Screening for Lung Cancer

Lung cancer is the most common fatal malignancy in the United States. Each year, it claims the lives of over 160,000 persons in the United States, as many as do tumors of the colon and rectum, breast, and prostate combined. The incidence of lung tumors in men has been rising dramatically since 1930. More recently, a dramatic increase among women has occurred. Approximately 10% of American men and 5% of American women alive today will have lung cancer during their lifetime; of these, greater than 85% will die of the disease.

Overall survival rates associated with treatment for lung cancer remain modest, limited in part by patients typically presenting at relatively late stages of disease (see Chapter 53). Efforts to markedly improve survival have focused on detection of early-stage disease, which is amenable to surgical cure. Screening high-risk persons by chest x-ray has failed to improve survival, but reports of reduced mortality associated with use of low-dose computed tomography (CT) have rekindled interest in screening for lung cancer.

Enthusiasm for CT-based screening is growing, and new lung cancer screening guidelines are emerging. As with any screening modality, optimal application will require identification of best candidates and thorough consideration of risks and costs as well as benefits. Because such testing and subsequent imaging studies are likely to increase exposure to ionizing radiation, total dose needs to be taken into account as do other potentially adverse consequences of utilizing a very sensitive, expensive test for screening (e.g., high false-positive rate, economic burden, unnecessary psychological distress, complications from subsequent invasive diagnostic procedures).

The primary care physician and medical home team are in an ideal position to aid individual patients in screening for lung cancer by providing estimation of pretest disease risk, review of test risks and benefits, interpretation of test results, and coordination of any subsequent evaluation.

EPIDEMIOLOGY AND RISK FACTORS (1, 2, 3, 4 and 5)

The epidemiology of lung cancer is dominated by its association with smoking. The historic decades-long increase in cancer death rates among men since the 1930s and the more recent increase among women can be explained by trends in cigarette consumption. A dose-response relationship between duration and intensity of cigarette smoking and risk for lung cancer has been documented in both men and women. In comparison with the risk for lung cancer among nonsmokers, the risk is increased 5, 10, and 20 times for men who smoke less than one half a pack, one half to one pack, and one to two packs per day, respectively. A decrease in risk has been demonstrated in smokers who are able to stop and in those who smoke filter-tipped cigarettes. Cigar and pipe smokers incur much less risk, but again a dose-response relationship has been documented (see Chapter 54).

The association between smoking and cancer is strongest for the epidermoid (squamous cell) and small cell undifferentiated (oat cell) tumors. The relationship is less certain for adenocarcinoma (alveolar cell) and large cell undifferentiated (anaplastic) histologic types.

As noted, the observation that lung cancer occurs in men far more often than in women can be explained for the most part by differences in historical smoking patterns. In fact, lung cancer without a smoking history is more common among women. A slight apparent excess of lung cancer cases also occurs in urban areas and among low-income groups. The presence of polycyclic organic matter in urban pollution and in some occupational environments (see Chapter 39) may provide a partial explanation. Exposure to asbestos, chromate, nickel, uranium, or radon gas has also been associated with significantly increased rates of lung cancer. The combined effect of such exposures and smoking is generally more than additive. For example, smokers exposed to asbestos have a 90-fold greater risk for lung cancer than do unexposed nonsmokers. Women with such exposures may be at higher risk than men.

Other risk factors include older age, family history of lung cancer, and history of chronic obstructive pulmonary disease, pneumonia, or pulmonary fibrosis.

Risk stratification tools are under development to help identify high-risk persons for lung cancer screening. A simple, wellvalidated model with few variables would be optimal for use in primary care practice. One promising tool with such characteristics is the Liverpool Lung Project model. It uses a set of independent predictors of risk: age; sex; duration of smoking; history of cancer, pneumonia, or asbestos exposure; and family history of lung cancer (see Table 37-1).

NATURAL HISTORY OF LUNG CANCER AND EFFECTIVENESS OF THERAPY (6, 7, 8 and 9)

Lung cancer’s rapidly progressive and usually inexorable clinical course has frustrated clinicians for generations. The 5-year survival rate has been between 5% and 10%. At the time of symptomatic presentation, 75% of patients have lesions that are clearly unresectable. Of the remainder, 60% prove to be unresectable because of mediastinal involvement, discovered by further evaluation or at thoracotomy. Five-year survival rates after resection in the relatively few remaining patients vary from about 10% for patients with oat cell tumors to 30% for patients with squamous cell tumors.

Reports of 5-year survival rates based on the symptoms present at the time of diagnosis are relevant to the question of early detection. In a group of patients with an overall 5-year survival of 7%, the 6% with disease discovered before the appearance of symptoms had an 18% survival rate, compared with 10% to 15%
for patients with local symptoms and 6% for those with systemic symptoms. Nearly one third of the patients had symptoms of metastatic disease; all of these people died within 5 years.

TABLE 37-1 Revised LLP Risk Model Regression Coefficients and Internal Discriminative Validation

		Missing Risk Factor
Variable		Smoking Duration	History of Pneumonia	History of Cancer	Family History of Lung Cancer	Asbestos Exposure
Model Risk Factors
Smoking duration
	1-19 y	—	0.7908	0.7526	0.8159	0.7950
	20-39 y	—	1.4906	1.4562	1.4743	1.4704
	40-59 y	—	2.5216	2.5274	2.5708	2.5359
	≥60 y	—	2.6762	2.7624	2.7924	2.7424
History of pneumonia		0.5619	—	0.5893	0.5814	0.5917
History of cancer		0.8599	0.6620	—	0.6808	0.6795
Family history of lung cancer
	Early onset (age <60 y)	0.9351	0.6538	0.7096	—	0.6901
	Late onset (age ≥60 y)	0.2779	0.1850	0.1943	—	0.2009
Asbestos exposure		0.6659	0.6273	0.6367	0.6323	—
Internal Validation
AUC		0.6374	0.7554	0.7543	0.7537	0.7526
Estimated from the LLP case-control study.
AUC, area under the receiver operating characteristic curve; LLP, Liverpool Lung Project.
From Raji OY, Duffy SW, Agbaje OF, et al. Predictive accuracy of the Liverpool Lung Project risk model for stratifying patients for computed tomography screening for lung cancer: a case-control and cohort validation study. Ann Intern Med 2012;157:242. With Permission © 2012 American College of Physicians.