INTRODUCTION — Lung cancer is a serious health problem. Although the death rate from lung cancer declined slightly (by 3.6 percent) in the 1990s after increasing steadily since the 1960s, the number of cases of lung cancer continues to increase, particularly in women, as the population ages and increases in size.
Cigarette smoking is the primary risk factor for lung cancer. A smoker's risk of developing lung cancer is 10 to 30 times greater than the risk for a non-smoker. Occupational or environmental exposure to other substances (eg, second-hand tobacco smoke, asbestos, radon, arsenic, radiation, polycyclic hydrocarbons, and nickel) also increase a person's risk of developing lung cancer, but the largest factor by far is smoking.
TYPES OF LUNG CANCER — The type of lung cancer is defined by the kind of cells that make up the cancerous tissue. The majority of lung cancers belong to one of four types: Squamous cell carcinoma (20 to 30 percent of lung cancers) Adenocarcinoma (30 to 40 percent) Large cell carcinoma (10 percent) Small cell or "oat cell" carcinoma (20 percent)
The first three types (squamous cell carcinoma, adenocarcinoma, and large cell carcinoma) are often collectively referred to as "non-small cell lung cancer" or NSCLC. In general, these tumors tend to behave in a comparable fashion, and they are treated similarly. In contrast, small cell lung cancer (SCLC) tends to grow and spread more quickly than NSCLC, and differs in the way treatment is approached.
SYMPTOMS — In a small number of patients (about 10 percent), lung cancer is first identified through an X-ray performed for some other reason, and no cancer-related symptoms are evident at the time of diagnosis. The majority of patients, however, are symptomatic at the time the lung cancer is diagnosed. Symptoms may be caused directly by the presence of the tumor itself in the lungs and chest, or by tumor that has spread or metastasized to other parts of the body, or they can be caused indirectly because a cancer is present somewhere in the body (eg, weight loss, fatigue, or paraneoplastic syndromes, which are explained below).
Lung and chest — The most common symptom of lung cancer is a cough, which may be present with or without sputum (phlegm) production. In patients who have a longstanding (chronic) cough, such as those with emphysema (also called chronic obstructive pulmonary disease or COPD), the development of a lung cancer may be signaled by a change in the character of their chronic cough. Other common symptoms include shortness of breath, coughing up bloody phlegm, chest pain, and wheezing.
Additional symptoms may appear as the cancer grows locally and spreads to other parts of the chest: Shortness of breath may develop if the cancer causes fluid to accumulate between the lung and chest wall (a condition called a pleural effusion). The ability of the heart to pump the blood throughout the body may be impaired if fluid accumulates around the heart (a condition called a pericardial effusion). Hoarseness may develop if the tumor presses on the laryngeal nerve (a nerve that travels through the chest and stimulates the larynx or "voice box" during speaking). Headache, shortness of breath, and swelling of the face, arms, or neck veins can occur if the tumor presses on the superior vena cava, a large blood vessel in the chest. A tumor that is located at the top of the lung can cause the "Pancoast syndrome", in which there is shoulder or arm pain, weakening of the hand muscles (both due to involvement of the brachial plexus, the nerve that stimulates the arm), a droopy eyelid, blurred vision, and a lack of sweating of the face on the side of the tumor.
Distant metastases — As lung cancer progresses, it can spread or metastasizes to other parts of the body. The most common sites of metastasis are the brain, bones, liver, and adrenal glands. Bone metastases can produce localized pain, while metastasis to the liver may cause weakness, jaundice (yellowing of the skin) and weight loss. Brain metastases can cause a range of symptoms including headache, nausea and vomiting, seizures, confusion, and personality changes.
Paraneoplastic syndromes — Paraneoplastic syndrome is a term used to describe a number of conditions that arise because of substances that are produced by the tumor, which then enter the bloodstream and act on the body to cause abnormalities. Thus, they are indirect effects of the tumor. About 10 to 20 percent of patients with lung cancer will experience symptoms due to a paraneoplastic syndrome; they are more common with SCLC than with NSCLC.
Symptoms may include an increase in the calcium level in the blood (hypercalcemia), broadening and thickening of the fingernails (digital clubbing), painful swollen joints, and neurologic symptoms.
Overproduction of hormones can also be caused by the tumor, and result in breast enlargement or discharge of a milky substance from the nipples. A hormone called ADH may also be secreted in unusually large quantities resulting in a low blood sodium level and concentrated urine. If untreated, oversecretion of ADH can lead to more serious symptoms including weakness, confusion, coma, and seizures.
INITIAL TESTING AND DIAGNOSIS — Once a patient presents with symptoms that suggest lung cancer, a chest X-ray is performed to check for the presence of a lung mass. If a mass is found, additional testing is performed to confirm the diagnosis, and determine the type of cancer. The additional tests also allow the physician to determine the "stage" of the cancer, or how widely it has spread. Accurate staging is important since it helps to define treatment and predict the long-term outcome of the cancer (the prognosis).
The physician first obtains a detailed history, performs a thorough physical examination, and obtains blood samples for testing. One or more radiologic tests are then performed to evaluate the local extent of tumor in the chest, and the possibility that it has spread outside of the chest. These tests may include a CT (computed tomography) scan of the chest, abdomen and/or head, PET scan, MRI (magnetic resonance imaging) scan, and bone scan.
Other procedures may be recommended to obtain tissue samples to examine the cancer cells and determine their type. A piece of the tissue can be obtained for study under the microscope in one of three ways: Bronchoscopy is a procedure where a lighted tube is inserted through the mouth into the windpipe (trachea, show figure 1) while the patient is sedated to directly visualize the airways. Any obvious areas of abnormality are then biopsied. (See "Patient information: Fiberoptic bronchoscopy"). CT-guided fine needle aspirate biopsy is a biopsy that is performed by a radiologist who inserts a thin needle through the skin of the chest into the lung. The needle's location is guided by computed tomography (CT scan). Mediastinoscopy is done under general anesthesia by a thoracic surgeon using a thin tube, inserted through the chest wall into the mediastinum, the central portion of the chest that represents the space between the right and left lung (show figure 1). A sample of tissue can then be removed through the tube.
STAGING OF NON-SMALL CELL LUNG CANCER — Staging is a way to define the extent of the tumor involvement, both in the chest and at distant sites, and is important in determining the most appropriate treatment.
In assigning a tumor stage in NSCLC, three factors are considered: Characteristics of the primary tumor (the T category, ranging from T1 to T4) The degree of lymph node involvement (the N category) Spread or metastasis to distant locations in the body (the M category)
Each factor (T, N, and M) is evaluated separately and assigned a value depending upon the extent of involvement (show table 1). Combinations of T, N, and M levels are grouped together to form stage groupings, which range from stage I (the least advanced degree of tumor involvement) through stage IV, the most advanced (show table 1). Stages I, II, and III disease are further subdivided into A and B subcategories.
Staging of NSCLC can be accomplished clinically (nonoperatively through x-ray studies and by physical examination); however, the final surgical or pathologic stage requires an operation and examination of the surgical specimen. This is especially important for patients who appear to have early stage (stage I to II) tumors, since involvement of lymph nodes in the mediastinum significantly alters the treatment approach. Often, a mediastinoscopy will be recommended to evaluate these lymph nodes under the microscope. Radical surgery may be offered to patients with stage I or II disease, while stage III disease is often treated with radiation and chemotherapy, and less often with surgery.
The following is a general description of the different tumor stages:
Stage I — At stage I, tumor is present in the lungs but the cancer has not spread to the lymph nodes or metastasized to other locations. Stage I lung cancer is considered a limited, local disease, and is not associated with any regional lymph node involvement.
Stage I disease is subdivided into stages IA and IB, primarily based upon the size of the primary tumor. Stage IA is associated with a primary tumor that is less than 3 cm in diameter. In contrast, stage IB is associated with a larger tumor, or with partial collapse of the lung. (See "Patient information: Treatment of early stage (stage I and II) non-small cell lung cancer").
Stage II — Stage II cancers have either begun to involve the adjacent lymph nodes, or have invaded surrounding tissues in the chest more extensively. However, no distant metastases are apparent, and the cancer is still considered a local disease. Stage II NSCLC is subdivided into stages IIA and IIB, based upon the size of the primary tumor. Stage IIA — The tumor is 3 cm or smaller and has invaded nearby tissue minimally if at all. One or more lymph nodes on the same side of the chest are involved, and there is no evidence of disease in the mediastinum nor distant metastases (T1 N1 M0). Stage IIB — Stage IIB disease comprises at least two situations: there is a T2 tumor (larger than 3 cm with some invasion of nearby tissue) and the cancer involves one or more lymph nodes on the same side of the chest (T2 N1 M0). Stage IIB is also assigned to cancers that have no lymph node involvement, but have either invaded chest structures outside the lung or are located within 2 cm of the carina (T3 N0 M0). (The carina is the point at which the trachea, or the tube that carries air to the lungs, splits in two to reach the right and left lung).
Stage III — Stage III NSCLC represents more advanced disease. The tumor has invaded chest tissues more extensively than in stage II and/or the cancer has spread to more distant lymph nodes located in the mediastinum. However, distant metastases are still not present. Stage III NSCLC is subdivided into stages IIIA and IIIB. (See "Patient information: Treatment of locally advanced (stage III) non-small cell lung cancer"). Stage IIIA — Stage IIIA is assigned if the cancer involves an invasive T3 tumor and lymph nodes on the same side of the chest (T3 N1 M0). The disease is also staged IIIA if the tumor involves more distant lymph nodes such as those in the mediastinum, or below the carina, regardless of the primary T designation (T1-3 N2 M0). Stage IIIB — Stage IIIB includes cancers that have invaded local structures extensively (T4 tumor), and cancers that have spread to more distant lymph nodes including those on the opposite side of the mediastinum (N3). (Possible TNM categories include T1-4 N3 M0 or T4 N1-N4 M0).
Stage IV — In stage IV lung cancer, the cancer has metastasized to distant locations (M1). (See "Patient information: Treatment of advanced unresectable; metastatic; and recurrent non-small cell lung cancer").
STAGING SMALL CELL LUNG CANCER — The system used to stage NSCLC is of limited value in staging small cell lung cancer (SCLC). This is because surgery is rarely used in this disease. For treatment purposes, SCLC is categorized more simply as either "limited" or "extensive" disease. Limited disease refers to small cell lung cancers that are confined to one side of the chest. Extensive disease refers to small cell lung cancers that have spread to the other side of the chest or that have metastasized to more distant locations.
As is the case for NSCLC, treatment and prognosis for SCLC varies depending upon the classification. (See "Patient information: Treatment of small cell lung cancer").
CLINICAL TRIALS — Progress in treating lung cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:
www.cancer.gov/clinical_trials/learning/
www.cancer.gov/clinical_trials/
http://clinicaltrials.gov/
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
(www.cancernet.nci.nih.gov/)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
The American Cancer Society
(www.cancer.org)
Lung Cancer Alliance
(www.lungcanceralliance.org)
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3. Pretreatment evaluation of non-small-cell lung cancer. The American Thoracic Society and The European Respiratory Society. Am J Respir Crit Care Med 1997; 156:320.
4. Argiris, A, Murren, JR. Staging and clinical prognostic factors for small-cell lung cancer. Cancer J 2001; 7:437.
5. Micke, P, Faldum, A, Metz, T, et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer-what limits limited disease?. Lung Cancer 2002; 37:271.
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