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Screening for lung cancer Gary R. Epler To cite this article: Gary R. Epler (1990) Screening for lung cancer, Postgraduate Medicine, 87:6, 181-186, DOI: 10.1080/00325481.1990.11716342 To link to this article:

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Date: 11 August 2017, At: 15:43

Screening for lung cancer Is it worthwhile?

Gary R. Epler, MD

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lung cancer had caught up with breast cancer as the leading cause of cancer death in women. Also, we now know that one quarter of high school seniors who smoke had their first cigarette by sixth grade, half by eighth grade. Thus, education aimed at smoking prevention must begin in elementary school, and smoking cessation programs OGAREITE SMOKING-The are needed in high school. 11 Cigarette use and lung cancer 1964 Surgeon General's report stated that tobacco use was habituatrates are increasing in many countries. However, there are encouraging, and the 1988 report said cigarettes were addicting. The ing findings in the United States. 14 1989 report concluded that smok- Smoking prevalence among adults decreased from 40% in 1965 to ing is the single most important preventable cause of death in our 29% in 1987. Between 1964 and society. 14 1985, quitting and noninitiation of Cigarette smokers are at highest smoking postponed or avoided risk for lung cancer. Risk increases nearly 3 million smoking-related dramatically with the number of deaths. cigarettes smoked. The incidence PREVIOUS WNG CANCER-Persons who have had lung cancer are oflung cancer in persons who at high risk for recurrence. Among smoke two packs of cigarettes or more per day is 20 times greater 572 patients with lung cancer, 27 than in nonsmokers. Smokers un(5%) had a second lung cancer der 40 years of age are at risk. Stud- within 3 to 5 years. 16 BULIDUS EMPHYSEMA-Risk of ies have shown an inverse relationlung cancer is higher in smokers ship between age and extent of lung cancer at the time of detecwith giant bullous emphysema than in smokers without bullous tion: Cancer detected in younger lesions. Cancer is ofi:en contiguous patients may be more extensive with the bullae, and patients are (and less curable) than cancer in younger. According to one study, 17 older patients. 15 bullous disease among patients Hundreds of cigarette-related studies have been conducted, and aged 40 to 59 years occurred six new findings are published contin- times more frequently in those uously.14 For example, by 1986, with lung cancer. In another

Lung cancer is a killer. The search for a diagnostic screening test has been intense, and studies have identified the advantages and disadvantages of routine lung cancer screening. Who is at risk for lung cancer? How effective are the various screening tests? Dr Epler answers these questions and emphasizes the importance of patient education and prevention in the battle against lung cancer. .

Lung cancer causes 140,000 deaths per year in the United States. 1 Thus far, studies of more than 100,000 smokers worldwide have shown that lung cancer screening has led to earlier detection and improved 5-year survival rates, but lung cancer mortality rates remain unchanged 2-11 Although some investigators recommend routine radiographic screening based on these findings, 10 the American Cancer Society has withdrawn its recommendation of annual chest radiographs for asymptomatic persons.12 Most scientific societies do not recommend routine screening for lung cancer, because mortality rates have not improved and the risk associated with false-positive results outweighs the benefit of earlier detection. Ll Risk factors Several risk factors for lung cancer have been identified (table 1). Jacob J. Lokich, MD, was the Editorial Board coordinator for this article.




The incidence of lung cancer in persons who smoke two packs of cigarettes or more per day is 20 times greater than in nonsmokers.

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Table 1. Risk factors for lung

cancer Cigarette smoking Previous lung cancer Giant bullous emphysema Chronic airflow obstruction Asbestos exposure Radon gas exposure Exposure to certain environmental agents (eg, alkylating compounds. chromates, nickel, halo ethers. carcinogenic polyhydrocarbons)

study, IH risk oflung cancer was calculated to be 32 times higher in smokers with bullous disease than in a healthy population. The increased risk may be attributed to poor clearance mechanisms and trapping of carcinogens in the large cysts. O~UCTIONOFM~-­

Smokers with airway obstruaion have an increased risk oflung cancer. According to one study, 19 27 (2.6%) of 1,031 smokers with airway obstruaion had lung cancer, compared with 14 (0.4%) of3,364 smokers without obstruaion. Airway obstruaion was a greater prediaor oflung cancer than was patient age or amount of cigarenes smoked. Risk of lung cancer increased with the degree of airway obstruaion. ASBFSfOS-Risk oflung cancer is high in smokers who are exposed to asbestos. In a study of 18,000


aaivate dominant cellular protoasbestos insulation workers, 20 relaoncogenes and inactivate recessive tive risk in two-pack-per-day smokers was almost 90 times high- tumor-suppressor genes. 25 er than in nonsmokers who were Screening tes15 not exposed to asbestos. Risk was Various screening methods to more than 50 times higher in workers who smoked fewer than detea lung cancer have been studied, including chest radiographs, 20 cigarenes per day. RADON GAS-Radon gas, a sputum cytology, serologic testing, natural decay produa of radium water-suppressed magnetic resothat is found in soil and rock, has nance spearoscopy, and breath a half-life of 4 days. The alphaanalysis. DIFSf RADIOGRAPHS AND SPUpanicle emissions from radon deTIJM CYI"OLOGY--The use of chest cay (polonium 218 and polonium 214) can damage cells lining airradiographs in lung cancer screenways, which could lead to lung ing has been studied extensively. In cancer. 21 A study of516 nonsmok- 1971 , a large lung cancer screening ing miners exposed to radon gas re- projea, known as the National vealed a 12-fold risk of death from Cancer Institute Cooperative Earlung cancer (14 deaths and 1 exly Lung Cancer Deteaion Propeaed death). 22 Smoking and gram, was begun at Johns Hopkins radon exposure combine synergisti- Hospital, Baltimore; Memorial cally.21 The Environmental Protec- Sloan-Kenering Cancer Center, tion Agency has established a maxi- New York; and the Mayo Clinic, Rochester, Minnesota. Almost 10 mum radon exposure guideline of 4 pCi/L. Results of studies on years later, 31,000 men aged 45 lung cancer and radon exposure years or older who smoked at least throughout the United States are one pack of cigarenes per day were now being reviewed. 23'24 enrolled. 2 arnER RISK FACTORS-Other The first pan of the lung cancer risk faaors for lung cancer include screening projea focused on prevaexposure to certain environmental lence of lung cancer. At Johns agents, such as alkylating comHopkins Hospital, lung cancer was pounds, chromates, nickel, halo deteaed in 79 of 10,387 persons ethers, and carcinogenic polyhyscreened:~ At Memorial Sloandrocarbons found in automobile Kenering Cancer Center, 53 lung and truck exhaust. Genetic events cancers were deteaed among may be involved in the pathogene- 10,040 persons screened, 23 by sis oflung cancer. For example, chest radiography alone and 30 by lung cancer cells may be able to dual screening with sputum cytolo-


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Sputum cytology is not recommended as a routine screening test for lung cancer.

gy and chest radio~phy. 4 Twentytwo patients (42%) had stage I disease and had a 5-year swvival rate of85%. The cancers detected by sputum cytology were squamous cell carcinomas, and two thirds of the cancers detected by radiography were adenocarcinomas. At the Mayo Clinic, dual screening detected 91 early-stage cancers among 10,933 persons tested. 5 Of the lesions detected by chest radiography, 50% were resected. All of the 20% detected by sputum cytology were resected. This screening program resulted in earlier identification of cancer but did not affect overall survival rates. Subsequently, the American Cancer Society withdrew its recommendation for annual chest radiographs in asymptomatic persons.12 The second part of the lung cancer s~reening p~oject involved an ongomg screenmg program. Analysis of the Mayo Clinic program, which consisted of dual screening every 4 months, indicated that, contrary to early expectations, chest radiography was more effective than sputum cytology in early detection oflung cancer; however, sputum cytology was effective in early detection of squamous cell carcinoma.6 Neither screening method was of value in early detection of small-cell carcinoma. Additional analysis indicated that during 6 years of moni-

toring, 50 of92 subjects had a peripheral nodule that, in retrospect, was visible in 90% of them months or years earlier.7 The central cancers grew rapidly. Patients usually presented with hilar or mediastinal enlargement after normal findings on radiographs obtained 4 months earlier. Most cancers were in a noncurable stage. The Mayo Clinic ongoing screening program also showed an improved 5-year swvival rate: more than 80% among patients with cytologically detected lung cancer and 40% among patients with radiographically detected lung cancer. Symptomatic patients had a 5-year swvival rate ofless than 10%. However, despite earlier detection oflung cancer and improved 5-year swvival rates, the mortality rate was slightly higher in subjects who had 4-month Jual screening (122lung cancer deaths) than in the control group (115 lung cancer deaths). 9 Findings were similar in a European study. 10 A group of 40,000 men who were screened by chest fluorography every 6 months had a resection rate of28%, a 5-year survival rate of 52%, and a 10-year swvival rate of 39%. In contrast, a group of 100,000 men who were screened by chest fluorography every 18 months had a resection rate of 19%, a 5-year swvival rate of 27%, and a 10-year swvival rate of 19%. There was no reduction in


Gary R. Epler, MD Dr Epler is chairman, department of medicine, New England Baptist Hospital, Boston, and associate clinical professor of pulmonary medicine, Boston University School of Medicine.

lung cancer mortality. Sputum cytology is not recommended as a routine screening test for lung cancer, even when combined with chest radiography, because early detection of small-cell carcinoma is not achieved and lung cancer mortality rates are not improved.2-9'1u3 Studies have shown that monoclonal antibodies can be attached to cells for improved yield. Nearly 100 monoclonal antibodies are being investigated as tools for detecting small-cell and continued 183

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Screening for lung cancer may result in earlier detection of disease and improved survival rates, but it does not reduce mortality rates.

non-small-cell lung cancer. In one study, 16 monoclonal antibodies were attached to a glycolipid antigen of a small-cell carcinoma and a protein antigen of a non-small-cell lung carcinoma and were then applied to sputum specimens from 5,000 men who participated in the Johns Hopkins Lung Project. During the next 8 years, 12% of subjects showed definite atypia. Among the 62 subjects who had monoclonal antibody testing, lung cancer developed in 14 of 22 who had positive stains but did not develop in 35 of 40 who had negative stains. Of the patients with positive stains, screening had been performed 24 months earlier in those with cancer and 57 months earlier in those without cancer. These findings suggest that the antigen associated with tumor may be expressed 2 years, but not 4 years, in advance. SEROLOGIC TESTING-Serologic testing is useful for monitoring therapeutic response, but it is not useful as a screening test to distinguish localized from advanced cancer. In a study of diagnostic markers for lung cancer/7 sera from 127 patients with localized lung cancer, 341 patients with advanced lung cancer, 148 patients with benign lung disease, and 145 healthy subjects were tested for 10 markers: ferritin, lipid-bound sialic acid, total sialic acid, beta2-microglobulin, lipotropin, alpha and beta subunits of human chorionic gonadotropin, 184

two assays of calcitonin, parathyroid hormone, and carcinoembryonic antigen. Only ferritin and carcinoembryonic antigen seemed potentially valuable for detecting localized lung cancer. Furthermore, age and carcinoembryonic antigen together were as valuable as more elaborate combinations. Statistical review indicates that the positive predictive value of these markers is too low; iflung cancer occurred in 1% of a clinical population, only 7% of patients who tested positive would have cancer. 11 These markers are too nonspecific to be considered for an effective screening program. MAGNETIC RFSONANCE SPEC-

TROSCOPY-Water-suppressed magnetic resonance spectroscopy of plasma has identified a new potential cancer marker-measurement of lipoprotein-lipid line widths. In a recent study of331 subjects (normal controls, patients with malignant and benign tumors, patients without tumors, and pregnant patients)/8 mean spectroscopy line width was found to be 39.5 Hz for 44 healthy subjects and 29.9 Hz for 81 patients with untreated cancer (P< .0001). A line width of 33 Hz or lower was indicative of the presence of cancer in this study. However, pregnant patients and those with benign prostatic hyperplasia had line widths consistent with the presence of malignant tumors. The cancerrelated spectroscopy line width

may be due to actions of tumor necrosis factor. Additional studies are needed to determine whether such testing will be valuable in detecting cancer or monitoring theraPY· BRFA1H ANAIXSIS-The use of breath analysis for lung cancer screening has been evaluated by a computerized classification technique.29 The noninvasive nature and ease of testing are distinct advantages, but the disadvantages of false negatives and false positives and exogenous pollutants must be overcome. Also, it has yet to be determined whether a lung cancer patient would release a substance ~at could be detected in expired air. WEIGHING TilE BENEFITS-

Screening for lung cancer may result in earlier detection of disease and improved survival rates, but it does not reduce mortality rates. Lead-time bias is a possible explanation. Lead-time bias occurs because screening allows earlier diagnosis without necessarily delaying the time of death; moving the time of diagnosis forward increases the 5-year survival rate but does not affect mortality. 13 When the benefits of earlier detection and improved 5-year survival rates are weighed against the lack of improvement in mortality rates, false-positive test results must be considered. Detection of noncancerous lesions on screening tests results in patient inconvenience, continued


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discomfort, anxiety, and expense. For example, chest radiographs may be abnormal in about 10% of patients, necessitating additional studies to rule out cancer, and 5% of these patients may require bronchoscopy, needle aspiration, or thoracotomy. For every cancer found, about 100 patients are evaluated. u

Summary and conclusion Prevention of lung cancer remains the best method of de-

screening may detect lung cancreasing lung cancer mortality. cer earlier and lead to increased Patients who smoke should be 5-year survival rates, it does not urged to quit, and children, reduce lung cancer mortality teenagers, and yo~ _adults must not begin smoking. At high rates. Rl't'l risk are smokers, especially those under 40 years of age who may Earn credit on this article. have smoked two to four packs of cigarettes per day for 20 years; See CME Quiz. persons who have had a previous lung cancer; patients with bullous emphysema; patients with Address for correspondence: Gary R asbestosis; and patients with evi- Epler, MD, New England Baptist dence of chronic airB.ow obstruc- Hospital, 125 Parker Hill Ave, Boston, MA02120. tion. Although radiographic



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1988;80(5):337-44 9. Fontana RS, Sanderson DR, Woolner LB, et al. Lung cancer screening: the Mayo program. J Occup Med 1986;28(8):746-50 10. Wdde J. A 10 year follow-up of semi-annual screening for early detection oflung cancer in the Erfutt Counry, GDR. Eur Respir J 1989;2(7):656-62 11. Sanderson DR, Jett JR Lung cancer: the American view. Eur Respir J 1989;2: 1002-7 12. Ruckd~dJC. Whither screening for lung cancer' (Editorial) J Narl Cancer lnsr 1988;80(2): 78-9 13. Eddy OM. Screening for lung cancer. Ann Inrem Med 1989;111(3):232-7 14. The Surgeon General's 1989 Repott on Reducing the Health Consequences of Smoking: 25 Years of Progress. MMWR 1989;38(Suppl2): 1-32 15. Mor V, Guadagnoli E, Masterson-Allen S, et al. Lung, breast, and colorecral cancer: the relationship between extent of disease and age ar diagnosis. JAm Geriarr Soc 1988;36(1 0):873-6 16. The Lung Cancer Study Group. Postoperative T1 NO non-small cell lung cancer: squamous versus nonsquamous recurrences. J Thorac Cardiovasc Surg 1987;94(3):349-54 17. Goldstein MJ, Snider GL, Liberson M, et al. Bronchogenic carcinoma and giant bullous disease. Am Rev Respir Dis 1968;97(6):1062-70 18. StololfiL, Kano&ky P, Magilner L. The risk of lung cancer in males with bullous disease of the lung. Arch Environ Health 1971 ;22( 1): 163-7 19. Tockman MS, Anthonisen NR, Wright EC, et al. Airways obstruction and the risk for lung can-

cer. Ann Intern Med 1987;106(4):512-8 20. Hammond EC, SdikolfiJ, Seidman H. Asbestos exposure, cigarette smoking and death rates. Ann N Y Acad Sci 1979;330:473-90 21. Samet JM Radon and lung cancer: how great is the risk? J Respir Dis 1989;10{7):73-86 22. Roswe RJ, Steenland K, Halperin WE, et al. Lung cancer monaliry among nonsmoking uranium miners exposed to radon daughters. JAMA 1989; 262(5):629-33 23. Radon exposure assessment Connecticut. MMWR 1989;38(42):713-5 24. Lung cancer and exposure to radon in women: New Jersey. MMWR 1989;38(42):715-8 25. Minna JD. Generic events in the pathogenesis oflungcancer. Chest 1989;96(1 Suppl):17-23S 26. T ockman MS, Gupta PK, Myers JD, et aL Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection. J Clin Oncol1988;6(11):1685-93 27. Gail MH, Muenz L, Mcintire KR, et aL Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer. J Nad Cancer lnst 1988;80(2):97-101 28. Fosse! ET, Carr JM, McDonagh}. Detection of malignant rumors: water-suppressed proton nuclear magnetic resonance spectroscopy of plasma. N Eng!J Med 1986;315(22):1369-76 29. O'Neill HJ, Gordon SM, O'Neill MH, et aL A computerized classification technique for screening for the presence of breath biomarkers in lung cancer. ClinChem 1988;34(8):1613-8


Screening for lung cancer. Is it worthwhile?

Prevention of lung cancer remains the best method of decreasing lung cancer mortality. Patients who smoke should be urged to quit, and children, teena...
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