11.	Screening for Lung Cancer



RECOMMENDATION



Routine screening for lung cancer with chest radiography or sputum

cytology in asymptomatic persons is not recommended. All patients should

be counseled against tobacco use (see Chapter 54).



Burden of Suffering



Cancer of the lung is the leading cause of death from cancer in both men

and women in the U.S. An estimated 172,000 new cases will be diagnosed

in 1995, with an estimated 153,000 deaths.1 Lung cancer has one of the

poorest prognoses of all cancers, with a 5-year survival rate of less than

13%.1 Important risk factors for lung cancer include tobacco use and

certain environmental carcinogen exposures. Tobacco is associated with

87% of all cases of cancer of the lung, trachea, and bronchus.2



Accuracy of Screening Tests



The chest radiograph (x-ray) and sputum cytomorphologic examination

(cytology) lack sufficient accuracy to be used in routine screening of

asymptomatic persons. The accuracy of the chest x-ray is limited by the

capabilities of the technology and observer variation among radiologists.

Suboptimal technique, insufficient exposure, and poor positioning and

cooperation of the patient can obscure pulmonary nodules or introduce

artifacts.3 Radiologists frequently disagree on the interpretation of chest

x-rays (interobserver variability). In one study, over 40% of these

disagreements were considered potentially significant.4 Most errors are

false-negative interpretations, and pulmonary and hilar masses are among

the most commonly missed diagnoses. From 10% to 20% of the incorrect

radiologic diagnoses or indeterminate results require follow-up testing

for clarification.4 Interpretation of chest x-rays by primary care

physicians is less accurate than interpretation by radiologists.

Discrepancies were identified in 58% of chest x-rays read by both family

physicians and radiologists.5 Current radiographic technologies require

greater than 20 doublings of tumor size to reach the 1 cm3 needed for the

lower limit of chest imaging sensitivity. By the time lung cancer is

suspected on chest x-ray, micrometastatic dissemination has often

occurred, limiting the effectiveness of early detection.6



Furthermore, the yield of screening chest radiography is low, largely due

to the low prevalence of lung cancer in asymptomatic individuals, even

those at high risk. Of the initial 31,360 screening x-rays of asymptomatic

smokers in the National Cancer Institute (NCI) Cooperative Early Lung

Cancer Detection Program, 256 (0.82%) were interpreted as "suspicious

for cancer," and only 121 (0.39% of those screened) were diagnosed with

lung cancer.7 Other studies have confirmed a low yield of performing

chest x-rays on asymptomatic persons.8,9



Sputum cytology is an even less effective screening test, largely due to

its low sensitivity compared to chest x-ray.6 Of the 160 lung cancers

detected by dual screening in the NCI study, 123 (77%) would have been

detected by chest x-ray alone and 67 (42%) would have been detected by

cytologic examination alone.7 The majority of incident cases detected in

subsequent screenings were detected by chest x-ray.10 In other trials

using dual screening, sensitivity of chest x-ray ranges from 40% to 50%,

versus 10% to 20% for sputum cytology.11 Mass screening to detect lung

cancer with tests that lack a high sensitivity will be inefficient.12



Effectiveness of Early Detection



Lung cancer is usually asymptomatic until it has reached an advanced

stage, when the treatment outcome is poor. Five-year survival for all

stages is 11-14%; for Stage I it is 42-47%.1 Under optimal conditions,

survival can be higher.10,12,13 Early detection of Stage I cases through

screening might be expected to improve survival, but the small amount of

available evidence does not show that screening reduces lung cancer

mortality.



The efficacy of chest radiographic screening for lung cancer was first

investigated in the 1960s. A controlled prospective study involving over

55,000 persons found that those receiving chest x-rays every 6 months

had a larger proportion of resectable tumors, but mortality for lung cancer

remained the same when compared with controls who received

examinations only at the beginning and end of the trial.14 Similar findings

were reported in the Philadelphia Pulmonary Neoplasm Research Project15

and, more recently, in a case-control study.16 In addition, the results of

one of the three centers participating in the NCI Cooperative Early Lung

Cancer Detection Program provide indirect evidence of the limited

efficacy of radiographic screening. In this study, persons receiving chest

x-rays and sputum cytology every 4 months had the same lung cancer

mortality as persons advised to obtain annual testing.17



No prospective randomized study with adequate follow-up time has

compared radiographic screening with no screening. A case-control study

in Japan compared the screening histories of 273 fatal cases of lung

cancer to 1,269 controls, and although the data suggest a trend toward a

decreased risk of lung cancer mortality in those screened with chest x-

rays (with or without sputum cytologic tests), the difference was not

statistically significant.18



Three large clinical trials published by the NCI Cooperative Early Lung

Cancer Detection Program examined the efficacy of dual screening (chest

x-ray and sputum cytology) in over 30,000 male smokers aged 45 or

older.7,10,19-23 Two trials comparing annual dual screening with annual

radiographic screening tested the incremental benefit of adding sputum

cytology to radiographic screening.20,21 The third trial, which compared

dual screening every 4 months with advice to receive the same tests

annually, examined the benefit of frequent dual screening compared to

usual medical care.22 In each study, lung cancer mortality did not differ

between experimental and control groups. Although early-stage,

resectable tumors were more common and 5-year survival significantly

higher in groups receiving regular dual screening, lead-time and length

biases may have been responsible for these findings. A randomized

prospective trial of dual screening in Czechoslovakia produced similar

results.24 The investigators found no substantial difference in the number

or causes of death between study groups.



The NCI is currently conducting the multicenter PLCO (prostate, lung,

colorectal, and ovarian cancers) Trial, which will compare annual chest

radiographic testing with usual care in both men and women.25



Recommendations of Other Groups



No organizations currently recommend routine screening of either the

general population or of smokers for lung cancer with either chest x-rays

or sputum cytology.26-31



Discussion



Lung cancer is the leading cause of cancer mortality. Although screening

may increase early detection of resectable early cancers, controlled trials

provide no significant evidence that lung cancer screening reduces

mortality from this disease. To the weakness of the evidence for

screening must be added the substantial costs of routine testing,9

including false-positive results that lead to unnecessary expense and

morbidity from follow-up procedures.32 Current research and clinical

trials of chemoprevention,33 as well as research in early detection

markers such as monoclonal antibodies,6,34 may improve efficacy in

prevention or early identification of lung cancer. Primary prevention-

mainly through discouraging tobacco use-is a more effective strategy than

screening to reduce lung cancer morbidity and mortality.11 Unless ongoing

trials find a benefit of periodic chest x-rays, the cost, inconvenience, and

potential harms of screening cannot be justified.



CLINICAL INTERVENTION



Routine screening of asymptomatic persons for lung cancer with chest

radiography or sputum cytology is not recommended ("D" recommendation).

All patients should be counseled against tobacco use (see Chapter 54).



The draft update of this chapter was prepared for the U.S. Preventive

Services Task Force by Kathlyne Anderson, MD, MOH, and Donald M.

Berwick, MD, MPP.



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