Non-Small-Cell Lung Cancer

Non-Small-Cell Lung Cancer

Non–Small-Cell Lung Cancer Overview

Cancers are diseases in which normal cells transform so that they grow and multiply without normal controls. In many types of cancer, this results in the growth of one or more large masses, or tumors, of these transformed cells. This can happen in almost any part of the body. When it happens in the lungs, the disease is called lung cancer.
 
Lung cancer is one of the most common types of cancer; this is because the lungs are exposed to the external environment more than most other organs are. In many cases, cancer-causing substances (carcinogens) in the air are inhaled and cause cell damage that later becomes cancer. The most common cause of lung cancer, by far, is smoking.
 
Two main types of lung cancer exist: small cell lung cancer and non-small-cell lung cancer. Non-small-cell lung cancer is a catchall term for all lung cancers that are not small-cell type. They are grouped together because the treatment is the same for all non-small-cell types. Together, non-small-cell lung cancers, or NSCLCs, make up about 75% of all lung cancers. Each type is named for the types of cells that were transformed to become cancer. The following are the 3 most common types of NSCLC in the United States: 

• Adenocarcinoma/bronchoalveolar - 35-40%



• Squamous cell carcinoma - 25-30%



• Large-cell carcinoma - 10-15% 

Like all cancers, lung cancer is most easily and successfully treated if it is caught early. An early-stage cancer is less likely to have grown to a large size or to have spread to other parts of the body (metastasized). Large or metastasized cancers are much more difficult to treat.

 

Non–Small-Cell Lung Cancer Causes

Tobacco smoking

• Tobacco smoking is the cause of lung cancer in as many as 90% of cases.



• A person who smokes is 13.3 times as likely to develop lung cancer as is a person who has never smoked. The risk also varies with the number of cigarettes smoked per day; people who smoke more than 20 cigarettes per day have a much greater risk of developing lung cancer than do those who smoke fewer than 20 cigarettes per day.



• Once a person quits smoking, the risk of lung cancer increases for the first 2 years and then gradually decreases, but the risk never returns to the same level as that of a person who has never smoked.



• Not all people who smoke develop lung cancer, and not all people with lung cancer smoke. Clearly, other factors, including genetic predisposition, also play a role.

Passive smoking (secondhand smoke)

• As many as 15% of lung cancer cases involving nonsmokers may be caused by secondhand smoke.



• The Environmental Protection Agency has recognized passive smoking as a potential cause of cancer.

Asbestos

• Asbestos exposure has been linked to lung cancer and other lung diseases.



• The silicate type of asbestos fiber is an important carcinogen.



• Asbestos exposure increases the risk of lung cancer by as much as 5 times.



• People who both smoke and have been exposed to asbestos are at an especially high risk of developing lung cancer.

Radon

• Radon is a gas produced as a result of uranium decay. Radon exposure is a risk factor for lung cancer in uranium miners.



• Radon exposure is believed to account for about 2-3% of lung cancers each year.



• Household exposure to radon has never been clearly shown to cause lung cancer.

Other environmental agents
 
Exposures to the following agents account, at least partly, for some cases of lung cancer: 

• Petroleum-based chemicals called aromatic polycyclic hydrocarbons



• Beryllium



• Nickel



• Copper



• Chromium



• Cadmium



• Diesel exhaust

 

Non–Small-Cell Lung Cancer Symptoms

The symptoms of lung cancer are caused by the primary tumor or by metastatic disease. The primary tumor may press on, infiltrate, or damage surrounding tissues, blood vessels, or nerves. Metastatic lung cancer may cause similar problems in other parts of the body. As many as 10% of people with lung cancer have no symptoms. Their cancers are detected on chest x-ray films performed for other reasons.
 
The symptoms depend on the primary tumor’s size, its location in the lung, the surrounding areas affected by the tumor, and the sites of tumor metastasis, if any. Symptoms related to the primary tumor may include any of the following: 

• Cough



• Shortness of breath



• Difficulty taking a deep breath



• Wheezing



• Coughing or spitting blood (hemoptysis)



• Pneumonia or other recurrent respiratory infection



• Pain in the chest, side, or back (usually due to infiltration by the tumor of areas surrounding the lungs)



• Hoarseness, difficulty swallowing, or other symptoms in the face, neck, or arms due to infiltration by a tumor

Symptoms of metastatic lung tumors depend on location and size. Lung cancer most often spreads to the liver, the adrenal glands, the bones, and the brain. About 30-40% of people with lung cancer have some symptoms or signs of metastatic disease.

• Metastatic lung cancer in the liver usually does not cause any symptoms, at least at the time of diagnosis.



• Typically, metastatic lung cancer in the adrenal glands also causes no symptoms at the time of diagnosis.



• Metastasis to the bones is most common with small cell lung cancer but can occur with NSCLC. Lung cancer that has metastasized to the bone causes deep pain, usually in the backbone (vertebrae), thighbones, and ribs.



• Lung cancer that spreads to the brain can cause difficulties with vision, weakness on one side of the body, seizures, or a combination thereof.



• Weight loss may be a symptom of metastatic disease.

Paraneoplastic syndromes are conditions that the disease causes indirectly. These are less common with NSCLC than with small cell lung cancers, but they do occur.

• High level of calcium in the blood (hypercalcemia) - Can cause problems with muscle and nerve functioning



• Increased production of one or more hormones



•  Increased blood coagulation (hypercoagulability) - Increases risk of blood clots
•  

  When to Seek Medical Care

  Any pain in the chest, side, or back; breathing problem; or cough that persists, worsens, or produces blood warrants an immediate visit to a health care provider.

Exams and Tests

Medical evaluation and tests
 
The symptoms of lung cancer can be caused by many different medical conditions. Even a chest x-ray film that shows what looks like a tumor is not enough to make the diagnosis of lung cancer. The health care provider’s job is to gather all available information and to make the diagnosis. Correct and prompt diagnosis is essential so that appropriate treatment can be started as soon as possible.
 
The first step in the evaluation is the medical interview. The health care provider asks the patient questions about symptoms and when they started, current or past medical problems, medications taken, family medical problems, work and travel history, and habits and lifestyle. This is followed by a thorough physical examination.
 
The remainder of the evaluation focuses on confirming the presence of lung cancer and staging the tumor. Although primary care providers are able to conduct this evaluation, they may prefer to refer the patient a specialist. At any time during this evaluation, the primary care provider may refer the patient to a surgeon or to a specialist in lung diseases (pulmonologist) or cancer (oncologist).
 
Lab tests 
No blood test can confirm that a patient has lung cancer. Blood tests are performed to check the patient’s general health, to rule out other conditions that might cause similar symptoms, and to detect certain paraneoplastic syndromes. The usual blood tests include the following:

• Complete blood cell counts



• Liver and kidney function tests



• Blood chemistry and electrolyte levels

Imaging studies
 
Respiratory symptoms are usually evaluated with a chest x-ray film, CT scan of the chest, or both. X-ray films are limited in the amount of detail they provide, but they clearly show some tumors. CT scans shows much greater detail in a 3-dimensional format. A CT scan is needed if the x-ray film findings are not definitive. If imaging studies show evidence of a tumor, further testing is needed.
 
Other tests
Sputum analysis: Sputum is mucus in the lungs. Sputum is the body’s natural system for removing small particles and contaminants from the airways. Many people, especially those who smoke, produce sputum when they cough. In some cases of lung cancer, tumor cells are sloughed off into the sputum and can be detected by cytologic (cell) testing. For this test, the patient is asked to cough, and the sputum is collected and examined.

• This simple test, if the result is positive for tumor cells, confirms the diagnosis of cancer. A result negative for tumor cells, however, does not confirm that no cancer is present.



• In either case, further testing is needed: if positive for tumor cells, to determine the type of cancer; if negative for tumor cells, to seek definitive evidence of whether a tumor is present.

Bronchoscopy: This is the use of a device called an endoscope to view the lungs directly. An endoscope is a thin tube with a light and a tiny camera on the end. The endoscope is inserted through the mouth or nose into the bronchus (airway) and down to the lung. The camera transmits pictures of the inside of the patient’s airways that can be viewed on a video screen.

• Bronchoscopy allows the doctor to look directly at the tumor (if one is present). This allows the doctor to determine the tumor’s size and the extent to which it is blocking the airway.



• The bronchoscope can also be used to collect a biopsy. A biopsy is a small sample of the tumor or any abnormal-appearing lung tissue, for further testing.



• The biopsy is examined under a microscope by a pathologist, a specialist in diagnosing diseases in this way. The pathologist confirms whether the mass is cancer and, if so, the type of cancer.



• This technique is also used to examine the area around the main airway, between the lungs in the middle of the chest (mediastinum). The cancer can infiltrate the lymph nodes in this area. The endoscope is inserted through a small incision just above or to the side of the breastbone. This technique is called mediastinoscopy. Enlarged lymph nodes and other abnormal tissues can be removed during this procedure.

CT-guided biopsy: This procedure involves a CT scan to guide the removal of a biopsy. It is used for tumors that cannot be reached with a bronchoscope, usually because they are in the outer part of the lung. Again, this material is examined to confirm the presence of a tumor and to determine the type of tumor.
 
Biopsies from other sites: Material can also be obtained from other sites with abnormalities to confirm the diagnosis. These sites include enlarged lymph nodes or liver and collections of fluid around the lung (pleural effusion) or heart (pericardial effusion).
 
Staging
 
Staging is a system of classifying cancers based on the extent of the disease. In general, the lower the stage, the better the outlook for remission and survival. In NSCLC, staging is based on the size of the primary tumor, the number of cancerous lymph nodes, and the presence of any metastatic tumors. Accurate staging is essential in NSCLC because the stage of the cancer determines which treatment may offer the best results.
 
For people with lung cancer, the first step is to undergo a staging evaluation. The patient’s medical team cannot make recommendations for the best treatment until they know the cancer’s exact stage.
 
This evaluation includes many of the tests already described. Other tests are as follows:

• CT scan of the chest and upper abdomen: The purposes of this scan are to measure the exact size of the primary tumor, to look for enlarged lymph nodes that may be cancerous, and to look for signs of metastatic disease in the liver and adrenal glands.



• CT scan or MRI of the brain: This is needed only if the patient is experiencing neurologic symptoms that suggest that the cancer has metastasized to the brain.



• Positron emission tomography (PET) scan: This scan detects cancer cells throughout the body based on the rate they use glucose (sugar); this rate is higher than that of normal cells. PET scan is available only at some large medical centers.



• Bone scan: This test, formally known as scintigraphy, looks for metastasis to the bones. A harmless radioactive substance is inserted into the bloodstream. It concentrates in areas where the infiltrating cancer has weakened the bone. A scan of the entire skeleton highlights these areas. Generally, this test is performed only if the patient is experiencing bone pain or other signs of bony metastasis.



• MRI of the spine: MRI is the best test for compression of the spinal cord. This happens when the metastatic disease and the collapse on the spinal cord weaken the bones of the spine. This is a serious complication of lung cancer. It usually causes pain in the neck, back, or hip. Compression of the spinal cord can also cause numbness or paralysis in the arms, legs, or both; problems controlling bladder or bowels; and other problems.

The stage is determined by a combination of the following 3 characteristics:

• T - Size and extent of primary tumor (X,1,2,3,4)



• N - Involvement of lymph nodes in the region of the lungs (0,1,2,3)



• M - Metastatic involvement

For each tumor, a number is assigned for each of the 3 letters—for example, T2N1M0. These 3 numbers determine the stage. NSCLC has 4 stages, designated I, II, III, and IV. Stages I-III are subdivided into A and B subtypes. The stage groupings are as follows: 

• IA: T1N0M0; The tumor is limited to the lung, and the tissue around the tumor is normal.



• IB: T2N0M0; The tumor is limited to the lung but is larger than in stage IA. The tissue around the tumor is normal.



• IIA: T1N1M0; The tumor has spread to the area around the lung, such as lymph nodes, the chest wall, the diaphragm, or the sacs surrounding the lung or heart.



• IIB: T2N1M0, T3N0M0; This stage is similar to stage IIA but the tumor is larger or nearby lymph nodes are involved.



• IIIA: T1-3N2M0, T3N1M0; The tumor has spread to the lymph nodes in the mediastinum, on the other side of the chest, or in the lower neck.



• IIIB: Any T4 or any N3M0; This stage is similar to stage IIIA but the tumor is larger.



• IV: Any M1; Tumor has spread to another section of the lungs or elsewhere in the body.

Non–Small-Cell Lung Cancer Treatment

Tissue diagnosis is mandatory prior to any treatment. The goals of treatment are to remove or shrink the tumor, to kill all residual tumor cells, to prevent or minimize complications and paraneoplastic syndromes, and to relieve the symptoms and side effects associated with the disease and treatment. Available therapies cure only a small number of people with lung cancer. Other people’s tumors shrink substantially or even disappear, although residual cancer cells remain in the body. This is called remission. Most people feel well during remission and are able to resume their everyday activities. Remissions can last a few months, a few years, or even indefinitely. If and when the disease comes back, it is called recurrence or relapse. The disease may recur in the lung or in another part of the body. A loss of weight of more than 5% indicates a poor prognosis.

Medical Treatment

The 3 major therapies used in NSCLC are surgery, chemotherapy, and radiation therapy. A newer fourth therapy, laser therapy, is becoming more widely used.  

• Surgery: The tumor is removed through an incision in the skin and muscle.



• Chemotherapy: Strong chemicals and drugs are taken internally, either by mouth or through a vein into the bloodstream, to kill tumor cells.



• Radiation therapy: A powerful radiation beam is pointed at the tumor (external beam) or a radiation source is placed within the body next to the tumor (internal beam). The radiation kills the tumor cells.



• Laser therapy: A narrow beam of intense light called a laser is used to kill tumor cells.

Each person with NSCLC should be offered a customized treatment regimen, which should consist of some combination of these therapies depending on disease stage and location.
 
After the staging evaluation, a decision is made whether the tumor is operable. Operable (or resectable) tumors are those that can be removed completely or almost completely by surgery. Generally, only stage I and some stage II and III tumors can be removed by surgery. Sometimes, people with stage III or IV inoperable disease undergo surgery, but this is usually performed to remove enough of the tumor to relieve symptoms such as breathing problems or severe pain. Surgery does not cure people with stage IV or most stage III diseases. For more information see Surgery. 
 
Chemotherapy  
NSCLC is only moderately sensitive to chemotherapy. Chemotherapy alone does not have the potential to cure people with NSCLC. When the goal is cure, chemotherapy is given in combination with surgery or radiation therapy. Chemotherapy alone is given only to people who cannot undergo surgery or radiation therapy or, in some cases, people whose disease has relapsed after surgery. When given in combination with surgery, the chemotherapy is usually given after surgery (adjuvant chemotherapy). Adjuvant chemotherapy is recommended to treat cancer in stages I-III after surgery has been performed to remove the cancer.

Before beginning treatment, the patient undergoes testing to determine the extent of her disease. In general, chemotherapy is given in cycles. Treatment usually lasts a few days and is then followed by a recovery period of a few weeks. When side effects have subsided and blood cell counts have started to return to normal, the next cycle begins. Usually, chemotherapy is given in regimens of 2 or 4 cycles. After these cycles are over, the patient undergoes repeat CT scans and other tests to see what effect the chemotherapy has had on the tumor.
 
Radiation therapy  
Radiation therapy may be given in combination with surgery or chemotherapy or alone. Generally, radiation therapy is given alone only for persons who are not candidates for surgery.