Lung cancer has been the leading cause of cancer death among men in the United States for years, and since 1988, it has become the number-one cause of cancer death among women. An estimated 220,020 new cases of lung cancer are expected in 2008, and 162,610 deaths due to this disease are expected to occur. This exceeds the combined number of deaths from the leading causes of cancer (breast, prostate, and colon cancers). It accounts for 6% of all deaths in the United States.
Lung cancer develops from pulmonary parenchymal or bronchial supportive tissues. Although multiple cell types are often found within a single lung tumor, one type usually predominates. Based on the therapeutic approach, there are two major subdivisions of lung cancer: small-cell lung cancer (SCLC), for which chemotherapy is the primary treatment, and non–small-cell lung cancer (NSCLC), which in its early stages (I and II) is treated primarily with surgery.
This chapter provides basic information on the epidemiology, etiology, screening, prevention, and signs and symptoms of lung cancer in general and then focuses specifically on the diagnosis, staging, pathology, and treatment of NSCLC and carcinoid tumors of the lungs, as well as the pulmonary evaluation of lung cancer patients and follow-up of long-term survivors.
Chapter 7 provides information on the staging, pathology and pathophysiology, and treatment of the far less common SCLC and concludes with brief discussions of mesothelioma and thymoma.
Epidemiology
Gender In the United States, the estimated number of new lung cancer cases for 2008 is 118,200 for men and 101,820 for women. Although the incidence of lung cancer had been rising in women, the rate of increase has begun to slow recently. The incidence is decreasing in men.
Age The age at which lung cancer patients are diagnosed varies widely, but the median age at diagnosis is approximately 70 years.
Race In the United States, the highest incidence of lung cancer in men and women is found in African Americans (110.6/100,000 for men and 50.3/100,000 for women) followed by Caucasians (88.8/100,000 for men and 56.2/100,000 for women).
Geography There are geographic variations in the incidence of lung cancer, with the highest rates worldwide observed in North America and Eastern Europe; in the United States, the highest rates are found in northern urban areas and along the southern coast from Texas to Florida. The state with the highest incidence of lung cancer is Kentucky, with an incidence of 137.9/100,000 in men and 73.5/100,000 in women.
Survival The overall 5-year survival rate for lung cancer is 15%, of which there has been a 1% improvement each decade for the past 30 years.
Etiology and risk factors
Cigarette smoking Approximately 87% of all cases of lung cancer are related to cigarette smoking. There is a relatively strong dose-response relationship between cigarette smoking and the development of this cancer. The greater the number of cigarettes smoked on a daily basis and the greater the number of years of smoking, the greater is the risk of lung cancer. An individual who smokes one pack of cigarettes daily has a 20-fold increased risk of lung cancer compared to a nonsmoker.
The overall incidence of cigarette smoking decreased from 1974 through 1992. Smoking cessation decreases the risk of lung cancer, but a significant decrease in risk does not occur until approximately 5 years after stopping, and the risk remains higher in former smokers than in nonsmokers for at least 25 years. The benefit of smoking cessation is greater if it occurs at a younger age.
Smoking cessation is difficult. Recent data have suggested that a variety of hereditary factors increase the risk of addiction to nicotine among some individuals. Nevertheless, millions of former smokers have quit successfully. Smoking cessation programs that address both physical withdrawal from nicotine and psychological dependence appear to be more effective than either of these approaches alone. In addition, continued efforts are needed to prevent adolescents and preadolescents from beginning to smoke or to encourage them to quit after a brief period of experimentation.
Several cancer centers have recently reported that more than half of their patients with newly diagnosed lung cancer are former smokers, having quit more than 1 year before diagnosis. Healthy ex-smokers represent a large group of individuals who may benefit from effective tools for early detection and/or chemoprevention of lung cancer.
Secondhand smoke Not only is smoking risky for those who smoke, but it also poses a hazard to nonsmokers who either live or work with smokers. It is estimated that approximately 3,000 lung cancer deaths per year in the United States are due to secondhand smoke. Individuals who live in a household with a smoker have a 30% increase in the incidence of lung cancer compared to nonsmokers who do not live in such an environment.
Asbestos exposure is another risk factor for lung cancer. Cigarette smokers who are exposed to asbestos develop lung cancer at an extremely high rate. There is a 90-fold increase compared with unexposed individuals. Exposure to asbestos is also a major risk factor for the development of mesothelioma (see discussion of this cancer in the following chapter).
Radioactive dust and radon exposure Uranium miners who have been exposed to radioactive dust and radon gas also have an increased incidence of lung cancer. Although there has been some controversy about the risk posed by exposure to residential radon gas, a study conducted in Sweden showed an increased incidence of lung cancer in individuals who were exposed to a high level of radon in their homes.
Screening and prevention
Screening
Currently, screening for lung cancer among asymptomatic individuals at elevated risk due to smoking history or occupational exposures is not recommended. An unfortunate result of this policy is that most patients present in advanced stage, and cure rates have improved little over the past 30 years. Only 7% of NSCLC patients are diagnosed in stage IA.
Three randomized screening trials conducted in the United States in the 1970s failed to show a reduction in lung cancer mortality among the smokers who were screened by sputum cytology and chest x-ray for lung cancer. Despite the fact that these American trials were not designed to evaluate chest x-ray as a screening tool, the results led most experts to conclude that screening for lung cancer was not worthwhile. In addition, most investigators recommended that research efforts and resources be allocated to the prevention of lung cancer. A more recent, randomized, prospective trial from Czechoslovakia showed that screening with a chest x-ray increased the diagnosis of early-stage lung cancer but failed to reduce the mortality from lung cancer.
The potential to screen for lung cancer has received renewed interest due to the superior performance of low-dose helical CT compared with chest radiography in detecting small lesions. Although there is insufficient evidence to establish policy related to routine screening for lung cancer with spiral CT, there is a growing trend toward promoting screening with this new technology to individuals at increased risk for lung cancer.
Numerous studies are currently under way to evaluate chest CT scan for lung cancer screening. Several recent reports from Japan, Germany, and the United States have documented the ability of low-dose spiral CT scans to detect lung cancer at an early stage. In some recent trials, more than 80% of lung cancers detected by screening were diagnosed in stage I.
Kaneko screened male smokers > 50 years of age. Of the 15 cancers detected by CT scan, only 4 were seen on chest x-ray; 14 of the 15 cancers were stage I, with an average diameter of 1.6 cm. Ohmatsu found 35 lung cancers (0.37% detection rate) with 9,452 CT scans. Of these cancers, 27 were stage IA. These patients had a 3-year survival rate of 83%.
