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Communications to the Editor |

Hazards of Lung Cancer ScreeningHazards of Lung Cancer Screening: Three Vignettes and a Critique FREE TO VIEW

Jerome Reich, MD, FCCP
Author and Funding Information

Affiliations: Center for Health Research, Kaiser Foundation Hospitals Portland, OR,  Denver, Colorado

Correspondence to: Jerome Reich, MD, FCCP, Center for Health Research, Kaiser Permanente, NW Region, 3800 North Kaiser Center Dr, Portland, OR 97227-1098; e-mail: Reichje@dnamail.com



Chest. 2001;119(2):659-673. doi:10.1378/chest.119.2.659
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The recently published article in CHEST by Kennedy et al (April 2000, Supplement 1),1 advocating lung cancer screening, contained a number of errors and it omitted mention of the potential for adverse consequences of this policy, both for true- and false-positives, exemplified by the following vignettes. The case radiographs are analogous to screening films because they were not obtained to investigate symptoms suggestive of lung cancer.

1. A 3-cm mass was identified in a 55-year-old heavy smoker. We were unable to exclude malignancy, and he underwent an uncomplicated pulmonary resection for a granuloma. I last saw him a few years later in an ICU where he was dying of respiratory failure. Comment: In contradistinction to other neoplasms for which screening is advocated, one can live as long (if not as well) when lacking part or all of one’s breast, uterus, colon, or prostate. Individuals who undergo pulmonary resection frequently have COPD. Loss of lung tissue advances the time to respiratory failure by roughly 4 years per resected segment. Anatomic distortion of the bronchial tree, in combination with pleural scarring, predisposes to the development of pneumonia. Hypoxemia in combination with respiratory infections would be expected to hasten mortality from comorbid coronary artery disease.

2. A 3-cm centrally located mass was identified in a nonsmoking man in his mid-thirties. CT showed a small area of fat density within the mass, leading to a provisional diagnosis of hamartoma. Due to unassuageable fear of malignancy, he and his wife declined my advice to observe the mass with serial radiographs, insisting on surgery that was uneventful and that confirmed the clinical impression. Comment: It may be impossible to avert unnecessary surgery when malignancy cannot be excluded with certainty.

3. An upper-lobe, 2-cm mass was identified in a heavy smoker. He underwent a successful resection of a stage I adenocarcinoma. On review, the tumor was clearly evident (although smaller) on a radiograph taken 5 years earlier, leading to the irreverent observation that had his neoplasm been recognized and treated at that time he would have experienced a 5-year cure. Comment: Screening radiographs impose the potential liability of “failure to diagnose.” Lung cancer biology is highly variable; it cannot be confidently predicted either by tumor size or cell type.23

Considering the eightfold detection enhancement of current imaging techniques,4 and the recent availability of tomographic screening on request, fostered by advertisements, the hazards of lung cancer screening deserve emphasis.

Citing The Mayo Clinic experience,5 the statement by Kennedy et al1 that “. . . there was no disease-specific reduction in mortality. . .” is misleading. There were seven more lung cancer deaths in the screened group (n = 122) than in the control group (n = 115).5 Furthermore, the all-cause mortality per 1,000 person-years was higher in the screened group than in the control group (24.8 vs 24.6), and eightfold the lung cancer mortality (3.2 vs 3.0). A skeptical observer might speculate that any gains attributable to earlier diagnosis—46 more cases of lung cancer were identified in the former than the latter group—were offset by the long-term effects of a higher resection rate.

The authors confound the lung cancer cases in the Mayo study with those of the Czechoslovakian study6: in the latter, 108 cancers were found in the screened group vs 82 cancers in the control subjects, not 206 and 160, respectively, as stated. As in the Mayo study, deaths from lung cancer were higher in the screened group (n = 85) than in the control group (n = 67).

The authors incorrectly cite the 1986 article by McFarlane et al7in support of their belief that overdiagnosis of lung cancer—advanced by Eddy8 as an explanation for the 29% higher identification rate in screened vs controlled groups in the Mayo study—lacked plausibility. The cited article7 did not address this issue; it pointed out that, of the 28% of lung cancers first identified at autopsy, most of the diagnostic failures were ascribable to the patient’s terminal state, usually from other conditions. The relevant article was authored by McFarlane et al9 in 1987, when they identified at autopsy a large“ reservoir” of undiagnosed lung cancer cases that had neither caused nor contributed to the deaths of their patients. After age adjustment, the incidence of lung cancer unsuspected during life was almost quadruple the community incidence rate in men, and almost 15 times higher in women. This conclusion provides firm support of Eddy’s concept of overdiagnosis by screening,8 precisely opposite to what the authors1 purported it to state.

Overdiagnosis of cancer can occur, broadly speaking, in two ways: when cancers with limited biological potential (ie, cancers)—prostate cancer in the elderly is a familiar example—are identified, and when death from a comorbidity overtakes the course of biologically aggressive cancers (ie, CANCER). In the Mayo experience,5 the numbers of advanced and unresectable CANCERS were equal in the two groups, which suggests that the excess cancers resected in the screened group were not potential progenitors of the former. It should be well considered that the participants were judged at high risk for lung cancer; that they were selected because their health status suited them for major surgery; and that deaths from other morbidities—chiefly heart and lung disease—were sevenfold higher than lung cancer deaths.

Due to space limitations, I have confined my comments principally to the potential hazards of a true-positive screen. I know of no more penetrating discussion of lung cancer screening and the risks of false-positive tests than that provided by Eddy.8 A more recent review10 cites additional studies, each of which mirrors the Mayo and Czechoslovakian experience.

One cannot doubt the importance of lung cancer. However, one should avoid compounding the problem by advocating radiographic screening that, on available evidence, is likely to prove not only unhelpful and excessively costly, but injurious as well.

Kennedy, TC, Miller, Y, Prindiville, S (2000) Screening for lung cancer revisited and the role of sputum cytology and fluorescence bronchoscopy in a high-risk groupChest117(suppl 1),72S-79S
 
Patz, EF, Jr, Rossi, S, Harpole, DH, Jr, et al Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer.Chest2000;117,1568-1571. [CrossRef] [PubMed]
 
Shore, DF, Paneth, M Survival after resection of small cell carcinoma of the bronchus.Thorax1980;35,819-822. [CrossRef] [PubMed]
 
Henschke, CI, McCauly, DI, Yankelevitz, DF, et al Early lung cancer action project: overall design and findings from baseline screeningLancet1999;354,99-105. [CrossRef] [PubMed]
 
Fontana, RS, Sanderson, DR, Woolner, LB, et al Lung cancer screening: the Mayo program.J Occup Med1986;28,746-750. [CrossRef] [PubMed]
 
Kubik, A, Parkin, DM, Khlat, M, et al Lack of benefit from semi-annual screening for cancer of the lung: follow-up report of a randomized controlled trial on a population of high-risk males in CzechoslovakiaInt J Cancer1990;45,26-33. [CrossRef] [PubMed]
 
McFarlane, MJ, Feinstein, AR, Wells, CK Clinical features of lung cancers discovered as a postmortem “surprise.”Chest1986;90,520-523. [CrossRef] [PubMed]
 
Eddy, DM Screening for lung cancer.Ann Intern Med1989;111,232-237. [PubMed]
 
McFarlane, MJ, Feinstein, AR, Wells, CK, et al The “epidemiologic necropsy”: unexpected detections, demographic selections, and changing rates of lung cancerJAMA1987;258,331-338. [CrossRef] [PubMed]
 
Richter-Boe, KE, Humphrey, LL Screening for cancers of the lung and colon.Arch Intern Med1992;152,2398-2405. [CrossRef] [PubMed]
 
To the Editor:

We appreciate Dr. Reich’s interest in our review article (Supplement 1, April 2000).1We do not, as he states, advocate lung cancer screening, but rather we support “trials…to retest the premise that aggressive seeking of early lung cancer will reduce mortality rates,” as summarized in the last sentence of our article. The lung cancer screening trials undertaken over a quarter of a century ago have serious deficiencies when evaluated with the benefit of hindsight provided by more recent advances. Specifically, these trials stated that high-risk individuals were enrolled, but we now know that the presence of airflow obstruction defines a group of smokers who are at significantly increased risk compared to smokers without airflow obstruction. Considerable care needs to be devoted to defining study populations for future screening studies so that risk of lung cancer is high, but comorbidity is low, so that the subjects may actually benefit from early detection. Perhaps criteria similar to those (mild airflow obstruction) of the Lung Health Study,2 in which lung cancer exceeded cardiovascular disease as a cause of death, would be appropriate.

We thank Dr. Reich for pointing out our error in the number of lung cancer cases in the Czechoslovakian study and for providing the additional reference by McFarlane et al.3 We do not believe that our statement that “there was no disease-specific reduction in mortality rates” is misleading, as there is no statistically significant difference between lung cancer deaths in the screened (122 subjects) and control (115 subjects) groups.

We believe that the magnitude of the health burden imposed by lung cancer warrants the initiation of carefully planned trials to evaluate the new technologic advances that are now available. We agree with Dr. Reich that these trials should be designed to determine both the beneficial and harmful effects of screening.

References
Kennedy, TC, Miller, Y, Prindiville, S Screening for lung cancer revisited and the role of sputum cytology and fluorescence bronchoscopy in a high-risk groupChest2000;117(suppl 1),72S-79S
 
Anthonisen, NR, Connett, JE, Kiley, JP, et al Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health StudyJAMA1994;272,1497-1505. [CrossRef] [PubMed]
 
McFarlane, MJ, Feinstein, AR, Wells, CK, et al The “epidemiologic necropsy”: unexpected detections, demographic selections, and changing rates of lung cancerJAMA1987;258,331-338. [CrossRef] [PubMed]
 

Figures

Tables

References

Kennedy, TC, Miller, Y, Prindiville, S (2000) Screening for lung cancer revisited and the role of sputum cytology and fluorescence bronchoscopy in a high-risk groupChest117(suppl 1),72S-79S
 
Patz, EF, Jr, Rossi, S, Harpole, DH, Jr, et al Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer.Chest2000;117,1568-1571. [CrossRef] [PubMed]
 
Shore, DF, Paneth, M Survival after resection of small cell carcinoma of the bronchus.Thorax1980;35,819-822. [CrossRef] [PubMed]
 
Henschke, CI, McCauly, DI, Yankelevitz, DF, et al Early lung cancer action project: overall design and findings from baseline screeningLancet1999;354,99-105. [CrossRef] [PubMed]
 
Fontana, RS, Sanderson, DR, Woolner, LB, et al Lung cancer screening: the Mayo program.J Occup Med1986;28,746-750. [CrossRef] [PubMed]
 
Kubik, A, Parkin, DM, Khlat, M, et al Lack of benefit from semi-annual screening for cancer of the lung: follow-up report of a randomized controlled trial on a population of high-risk males in CzechoslovakiaInt J Cancer1990;45,26-33. [CrossRef] [PubMed]
 
McFarlane, MJ, Feinstein, AR, Wells, CK Clinical features of lung cancers discovered as a postmortem “surprise.”Chest1986;90,520-523. [CrossRef] [PubMed]
 
Eddy, DM Screening for lung cancer.Ann Intern Med1989;111,232-237. [PubMed]
 
McFarlane, MJ, Feinstein, AR, Wells, CK, et al The “epidemiologic necropsy”: unexpected detections, demographic selections, and changing rates of lung cancerJAMA1987;258,331-338. [CrossRef] [PubMed]
 
Richter-Boe, KE, Humphrey, LL Screening for cancers of the lung and colon.Arch Intern Med1992;152,2398-2405. [CrossRef] [PubMed]
 
Kennedy, TC, Miller, Y, Prindiville, S Screening for lung cancer revisited and the role of sputum cytology and fluorescence bronchoscopy in a high-risk groupChest2000;117(suppl 1),72S-79S
 
Anthonisen, NR, Connett, JE, Kiley, JP, et al Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health StudyJAMA1994;272,1497-1505. [CrossRef] [PubMed]
 
McFarlane, MJ, Feinstein, AR, Wells, CK, et al The “epidemiologic necropsy”: unexpected detections, demographic selections, and changing rates of lung cancerJAMA1987;258,331-338. [CrossRef] [PubMed]
 
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