Lung Cancer

Peter Mazzone and Hilary Petersen

Key Terms

adenocarcinoma

chemotherapy

computed tomography (CT)

flexible bronchoscopy

large cell carcinoma

magnetic resonance imaging (MRI)

mass

nodule

non–small cell carcinoma

Pancoast syndrome

paraneoplastic syndrome

positron emission tomography (PET)

radiotherapy

screening

small cell carcinoma

squamous cell carcinoma

staging system

surgical resection

TNM staging

transbronchial needle aspiration

transthoracic needle biopsy

Lung cancer is a major public health problem. In the United States, approximately 28% of cancer deaths are due to lung cancer.¹ Most of these deaths could be avoided if people did not smoke tobacco-related products. Worldwide tobacco consumption has not been declining, however, suggesting lung cancer will remain an epidemic for years to come. Advances in early detection and treatment have been slow, leaving the overall prognosis very poor when lung cancer has been detected. Just over one in eight lung cancer patients is still living 5 years after diagnosis. This chapter provides an overview of lung cancer for the respiratory therapist (RT).

Epidemiology

New Cases

In 2010, an estimated 222,520 new cases of lung cancer were diagnosed in the United States.¹ Lung cancer is the second most frequently diagnosed cancer in men and women (prostate and breast cancers are most frequent in men and women) (Figure 28-1). The incidence of lung cancer peaked in men in 1984 (86.5 per 100,000 men) and has since been declining (69.1 per 100,000 in 1997). In women, the incidence increased during the 1990s, with a leveling off toward the end of the decade (43.1 per 100,000 women). These trends parallel the smoking patterns of men and women.¹ The World Health Organization estimates that there are 2 million cases of lung cancer worldwide each year.

FIGURE 28-1 Age-adjusted cancer incidence rates for women and men, United States, 1975-2006. Rates are per 100,000 female population, adjusted to the 2000 U.S. standard population. The incidence of lung cancer in men and women has paralleled smoking habits. (Modified from Jemal A, Siegal R, Xu J, et al: Cancer statistics, 2010. CA Cancer J Clin 60:277–300, 2010.)

Deaths

Lung cancer is the leading cause of cancer-related mortality in men and women; it surpassed colon cancer in the early 1950s in men and breast cancer in the late 1980s in women. Mortality rates in men declined significantly in the 1990s, whereas a slow increase occurred in women. These rates parallel the smoking patterns of men and women (Figures 28-2 and 28-3). In 2010 in the United States, an estimated 157,300 deaths were due to lung cancer. In men, lung cancer is the leading cause of cancer-related mortality from age 40 on. In women, lung cancer surpasses breast cancer in the age group of 60 and older.¹

FIGURE 28-2 Age-adjusted cancer death rates for women, United States, 1930-2006. Rates are per 100,000, adjusted to the 2000 U.S. standard population. Lung cancer surpassed breast cancer as the leading cause of cancer-related mortality in women in the late 1980s. (Modified from Jemal A, Siegal R, Xu J, et al: Cancer statistics, 2010. CA Cancer J Clin 60:277–300, 2010.)

Risk Factors

Tobacco-Related Products

Direct exposure to tobacco has occurred in 85% to 90% of individuals with lung cancer. Many tobacco-related carcinogens have been identified. The two major classes are the N-nitrosamines and polycyclic aromatic hydrocarbons. A dose-response relationship exists between the degree of exposure to cigarette smoke and the development of lung cancer. The age at which smoking began, the number of cigarettes smoked per day, and the duration of smoking all influence the likelihood of developing lung cancer. Also, the intensity of smoking, the depth of inhalation, and the composition of the cigarette influence the risk. All types (see later) of lung cancer are associated with smoking. The strongest associations are with two of the cell types: small cell and squamous cell carcinoma. The risk of developing lung cancer decreases over time after smoking cessation, although it never reaches that of a lifelong nonsmoker.

There is evidence that nicotine, a chemical in tobacco, is highly addictive.² Approximately one-fifth of all adults in the United States smoke cigarettes. Progress had been made in the fight against cigarette use; in the decades from 1970-1990, the percentage of women who smoked declined from 33% to 25%, and the rate of smoking among men decreased from 43% to 28%. The annual decline that had occurred since the early 1970s began to slow through the 1990s despite mounting evidence associating smoking with disease and death.³ In addition, a decrease in smoking has not been observed among adults 18 to 24 years old. Cigarette smoking among young people remains a major public health concern. Of young adults (18 to 24 years old), 33% have been reported to be current users of tobacco,⁴ and 3000 teenagers begin smoking each day.⁵ Approximately 13% of middle school children and 28% of high school students use tobacco products. In the context that a person who has not started smoking as a teenager is unlikely ever to become a smoker, the tobacco industry has focused on young people and developing countries as the primary sources of new customers.^6,7

Other forms of exposure to tobacco-related products also pose risk of promoting lung cancer. Cigar smoking, which has increased considerably over the past several years, is known to be an independent risk factor for developing lung cancer.⁸

Exposure to sidestream smoke, or passive smoking, may also lead to an increased risk of lung cancer. The risk is generally much lower than active smoking but varies with the intensity of exposure.⁷ The risk of developing lung cancer has been reported to be 30% higher in individuals exposed to sidestream smoke. It has been estimated that 3000 to 5000 deaths in the United States and 21,400 deaths worldwide from lung cancer occur each year because of second-hand smoke exposure.^9,10

Occupational Agents and Other Risks

Many other risk factors have been identified (Box 28-1). Occupational agents are known to act as lung cancer carcinogens. Arsenic, asbestos, and chromium confer the highest risk. Of lung cancers, 2% to 9% have been estimated to be related to occupational exposures. This risk is increased when there is concomitant exposure to tobacco products. Indoor radon exposure is also a risk factor for developing lung cancer.¹¹ Radon is a product generated by the breakdown of uranium. Particulates in the atmosphere (i.e., pollution) can increase the risk of lung diseases including lung cancer.

Box 28-1

Lung Cancer Risk Factors

Tobacco smoke exposure

Active (mainstream)—cigarette, cigar

Passive (sidestream)

Occupational and environmental exposures

Polycyclic aromatic hydrocarbons

Bis(chloromethyl)ether

Radon

Cadmium

Vinyl chloride

Genetic predisposition

Courtesy The Cleveland Clinic, Cleveland, Ohio.

An inherited genetic predisposition has epidemiologic support as a risk factor, but the mechanisms are not proven. Family members of people who develop lung cancer have an increased risk.12,13 Women seem to have a higher baseline risk of developing lung cancer and a greater susceptibility to the effects of smoking. Differences in the metabolism of tobacco-related carcinogens and their metabolites, an effect of hormone differences, or both are thought to account for the increased susceptibility.¹⁴ Dietary factors can also modify risks. Higher consumption of fruits and vegetables is associated with a reduced lung cancer risk, and increased dietary fat intake may lead to a higher risk.^15,16 Supplementation with vitamin A, vitamin E, or beta-carotene has not positively influenced risk.¹⁵ The presence of chronic obstructive pulmonary disease (COPD) is an independent risk factor.¹⁷ This risk increases as the forced expiratory volume in 1 second (FEV₁) decreases.^18,19

Lung Cancer Classification

Lung cancers are divided into two major groups—small cell carcinoma and non–small cell carcinoma—based on pathologic features that are visible under light microscopy. The evaluation and management of a patient are guided by the category and stage (see later) of lung cancer. The non–small cell cancer category consists of adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and variants (Figure 28-4). Table 28-1 presents the pathologic and epidemiologic features of the four most common types of lung cancer: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell carcinoma.

TABLE 28-1

Classification of Most Common Types of Lung Cancer

Category	Cell Type	Pathologic Features (Light Microscopy)	Epidemiology
Non–small cell carcinoma	Adenocarcinoma	Formation of glandular structures; heterogeneous differentiation	Accounts for >40% of lung cancers in North America; increasing frequency in women
	Squamous cell carcinoma	Cytokeratin and intercellular bridges	Second most frequent type of lung cancer in United States
	Large cell carcinoma	Sheets and nests of cells, necrosis, lack of squamous cell or glandular features	Less common than adenocarcinoma or squamous cell carcinoma
Small cell carcinoma	Small cell carcinoma	Round to fusiform nuclei; faint to absent nucleoli; scant cytoplasm	Accounts for 13% of lung cancers

Pathophysiology

The pathophysiology of lung cancer development is complex and incompletely understood. Damage to genetic material in lung cells is the result of exposure to chemical carcinogens such as the carcinogens contained in tobacco smoke.²⁰ People who develop lung cancer may have a genetic predisposition to the effects of these carcinogens. The genes influenced in the pathogenesis of lung cancer produce proteins involved in cell growth and differentiation, cell cycle processes, apoptosis (programmed cell death), angiogenesis (production of new blood vessels), tumor progression, and immune regulation. If enough of these pathways have been affected, the uncontrolled growth of cells that defines cancer occurs. If the mechanisms that lead to genetic damage can be identified and the means by which the pathways involved are controlled, novel means of risk stratification, prevention, early detection, and therapy should be able to be developed.