the two screening intervals. Further, the rate of “futile” thoracotomies remained low, at 18.9% and 15.9%, respectively, across the two screening intervals.

These outcomes are favorable, although they might be improvable, but recall that the NLST protocol did not dictate the precise method of screening management.2 Therefore, these results truly reflect the “community” standard for screening outcomes, which suggests they may be generalizable as national screening is implemented.

False-Positives and Stage Shift

The discussion also reviews the critical issue of the definition of a false-positive nodule. The authors note that the NELSON research group uses a two-step process for interpreting nodule status that initially characterizes noncalcified nodules above a certain size as “indeterminate”; only nodules that show rapid growth are subsequently characterized as positive.3 This approach results in a lower rate of false-positive diagnoses and correspondingly reduces the stress on the screening subjects.

Another finding of this study was the emergence of a favorable stage shift.1 For a cancer screening approach to be truly successful, it must advance the diagnosis of detected cancers. This means that an increased number of cases must be found in a defined cohort at an early stage, and eventually this number would be offset by a correspondingly lower frequency of advanced-stage cancer cases found in that cohort.

This dynamic was in fact observed in this cohort, with the CT arm showing a higher frequency of curable stage I lung cancer detection and a lower frequency of stage III/IV at both intervals, compared to the x-ray arm. This stage shift is important, as it reflects the potential for increasing curative outcomes with the screening process.

Conclusions

These results are consistent with other recent screening reports, and the data in aggregate support the favorable recommendation for national implementation in high-risk individuals aged 55 to 74 years that was recently proposed by the USPSTF.4 Clearly, there is much to do in further improving this service, especially with regard to providing a consistent quality of screening care such as proposed in the Lung Cancer Alliance’s framework approach.5

The critical issue, however, is that the people of the United States invested a quarter of a billion dollars in the NLST trial. This very large, complex study was executed in a decisive fashion and provided an unambiguous answer that CT screening for lung cancer can be delivered and can save lives. This result can now be implemented nationally. If we execute this complex process and improve mortality outcomes for this most lethal cancer, then the national cancer program will have served its critical role.■

Dr. Mulshine is Associate Provost for Research and Director of the Translational Sciences Consortium at Rush Medical College, Chicago.

Disclosure: Dr. Mulshine reported no potential conflicts of interest.

References

1. Aberle DR, DeMello S, Berg CD, et al: Results of the two incidence screenings in the National Lung Screening Trial. N Engl J Med 369:920-931, 2013.

2. Aberle D, Adams A, Berg C, et al: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.

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. Humphrey LL, Deffebach M, Pappas M, et al: Screening for lung cancer with low-dose computed tomography: A systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med 159:411-420, 2013.

5. Lung Cancer Alliance: National Framework for Excellence in Lung Cancer Screening and Continuum of Care. Available at http://www.lungcanceralliance.org/get-information/am-i-at-risk/national-framework-for-lung-screening-excellence.html. Accessed October 9, 2013.


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