Screening for Lung Cancer: Moving Into a New Era Free

Jerome M. Reich, MD, Jong Sung Kim, PhD

Earle A Chiles Research Institute, Portland State University

January 24, 2014

Comment

We second Drs. Detterbeck’s and Unger’s ( 1) concern that, as in PSA and fifth decade mammographic screening, self-selection ( worried well, inappropriate age, serious comorbidities, limited risk) will lead to lung cancer screening a substantial number of persons for whom it is not recommended by U.S. Preventive Services Task Force ( 2), and in whom harm may outweigh benefit. We add these caveats:
1. The National Lung Screening Trial (NLST) findings do not accord with the Italian or Danish CT screening trial outcomes, which employed an unscreened control (vs. CXR screening of controls in the NLST). The Multicentre Italian Lung Detection study screened 4K participants, evaluated over 6-years, with 10K person-years of follow-up.(3 ) There were 20 lung cancer diagnoses in unscreened controls, 25 in biennial screenees and 34 in annual screenees. The number of lung–cancer-deaths/ (all-cause-deaths) was higher with more frequent screening: annual screenees 12/ (31); biennial screenees, 6/ (20); controls, 7/ (20). The Danish Lung Cancer Screening Trial involved 4K randomized persons, half CT-screened annually for five-years: There were 69 lung cancers in the screenees vs. 24 in the controls, with no reciprocal reduction in the number of advanced lung cancers. All-cause deaths were higher in screenees, 61 vs. 42 in controls (p=0.059).( 4)
2. The reported null value of CXR screening in the 30K NLST-eligible portion of the Prostate, Lung, Colorectal, Ovary (PLCO) trial (5 ) is suspect due to:1) biological implausibility reflecting variability of individual cancer growth rates; and 2) an unprecedented higher lung cancer incidence (520) in unscreened controls than in CXR screened intervention cohort (518) through 6 years of follow-up..
3. A deficit in long-term, post-surgical, disease-free survival, the bulk of which appears after a 6-year latency (Reich JM, Kim JS, Asaph JW, unpublished data), will prove harmful to those with clinically irrelevant lung cancers (overdiagnosed) who appear to constitute >40% of CT-screen-identified cases.( 6, 7)

   1.Detterbeck FC, Unger M. Screening for Lung Cancer: Moving Into a New Era (editorial). Ann Intern Med. Published online 31 December 2013 doi:10.7326/M13-2904
   2.Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. Published online 31 December 2013 doi: 10.7326/M13-2771
   3.Pastorino U, Rossi M, Rosato V, Marchiano A, Sverzellatig N, Morosi C, et al.
Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev 2012;21:308–15.
   4.Saghir Z, Dirksen A, Ashraf H, Bach KS, Brodersen J, Clementsen PF, et al. CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax. 2012;67(4):296-301.
  5.Oken MM, Hocking WG, Kvale PA, Andriole GL, Buys SS, Church TR, et al. Screening by chest radiograph and lung cancer mortality: the prostate, lung, colorectal, and ovarian (PLCO) randomized trial. JAMA 2011(306, No. 17):1865-73.
  6.Reich JM. A critical appraisal of overdiagnosis: estimates of its magnitude and implications for lung cancer screening (Review). Thorax 2008;63:377-83.
  7.Patz Jr EF, Pinsky P, Gatsonis C, Sicks JD, Kramer BS, Tammemägi MC, et al. Overdiagnosis in low-dose computed tomography screening for lung cancer.
JAMA Intern Med. doi:10.1001/jamainternmed.2013.12738
Published online December 9, 2013.