What is lung cancer?
Cancer of the lung, like all cancers, results from an abnormality in the body's basic unit of life, the cell. Normally, the body maintains a system of checks and balances on cell growth so that cells divide to produce new cells only when new cells are needed. Disruption of this system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor.
Tumors can be benign or malignant; when we speak of "cancer," we are referring to those tumors that are malignant. Benign tumors usually can be removed and do not spread to other parts of the body. Malignant tumors, on the other hand, grow aggressively and invade other tissues of the body, allowing entry of tumor cells into the bloodstream or lymphatic system and then to other sites in the body. This process of spread is termed metastasis; the areas of tumor growth at these distant sites are called metastases. Since lung cancer tends to spread or metastasize very early after it forms, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs -- particularly the adrenal glands, liver, brain, and bone -- are the most common sites for lung cancer metastasis.
The lung also is a very common site for metastasis from tumors in other parts of the body. Tumor metastases are made up of the same type of cells as the original (primary) tumor. For example, if prostate cancer spreads via the bloodstream to the lungs, it is metastatic prostate cancer in the lung and is not lung cancer.
Lung Cancer Picture
The principal function of the lungs is to exchange gases between the air we breathe and the blood. Through the lung, carbon dioxide is removed from the bloodstream and oxygen from inspired air enters the bloodstream. The right lung has three lobes, while the left lung is divided into two lobes and a small structure called the lingula that is the equivalent of the middle lobe on the right. The major airways entering the lungs are the bronchi, which arise from the trachea. The bronchi branch into progressively smaller airways called bronchioles that end in tiny sacs known as alveoli where gas exchange occurs. The lungs and chest wall are covered with a thin layer of tissue called the pleura.
Lung cancers can arise in any part of the lung, but 90%-95% of cancers of the lung are thought to arise from the epithelial cells, the cells lining the larger and smaller airways (bronchi and bronchioles); for this reason, lung cancers are sometimes called bronchogenic cancers or bronchogenic carcinomas. (Carcinoma is another term for cancer.) Cancers also can arise from the pleura (called mesotheliomas) or rarely from supporting tissues within the lungs, for example, the blood vessels.
How common is lung cancer?
Lung cancer is the most common cause of death due to cancer in both men and women throughout the world. The American Cancer Society estimates that 219,440 new cases of lung cancer in the U.S. will be diagnosed and 159,390 deaths due to lung cancer will occur in 2009. According to the U.S. National Cancer Institute, approximately one out of every 14 men and women in the U.S. will be diagnosed with cancer of the lung at some point in their lifetime.
Lung cancer is predominantly a disease of the elderly; almost 70% of people diagnosed with lung cancer are over 65 years of age, while less than 3% of lung cancers occur in people under 45 years of age.
Lung cancer was not common prior to the 1930s but increased dramatically over the following decades as tobacco smoking increased. In many developing countries, the incidence of lung cancer is beginning to fall following public education about the dangers of cigarette smoking and the introduction of effective smoking-cessation programs. Nevertheless, lung cancer remains among the most common types of cancers in both men and women worldwide. In the U.S., lung cancer has surpassed breast cancer as the most common cause of cancer-related deaths in women.
What causes lung cancer?
Smoking
The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked and the time over which smoking has occurred; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history. While the risk of lung cancer is increased with even a 10-pack-year smoking history, those with 30-pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.
Pipe and cigar smoking also can cause lung cancer, although the risk is not as high as with cigarette smoking. Thus, while someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.
Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking.
Passive smoking
Passive smoking or the inhalation of tobacco smoke by nonsmokers who share living or working quarters with smokers, also is an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with nonsmokers who do not reside with a smoker. An estimated 3,000 lung cancer deaths that occur each year in the U.S. are attributable to passive smoking.
Asbestos fibers
Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past as both thermal and acoustic insulation. Today, asbestos use is limited or banned in many countries, including the U.S. Both lung cancer and mesothelioma (cancer of the pleura of the lung as well as of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos. Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in workers exposed to asbestos. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, but asbestos workers who smoke have a risk that is 50- to 90-fold greater than nonsmokers.
Radon gas
Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. Uranium decays to form products, including radon, that emit a type of ionizing radiation. Radon gas is a known cause of lung cancer, with an estimated 12% of lung-cancer deaths attributable to radon gas, or about 20,000 lung-cancer-related deaths annually in the U.S., making radon the second leading cause of lung cancer in the U.S. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings. The U.S. Environmental Protection Agency estimates that one out of every 15 homes in the U.S. contains dangerous levels of radon gas. Radon gas is invisible and odorless, but it can be detected with simple test kits.
Familial predisposition
While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and non-smoking relatives of those who have had lung cancer than in the general population. Recently, the largest genetic study of lung cancer ever conducted, involving over 10,000 people from 18 countries and led by the International Agency for Research on Cancer (IARC), identified a small region in the genome (DNA) that contains genes that appear to confer an increased susceptibility to lung cancer in smokers. The specific genes, located the q arm of chromosome 15, code for proteins that interact with nicotine and other tobacco toxins (nicotinic acetylcholine receptor genes).
Lung diseases
The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with an increased risk (four- to sixfold the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.
Prior history of lung cancer
Survivors of lung cancer have a greater risk of developing a second lung cancer than the general population has of developing a first lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs, see below), the risk for development of second lung cancers approaches 6% per year.
Air pollution
Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk for the development of lung cancer similar to that of passive smoking.
What are the types of lung cancer?
Lung cancers, also known as bronchogenic carcinomas, are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways and may have different treatment options, so a distinction between these two types is important.
SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking, with only 1% of these tumors occurring in nonsmokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell appearance often seen when examining samples of SCLC under the microscope, these cancers are sometimes called oat cell carcinomas.
NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC can be divided into three main types that are named based upon the type of cells found in the tumor:
- Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC. While adenocarcinomas are associated with smoking, like other lung cancers, this type is observed as well in nonsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.
- Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi.
- Large cell carcinomas, sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC.
- Mixtures of different types of NSCLC are also seen.
Other types of cancers can arise in the lung; these types are much less common than NSCLC and SCLC and together comprise only 5%-10% of lung cancers:
- Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3-4 cm or less) when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances that may cause specific symptoms related to the hormone being produced. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection.
- Cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response can rarely occur in the lung.
As discussed previously, metastatic cancers from other primary tumors in the body are often found in the lung. Tumors from anywhere in the body may spread to the lungs either through the bloodstream, through the lymphatic system, or directly from nearby organs. Metastatic tumors are most often multiple, scattered throughout the lung, and concentrated in the peripheral rather than central areas of the lung.
What are the signs and symptoms of lung cancer?
Symptoms of lung cancer are varied depending upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. A person with lung cancer may have the following kinds of symptoms:
- No symptoms: In up to 25% of people who get lung cancer, the cancer is first discovered on a routine chest X-ray or CT scan as a solitary small mass sometimes called a coin lesion, since on a two-dimensional X-ray or CT scan, the round tumor looks like a coin. These patients with small, single masses often report no symptoms at the time the cancer is discovered.
- Symptoms related to the cancer: The growth of the cancer and invasion of lung tissues and surrounding tissue may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder pain that travels down the outside of the arm (called Pancoast's syndrome) or paralysis of the vocal cords leading to hoarseness. Invasion of the esophagus may lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses, pneumonia) in the obstructed area.
- Symptoms related to metastasis: Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may include blurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.
- Paraneoplastic symptoms: Lung cancers frequently are accompanied by symptoms that result from production of hormone-like substances by the tumor cells. These paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type. A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing's syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.
- Nonspecific symptoms: Nonspecific symptoms seen with many cancers, including lung cancers, include weight loss, weakness, and fatigue. Psychological symptoms such as depression and mood changes are also common.
When should one consult a doctor?
One should consult a health-care provider if he or she develops the symptoms associated with lung cancer, in particular, if they have
- a new persistent cough or worsening of an existing chronic cough,
- blood in the sputum,
- persistent bronchitis or repeated respiratory infections,
- chest pain,
- unexplained weight loss and/or fatigue,
- breathing difficulties such as shortness of breath or wheezing.
How is lung cancer diagnosed?
Doctors use a wide range of diagnostic procedures and tests to diagnose lung cancer. These include...
- The history and physical examination may reveal the presence of symptoms or signs that are suspicious for lung cancer. In addition to asking about symptoms and risk factors for cancer development such as smoking, doctors may detect signs of breathing difficulties, airway obstruction, or infections in the lungs. Cyanosis, a bluish color of the skin and the mucous membranes due to insufficient oxygen in the blood, suggests compromised function due to chronic disease of the lung. Likewise, changes in the tissue of the nail beds, known as clubbing, also may indicate chronic lung disease.
- The chest X-ray is the most common first diagnostic step when any new symptoms of lung cancer are present. The chest X-ray procedure often involves a view from the back to the front of the chest as well as a view from the side. Like any X-ray procedure, chest X-rays expose the patient briefly to a small amount of radiation. Chest X-rays may reveal suspicious areas in the lungs but are unable to determine if these areas are cancerous. In particular, calcified nodules in the lungs or benign tumors called hamartomas may be identified on a chest X-ray and mimic lung cancer.
- CT (computerized tomography, computerized axial tomography, or CAT) scans may be performed on the chest, abdomen, and/or brain to examine for both metastatic and lung tumors. A CT scan of the chest may be ordered when X-rays do not show an abnormality or do not yield sufficient information about the extent or location of a tumor. CT scans are X-ray procedures that combine multiple images with the aid of a computer to generate cross-sectional views of the body. The images are taken by a large donut-shaped X-ray machine at different angles around the body. One advantage of CT scans is that they are more sensitive than standard chest X-rays in the detection of lung nodules, that is, they will demonstrate more nodules. Sometimes intravenous contrast material is given prior to the scan to help delineate the organs and their positions. A CT scan exposes the patient to a minimal amount of radiation. The most common side effect is an adverse reaction to intravenous contrast material that may have been given prior to the procedure. This may result in itching, a rash, or hives that generally disappear rather quickly. Severe anaphylactic reactions (life-threatening allergic reactions with breathing difficulties) to contrast material are rare. CT scans of the abdomen may identify metastatic cancer in the liver or adrenal glands, and CT scans of the head may be ordered to reveal the presence and extent of metastatic cancer in the brain.
- A technique called a low-dose helical CT scan (or spiral CT scan) is sometimes used in screening for lung cancers. This procedure requires a special type of CT scanner and has been shown to be an effective tool for the identification of small lung cancers in smokers and former smokers. However, it has not yet been proven whether the use of this technique actually saves lives or lowers the risk of death from lung cancer. The heightened sensitivity of this method is actually one of the sources of its drawbacks, since lung nodules requiring further evaluation will be seen in approximately 20% of people with this technique. Of the nodules identified by low-dose helical screening CTs, 90% are not cancerous but require up to two years of costly and often uncomfortable follow-up and testing. Trials are underway to further determine the utility of spiral CT scans in screening for lung cancer.
- Magnetic resonance imaging (MRI) scans may be appropriate when precise detail about a tumor's location is required. The MRI technique uses magnetism, radio waves, and a computer to produce images of body structures. As with CT scanning, the patient is placed on a moveable bed which is inserted into the MRI scanner. There are no known side effects of MRI scanning, and there is no exposure to radiation. The image and resolution produced by MRI is quite detailed and can detect tiny changes of structures within the body. People with heart pacemakers, metal implants, artificial heart valves, and other surgically implanted structures cannot be scanned with an MRI because of the risk that the magnet may move the metal parts of these structures.
- Positron emission tomography (PET) scanning is a specialized imaging technique that uses short-lived radioactive drugs to produce three-dimensional colored images of those substances in the tissues within the body. While CT scans and MRI scans look at anatomical structures, PET scans measure metabolic activity and the function of tissues. PET scans can determine whether a tumor tissue is actively growing and can aid in determining the type of cells within a particular tumor. In PET scanning, the patient receives a short half-lived radioactive drug, receiving approximately the amount of radiation exposure as two chest X-rays. The drug accumulates in certain tissues more than others, depending on the drug that is injected. The drug discharges particles known as positrons from whatever tissues take them up. As the positrons encounter electrons within the body, a reaction producing gamma rays occurs. A scanner records these gamma rays and maps the area where the radioactive drug has accumulated. For example, combining glucose (a common energy source in the body) with a radioactive substance will show where glucose is rapidly being used, for example, in a growing tumor.
- Bone scans are used to create images of bones on a computer screen or on film. Doctors may order a bone scan to determine whether a lung cancer has metastasized to the bones. In a bone scan, a small amount of radioactive material is injected into the bloodstream and collects in the bones, especially in abnormal areas such as those involved by metastatic tumors. The radioactive material is detected by a scanner, and the image of the bones is recorded on a special film for permanent viewing.
- Sputum cytology: The diagnosis of lung cancer always requires confirmation of malignant cells by a pathologist, even when symptoms and X-ray studies are suspicious for lung cancer. The simplest method to establish the diagnosis is the examination of sputum under a microscope. If a tumor is centrally located and has invaded the airways, this procedure, known as a sputum cytology examination, may allow visualization of tumor cells for diagnosis. This is the most risk-free and inexpensive tissue diagnostic procedure, but its value is limited since tumor cells will not always be present in sputum even if a cancer is present. Also, noncancerous cells may occasionally undergo changes in reaction to inflammation or injury that makes them look like cancer cells.
- Bronchoscopy: Examination of the airways by bronchoscopy (visualizing the airways through a thin, fiberoptic probe inserted through the nose or mouth) may reveal areas of tumor that can be sampled (biopsied) for diagnosis by a pathologist. A tumor in the central areas of the lung or arising from the larger airways is accessible to sampling using this technique. Bronchoscopy may be performed using a rigid or a flexible fiberoptic bronchoscope and can be performed in a same-day outpatient bronchoscopy suite, an operating room, or on a hospital ward. The procedure can be uncomfortable, and it requires sedation or anesthesia. While bronchoscopy is relatively safe, it must be carried out by a lung specialist (pulmonologist or surgeon) experienced in the procedure. When a tumor is visualized and adequately sampled, an accurate cancer diagnosis usually is possible. Some patients may cough up dark-brown blood for one to two days after the procedure. More serious but rare complications include a greater amount of bleeding, decreased levels of oxygen in the blood, and heart arrhythmias as well as complications from sedative medications and anesthesia.
- Needle biopsy: Fine needle aspiration (FNA) through the skin, most commonly performed with radiological imaging for guidance, may be useful in retrieving cells for diagnosis from tumor nodules in the lungs. Needle biopsies are particularly useful when the lung tumor is peripherally located in the lung and not accessible to sampling by bronchoscopy. A small amount of local anesthetic is given prior to insertion of a thin needle through the chest wall into the abnormal area in the lung. Cells are suctioned into the syringe and are examined under the microscope for tumor cells. This procedure is generally accurate when the tissue from the affected area is adequately sampled, but in some cases, adjacent or uninvolved areas of the lung may be mistakenly sampled. A small risk (3%-5%) of an air leak from the lungs (called a pneumothorax, which can easily be treated) accompanies the procedure.
- Thoracentesis: Sometimes lung cancers involve the lining tissue of the lungs (pleura) and lead to an accumulation of fluid in the space between the lungs and chest wall (called a pleural effusion). Aspiration of a sample of this fluid with a thin needle (thoracentesis) may reveal the cancer cells and establish the diagnosis. As with the needle biopsy, a small risk of a pneumothorax is associated with this procedure.
- Major surgical procedures: If none of the aforementioned methods yields a diagnosis, surgical methods must be employed to obtain tumor tissue for diagnosis. These can include mediastinoscopy (examining the chest cavity between the lungs through a surgically inserted probe with biopsy of tumor masses or lymph nodes that may contain metastases) or thoracotomy (surgical opening of the chest wall for removal or biopsy of a tumor). With a thoracotomy, it is rare to be able to completely remove a lung cancer, and both mediastinoscopy and thoracotomy carry the risks of major surgical procedures (complications such as bleeding, infection, and risks from anesthesia and medications). These procedures are performed in an operating room, and the patient must be hospitalized.
- Blood tests: While routine blood tests alone cannot diagnose lung cancer, they may reveal biochemical or metabolic abnormalities in the body that accompany cancer. For example, elevated levels of calcium or of the enzyme alkaline phosphatase may accompany cancer that is metastatic to the bones. Likewise, elevated levels of certain enzymes normally present within liver cells, including aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), signal liver damage, possibly through the presence of tumor metastatic to the liver. One current focus of research in the area of lung cancer is the development of a blood test to aid in the diagnosis of lung cancer. Researchers have preliminary data that has identified specific proteins, or biomarkers, that are in the blood and may signal that lung cancer is present in someone with a suspicious area seen on a chest X-ray or other imaging study.
Schematic illustration of a lung cancer located in the right upper lobe of the lung.
What is staging of lung cancer?
The stage of a cancer is a measure of the extent to which a cancer has spread in the body. Staging involves evaluation of a cancer's size and its penetration into surrounding tissue as well as the presence or absence of metastases in the lymph nodes or other organs. Staging is important for determining how a particular cancer should be treated, since lung-cancer therapies are geared toward specific stages. Staging of a cancer also is critical in estimating the prognosis of a given patient, with higher-stage cancers generally having a worse prognosis than lower-stage cancers.
Doctors may use several tests to accurately stage a lung cancer, including laboratory (blood chemistry) tests, X-rays, CT scans, bone scans, MRI scans, and PET scans. Abnormal blood chemistry tests may signal the presence of metastases in bone or liver, and radiological procedures can document the size of a cancer as well as its spread.
NSCLC are assigned a stage from I to IV in order of severity:
- In stage I, the cancer is confined to the lung.
- In stages II and III, the cancer is confined to the chest (with larger and more invasive tumors classified as stage III).
- Stage IV cancer has spread from the chest to other parts of the body.SCLC are staged using a two-tiered system:
- Limited-stage (LS) SCLC refers to cancer that is confined to its area of origin in the chest.
- In extensive-stage (ES) SCLC, the cancer has spread beyond the chest to other parts of the body.
How is lung cancer treated?
Treatment for lung cancer can involve surgical removal of the cancer, chemotherapy, or radiation therapy, as well as combinations of these treatments. The decision about which treatments will be appropriate for a given individual must take into account the location and extent of the tumor as well as the overall health status of the patient.
As with other cancers, therapy may be prescribed that is intended to be curative (removal or eradication of a cancer) or palliative (measures that are unable to cure a cancer but can reduce pain and suffering). More than one type of therapy may be prescribed. In such cases, the therapy that is added to enhance the effects of the primary therapy is referred to as adjuvant therapy. An example of adjuvant therapy is chemotherapy or radiotherapy administered after surgical removal of a tumor in an attempt to kill any tumor cells that remain following surgery.
Surgery: Surgical removal of the tumor is generally performed for limited-stage (stage I or sometimes stage II) NSCLC and is the treatment of choice for cancer that has not spread beyond the lung. About 10%-35% of lung cancers can be removed surgically, but removal does not always result in a cure, since the tumors may already have spread and can recur at a later time. Among people who have an isolated, slow-growing lung cancer removed, 25%-40% are still alive five years after diagnosis. Surgery may not be possible if the cancer is too close to the trachea or if the person has other serious conditions (such as severe heart or lung disease) that would limit their ability to tolerate an operation. Surgery is less often performed with SCLC because these tumors are less likely to be localized to one area that can be removed.
The surgical procedure chosen depends upon the size and location of the tumor. Surgeons must open the chest wall and may perform a wedge resection of the lung (removal of a portion of one lobe), a lobectomy (removal of one lobe), or a pneumonectomy (removal of an entire lung). Sometimes lymph nodes in the region of the lungs also are removed (lymphadenectomy). Surgery for lung cancer is a major surgical procedure that requires general anesthesia, hospitalization, and follow-up care for weeks to months. Following the surgical procedure, patients may experience difficulty breathing, shortness of breath, pain, and weakness. The risks of surgery include complications due to bleeding, infection, and complications of general anesthesia.
Radiation: Radiation therapy may be employed as a treatment for both NSCLC and SCLC. Radiation therapy uses high-energy X-rays or other types of radiation to kill dividing cancer cells. Radiation therapy may be given as curative therapy, palliative therapy (using lower doses of radiation than with curative therapy), or as adjuvant therapy in combination with surgery or chemotherapy. The radiation is either delivered externally, by using a machine that directs radiation toward the cancer, or internally through placement of radioactive substances in sealed containers within the area of the body where the tumor is localized. Brachytherapy is a term used to describe the use of a small pellet of radioactive material placed directly into the cancer or into the airway next to the cancer. This is usually done through a bronchoscope.
Radiation therapy can be given if a person refuses surgery, if a tumor has spread to areas such as the lymph nodes or trachea making surgical removal impossible, or if a person has other conditions that make them too ill to undergo major surgery. Radiation therapy generally only shrinks a tumor or limits its growth when given as a sole therapy, yet in 10%-15% of people it leads to long-term remission and palliation of the cancer. Combining radiation therapy with chemotherapy can further prolong survival when chemotherapy is administered. External radiation therapy can generally be carried out on an outpatient basis, while internal radiation therapy requires a brief hospitalization. A person who has severe lung disease in addition to a lung cancer may not be able to receive radiotherapy to the lung since the radiation can further decrease function of the lungs. A type of external radiation therapy called the "gamma knife" is sometimes used to treat single brain metastases. In this procedure, multiple beams of radiation coming from different directions are focused on the tumor over a few minutes to hours while the head is held in place by a rigid frame. This reduces the dose of radiation that is received by noncancerous tissues.
For external radiation therapy, a process called simulation is necessary prior to treatment. Using CT scans, computers, and precise measurements, simulation maps out the exact location where the radiation will be delivered, called the treatment field or port. This process usually takes 30 minutes to two hours. The external radiation treatment itself generally is done four or five days a week for several weeks.
Radiation therapy does not carry the risks of major surgery, but it can have unpleasant side effects, including fatigue and lack of energy. A reduced white blood cell count (rendering a person more susceptible to infection) and low blood platelet levels (making blood clotting more difficult and resulting in excessive bleeding) also can occur with radiation therapy. If the digestive organs are in the field exposed to radiation, patients may experience nausea, vomiting, or diarrhea. Radiation therapy can irritate the skin in the area that is treated, but this irritation generally improves with time after treatment has ended.
Chemotherapy: Both NSCLC and SCLC may be treated with chemotherapy. Chemotherapy refers to the administration of drugs that stop the growth of cancer cells by killing them or preventing them from dividing. Chemotherapy may be given alone, as an adjuvant to surgical therapy, or in combination with radiotherapy. While a number of chemotherapeutic drugs have been developed, the class of drugs known as the platinum-based drugs have been the most effective in treatment of lung cancers.
Chemotherapy is the treatment of choice for most SCLC, since these tumors are generally widespread in the body when they are diagnosed. Only half of people who have SCLC survive for four months without chemotherapy. With chemotherapy, their survival time is increased up to four- to fivefold. Chemotherapy alone is not particularly effective in treating NSCLC, but when NSCLC has metastasized, it can prolong survival in many cases.
Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments usually are given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles. Unfortunately, the drugs used in chemotherapy also kill normally dividing cells in the body, resulting in unpleasant side effects. Damage to blood cells can result in increased susceptibility to infections and difficulties with blood clotting (bleeding or bruising easily). Other side effects include fatigue, weight loss, hair loss, nausea, vomiting, diarrhea, and mouth sores. The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.
Prophylactic brain radiation: SCLC often spreads to the brain. Sometimes people with SCLC that is responding well to treatment are treated with radiation therapy to the head to treat very early spread to the brain (called micrometastasis) that is not yet detectable with CT or MRI scans and has not yet produced symptoms. Brain radiation therapy can cause short-term memory problems, fatigue, nausea, and other side effects.
Treatment of recurrence: Lung cancer that has returned following treatment with surgery, chemotherapy, and/or radiation therapy is referred to as recurrent or relapsed. If a recurrent cancer is confined to one site in the lung, it may be treated with surgery. Recurrent tumors generally do not respond to the chemotherapeutic drugs that were previously administered. Since platinum-based drugs are generally used in initial chemotherapy of lung cancers, these agents are not useful in most cases of recurrence. A type of chemotherapy referred to as second-line chemotherapy is used to treat recurrent cancers that have previously been treated with chemotherapy, and a number of second-line chemotherapeutic regimens have been proven effective at prolonging survival. People with recurrent lung cancer who are well enough to tolerate therapy also are good candidates for experimental therapies (see below), including clinical trials.
Targeted therapy: One alternative to standard chemotherapy is the drug erlotinib (Tarceva), which may be used in patients with NSCLC who are no longer responding to chemotherapy. It is a so-called targeted drug, a drug that more specifically targets cancer cells, resulting in less damage to normal cells. Erlotinib targets a protein called the epidermal growth factor receptor (EGFR) that is important in promoting the division of cells. This protein is found at abnormally high levels on the surface of some types of cancer cells, including many cases of non-small cell lung cancer. Erlotinib is taken by mouth in pill form.
Other attempts at targeted therapy include drugs known as antiangiogenesis drugs, which block the development of new blood vessels within a cancer. Without adequate blood vessels to supply oxygen-carrying blood, the cancer cells will die. The antiangiogenic drug bevacizumab (Avastin) has recently been found to prolong survival in advanced lung cancer when it is added to the standard chemotherapy regimen. Bevacizumab is given intravenously every two to three weeks. However, since this drug may cause bleeding, it is not appropriate for use in patients who are coughing up blood, if the lung cancer has spread to the brain, or in people who are receiving anticoagulation therapy ("blood thinner" medications). Bevacizumab also is not used in cases of squamous cell cancer because it leads to bleeding from this type of lung cancer.
Vadimezan is a newer, experimental medication that disrupts blood vessels within tumors and thereby inhibits blood flow to the tumor. Vadimezan with its different way of acting on the blood vessels than bevacizumab seems to have fewer side effects. It also was shown in preliminary studies that vadimezan prolonged survival in patients receiving chemotherapy for NSCLC. Research still is under way to further characterize the safety and effectiveness of this newer drug.
Photodynamic therapy (PDT): One newer therapy used for different types and stages of lung cancer (as well as some other cancers) is photodynamic therapy. In photodynamic treatment, a photosynthesizing agent (such as a porphyrin, a naturally occurring substance in the body) is injected into the bloodstream a few hours prior to surgery. During this time, the agent is taken up in rapidly growing cells such as cancer cells. A procedure then follows in which the physician applies a certain wavelength of light through a handheld wand directly to the site of the cancer and surrounding tissues. The energy from the light activates the photosensitizing agent, causing the production of a toxin that destroys the tumor cells. PDT has the advantages that it can precisely target the location of the cancer, is less invasive than surgery, and can be repeated at the same site if necessary. The drawbacks of PDT are that it is only useful in treating cancers that can be reached with a light source and is not suitable for treatment of extensive cancers. Research is ongoing to further determine the effectiveness of PDT in lung cancer.
Radiofrequency ablation (RFA): Radiofrequency ablation is being studied as an alternative to surgery, particularly in cases of early stage lung cancer. In this newer type of treatment, a needle is inserted through the skin into the cancer, usually under guidance by CT scanning. Radiofrequency (electrical) energy is then transmitted to the tip of the needle where it produces heat in the tissues, killing the cancerous tissue and closing small blood vessels that supply the cancer. RFA usually is not painful and has been approved by the U.S. Food and Drug Administration for the treatment of certain cancers, including lung cancers. Studies have shown that this treatment can prolong survival similarly to surgery when used to treat early stages of lung cancer but without the risks of major surgery and the prolonged recovery time associated with major surgical procedures.
Experimental therapies: Since no therapy is currently available that is absolutely effective in treating lung cancer, patients may be offered a number of new therapies that are still in the experimental stage, meaning that doctors do not yet have enough information to decide whether these therapies should become accepted forms of treatment for lung cancer. New drugs or new combinations of drugs are tested in so-called clinical trials, which are studies that evaluate the effectiveness of new medications in comparison with those treatments already in widespread use. Experimental treatments known as immunotherapies are being studied that involve the use of vaccine-related therapies or other therapies that attempt to utilize the body's immune system to fight cancer cells.
What is the prognosis (outcome) of lung cancer?
The prognosis of lung cancer refers to the chance for cure or prolongation of life (survival) and is dependent upon where the cancer is located, the size of the cancer, the presence of symptoms, the type of lung cancer, and the overall health status of the patient.
SCLC has the most aggressive growth of all lung cancers, with a median survival time of only two to four months after diagnosis when untreated. (That is, by two to four months, half of all patients have died.) However, SCLC is also the type of lung cancer most responsive to radiation therapy and chemotherapy. Because SCLC spreads rapidly and is usually disseminated at the time of diagnosis, methods such as surgical removal or localized radiation therapy are less effective in treating this type of lung cancer. When chemotherapy is used alone or in combination with other methods, survival time can be prolonged four- to fivefold; however, of all patients with SCLC, only 5%-10% are still alive five years after diagnosis. Most of those who survive have limited-stage SCLC.
In non-small cell lung cancer (NSCLC), results of standard treatment are generally poor in all but the most smallest of cancers that can be surgically removed. However, in stage I cancers that can be completely removed surgically, five-year survival approaches 75%. Radiation therapy can produce a cure in a small minority of patients with NSCLC and leads to relief of symptoms in most patients. In advanced-stage disease, chemotherapy offers modest improvements in survival although rates of overall survival are poor.
The overall prognosis for lung cancer is poor when compared with some other cancers. Survival rates for lung cancer are generally lower than those for most cancers, with an overall five-year survival rate for lung cancer of about 16% compared to 65% for colon cancer, 89% for breast cancer, and over 99% for prostate cancer.
How can lung cancer be prevented?
Cessation of smoking is the most important measure that can prevent lung cancer. Many products, such as nicotine gum, nicotine sprays, or nicotine inhalers, may be helpful to people trying to quit smoking. Minimizing exposure to passive smoking also is an effective preventive measure. Using a home radon test kit can identify and allow correction of increased radon levels in the home. Methods that allow early detection of cancers, such as the helical low-dose CT scan, also may be of value in the identification of small cancers that can be cured by surgical resection and prevented from becoming widespread, incurable, metastatic cancer.
Lung Cancer At A Glance
- Lung cancer is the number-one cause of cancer deaths in both men and women in the U.S. and worldwide.
- Cigarette smoking is the principal risk factor for development of lung cancer.
- Passive exposure to tobacco smoke also can cause lung cancer.
- The two types of lung cancer, which grow and spread differently, are the small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC).
- The stage of lung cancer refers to the extent to which the cancer has spread in the body.
- Treatment of lung cancer can involve a combination of surgery, chemotherapy, and radiation therapy as well as newer experimental methods.
- The general prognosis of lung cancer is poor, with overall survival rates of about 16% at five years.
- Smoking cessation is the most important measure that can prevent the development of lung cancer.
REFERENCES:
Hung, R.J., et al. A Susceptibility Locus for Lung Cancer Maps to Nicotinic Acetylcholine Receptor Subunit Genes on 15q25." Nature 452.7187 Apr. 3, 2008: 633-637.
McKeage, Mark J., et al. "Phase II Study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800 mg/m2 Combined With Carboplatin and Paclitaxel in Previously Untreated Advanced Non-Small Cell Lung Cancer." Lung Cancer 65.2 Aug. 2009: 192-197.
"What Are the Key Statistics About Lung Cancer?" American Cancer Society. Oct. 20, 2009. <http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Are_the_Key_Statistics_About_Lung_Cancer_15.asp?sitearea=>.
"What You Need to Know About Lung Cancer." National Cancer Institute, U.S. National Institutes of Health. July 26, 2007. <http://www.cancer.gov/cancertopics/types/lung>.
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