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Lung Cancer - Non-Small Cell

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What is non-small cell lung cancer?

Lung cancer is a cancer that starts in the lungs. To understand lung cancer, it helps to know about the normal structure and function of the lungs.

Start and spread of lung cancer: Lung cancers can start in the cells lining the bronchi and parts of the lung such as the bronchioles or alveoli.

 

Lung cancers are thought to start as areas of pre-cancerous changes in the lung. The first changes happen in the genes of the cells themselves and may cause them to grow faster. The cells may look a bit abnormal if seen under a microscope, but at this point they do not form a mass or tumor. They cannot be seen on an x-ray and they do not cause symptoms.

Over time, these pre-cancerous changes in the cells may progress to true cancer. As a cancer develops, the cancer cells may make chemicals that cause new blood vessels to form nearby. These new blood vessels nourish the cancer cells, which can continue to grow and form a tumor large enough to be seen on imaging tests such as x-rays.

At some point, cells from the cancer may break away from the original tumor and spread (metastasize) to other parts of the body. Lung cancer is often a life-threatening disease because it tends to spread in this way even before it can be detected on an imaging test such as a chest x-ray.

At some point, cells from the cancer may break away from the original tumor and spread (metastasize) to other parts of the body. Lung cancer is often a life-threatening disease because it tends to spread in this way even before it can be detected on an imaging test such as a chest x-ray.

The lymph (lymphatic) system: The lymph system is important to understand because it is one of the ways in which lung cancers can spread. This system has several parts.

Lymph nodes are small, bean-shaped collections of immune system cells (cells that fight infections) that are connected by lymphatic vessels. Lymphatic vessels are like small veins, except that they carry a clear fluid called lymph (instead of blood) away from the lungs. Lymph contains excess fluid and waste products from body tissues, as well as immune system cells.

Lung cancer cells can enter lymphatic vessels and begin to grow in lymph nodes around the bronchi and in the mediastinum (the area between the 2 lungs). When lung cancer cells have reached the lymph nodes, they are more likely to have spread to other organs of the body as well. The stage (extent) of the cancer and decisions about treatment are based on whether or not the cancer has spread to the nearby lymph nodes in the mediastinum. 

What are the risk factors for non-small cell lung cancer?

A risk factor is anything that affects a person's chance of getting a disease such as cancer. Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor for skin cancer.

But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may not have had any known risk factors. Even if a person with lung cancer has a risk factor, it is often very hard to know how much that risk factor may have contributed to the cancer.

Several risk factors can make you more likely to develop lung cancer.

Tobacco smoke: Smoking is by far the leading risk factor for lung cancer. In the early 20th century, lung cancer was much less common than some other types of cancer. But this changed once manufactured cigarettes became readily available and more people began smoking.

About 80% of lung cancer deaths are thought to result from smoking. The risk for lung cancer among smokers is many times higher than among non-smokers. The longer you smoke and the more packs a day you smoke, the greater your risk.

Cigar smoking and pipe smoking are almost as likely to cause lung cancer as cigarette smoking. Smoking low-tar or "light" cigarettes increases lung cancer risk as much as regular cigarettes. There is concern that menthol cigarettes may increase the risk even more since the menthol allows smokers to inhale more deeply.

If you stop smoking before a cancer develops, your damaged lung tissue gradually starts to repair itself. No matter what your age or how long you've smoked, quitting may lower your risk of lung cancer and help you live longer. People who stop smoking before age 50 cut their risk of dying in the next 15 years in half compared with those who continue to smoke. 

Secondhand smoke: If you don't smoke, breathing in the smoke of others (called secondhand smoke or environmental tobacco smoke) can increase your risk of developing lung cancer. A non-smoker who lives with a smoker has about a 20% to 30% greater risk of developing lung cancer. Workers who have been exposed to tobacco smoke in the workplace are also more likely to get lung cancer. Secondhand smoke is thought to cause more than 3,000 deaths from lung cancer each year.

Some evidence suggests that certain people are more susceptible to the cancer-causing effect of tobacco smoke than others.

Radon: Radon is a naturally occurring radioactive gas that results from the breakdown of uranium in soil and rocks. It cannot be seen, tasted, or smelled. According to the US Environmental Protection Agency (EPA), radon is the second leading cause of lung cancer in this country, and is the leading cause among non-smokers.

Outdoors, there is so little radon that it is not likely to be dangerous. But indoors, radon can be more concentrated. When it is breathed in, it enters the lungs, exposing them to small amounts of radiation. This may increase a person's risk of lung cancer. Houses in some parts of the United States built on soil with natural uranium deposits can have high indoor radon levels (especially in basements). Studies from these areas have found that the risk of lung cancer is higher in those who have lived for many years in a radon-contaminated house.

The lung cancer risk from radon is much lower than that from tobacco smoke. However, the risk from radon is much higher in people who smoke than in those who don't.

Radon levels in the soil vary across the country, but they can be high almost anywhere. If you are concerned about radon exposure, you can use a radon detection kit to test the levels in your home. State and local offices of the EPA can also give you the names of reliable companies that can test your home (or other buildings) for radon and help you fix the problem, if needed. 

Asbestos: Workplace exposure to asbestos fibers is an important risk factor for lung cancer. Studies have found that people who work with asbestos (in some mines, mills, textile plants, places where insulation is used, shipyards, etc.) are several times more likely to die of lung cancer. In workers exposed to asbestos who also smoke, the lung cancer risk is much greater than even adding the risks from these exposures separately. It's not clear to what extent low-level or short-term exposure to asbestos might raise lung cancer risk.

Both smokers and non-smokers exposed to asbestos also have a greater risk of developing mesothelioma, a type of cancer that starts in the pleura (the lining surrounding the lungs). Because it is not usually considered a type of lung cancer, mesothelioma is discussed in our document called Malignant Mesothelioma.

In recent years, government regulations have greatly reduced the use of asbestos in commercial and industrial products. It is still present in many homes and other older buildings, but it is not usually considered harmful as long as it is not released into the air by deterioration, demolition, or renovation. 

Other cancer-causing agents in the workplace: Other carcinogens (cancer-causing agents) found in some workplaces that can increase lung cancer risk include:    Radioactive ores such as uranium, Inhaled chemicals or minerals such as arsenic, beryllium, cadmium, silica, vinyl chloride, nickel compounds, chromium compounds, coal products, mustard gas, and chloromethyl ethers, Diesel exhaust

The government and industry have taken steps in recent years to help protect workers from many of these exposures. But the dangers are still present, and if you work around these agents, you should be careful to limit your exposure whenever possible.

Radiation therapy to the lungs: People who have had radiation therapy to the chest for other cancers are at higher risk for lung cancer, particularly if they smoke. Typical patients are those treated for Hodgkin disease or women who get radiation after a mastectomy for breast cancer. Women who receive radiation therapy to the breast after a lumpectomy do not appear to have a higher than expected risk of lung cancer.

Arsenic: High levels of arsenic in drinking water may increase the risk of lung cancer. This is even more pronounced in smokers.

Personal or family history of lung cancer: If you have had lung cancer, you have a higher risk of developing another lung cancer. Brothers, sisters, and children of those who have had lung cancer may have a slightly higher risk of lung cancer themselves, especially if the relative was diagnosed at a younger age. It is not clear how much of this risk might be due to genetics and how much might be from shared household exposures (such as tobacco smoke or radon).

Researchers have found that genetics does seem to play a role in some families with a strong history of lung cancer. For example, people who inherit certain DNA changes in a particular chromosome (chromosome 6) are more likely to develop lung cancer, even if they only smoke a little. At this time these DNA changes cannot be routinely tested for. Research is ongoing in this area.

Certain dietary supplements: Studies looking at the possible role of antioxidant supplements in reducing lung cancer risk have not been promising so far. In fact, 2 large studies found that smokers who took beta carotene supplements actually had an increased risk of lung cancer. The results of these studies suggest that smokers should avoid taking beta carotene supplements.

Air pollution: In cities, air pollution (especially from heavily trafficked roads) appears to raise the risk of lung cancer slightly. This risk is far less than the risk caused by smoking, but some researchers estimate that worldwide about 5% of all deaths from lung cancer may be due to outdoor air pollution.

Factors with uncertain or unproven effects on lung cancer risk

Talc and talcum powder: Talc is a mineral that in its natural form may contain asbestos. In the past, some studies suggested that talc miners and millers have a higher risk of lung cancer and other respiratory diseases because of their exposure to industrial grade talc. Recent studies of talc miners have not found an increase in lung cancer rate.

Do we know what causes non-small cell lung cancer?

Smoking: Tobacco smoking is by far the leading cause of lung cancer. About 80% of lung cancer deaths are caused directly by smoking, and many others are caused by exposure to secondhand smoke. Smokers exposed to other known risk factors such as radon and asbestos are at even higher risk.

Lung cancer in non-smokers: Still, not all people who get lung cancer are smokers. Many people with lung cancer are former smokers, but many others never smoked at all. Some of the causes for lung cancer in non-smokers were described in the section called "What are the risk factors for non-small cell lung cancer?" These include exposure to radon, which accounts for about 20,000 cases of lung cancer each year, and exposure to secondhand smoke.

Workplace exposures to asbestos, diesel exhaust, or certain other chemicals can also cause lung cancers in some people who do not smoke. A small portion of lung cancers occur in people with no known risk factors for the disease, so there must be other factors that we don't yet know about.

Genetic factors seem to play a role in at least some of these cancers. Lung cancers in non-smokers are often different in some ways from those that occur in smokers. They tend to occur at younger ages, often affecting people in their 30s or 40s (while in smokers the average age at diagnosis is over 70). The cancers that occur in non-smokers often have certain gene changes that are different from those in tumors from smokers. In some cases, these changes can be used to guide therapy.

Gene changes that may lead to lung cancer: Scientists have begun to understand how the known risk factors for lung cancer may produce certain changes in the DNA of cells in the lungs, causing them to grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look. It also can influence our risk for developing certain diseases, such as some kinds of cancer.

Some genes contain instructions for controlling when cells grow and divide. Genes that promote cell division are calledoncogenes. Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

Inherited gene changes: Some people inherit DNA mutations (changes) from their parents that greatly increase their risk for developing certain cancers. However, inherited mutations are not thought to cause very many lung cancers.

Still, genes do seem to play a role in some families with a history of lung cancer. For example, some people seem to inherit a reduced ability to break down or get rid of certain types of cancer-causing chemicals in the body, such as those found in tobacco smoke. This could put them at higher risk for lung cancer.

Other people may inherit faulty DNA repair mechanisms that make it more likely they will end up with DNA changes. Every time a cell prepares to divide into 2 new cells, it must make a new copy of its DNA. This process is not perfect, and copying errors sometimes occur. Cells normally have repair enzymes that proofread the DNA to help prevent this. People with repair enzymes that don't work as well might be especially vulnerable to cancer-causing chemicals and radiation.

Researchers are developing tests that may help identify such people, but these tests are not yet reliable enough for routine use. For now, doctors recommend that all people avoid tobacco smoke and other exposures that might increase their cancer risk.

Acquired gene changes: Gene changes related to lung cancer are usually acquired during life rather than inherited. Acquired mutations in lung cells often result from exposure to factors in the environment, such as cancer-causing chemicals in tobacco smoke. But some gene changes may just be random events that sometimes happen inside a cell, without having an external cause.

Acquired changes in certain genes, such as the p53 or p16 tumor suppressor genes and the K-RAS oncogene, are thought to be important in the development of non-small cell lung cancer. Changes in these and other genes may also make some lung cancers likely to grow and spread more rapidly than others. Not all lung cancers share the same gene changes, so there are undoubtedly changes in other genes that have not yet been found.

How is non-small cell lung cancer diagnosed?

Most lung cancers are not found until they start to cause symptoms. Symptoms can suggest that a person may have lung cancer, but the actual diagnosis is made by looking at lung cells under a microscope.

Common signs and symptoms of lung cancer: Most lung cancers do not cause any symptoms until they have spread too far to be cured, but symptoms do occur in some people with early lung cancer. If you go to your doctor when you first notice symptoms, your cancer might be diagnosed at an earlier stage, when treatment is more likely to be effective.

The most common symptoms of lung cancer are:                                                                       A cough that does not go away or gets worse, Chest pain that is often worse with deep breathing, coughing, or laughing, Hoarseness, Weight loss and loss of appetite, Coughing up blood or rust-colored sputum (spit or phlegm), Shortness of breath, Feeling tired or weak, Infections such as bronchitis and pneumonia that don’t go away or keep coming back, New onset of wheezing

When lung cancer spreads to distant organs, it may cause:                                                      Bone pain (like pain in the back or hips), Neurologic changes (such as headache, weakness or numbness of an arm or leg, dizziness, balance problems, or seizures), Jaundice (yellowing of the skin and eyes), Lumps near the surface of the body, due to cancer spreading to the skin or to lymph nodes (collections of immune system cells) in the neck or above the collarbone

Most of the symptoms listed above are more likely to be caused by conditions other than lung cancer. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed.

Some lung cancers can cause a group of very specific symptoms. These are often described as syndromes.

Horner syndrome: Cancers of the top part of the lungs (sometimes called Pancoast tumors) may damage a nerve that passes from the upper chest into your neck. This can cause severe shoulder pain. Sometimes these tumors also cause a group of symptoms called Horner syndrome: 

Drooping or weakness of one eyelid

Having a smaller pupil (dark part in the center of the eye) in the same eye

Reduced or absent sweating on the same side of the face

Conditions other than lung cancer can also cause Horner syndrome.

Superior vena cava syndrome: The superior vena cava (SVC) is a large vein that carries blood from the head and arms back to the heart. It passes next to the upper part of the right lung and the lymph nodes inside the chest. Tumors in this area may push on the SVC, which can cause the blood to back up in the veins. This can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. While SVC syndrome can develop gradually over time, in some cases it can become life-threatening, and needs to be treated right away.

Paraneoplastic syndromes: Some lung cancers may make hormone-like substances that enter the bloodstream and cause problems with distant tissues and organs, even though the cancer has not spread to those tissues or organs. These problems are calledparaneoplastic syndromes. Sometimes these syndromes may be the first symptoms of lung cancer. Because the symptoms affect other organs, patients and their doctors may suspect at first that diseases other than lung cancer are causing them.

Some of the more common paraneoplastic syndromes that can be caused by non-small cell lung cancer include:

High blood calcium levels (hypercalcemia), which can cause frequent urination, constipation, nausea, vomiting, weakness, dizziness, confusion, and other nervous system problems

Excess growth of certain bones, especially those in the finger tips, which is often painful

Blood clots

Excess breast growth in men (gynecomastia)

Again, many of the symptoms listed above are more likely to be caused by conditions other than lung cancer. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed.

Medical history and physical exam: If you have any signs or symptoms that suggest you might have lung cancer, your doctor will want to take a medical history to check for risk factors and learn more about your symptoms. Your doctor will also examine you to look for signs of lung cancer and other health problems.

If the results of the history and physical exam suggest you may have lung cancer, more involved tests will probably be done. These might include imaging tests and/or getting biopsies of lung tissue.

Imaging tests: Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done for a number of reasons both before and after a diagnosis of lung cancer, including:                  To help find a suspicious area that might be cancerous, To learn how far cancer may have spread, To help determine if treatment has been effective, To look for possible signs of cancer recurrence after treatment

Chest x-ray: This is often the first test your doctor will do to look for any masses or spots on the lungs. Plain x-rays of your chest can be done at imaging centers, hospitals, and even in some doctors' offices. If the x-ray is normal, you probably don't have lung cancer (although some lung cancers may not show up on an x-ray). If something suspicious is seen, your doctor may order additional tests.

Computed tomography (CT) scan: The CT or CAT scan is a test that uses x-rays to produce detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. A computer then combines these pictures into images of slices of the part of your body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body.

Before the CT scan, you may be asked to drink a contrast solution or you may get an injection of a contrast solution through an IV (intravenous) line. This helps better outline structures in your body.

The contrast may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or low blood pressure can occur. Be sure to tell the doctor if you have any allergies or if you ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays, and they expose you to a small amount of radiation. The test itself is painless, other than, perhaps, the insertion of the IV line. You need to lie still on a table while it is being done. During the test, the table slides in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.

A CT scan can provide precise information about the size, shape, and position of any tumors and can help find enlarged lymph nodes that might contain cancer that has spread from the lung. CT scans are more sensitive than routine chest x-rays in finding early lung cancers.

This test can also be used to look for masses in the adrenal glands, liver, brain, and other internal organs that may be affected by the spread of lung cancer.

CT guided needle biopsy: In cases where a suspected area of cancer lies deep within the body, a CT scan can be used to guide a biopsy needle precisely into the suspected area. For this procedure, you stay on the CT scanning table, while the doctor advances a biopsy needle through the skin and toward the mass. CT scans are repeated until the doctor can see that the needle is within the mass. A biopsy sample is then removed and looked at under a microscope.

Magnetic resonance imaging (MRI) scan: Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details.

MRI scans are a little more uncomfortable than CT scans. First, they take longer – often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). Special “open” MRI machines can sometimes help with this if needed, but the images may not be as sharp in some cases. MRI machines make buzzing and clicking noises that you may find disturbing. Some centers provide earplugs to help block this noise out.

MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal cord.

Positron emission tomography (PET) scan: For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. The amount of radioactivity used is very low. Because cancer cells in the body are growing rapidly, they absorb large amounts of the radioactive sugar. After about an hour, you will be moved onto a table in the PET scanner. You lie on the table for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it provides helpful information about your whole body.

This can be a very important test if you appear to have early stage lung cancer. Your doctor can use this test to help see if the cancer has spread to nearby lymph nodes or other areas, which can help determine if surgery may be an option for you. A PET scan can also be helpful in getting a better idea whether an abnormal area on your chest x-ray may be cancer.

PET scans are also useful if your doctor thinks the cancer may have spread but doesn't know where. PET can reveal spread of cancer to the liver, bones, adrenal glands, or some other organs. It is not as useful for looking at the brain, since all brain cells use a lot of glucose.

Special machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This lets the doctor compare areas of higher radioactivity on the PET with the more detailed appearance of that area on the CT.

Bone scan: A bone scan can help show if a cancer has metastasized (spread) to the bones. For this test, a small amount of low-level radioactive material is injected into a vein (intravenously, or IV). The substance settles in areas of bone changes throughout the entire skeleton over the course of a couple of hours. You then lie on a table for about 30 minutes while a special camera detects the radioactivity and creates a picture of your skeleton.

Areas of active bone changes show up as "hot spots" on your skeleton – that is, they attract the radioactivity. These areas may suggest the presence of metastatic cancer, but arthritis or other bone diseases can also cause the same pattern. To distinguish among these conditions, your cancer care team may use other imaging tests such as simple x-rays or MRI scans to get a better look at the areas that light up, or they may even take biopsy samples of the bone.

PET scans, which are often done in patients with non-small cell lung cancer, can usually show if cancer has spread to the bones, so bone scans aren't needed very often. Bone scans are done mainly when there is reason to think the cancer may have spread to the bones (because of symptoms such as bone pain) and other test results aren't clear.

Tests to diagnose lung cancer: The results of a CT scan or another imaging test may strongly suggest that lung cancer is present, but to confirm the diagnosis a sample of the tumor cells needs to be looked at under the microscope. To get this sample, one or more of the tests below may be used. Some of these tests may also be used to see how far a lung cancer has spread.

Bronchoscopy: For this exam, a lighted, flexible fiber-optic tube (bronchoscope) is passed through your mouth or nose and down into the windpipe and bronchi. The mouth and throat are sprayed first with a numbing medicine. You may also be given medicine through an intravenous (IV) line to make you feel relaxed.

Bronchoscopy can help the doctor find some tumors or blockages in the larger airways of the lungs. At the same time, small instruments can be passed down the bronchoscope to take biopsies (samples of tissue). The doctor can also sample cells from the lining of the airways with a small brush (bronchial brushing) or by rinsing the airways with sterile saltwater (bronchial washing). These tissue and cell samples are then looked at under a microscope.

Endobronchial ultrasound: Ultrasound is a type of imaging test that uses sound waves to create pictures of the inside of your body. For this test, a small, microphone-like instrument called a transducer emits sound waves and picks up the echoes as they bounce off body tissues. The echoes are converted by a computer into a black and white image on a computer screen.

For endobronchial ultrasound, a bronchoscope is fitted with an ultrasound transducer at its tip and is passed down into the windpipe. This is done with numbing medicine (local anesthesia) and light sedation.

The transducer can be pointed in different directions to look at lymph nodes and other structures in the mediastinum (the area between the lungs). If suspicious areas (such as enlarged lymph nodes) are seen on the ultrasound, a hollow needle can be passed through the bronchoscope and guided into these areas to obtain a biopsy. The samples are then sent to a lab to be looked at under a microscope.

Endoscopic esophageal ultrasound: This technique is similar to endobronchial ultrasound, except the doctor passes an endoscope (a lighted, flexible scope) down the throat and into the esophagus (the tube connecting the throat to the stomach). This is done with numbing medicine (local anesthesia) and light sedation.

The esophagus lies just behind the windpipe and is close to some lymph nodes inside the chest to which lung cancer may spread. Ultrasound images taken from inside the esophagus can help find large lymph nodes inside the chest that might contain lung cancer. If enlarged lymph nodes are seen on the ultrasound, a hollow needle can be passed through the endoscope to get biopsy samples of them. The samples are then sent to a lab to be looked at under a microscope.

Mediastinoscopy and mediastinotomy: These procedures may be done to look more directly at and get samples from the structures in the mediastinum (the area between the lungs). They are done in an operating room while you are under general anesthesia (in a deep sleep). The main difference between the two is in the location and size of the incision.

Mediastinoscopy: A small cut is made in the front of the neck and a thin, hollow, lighted tube is inserted behind the sternum (breast bone) and in front of the windpipe to look at the area. Special instruments can be passed through this tube to take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas. Looking at the samples under a microscope can show whether cancer cells are present.

Mediastinotomy: The surgeon makes a slightly larger incision (usually about 2 inches long) between the left second and third ribs next to the breast bone. This allows the surgeon to reach lymph nodes that cannot be reached by mediastinoscopy.

Thoracentesis: Thoracentesis is done to find out if a buildup of fluid around the lungs (pleural effusion) is the result of cancer spreading to the lining of the lungs (pleura). The buildup might also be caused by other conditions, such as heart failure or an infection.

For this procedure, the skin is numbed and a hollow needle is inserted between the ribs to drain the fluid. (In a similar test called pericardiocentesis, fluid is removed from within the sac around the heart.) The fluid is checked under a microscope to look for cancer cells. Chemical tests of the fluid are also sometimes useful in telling a malignant (cancerous) pleural effusion from a benign (non-cancerous) one.

If a malignant pleural effusion has been diagnosed, thoracentesis may be repeated to remove more fluid. Fluid build-up can keep the lungs from filling with air, so thoracentesis can help the patient breathe better.

Thoracoscopy: Thoracoscopy can be done to find out if cancer has spread to the space between the lungs and the chest wall, or to the linings of these spaces. It can also be used to sample tumors on the outer parts of the lungs as well as nearby lymph nodes and fluid, and to assess whether a tumor is growing into nearby tissues or organs. This procedure is not often done just to diagnose lung cancer, unless other tests such as needle biopsies are unable to get sufficient samples for the diagnosis.

Thoracoscopy is done in the operating room while you are under general anesthesia (in a deep sleep). A small cut (incision) is made in the side of the chest wall. (Sometimes more than one cut is made.) The doctor then inserts a lighted tube with a small video camera on the end through the incision to view the space between the lungs and the chest wall. Using this, the doctor can see potential cancer deposits on the lining of the lung or chest wall and remove small pieces of tissue to be looked at under the microscope. (When certain areas can't be reached with thoracoscopy, the surgeon may need to make a larger incision in the chest wall, known as a thoracotomy.)

Thoracoscopy can also be used as part of the treatment to remove part of a lung in some early-stage lung cancers. 

Sampling tissues and cells: Symptoms and the results of certain tests may strongly suggest that lung cancer is present, but the actual diagnosis of non-small cell lung cancer is made by looking at lung cells under a microscope.

The cells can be taken from lung secretions (sputum or phlegm), removed from a suspicious area (known as a biopsy), or found in fluid removed from the area around the lung (thoracentesis).

A pathologist, a doctor who uses lab tests to diagnose diseases such as cancer, will look at the cells under a microscope. The results will be described in a pathology report, which is usually available within about a week. If you have any questions about your pathology results or any diagnostic tests, talk to your doctor. If needed, you can get a second opinion of your pathology report by having your tissue samples sent to a pathologist at another lab recommended by your doctor.

Sputum cytology: A sample of sputum (mucus you cough up from the lungs) is looked at under a microscope to see if cancer cells are present. The best way to do this is to get early morning samples from you 3 days in a row. This test is more likely to help find cancers that start in the major airways of the lung, such as most squamous cell lung cancers. It may not be as helpful for finding other types of non-small cell lung cancer.

Fine needle aspiration (FNA) biopsy: A needle biopsy can often be used to get a small sample of cells from a suspicious area (mass). For this test, the skin on the chest wall where the needle is to be inserted may be numbed with local anesthesia. The doctor then guides a thin, hollow needle into the area while looking at your lungs with either fluoroscopy (which is like an x-ray, but the image is shown on a screen rather than on film) or CT scans. Unlike fluoroscopy, CT doesn't give a continuous picture, so the needle is inserted toward the mass, a CT image is taken, and the direction of the needle is guided based on the image. This is repeated a few times until the needle is within the mass.

A small sample of the mass is then sucked into a syringe and sent to a lab, where it is looked at under the microscope to see if cancer cells are present. (In some cases, if the diagnosis isn't clear based on the FNA biopsy, a larger needle may be used to remove a slightly bigger piece of lung tissue. This is known as a core needle biopsy.)

A needle biopsy may be useful for getting samples from tumors in the outer portions of the lungs, where other tests such as bronchoscopy (described below) may not be as helpful.

A possible complication of this procedure is that air may leak out of the lung at the biopsy site and into the space between the lung and the chest wall. This can cause part of the lung to collapse and may cause trouble breathing. This complication, called a pneumothorax, often gets better without any treatment. If not, it is treated by putting a small tube into the chest space and sucking out the air over a day or two, after which it usually heals on its own.

An FNA biopsy may also be done to take samples of lymph nodes around the trachea (windpipe) and bronchi (the large airways leading into the lungs). This can be done during bronchoscopy or endoscopic ultrasound. When done during bronchoscopy this procedure is called transtracheal FNA or transbronchial FNA.

Lab tests of biopsy and other samples: Samples that have been collected during biopsies or other tests are sent to a pathology lab. There, a doctor looks at the samples under a microscope to find out if they contain cancer and if so, what type of cancer it is. Special tests may be needed to help better classify the cancer. Cancers from other organs can spread to the lungs. It's very important to find out where the cancer started, because treatment is different depending on the type of cancer.

Immunohistochemistry: For this test, very thin slices of the sample are attached to glass microscope slides. The samples are then treated with special proteins (antibodies) designed to attach only to a specific substance found in certain cancer cells. If the patient's cancer contains that substance, the antibody will attach to the cells. Chemicals are then added so that antibodies attached to the cells change color. The doctor who looks at the sample under a microscope can see this color change.

Molecular tests: In some cases, doctors may look for specific gene changes in the cancer cells that might affect how they are best treated. For example, the epidermal growth factor receptor (EGFR) is a protein that sometimes appears in high amounts on the surface of adenocarcinoma cells and helps them grow. Some newer anti-cancer drugs target EGFR, but they seem to work best against lung cancers with certain changes in the EGFR gene. These changes are more common in certain groups, such as non-smokers, women, and Asians. But these drugs don’t seem to help patients whose cancer cells have changes in the KRAS gene. Many doctors now test for changes in genes such as EGFR andKRAS to determine if these newer treatments are likely to be helpful.

About 5% of non-small cell lung cancers have been found to have a rearrangement in a gene called ALK. This change is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC. A drug has been developed that targets this gene change, and so now doctors may test some adenocarcinoma lung cancers for changes in this gene to see if this drug may help them.

Blood tests: Blood tests are not used to diagnose lung cancer, but they are done to get a sense of a person's overall health. For example, before surgery, blood tests can help tell if a person is healthy enough to have an operation.

A complete blood count (CBC) determines whether your blood has normal numbers of various cell types. For example, it can show if you are anemic (have a low number of red blood cells), if you may have trouble with bleeding (due to a low number of blood platelets), or if you are at increased risk for infections (because of a low number of white blood cells). This test will be repeated regularly if you are treated with chemotherapy, because these drugs can affect blood-forming cells of the bone marrow.

Blood chemistry tests can help spot abnormalities in some of your organs, such as the liver or kidneys. For example, if cancer has spread to the liver and bones, it may cause abnormal levels of certain chemicals in the blood, such as a higher than normal level of lactate dehydrogenase (LDH).

Pulmonary function tests: Pulmonary function tests (PFTs) are often done after lung cancer is diagnosed to see how well your lungs are working (for example, how much emphysema or chronic obstructive lung disease is present). This is especially important if surgery might be an option in treating the cancer. Surgery to remove lung cancer may mean removing part or all of a lung, so it's important to know how well the lungs are working beforehand. Some people with poor lung function (like those with lung damage from smoking) don’t have enough lung reserve to tolerate removing even part of a lung. These tests can give the surgeon an idea of whether surgery is a good option, and if so, how much lung can safely be removed.

There are different types of PFTs, but they all basically have you breathe in and out through a tube that is connected to a machine that measures airflow. Sometimes this is coupled with a test called an arterial blood gas. In this test, blood is removed from an artery (most blood tests use blood removed from a vein) to measure the amount of oxygen and carbon dioxide that it contains.

How is non-small cell lung cancer staged?

Staging is the process of finding out how far a cancer has spread. Your treatment and prognosis (outlook) depend, to a large extent, on the cancer's stage. The stage of a cancer does not change over time, even if the cancer progresses. A cancer that comes back or spreads is still referred to by the stage it was given when it was first found and diagnosed, only information about the current extent of the cancer is added. A person keeps the same diagnosis stage, but more information is added to the diagnosis to explain the current disease status.

There are actually 2 types of stages.

The clinical stage is based on the results of the physical exam, biopsies, and imaging tests (CT scan, chest x-ray, PET scan, etc.).

If you have surgery, your doctor can also determine a pathologic stage, which is based on the same factors as the clinical stage, plus what is found as a result of the surgery.

The clinical and pathologic stages may be different in some cases. For example, during surgery the doctor may find cancer in an area that did not show up on imaging tests, which might give the cancer a more advanced pathologic stage.

Because many patients with non-small cell lung cancer do not have surgery, the clinical stage is often used when describing the extent of this cancer. However, when it is available, the pathologic stage is likely to be more accurate than the clinical stage, as it uses the additional information obtained at surgery.

The TNM staging system: The system used to describe the growth and spread of non-small cell lung cancer (NSCLC) is the American Joint Committee on Cancer (AJCC) TNM staging system. The TNM system is based on 3 key pieces of information:

T indicates the size of the main (primary) tumor and whether it has grown into nearby areas.

N describes the spread of cancer to nearby (regional) lymph nodes. Lymph nodes are small bean-shaped collections of immune system cells that help fight infections. Cancers often spread to the lymph nodes before going to other parts of the body.

M indicates whether the cancer has spread (metastasized) to other organs of the body. (The most common sites are the brain, bones, adrenal glands, liver, kidneys, and the other lung.)

Numbers or letters appear after T, N, and M to provide more details about each of these factors. The numbers 0 through 4 indicate increasing severity. The letter X means "cannot be assessed because the information is not available."

The TNM staging system is complex and can be difficult for patients (and even some doctors) to understand. If you have any questions about the stage of your cancer, ask your doctor to explain it to you.

T categories for lung cancer: TX: The main (primary) tumor can't be assessed, or cancer cells were seen on sputum cytology but no tumor can be found.

T0: There is no evidence of a primary tumor.

Tis: The cancer is found only in the top layers of cells lining the air passages. It has not invaded into deeper lung tissues. This is also known as carcinoma in situ.

T1: The tumor is no larger than 3 cm (slightly less than 1¼ inches) across, has not reached the membranes that surround the lungs (visceral pleura), and does not affect the main branches of the bronchi.

If the tumor is 2 cm (about 4/5 of an inch) or less across, it is called T1a. If the tumor is larger than 2 cm but not larger than 3 cm across, it is called T1b.

T2: The tumor has 1 or more of the following features:

T3: The tumor has 1 or more of the following features:

T4: The cancer has 1 or more of the following features:

N categories for lung cancer: NX: Nearby lymph nodes cannot be assessed.

N0: There is no spread to nearby lymph nodes.

N1: The cancer has spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). Affected lymph nodes are on the same side as the primary tumor.

N2: The cancer has spread to lymph nodes around the carina (the point where the windpipe splits into the left and right bronchi) or in the space between the lungs (mediastinum). Affected lymph nodes are on the same side as the primary tumor.

N3: The cancer has spread to lymph nodes near the collarbone on either side, and/or spread to hilar or mediastinal lymph nodes on the side opposite the primary tumor.

M categories for lung cancer: M0: No spread to distant organs or areas. This includes the other lung, lymph nodes further away than those mentioned in the N stages above, and other organs or tissues such as the liver, bones, or brain.

M1a: Any of the following: cancer has spread to the other lung, cells are found in the fluid around the lung (called a malignant pleural effusion), cells are found in the fluid around the heart (called a malignant pericardial effusion),

M1b: The cancer has spread to distant lymph nodes or to other organs such as the liver, bones, or brain.

Stage grouping for lung cancer: Once the T, N, and M categories have been assigned, this information is combined to assign an overall stage of 0, I, II, III, or IV. This process is called stage grouping. Some stages are subdivided into A and B. The stages identify cancers that have a similar prognosis and thus are treated in a similar way. Patients with lower stage numbers tend to have a better prognosis.

Occult cancer: TX, N0, M0: Cancer cells are seen in a sample of sputum or other lung fluids, but the cancer isn't found with other tests, so its location can't be determined.

Stage 0: Tis, N0, M0: The cancer is found only in the top layers of cells lining the air passages. It has not invaded deeper into other lung tissues and has not spread to lymph nodes or distant sites.

Stage IA: T1a/T1b, N0, M0: The cancer is no larger than 3 cm across, has not reached the membranes that surround the lungs, and does not affect the main branches of the bronchi. It has not spread to lymph nodes or distant sites.

Stage IB: T2a, N0, M0: The cancer has 1 or more of the following features:                       main tumor is between 3 and 5 cm across (larger than 3 cm but not larger than 5 cm), tumor has grown into a main bronchus, but is not within 2 cm of the carina (and it is not larger than 5 cm), tumor has grown into the visceral pleura (the membranes surrounding the lungs) and is not larger than 5 cm, tumor is partially clogging the airways (and is not larger than 5 cm).

The cancer has not spread to lymph nodes or distant sites.

Stage IIA: Three main combinations of categories make up this stage.

T1a/T1b, N1, M0: The cancer is no larger than 3 cm across, has not grown into the membranes that surround the lungs, and does not affect the main branches of the bronchi. It has spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites.                                    OR                                          

T2a, N1, M0: The cancer has 1 or more of the following features:          

main tumor is between 3 and 5 cm across (larger than 3 cm but not larger than 5 cm).

tumor has grown into a main bronchus, but is not within 2 cm of the carina (and it is not larger than 5 cm).

tumor has grown into the visceral pleura (the membranes surrounding the lungs) and is not larger than 5 cm.

tumor is partially clogging the airways (and is not larger than 5 cm).

The cancer has also spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites.            OR

T2b, N0, M0: The cancer has 1 or more of the following features:

main tumor is between 5 and 7 cm across (larger than 5 cm but not larger than 7 cm).

tumor has grown into a main bronchus, but is not within 2 cm of the carina (and it is between 5 and 7 cm across).

tumor has grown into the visceral pleura (the membranes surrounding the lungs) and is between 5 and 7 cm across.

tumor is partially clogging the airways (and is between 5 and 7 cm across).

The cancer has not spread to lymph nodes or distant sites.

Stage IIB: Two combinations of categories make up this stage.

T2b, N1, M0: The cancer has 1 or more of the following features:

main tumor is between 5 and 7 cm across (larger than 5 cm but not larger than 7 cm).

tumor has grown into a main bronchus, but is not within 2 cm of the carina (and it is between 5 and 7 cm across).

tumor has grown into the visceral pleura (the membranes surrounding the lungs) and is between 5 and 7 cm across.

cancer is partially clogging the airways (and is between 5 and 7 cm across).

It has also spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites.                                   OR

T3, N0, M0: The main tumor has 1 or more of the following features:

is larger than 7 cm across.

has grown into the chest wall, the breathing muscle that separates the chest from the abdomen (diaphragm), the membranes surrounding the space between the lungs (mediastinal pleura), or membranes of the sac surrounding the heart (parietal pericardium).

invades a main bronchus and is closer than 2 cm (about ¾ inch) to the carina, but it does not involve the carina itself.

has grown into the airways enough to cause an entire lung to collapse or to cause pneu

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