|Back to Main Print This Page Email to a Friend|
Although lung cancer accounts for only 14% of all newly-diagnosed cancers in the United States, it is the leading cause of cancer death in U.S. men and women. It is more deadly than colon, breast, and prostate cancers combined. About 160,000 patients die from lung cancer each year. Death rates have been declining in men over the past decade, and they have about stabilized in women.
The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air. Only 10% is solid tissue.
The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.
Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.
The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues). Some experts believe all primary lung cancers come from a single common cancerous (malignant) stem cell. As it copies itself, that stem cell can develop into any one of these cancer types in different people.
In addition, cancers in the lung may have spread from other sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location, such as "breast cancer with lung metastases."
Non-small cell lung cancers are categorized into three types:
These separate types are grouped together because, in the early stages before the cancers have spread, they all can be treated with surgery.
Squamous Cell Carcinoma. Squamous cells are formed from reserve cells. These are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.
When squamous cell cancer spreads, it may travel to the bone, adrenal glands, liver, small intestine, and brain.
Squamous cell carcinoma is nearly always caused by smoking, and it used to be the most common cancer. It still makes up 25 - 30% of all lung cancers.
Adenocarcinoma. Adenocarcinomas usually start from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung.
In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 40% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women, and their rates are increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in this lung cancer type in recent decades may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into their lungs.
The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. It also can spread to the other lung, liver, adrenal glands, and bone.
Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.
Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 15% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.
Small cell lung cancer may, like squamous cells, originate from reserve cells or other cells in the epithelium. It causes 10 - 15% of all lung cancers. Without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.
Cigarette Smoke. Smoking causes at least 80% of lung cancer deaths, and accounts for 30% of all cancer-related deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:
In general, chronic exposure to tobacco may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.
Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon is the second leading cause of lung cancer.
Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. Multiple studies report an association between abnormal lung changes and marijuana smoking.
There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts).
Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.
Genetic mutations that cause cancer generally occur in two types of genes:
Damage to either type of gene can cause a mutation that results in uncontrolled division of cells. This uncontrolled division forms tumors.
It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:
Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of cancerous cells to other organs.
The first symptoms of lung cancer may include some of the following:
Later-stage symptoms and complications include the following:
Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.
Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. It now strikes about 228,000 Americans per year, and some 160,000 die from it annually. The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing. However, lung cancer deaths among female nonsmokers seem to be on the rise.
Smoking is the primary cause of 85 - 90% of lung cancers. The risk of lung cancer in smokers is about 20 times that of nonsmokers. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.
People who smoked can be at increased risk for lung cancer more than 20 years after quitting, although the risk drops significantly even in the first year after quitting. There are benefits to quitting smoking, even for people who are well into middle age. Evidence suggests that quitting smoking, after a diagnosis of early stage lung cancer, improves outcomes significantly.
Risk for Lung Cancer by Age 75 According to Quitting Age
Secondhand Smoke. The Environmental Protection Agency has classified secondhand smoke as a carcinogen (cancer-causing chemical). Exposure to secondhand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.
There may be some ethnic differences in lung cancer risk. For example, African-American men have about a 45% higher risk of developing lung cancer than Caucasian men. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.
In China, about one-third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. The lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.
Low income and a lack of education have been linked to an increased risk for lung cancer. Researchers say socioeconomic status is connected to other factors involved in lung cancer risk, such as smoking, diet, and exposure to cancer-causing chemicals in the workplace.
People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes. Homes or buildings built on landfills that contain high levels of radon are the most likely sources of this low level, chronic exposure.
A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for a while in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend a long time in basements with detectable but moderate levels should consider taking protective measures.
Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer. With better protective measures, these rates are expected to fall in the future.
Other chemicals that put workers at risk for lung cancer include:
By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals, and it may have cancer-preventing effects on the immune system.
Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, in polluted air. The risk, if any, is very small.
A family history of lung cancer may play a role in increasing susceptibility to this disease. Women who had mothers or sisters with lung cancer have triple the risk. The risk is higher in both smokers and nonsmokers. There is no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appear to contribute to the danger in these individuals.
Research suggests that postmenopausal women taking combined hormone replacement therapy (estrogen plus progestin) may have a higher risk of death from non-small cell lung cancer than women not taking hormones.
Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.
Quitting smoking improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. Furthermore, quitting, even after a diagnosis of lung cancer, improves your chance of survival significantly. It is estimated that patients with early stage lung cancer who quit smoking have a 70% chance of survival, compared to 33% in those who continue to smoke.
It can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to full health and the risk for lung cancer to be reduced as low as it is for nonsmokers. Quitting is extremely difficult. There are many smoking cessation programs available that can become part of a patient's overall treatment plan. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.
The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and prescription medication.
At this time, perhaps the most effective method for quitting is a combination of the following:
While people are in the process of quitting (and afterward), they should maintain as healthy a lifestyle as possible.
The research on diet and cancer suggests that antioxidants in certain foods may protect against the DNA damage that can lead cells to turn cancerous. It's important to note that, although studies have suggested an association between these factors and cancer risk, no cause-and-effect has been proven. It is also important to note that while the antioxidants in foods may be protective, antioxidant supplements actually increase risk in smokers. That makes a healthy diet even more desirable.
Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may protect against lung cancer in both smokers and nonsmokers. Those most studied in relationship to protection from lung cancer include phytoestrogens, flavonoids, and glucosinoids.
Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that any benefit comes from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.
Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection against lung cancer comes from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). However, the ability of these substances to protect against lung cancer remains controversial, and quitting smoking remains the best advice.
Vitamin Supplements. Even in those who eat a healthful diet, smoking reduces the body's levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any benefit from taking antioxidant supplements, including vitamins C, E, A, folate, or beta carotene.
In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and especially beta carotene supplements have harmful effects. The strongest studies on the effects of antioxidant supplements have reported an increase in lung cancer and overall mortality rates among smokers who took beta carotene or vitamin E supplements. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years before developing the disease. The best way to get healthy levels of important nutrients is by eating healthy foods.
Trace Element Supplements. Trace elements such as zinc and selenium have been studied for potential protection against lung cancer without any clear evidence to support their benefits.
People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. One way to remove radon is by installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.
Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the patient's general condition. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain. Bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might indicate other tumors. Also, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.
Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or a lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. CT scans have shown to be better than chest x-rays in detecting nodules and lung cancer. Regular screening for lung cancer using x-rays is therefore not recommended.
Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.
CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around an area of the body. Using very complicated mathematical processes called algorithms, the computer generates a 3-D image of a section of the body. CT scans are very detailed.
The use of helical CT for widespread early screening of asymptomatic patients is currently under debate.
A recent study, the National Lung Cancer Screening Trial, found that having low-dose CT scans yearly for 3 years can reduce lung cancer deaths in certain heavier smokers by 20%. The American Cancer Society, the American Lung Association, the National Comprehensive Cancer Network, and the U.S. Preventive Services Task Force now recommend low-dose CT screening for the following:
It is important to note that screening CT scans produce many false-positive results. This means that many people have suspicious findings on a CT scan that do not turn out to be cancer after a lung biopsy is done. More research is needed to determine whether there is an overall benefit to CT screening for smokers. People not meeting the above criteria are unlikely to benefit from lung cancer screening at this time.
While computed tomography is the standard imaging procedure for determining NSCLC, other imaging tests are also useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).
A bone scan is done to check for spread of cancer to the bones for those with bone pain, or other findings suggesting spread of cancer to the bones.
Positron Emission Tomography. Positron emission tomography (PET), specifically FDG-PET, can diagnose lung tumors as small as 1 centimeter with very high accuracy. With FDG-PET, the patient is first injected with a specially formulated, radioactive liquid sugar (called FDG), and then studied with a special machine.
PET is a good imaging technique for staging lung patients thought to have early stage lung cancer after other testing. These patients are considered candidates for surgery intended to cure. But if a PET scan identifies previously undetected spread of the cancer elsewhere in the body, the patient may be able to avoid unwarranted surgery.
PET works best when used with CT scans. An imaging tool known as PET/CT is often used, which allows both types of scans to be done at the same time. However, PET/CT may also wrongly diagnose some patients as having more advanced cancer than they actually have, possibly leading to the incorrect treatment.
Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone tumors that have spread from the lung. Importantly, since the brain always uses high amounts of sugar, a PET scan is not recommended for detecting brain metastases.
Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.
Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of CT scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA), endoscopic ultrasound-guided needle aspiration (EUS-NA) and transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) . Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 - 10% risk for bleeding or collapsed lung with needle aspiration.
Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber optic tube to view the area. The procedure requires general anesthesia. The surgeon passes surgical instruments and a fiber optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.
Bronchoscopy. Bronchoscopy can help locate cancer that develops in the central areas and major airways of the lung (usually squamous or small-cell cancer). The procedure is done as follows:
Bronchoscopy is usually very safe, but complications can occur. They include:
Patients may develop a fever after the procedure.
Mediastinoscopy. Mediastinoscopy uses a tube inserted in the central part of the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet spread to other parts of the body, and to confirm negative biopsy results. This procedure is slowly being replaced by endoscopic and endobronchial methods.
Sputum Analysis for Presence of Cancer Cells. Analysis of coughed-up sputum, performed as a screening test for lung cancer, is often done along with chest x-rays. This method has not reduced death rates. Recent improvements in this screening technique are under study.
Sputum analysis may also be used to diagnose lung cancer in someone with signs of lung cancer. However, it is not 100% accurate. If a sputum analysis does not show cancer cells, other tests are performed.
Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include:
A number of these biomarkers are being evaluated alone or in combination as either screening tools or as potential markers for the risk of disease progression. Some of these biomarkers may be detectable 1 - 3 years before a clinical diagnosis of lung cancer. The potential for this early diagnosis could mean an improvement in lung cancer survival in the future.
As part of the doctor's initial examination, patients may have a pulmonary function test and breath analysis to evaluate lung health and capacity. The doctor may also take a complete history of the heart and lungs, because they are often involved in complications following lung cancer surgery.
In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several areas of the body. However, some groupings with very different clinical features can have similar prognosis. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies. A combined approach is necessary for accurate staging. Research has shown that endosonography plus surgical staging produced more accurate staging results than surgical staging alone.
To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.
The TNM categories then determine the stage (numbered 0 to IV) of the cancer.
The International Association for the Study of Lung Cancer recently revised the non-small cell lung cancer staging system in 2009. Extensive analysis was performed on an international database to arrive at this revised system. The major staging categories remain the same, while additional subgroupings within the T, N, and M descriptors were added.
TNM stands for:
T refers to the size and spread of the tumor. In TX and T0, the tumor either cannot be assessed or is indicated by cancer cells in sputum or lung samples, but it cannot be seen.
T is: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading.
In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway. In T1a, the tumor is less than or equal to 2 cm and in T1b, the tumor is greater than 2 cm but less than or equal to 3 cm in diameter.
In T2, the tumor has one or more of the following features:
T2 is further broken down in the new staging system. T2a refers to a tumor greater than 3 cm but less than or equal to 5 cm in diameter. T2b is greater than 5 cm but less than or equal to 7 cm.
In T3, a tumor is greater than 7 cm or has directly invaded any of the following:
In addition, one or more of the following conditions are present:
In T4, the tumor has invaded any of the following:
In addition, one or both of the following occurs:
N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes.
M Stages refer to cancer spread (metastasis).
Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:
Researchers are always looking for more accurate ways to determine lung cancer treatment and outlook. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help predict the cancer's aggressiveness and determine the best treatment approach.
Using the information, lung cancer is divided into stages, I through IV. Stages I through III, are further divided into A or B (for example stage IA and IB). Each stage will usually have a different approach to treatment.
In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.
Treatment Options. Surgically removing the tumor (if one can be located) can allow doctors to identify the stage, and often results in a cure.
Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers. Only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.
In stage I, the cancer has reached the higher layers of the lung but has not spread into the lymph nodes or beyond the lung.
General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should have partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients who have radiation or chemotherapy in addition to surgery have higher survival rates.
The overall 5-year survival rates for early stage-cancer are around 70% for stage IA and close to 60% for stage IB. Patients should consider smoking cessation programs and clinical trials to prevent cancer from returning after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.
Treatment for stage IA (T1a,bN0M0) and IB (T2aN0M0) lung cancer includes:
In stage II the cancer cells have spread to nearby lymph nodes.
General Treatment Options. Surgery, usually a lobectomy or pneumonectomy, is the treatment of choice. Radiation treatment after surgery does not seem to improve survival, but may be performed after an incomplete surgical procedure.
If the tumor is completely removed, radiation therapy is usually not performed after surgery. Patients whose cancer is inoperable may consider radiation and chemotherapy treatments.
Patients who do well after surgical removal of the tumor often receive a platinum-based chemotherapy regimen. Sometimes chemotherapy is considered before surgery as well.
In patients who can complete treatment, 5-year survival rates average around 45% for stage IIA (T2bN0M0;T1a,bN1M0;T2aN1M0) and around 35% for stage IIB (T2bN1M0;T3N0M0).
In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.
General Treatment Options. Generally, the treatment options for stage III tumors are:
Combination approaches may be significantly more effective than single treatments.
Stage IIIA (T1a,b,T2a,b,N2M0;T3N1,N2M0;T4N0,N1M0).
Researchers have confirmed good survival rates with surgery after chemotherapy and radiation therapy.
Stage IIIB (T4N2M0;anyTN3M0). Some patients may consider surgery if the lymph nodes are not involved (T4, N0), and the tumor can be removed. Surgery may not be an acceptable option for other patients with stage IIIB cancer.
In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.
Recurring or new tumors occur (usually in the lung again) in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.
Surgery is considered in the following circumstances:
Surgery is often combined with other treatment options. Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.
Newer risk profiles for surgery are being looked at, and patients are participating in decisions about surgery based on the likely risks and benefits.
The type of surgery a patient needs depends on the amount of lung or other tissue that needs to be removed.
Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient must have satisfactory lung function to undergo this procedure. The patient has a 3 - 5% risk of death after this operation, with older patients having the highest risk.
Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung. They preserve almost normal breathing function after the operation.
Pneumonectomy. Pneumonectomy removes the entire lung. The patient has a 5 - 8% risk of death after this procedure. The oldest patients have the greatest risk, and they almost always have a recurrence.
These surgeries may be combined with other surgical techniques such as lymphadenectomy and bronchoplasty to repair or remove additional diseased tissue.
Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in the late stages of the disease.
Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that uses a thin tube containing a miniature camera and surgical instruments. It involves much smaller incisions than open surgery (thoracotomy) and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those after conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I non-small cell lung cancer treated with VATS were comparable to those in patients treated with traditional open chest surgeries. The number of VATS surgeries has steadily increased every year as physicians gain experience with the technique. Initially it was primarily used in wedge resections, but is now used for lobectomies and segmentectomies as well.
Laser Surgery. Laser surgery allows surgeons to remove small amounts of lung tissue, and it is proving useful for improving symptoms in stage II and IIIA patients. Laser surgery may also be beneficial in treating cancers that have spread to, and are obstructing, the throat.
Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Bleeding in the lungs is a more serious side effect. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.
Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact. It is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.
Electric Cauterization and Thermal Ablation. Electric cauterization, which uses electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.
Radiofrequency Ablation. This non-surgical technique that uses an x-ray guided electrode to deliver heat to tissues may benefit lung cancer patients who do not accept surgery, or are not eligible for surgery, radiation, or chemotherapy. In one study, 70% of patients treated with this method survived for at least one year. Because the technique spares damage to nearby tissues, patients tend to have minimal side effects. More research is needed to confirm the benefit of radiofrequency ablation over other, non-surgical treatment options.
In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.
Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. Chest
radiation therapy such as conventional radiotherapy or stereotactic body radiation therapy may be performed.
Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. Radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are also showing promise.
Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung function, or for those with cancer that has spread. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, superior vena cava syndrome, coughing up blood, and symptoms caused by cancer that has spread to the brain. Radiation in these cases is not generally used to reduce mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.
Delaying radiation therapy until symptoms develop in patients with minimal or no symptoms does not appear to reduce survival times or impair quality of life compared to starting it right away.
Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain, unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may deliver powerful, highly targeted radiation to specific areas in the brain. The procedure takes about 30 minutes to one hour and patients typically go home the same day. Up to five sessions may be performed.
Some trials are investigating the benefits of radiation to the head to prevent the cancer from damaging the brain.
The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread.
Hyperfractionated radiotherapy gives smaller-than-standard doses a number of times a day (usually two or three). This allows doctors to use a higher dose over the whole course of treatment. It is not as useful as therapy by itself, but can have survival benefits when combined with chemotherapy.
Continuous Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses of radiation per day but uses the standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART may give patients with localized cancer better survival rates than standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems, though. Modifying the treatment by stopping it for 2 days out of 7 may help reduce this effect.
Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation specifically to targeted organs or tissues. This allows doctors to administer significantly higher doses to attack the cancer, while reducing the risk to healthy cells. This technique is generally considered the standard method of delivering radiation to lung tumors.
Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or lungs (pneumonitis). Infection is also a danger.
The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications.
Chemotherapy is the use of drugs given by mouth or injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the combination of supportive care and sometimes surgery. Chemotherapy can offer an improvement in survival for several stages of advanced lung cancer.
Most chemotherapy regimens use platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin). The preferred regimen uses two drugs -- one of which is a platinum-based drug. Combinations may include third generation drugs such as paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, vinblastine (vindesine or vinorelbine), irinotecan, or pemetrexed. The gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Researchers are looking at genetic mutations and the effectiveness of customized chemotherapy options for specific mutations.
Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is a newer chemotherapy drug for first-line treatment of advanced nonsquamous non-small cell lung cancer, in combination with cisplatin. The drug targets a number of enzymes that play a role in how cancer cells increase in numbers. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements.
Attention is also being given to agents called biologic response modifiers, such as the EGFR gene inhibitor gefitinib (Iressa). This drug, a second-line therapy for non-small cell lung cancer, is available for a limited group of patients. It may also be recommended as first-line therapy in select patients with advanced disease and an EGFR mutation.
Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic non-small cell lung cancer who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). It is also prescribed as a maintenance treatment when cancer has not spread or grown after chemotherapy treatment. Erlotinib plus targeted therapy shows survival and progression free benefits compared to placebo. No studies comparing erlotinib to gefinitib have been conducted and further research is necessary to assess the overall survival benefits of both drugs. Both are taken orally, once daily.
Another agent, bevacizumab (Avastin) is combined with platinum-based chemotherapy as a first-line treatment choice for patients with advanced, non-squamous cancer. Bevacizumab is a monoclonal antibody (MAb) which inhibits growth of new blood vessels. Studies show that it increases survival, but unfortunately only for less than 2 months.
In select advanced lung cancer patients with EGFR mutation, cetuximab (Erbitux), a monoclonal antibody approved in 2012, may be added to a cisplatin/vinorelbine regimen as first-line therapy.
Chemotherapy treatments are usually performed in an outpatient setting. They are given in regular cycles for several months. Researchers are still investigating how many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs. For instance, a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. However, changing even one day in a drug sequence can sometimes significantly affect the outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.
Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.
Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some studies suggest that side effects can be reduced by giving the drugs for shorter durations, without losing the cancer-killing effects.
Common side effects include the following:
These side effects are nearly always temporary. Most patients are able to continue with their normal activities for all but perhaps 1 or 2 days per month.
Serious complications of chemotherapy can also occur, and vary depending on the specific drugs. These complications include:
Second-line chemotherapy is used for patients whose cancers have come back after the first round of chemotherapy. Several of these agents listed below have prolonged survival for patients with non-small cell lung cancer. Unfortunately, this survival benefit is usually only a matter of several months. Efforts are under way to identify which patients are more likely to benefit from these therapies. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy.
Commonly used second-line agents include:
Particularly for more aggressive or advanced cancers, different combinations of surgery, chemotherapy, and radiation therapy may be tried. These include:
Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.
Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.
There are many painkilling medications available. Research shows that aggressive pain relief can help patients better manage cancer treatment symptoms. For example, reducing pain in elderly cancer patients may markedly lower their fatigue levels, and improve other symptoms as well.
Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole. Chewing, inhaling, or injecting it can create a deadly overdose.
According to a 2001 article, of the nearly 500 cancer drugs in development, 58 (about 13%) were aimed at fighting lung cancer. Only breast cancer had a higher percentage of new drugs in development. Unfortunately, no drugs to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.
Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer. Cetuximab (Erbitux) was recently approved for recurrent local disease or metastatic squamous cell cancer of the head and neck. It is considered in patients with EGFR mutation. Trastuzumab (Herceptin) is also under investigation for the treatment of lung cancer.
All of these MAbs block epidermal growth factor. These drugs are of particular interest for patients who have cancers that produce too much of the protein called HER2. They show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, adding bevacizumab to platinum-based chemotherapy extends the disease-free survival time in patients with advanced non-small cell lung cancer.
Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379-86.
Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013; 143(5_suppl):e1S-e29S.
Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010;304(20):2245-52.
Azzoli C, Temin S, Alif T, et al. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer. JCO. 2011; vol. 29(28):3825-3831.
Cataldo VD, Gibbons DL, Pérez-Soler R, Quintás-Cardama A. Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med. 2011;364(10):947-55. Review.
Chlebowski RT, Schwartz AG, Wakelee H, et al; Women's Health Initiative Investigators. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374(9697):1243-51.
Ciuleanu T, Brodowicz T, Zielinski C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009;374(9699):1432-40.
Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013; 143(5_suppl):e78S-e92S.
Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136(1):260-71. Review.
Fischer B, Lassen U, Mortensen J, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med. 2009;361(1):32-39.
Gettinger S, Lynch T. A decade of advances in treatment for advanced non-smallcell lung cancer. Clin Chest Med. 2011;32(4):839-51. Review.
Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG, Shepherd FA. Non-small-cell lung cancer. Lancet. 2011;378(9804):1727-40.
Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med. 2008;359(13):1367-80. Review.
Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of Stage I and II Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines. Chest. 2013;143 (5_suppl):e278S-e313S.
Johnson DH, Blot WJ, Carbone DP, et al. Cancer of the lung: Non-small cell lung cancer and small cell lung cancer. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 4th ed. Philadelphia, Pa: Churchill Livingstone Elsevier; 2008:chap 76.
Lencioni R, Crocetti L, Cioni R, Suh R, Glenn D, Regge D, et al. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study). Lancet Oncol. 2008;9:621-628.
Lilly Inc. Alimta Prescribing Information. Rev. 10/2008.
Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-8.
Maziak DE, Darling GE, Inculet RI, et al. Positron emission tomography in staging early lung cancer: a randomized trial. Ann Intern Med. 2009;151(4):221-8,W-48.
Mehta HJ, Ross C, Silvestri GA, Decker RH. Evaluation and treatment of high-risk patients with early-stage lung cancer. Clin Chest Med. 2011;32(4):783-97. Review.
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-57.
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008; 83(5):584-594.
National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Accessed September 2, 2013.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 2.2013. Last accessed August 31, 2013.
National Lung Cancer Trial Research Team. Reduced Lung-Cancer Mortality with Low-dose Computed Tomographic Screening. N Eng J Med. 2011;365:395-409.
Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy and supportive care versus supportive care alone for advanced non-small cell lung cancer. Cochrane Database Syst Rev. 2010 May 12;(5):CD007309. Review.
NSCLC Meta-analyses Collaborative Group, Arriagada R, Auperin A, Burdett S, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operablenonsmall-cell lung cancer: two meta-analyses of individual patient data. Lancet.2010;375(9722):1267-77.
Paoletti L, Pastis NJ, Denlinger CE, Silvestri GA. A decade of advances in treatment of early-stage lung cancer. Clin Chest Med. 2011;32(4):827-38. Review.
Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569. Review.
Pirker R, Pereira JR, Szczesna A, et al; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373(9674):1525-31.
Ramnath N, Dilling TJ, Harris LJ, et al. Treatment of Stage III Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013;143(5_suppl):: e314S-e340S.
Rivera MP, Mehta AC, Wahidi MM. Establishing the Diagnosis of Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013;143(5_suppl):: e142S-e165S.
Robinson LA, Ruckdeschel J, Wagner H, Stevens CW. Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132:243S-265S.
Scott WJ, Howington J, Feigenberg S, Movsas B, Pisters K. Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132:234S-242S.
Shen KR, Meyers BF, Larner JM, Jones DR. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132:290S-305S.
Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for Staging Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest.
Silvestri GA, Jett J. Clinical Aspects of Lung Cancer. In: Mason and Nadel's Textbook of Respiratory Medicine. 5th ed. Philadelphia, Pa: Saunders Elsevier; 2010:chap 47.
Slatore CG, Littman AJ, Au DH, Satia JA, White E. Long-term use of supplemental vitamins, vitamin C, Vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med. 2008;177:524-530.
Suh JH. Stereotactic radiosurgery for the management of brain metastases. N Engl J Med. 2010;362(12):1119-27. Review.
Tassinari D, Scarpi E, Sartori S, et al. Second-line treatments in non-small cell lung cancer. A systematic review of literature and metaanalysis of randomized clinical trials. Chest. 2009;135(6):1596-1609.
Temel JS,Greer J, Muzikansky J, et al. Early palliative care for patients with metastatic non-small cell lung cancer. N Engl J Med. 2010; 363(8): 733-42.
U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.
Yang P, Sun Z, Krowka MJ, Aubry MC, Bamlet WR, Wampfler JA, et al. Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk. Arch Intern Med. 2008;168:1097-1103.