Lung Cancer, Non-Small Cell
Also found in: Dictionary.
Lung Cancer, Non-Small Cell
Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.
There are two kinds of lung cancers, primary and secondary. Primary lung cancer starts in the lung itself, and is divided into small cell lung cancer and non-small cell lung cancer. Small cell lung cancers are shaped like an oat and called oat-cell cancers; they are aggressive, spread rapidly, and represent 20% of lung cancers. Non-small cell lung cancer represents almost 80% of all primary lung cancers. Secondary lung cancer is cancer that starts somewhere else in the body (for example, the breast or colon) and spreads to the lungs.
The lungs are located along with the heart in the chest cavity. The lungs are not simply hollow balloons but have a very organized structure consisting of hollow tubes, blood vessels and elastic tissue. The hollow tubes, called bronchi, are highly branched, becoming smaller and more numerous at each branching. They end in tiny, blind sacs made of elastic tissue called alveoli. These sacs are where the oxygen a person breathes in is taken up into the blood, and where carbon dioxide moves out of the blood to be breathed out.
Normal healthy lungs are continually secreting mucus that not only keeps the lungs moist, but also protects the lungs by trapping foreign particles like dust and dirt in breathed air. The inside of the lungs is covered with small hairlike structures called cilia. The cilia move in such a way that mucus is swept up out of the lungs and into the throat.
Most lung cancers start in the cells that line the bronchi, and can take years to develop. As they grow larger they prevent the lungs from functioning normally. The tumor can reduce the capacity of the lungs, or block the movement of air through the bronchi in the lungs. As a result, less oxygen gets into the blood and patients feel short of breath. Tumors may also block the normal movement of mucus up into the throat. As a result, mucus builds up in the lungs and infection may develop behind the tumor. Once lung cancer has developed it frequently spreads to other parts of the body.
The speed at which non-small cell tumors grow depends on the type of cells that make up the tumor. The following three types account for the vast majority of non-small cell tumors:
- Adenocarcinomas are the most common and often cause no symptoms. Frequently they are not found until they are advanced.
- Squamous cell carcinomas usually produce symptoms because they are centrally located and block the lungs.
- Undifferentiated large cell and giant cell carcinomas tend to grow rapidly, and spread quickly to other parts of the body.
Worldwide, lung cancer is the most common cancer in males, and the fifth most common cancer in women. The worldwide mortality rate for patients with lung cancer is 86%. In the United States, lung cancer is the leading cause of death from cancer among both men and women. The World Health Organization estimates that the worldwide mortality from lung cancer will increase to three million by the year 2025. Of those three million deaths, almost two and a half million will result from non-small cell lung cancer.
The American Cancer Society (ACS) estimates that 173,770 Americans will develop lung cancer in 2004, 93,110 men and 80,660 women. Of these patients, 160,440 will die of the disease.
The incidence of lung cancer is beginning to fall in developed countries. This may be a result of antismoking campaigns. In developing countries, however, rates continue to rise, which may be a consequence of both industrialization and the increasing use of tobacco products.
Causes and symptoms
Tobacco smoking accounts for 87% of all lung cancers. Giving up tobacco can prevent most lung cancers. Smoking marijuana cigarettes is considered another risk factor for cancer of the lung. Second hand smoke also contributes to the development of lung cancer among nonsmokers.
Certain hazardous materials that people may be exposed to in their jobs have been shown to cause lung cancer. These include asbestos, coal products, and radioactive substances. Air pollution may also be a contributing factor. Exposure to radon, a colorless, odorless gas that sometimes accumulates in the basement of homes, may cause lung cancer in a tiny minority of patients. In addition, patients whose lungs are scarred from other lung conditions may have an increased risk of developing lung cancer.
Lung cancers tend to spread very early, and only 15% are detected in their early stages. The chances of early detection, however, can be improved by seeking medical care at once if any of the following symptoms appear:
- a cough that does not go away
- chest pain
- shortness of breath
- recurrent lung infections, such as bronchitis or pneumonia
- bloody or brown-colored spit or phlegm (sputum)
- persistent hoarseness
- significant weight loss that is not due to dieting or vigorous exercise; fatigue and loss of appetite
- unexplained fever
Although these symptoms may be caused by diseases other than lung cancer, it is important to consult a doctor to rule out the possibility of lung cancer.
If lung cancer has spread to other organs, the patient may have other symptoms such as headaches, bone fractures, pain, bleeding, or blood clots.
Physical examination and diagnostic tests
The doctor will first take a detailed medical history and assess risk factors. During a complete physical examination the doctor will examine the patient's throat to rule out other possible causes of hoarseness or coughing, and will listen to the patient's breathing and chest sounds.
If the doctor has reason to suspect lung cancer, particularly if the patient has a history of heavy smoking or occupational exposure to irritating substances, a chest x ray may be ordered to see if there are any masses in the lungs. Special imaging techniques, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), may provide more precise information about the size, shape, and location of any tumors.
Sputum analysis is a noninvasive test that involves microscopic examination of cells that are coughed up from the lungs. This test can diagnose at least 30% of lung cancers, even if tumors are not visible on chest x rays. In addition, the test can detect cancer in its very early stages, before it spreads to other regions. The sputum test does not provide any information about the location of the tumor.
Lung biopsy is the most definitive diagnostic tool for cancer. It can be performed in three different ways. Bronchoscopy involves the insertion of a slender, lighted tube, called a bronchoscope, down the patient's throat and into the lungs. This test allows the doctor to see the tubes inside the lungs, and to obtain samples of lung tissue. If a needle biopsy is to be performed, the location of the tumor is first identified using a computerized tomography (CT) scan or magnetic resonance imaging (MRI). The doctor then inserts a needle through the chest wall and collects a sample of tissue from the tumor. In the third procedure, known as surgical biopsy, the chest wall is opened up and a part of the tumor, or all of it, is removed. A doctor who specializes in the study of diseased tissue (a pathologist) examines the tumor to identify the cancer's type and stage.
Treatment for non-small cell lung cancer depends primarily on the stage of the cancer. Staging is a process that tells the doctor if the cancer has spread and the extent of its spread. The most commonly used treatments are surgery, radiation therapy, and chemotherapy.
Non-small cell lung cancer has six stages:
- Occult carcinoma. Cancer cells have been found in the sputum, but no tumor has yet been found.
- Stage 0. A small group of cancerous cells have been found in one location.
- Stage I. The cancer is only in the lung and has not spread anywhere else.
- Stage II. The cancer has spread to nearby lymph nodes.
- Stage III. The cancer has spread to more distant lymph nodes, and/or other parts of the chest like the diaphragm.
- Stage IV. The cancer has spread to other parts of the body.
Surgery is the standard treatment for the earlier stages of non-small cell lung cancer. The surgeon will decide on the type of surgery, depending on how much of the lung is affected. There are three different types of surgical procedures:
- Wedge resection is the removal of a small part of the lung.
- Lobectomy is the removal of one lobe of the lung. (The right lung has three lobes and the left lung has two lobes.)
- Pneumonectomy is the removal of an entire lung.
Lung surgery is a major procedure and patients can expect to experience pain, weakness in the chest, and shortness of breath. Air and fluid collect in the chest after surgery. As a result, patients will need help to turn over, cough, and breath deeply. Patients should be encouraged to perform these activities because they help get rid of the air and fluid and speed up recovery. It can take patients several months before they regain their energy and strength.
Patients whose cancer has progressed too far for surgery (Stages III and IV) may receive radiotherapy. Radiotherapy involves the use of high-energy rays to kill cancer cells. It is used either by itself or in combination with surgery or chemotherapy. The amount of radiation used depends on the size and the location of the tumor.
Radiation therapy may produce such side effects as tiredness, skin rashes, upset stomach, and diarrhea. Dry or sore throats, difficulty in swallowing, and loss of hair in the treated area are all minor side effects of radiation. These may disappear either during the course of the treatment or after the treatment is over.
Chemotherapy is also given to patients whose cancer has progressed too far for surgery. Chemotherapy is medication that is usually given intravenously to kill cancer cells. These drugs enter the bloodstream and travel to all parts of the body, killing cancer cells that have spread to different organs. Chemotherapy is used as the primary treatment for cancers that have spread beyond the lung and cannot be removed by surgery. It can also be used in addition to surgery or radiation therapy.
Chemotherapy for NSCLC has made significant advances since the early 1980s in improving the patient's quality of life as well as length of survival. Newer cytotoxic (cell-killing) agents developed in the 1990s, such as the taxanes, are typically combined with either cisplatin or carboplatin as first-line therapy for non-small cell lung cancer.
Newer drugs for lung cancer developed since 2000 include gefinitib (Iressa) and pemetrexed (Alimta). The FDA approved gefinitib in May 2003 as a treatment for patients with NSCLC who have not responded to platinum-based or taxane chemotherapy. It is taken by mouth and works by inhibiting an enzyme involved in the growth of tumor cells. Pemetrexed, which is given by injection, was approved by the FDA in February 2004 for the treatment of mesothelioma, a type of lung cancer caused by exposure to asbestos fibers. However, the drug appears to be effective in treating other types of lung cancer as well.
Chemotherapy is also used as palliative treatment for non-small cell lung cancer. Palliative refers to any type of therapy that is given to relieve the symptoms of a disease but not to cure it.
Chemotherapy for non-small cell lung cancer often has severe side effects, including nausea and vomiting, hair loss, anemia, weakening of the immune system, and sometimes infertility. Most of these side effects end when the treatment is over. Other medications can be given to lessen the unpleasant side effects of chemotherapy.
Because non-small cell lung cancer has a poor prognosis with conventional medical treatment, many patients are willing to try complementary and alternative therapies. These therapies are used to try to reduce stress, ease side effects and symptoms, or control disease. Two treatments sometimes used are shark cartilage and mistletoe. Although shark cartilage is thought to interfere with the tumor's blood supply, clinical trials have so far been inconclusive. Mistletoe is a poisonous plant that has been shown to kill cancer cells in the laboratory. Again, however, clinical trials with cancer patients have been inconclusive.
Patients who decide to try complementary and alternative therapies should tell their doctor. Some of these therapies may interfere with conventional treatment.
The prognosis for non-small cell lung cancer is better if the disease is found early, and removed surgically. For patients whose disease is caught in Stage I, the survival rate five years after surgery ranges from 60% to 80%. Up to 55% of Stage II patients are alive after five years, but only about 30% of Stage III patients make it to five years. Unfortunately, 85% of patients already have at least Stage III cancer by the time they are diagnosed. Many of these patients have disease that is too advanced for surgery. Despite treatment with radiotherapy and chemotherapy, the five-year survival for patients with inoperable disease is extremely low.
The best way to prevent lung cancer is not to start smoking or to quit smoking. Secondhand smoke from other people's tobacco should also be avoided. Appropriate precautions should be taken when working with cancer-causing substances (carcinogens). Testing houses for the presence of radon gas, and removing asbestos from buildings have also been suggested as preventive strategies.
Bronchi — The tubes that carry air into the lungs.
Lymph — Clear fluid containing white blood cells that is collected from the tissues of the body and flows in vessels called the lymphatic system.
Lymph node — Small oval-shaped filters in the lymphatic system that trap bacteria and other unwanted particles to ensure their removal from the body.
Palliative — Referring to any type of treatment that is given to relieve the symptoms of a disease rather than to cure it.
Respiratory distress — A condition in which patients with lung disease are not able to get enough oxygen.
Beers, Mark H., MD, and Robert Berkow, MD., editors. "Bronchogenic Carcinoma." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Brambilla, Christian, and Elisabeth Brambilla, editors. Lung Tumors. Fundamental Biology and Clinical Management. New York: Marcel Dekker, 1999.
Skarin, Harry S., editor. Multimodality Treatment of Lung Cancer. New York: Marcel Dekker, 2000.
Carney, Desmond N., and Heine H. Hansen. "Non-Small-Cell Lung Cancer: Stalemate or Progress?" New England Journal of Medicine 343, no. 17 (26 October 2000): 1261-3.
Cohen, M. H., G. A. Williams, R. Sridhara, et al. "United States Food and Drug Administration Drug Approval Summary: Gefitinib (ZD1839; Iressa) Tablets." Clinical Cancer Research 10 (February 15, 2004): 1212-1218.
Deslauriers, Jean, and Jocelyn Gregoire. "Clinical and Surgical Staging of Non-Small Cell Lung Cancer." Chest 117, no. 4, Supplement 1 (April 2000): 96S-103S.
Fossella, F. V. "Pemetrexed for Treatment of Advanced Non-Small Cell Lung Cancer." Seminars in Oncology 31 (February 2004): 100-105.
Frampton, J. E., and S. E. Easthope. "Gefitinib: A Review of Its Use in the Management of Advanced Non-Small-Cell Lung Cancer." Drugs 64 (2004): 2475-2492.
Johnson, David H. "Locally Advanced, Unresectable Non-Small Cell Lung Cancer. New Treatment Strategies." Chest 117, no.4, Supplement 1 (April 2000): 123S-126S.
Ramalingam, S., and C. P. Belani. "State-of-the-Art Chemotherapy for Advanced Non-Small Cell Lung Cancer." Seminars in Oncology 31 (February 2004): 68-74.
Rigas, J. R. "Taxane-Platinum Combinations in Advanced Non-Small Cell Lung Cancer: A Review." Oncologist 9, Supplement 2 (2004): 16-23.
Alliance for Lung Cancer Advocacy, Support and Education. PO Box 849 Vancouver, WA 98666. (800) 298-2436. http://www.alcase.org.
American Lung Association. 1740 Broadway New York, NY 10019. (212) 315-8700. http://www.lungusa.org.
National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422-6237. http://www.nci.nih.gov.
National Center for Complementary and Alternative Medicine (National Institutes of Health). PO Box 8218, Silver Spring, MD 20907-8218. (888) 644-6226. http://nccam.nih.gov.
American Cancer Society (ACS). Cancer Facts & Figures 2004. http://www.cancer.org/downloads/STT/CAFF_finalPWSecured.pdf.
FDA News, February 5, 2004. "FDA Approves First Drug for Rare Type of Cancer." http://www.fda.gov/bbs/topics/NEWS/2004/NEW01018.html.