Section 4. Lung and Airway Disorders

Chapter 57. Lung Cancer

Topic: Lung Cancer

Lung Cancer

Lung cancer is the most common cause of death from cancer in both men and women. It occurs most commonly between the ages of 45 and 70. Lung cancer is more common in women now than in the past because more women are smoking cigarettes.

Lung cancer that originates in the cells of the lungs is called primary lung cancer; however, cancer may also spread (metastasize) to the lung from other parts of the body. Metastatic cancers spread to the lungs most commonly from the breast, colon, prostate, kidney, thyroid gland, stomach, cervix, rectum, testis, bone, and skin (melanoma).

More than 90% of primary lung cancers start in the bronchi (the large airways that branch off the trachea to supply the lungs); such lung cancer is called bronchogenic carcinoma. The specific types of lung cancer are small cell (oat cell) carcinoma, squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. The last three types of lung cancer are often referred to as nonsmall cell lung cancers.

Alveolar cell carcinoma (a subtype of adenocarcinoma) originates in the small air sacs of the lung (alveoli). Although alveolar cell carcinoma can occur at a single site, it often develops simultaneously in more than one area of the lung.

Less common lung tumors are bronchial carcinoid (which may be cancerous or noncancerous), chondromatous hamartoma (noncancerous), and sarcoma (cancerous). Lymphoma is a cancer of the lymphatic system; it may start in the lungs or spread to them.

See the figure Deaths Due to Lung Cancer.

Causes

Cigarette smoking is the cause of about 90% of lung cancer cases in men and about 80% of cases in women. The greater the quantity and duration of smoking, the greater the risk of developing lung cancer. About 10 to 12% of all smokers eventually develop lung cancer.

A small proportion of lung cancers (about 10% in men and about 5% in women) are caused by substances encountered or breathed in at work. Working with asbestos, radiation, arsenic, chromates, nickel, chloromethyl ethers, mustard gas, and coke-oven emissions has been linked with lung cancer. The risk of contracting lung cancer is greater in people who are exposed to these substances and who also smoke cigarettes. Air pollution causes about 1% of lung cancer cases. Exposure to radon gas in the home causes lung cancer in less than 1% of cases. Occasionally, lung cancers, especially adenocarcinoma and alveolar cell carcinoma, develop in people whose lungs have been scarred by other lung diseases, such as tuberculosis and fibrosis.

Symptoms and Complications

The symptoms of lung cancer depend on its type, its location, and the way it spreads. Usually, the first and most common symptom is a persistent cough. People with chronic bronchitis who develop lung cancer often notice that their coughing becomes worse. If sputum can be coughed up, it may be streaked with blood (called hemoptysis (see Section 4, Chapter 39)). If a lung cancer grows into underlying blood vessels, it may cause severe bleeding.

Lung cancer may cause wheezing by narrowing the bronchus in or around which it is growing. Blockage of a bronchus may lead to the collapse of the part of the lung that the bronchus supplies, a condition called atelectasis (see Section 4, Chapter 48). Other consequences of a blocked bronchus are shortness of breath, and pneumonia, with coughing, fever, and chest pain. If the tumor grows into the chest wall, it may produce persistent chest pain.

Lung cancer may grow into certain nerves in the neck, causing a droopy eyelid, small pupil, sunken eye, and reduced perspiration on one side of the face--together these symptoms are called Horner's syndrome (see Section 6, Chapter 96). Cancers at the top of the lung may grow into the nerves that supply the arm, making the arm painful, numb, and weak--this condition is called Pancoast syndrome. Nerves to the voice box may also be damaged, making the voice hoarse. This damage happens mainly in people whose cancers involve the left lung.

Lung cancer may grow directly into the esophagus, or it may grow near it and put pressure on it, leading to difficulty in swallowing. Occasionally, an abnormal channel (fistula) between the esophagus and bronchi develops because of invasion by the cancer, causing severe coughing during swallowing because food and fluid enter the lungs.

A lung cancer may grow into the heart, causing abnormal heart rhythms, blockage of blood flow through the heart, or fluid in the pericardial sac surrounding the heart. The cancer may grow into or compress the superior vena cava (one of the large veins in the chest); this condition is called superior vena cava syndrome. Obstruction of this vein causes blood to back up in other veins of the upper body. The veins in the chest wall enlarge. The face, neck, and upper chest wall--including the breasts--swell and become tinged with purple. The condition also produces shortness of breath, headache, distorted vision, dizziness, and drowsiness. These symptoms usually worsen when the person bends forward or lies down.

Symptoms of lung cancer that usually arise later include loss of appetite, weight loss, fatigue, and weakness. Fluid accumulations around the lung (pleural effusions (see Section 4, Chapter 52)) occur when the cancer has spread into the pleural space. They can lead to shortness of breath. Severe shortness of breath, low levels of oxygen in the blood, and cor pulmonale (see Section 4, Chapter 54) may develop if cancer spreads within the lungs.

Lung cancer may also spread through the bloodstream to the liver, brain, adrenal glands, spinal cord, and bone; less commonly lung cancer may spread to other parts of the body. The spread of lung cancer may occur early in the disease, especially with small cell carcinoma. Symptoms--such as headache, confusion, seizures, and bone pain--may develop before any lung problems become evident, making an early diagnosis difficult.

Paraneoplastic syndromes (see Section 15, Chapter 181) consist of effects that are caused by lung cancer but occur far from the lungs, such as in the metabolic system, nerves, and muscles. These syndromes are not related to the size or location of the lung cancer and do not necessarily indicate that the cancer has spread outside the chest; rather, they are caused by substances secreted by the cancer (such as hormones, cytokines, and a variety of other proteins).

Diagnosis

A doctor explores the possibility of lung cancer when a person, especially a smoker, has a persistent or worsening cough or other lung symptoms (such as shortness of breath or coughed-up sputum tinged with blood). Sometimes a shadow on a chest x-ray of someone with no symptoms provides the first clue, although a shadow on an x-ray is not proof of cancer. A chest x-ray can detect most lung tumors, although it may miss small ones.

A computed tomography (CT) may show small nodules that do not appear on chest x-rays. CT can also reveal whether the lymph nodes are enlarged; a biopsy of enlarged lymph nodes is often needed to determine if inflammation or cancer is responsible for the enlargement.

A microscopic examination of lung tissue is usually needed to confirm the diagnosis. Sometimes a sample of coughed-up sputum can provide enough material for an examination (called sputum cytology). Bronchoscopy may be performed to obtain that tissue (see Section 4, Chapter 39). If the cancer is too deep in the lung to be reached with a bronchoscope, a doctor can usually obtain a specimen by inserting a needle through the skin while using CT for guidance; this procedure is called a needle biopsy (see Section 4, Chapter 39). Sometimes, a specimen can be obtained only by a surgical procedure called a thoracotomy (see Section 4, Chapter 39).

CT of the abdomen or head may be performed to determine if lung cancer has spread, especially to the liver, adrenal glands, or brain. A bone scan may show that it has spread to the bones. Because small cell carcinoma tends to spread to the bone marrow, a doctor sometimes performs a bone marrow biopsy. New techniques, such as positron emission tomography (PET) (see Section 4, Chapter 39) and a certain type of CT called spiral CT, show promise for improving the ability to detect small cancers.

Cancers are categorized based on how large the tumor is, whether it has spread to nearby lymph nodes, and whether it has spread to distant organs. The different categories are called stages (see Section 15, Chapter 181). The stage of a cancer suggests the most appropriate treatment and enables a doctor to estimate the person's prognosis.

Screening and Prevention

Screening for lung cancer using chest x-rays and sputum examination is not recommended for everyone at this time. However, for people at high risk of lung cancer, a chest x-ray or CT performed yearly may help to detect lung cancer before it has spread.

Prevention of lung cancer includes quitting smoking and avoiding exposure to potentially cancer-causing substances in the work environment.

Treatment

Noncancerous bronchial tumors (including carcinoid tumors and chondromatous hamartomas) are usually removed surgically because they may block the bronchi and some may become cancerous over time. Often, a doctor cannot be sure if such a tumor is cancerous until it has been removed and examined microscopically.

Surgery: Surgery is the treatment of choice for lung cancer that has not spread beyond the lung. However, surgery is not useful for small cell carcinoma. Older people should not be excluded from surgery based solely on their age. Surgery may not be possible if the cancer has spread beyond the lungs, if the cancer is too close to the trachea, or if the person has other serious conditions (such as severe heart or lung disease).

Before surgery, a doctor performs pulmonary function tests (see Section 4, Chapter 39) to determine if the amount of lung remaining after surgery will be able to provide enough breathing function. If the test results indicate that removing the cancerous part of the lung will result in inadequate lung function, surgery is not possible. The amount of lung to be removed is decided during surgery, with the amount varying from a small part of a lung segment to an entire lung.

Although 10 to 35% of cancers can be removed surgically, removal does not always result in a cure. Among people who have an isolated, slow-growing tumor removed, 25 to 40% survive at least 5 years after the diagnosis. A few people with small, early-stage nonsmall cell lung cancers have up to a 60 to 70% 5-year survival rate. People die mostly from recurrence of their cancer, either in the lung or at another site. Some people die because of another disorder, such as chronic obstructive pulmonary disease or coronary heart disease, or from the development of a new cancer. Survivors must have regular checkups, including periodic chest x-rays and CT scans.

Occasionally, cancer that begins elsewhere (for example, in the colon) and spreads to the lungs is removed from the lungs after being removed at the source. This procedure is recommended rarely, and tests must show that the cancer has not spread to any site outside of the lungs. Only about 10% of people who undergo this type of surgery survive 5 years or more.

Recent advances in the treatment of nonsmall cell lung cancer include using chemotherapy and radiation therapy before, after, or instead of the surgical removal of a cancer in some people who have cancer that has not spread beyond the lung.

Radiation Therapy: Radiation therapy may be given to people who refuse surgery, who cannot undergo surgery because they have another condition (such as severe coronary artery disease), or whose cancer has spread to the nearby structures, such as the lymph nodes. Although radiation therapy only partially shrinks the cancer or slows its growth in most of these people, it results in a long-term remission in 10 to 15% of them. Combining chemotherapy with radiation therapy further improves survival in this group. Radiation therapy is also useful for controlling the complications of lung cancer, such as coughing up of blood, bone pain, superior vena cava syndrome, and spinal cord compression.

Chemotherapy: Chemotherapy, sometimes coupled with radiation therapy, is the treatment of choice for small cell carcinoma of the lung. This is because the cancer has almost always spread to distant parts of the body by the time of diagnosis. In about 25% of people, chemotherapy substantially prolongs survival. Without chemotherapy, only half of the people with small cell carcinoma survive 4 months. With chemotherapy, there is a four-to fivefold increase in survival. People with small cell carcinoma of the lung who have been responding well to chemotherapy may benefit from radiation therapy to the head to treat cancer that has spread to the brain, even though the spread is early enough that no symptoms are apparent and nothing abnormal can be seen on a CT or MRI of the head.

The effectiveness of chemotherapy alone is very limited for nonsmall cell lung cancer. In metastatic nonsmall cell lung cancer, some people survive significantly longer when given chemotherapy than if they had not received it.

Other Treatments: Other treatments are often needed for people who have lung cancer. Because many people who have lung cancer experience a substantial decrease in lung function, whether or not they undergo treatment, oxygen therapy (see Section 4, Chapter 40) and bronchodilators (drugs that widen the airways) may aid breathing. Many people with advanced lung cancer develop such extreme pain and difficulty in breathing that they require large doses of opioids in the weeks or months before their death. Fortunately, opioids can help substantially if adequate doses are used.

Prognosis

Lung cancer has a poor prognosis. On average, people with untreated lung cancer survive 8 months. Overall, even with therapy, the 5-year survival rate is only 13%. Because small cell carcinoma has almost always spread beyond the lung at the time of diagnosis, its prognosis is generally worse than for other types of lung cancer. People who survive lung cancer but continue to smoke are at high risk of another cancer.

Because many people die from lung cancer, terminal care is usually necessary. Advances in end-of-life care, particularly the recognition that anxiety and pain are common in people with incurable lung cancer and that they can be alleviated by appropriate drugs, have led to an increasing number of people being able to die comfortably at home (see Section 1, Chapter 8).