Key Points for This Section

After lung cancer has been diagnosed, tests are done to find out if cancer cells have spread within the lungs or to other parts of the body. There are three ways that cancer spreads in the body. The following stages are used for non-small cell lung cancer: Occult (hidden) stage Stage 0 (carcinoma in situ) Stage I Stage II Stage IIIA Stage IIIB Stage IV

After lung cancer has been diagnosed, tests are done to find out if cancer cells have spread within the lungs or to other parts of the body.

The process used to find out if cancer has spread within the lungs or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. Some of the tests used to diagnose non-small cell lung cancer are also used to stage the disease. (See the General Information ¹⁰ section.) Other tests and procedures that may be used in the staging process include the following:

• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the brain and abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
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  PET (positron emission tomography) scan. The patient lies on a table that slides through the PET machine. The head rest and white strap help the patient lie still. A small amount of radioactive glucose (sugar) is injected into the patient's vein, and a scanner makes a picture of where the glucose is being used in the body. Cancer cells show up brighter in the picture because they take up more glucose than normal cells do.
• Radionuclide bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.
• Pulmonary function test (PFT): A test to see how well the lungs are working. It measures how much air the lungs can hold and how quickly air moves into and out of the lungs. It also measures how much oxygen is used and how much carbon dioxide is given off during breathing. This is also called lung function test.
• Endoscopic ultrasound (EUS): A procedure in which an endoscope is inserted into the body. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography. EUS may be used to guide fine needle aspiration (FNA) biopsy of the lung, lymph nodes, or other areas.
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  Endoscopic ultrasound-guided fine-needle aspiration biopsy. An endoscope that has an ultrasound probe and a biopsy needle is inserted through the mouth and into the esophagus. The probe bounces sound waves off body tissues to make echoes that form a sonogram (computer picture) of the lymph nodes near the esophagus. The sonogram helps the doctor see where to place the biopsy needle to remove tissue from the lymph nodes. This tissue is checked under a microscope for signs of cancer.
• Mediastinoscopy: A surgical procedure to look at the organs, tissues, and lymph nodes between the lungs for abnormal areas. An incision (cut) is made at the top of the breastbone and a mediastinoscope is inserted into the chest. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer.
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  Mediastinoscopy. A mediastinoscope is inserted into the chest through an incision above the breastbone to look for abnormal areas between the lungs. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a cutting tool. Tissue samples may be taken from lymph nodes on the right side of the chest and checked under a microscope for signs of cancer. In an anterior mediastinotomy (Chamberlain procedure), the incision is made beside the breastbone to remove tissue samples from the lymph nodes on the left side of the chest.
• Anterior mediastinotomy: A surgical procedure to look at the organs and tissues between the lungs and between the breastbone and heart for abnormal areas. An incision (cut) is made next to the breastbone and a mediastinoscope is inserted into the chest. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. This is also called the Chamberlain procedure.
• Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells.
• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

• Through tissue. Cancer invades the surrounding normal tissue.
• Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
• Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for non-small cell lung cancer:

Occult (hidden) stage

In the occult (hidden) stage, cancer cells are found in sputum (mucus coughed up from the lungs), but no tumor can be found in the lung by imaging or bronchoscopy, or the tumor is too small to be checked.

Stage 0 (carcinoma in situ)

In stage 0, abnormal cells are found in the lining of the airways. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I

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Stage I non-small cell lung cancer. In stage IA, cancer is in the lung only and is 3 cm or smaller. In stage IB, the cancer is (a) larger than 3 cm but not larger than 5 cm, (b) has spread to the main bronchus, and/or (c) has spread to the innermost layer of the lung lining. Part of the lung may have collapsed or become inflamed (not shown).

In stage I, cancer has formed. Stage I is divided into stages IA and IB:

• Stage IA: The tumor is in the lung only and is 3 centimeters or smaller.
• Stage IB: Cancer has not spread to the lymph nodes and one or more of the following is true:
  • The tumor is larger than 3 centimeters but not larger than 5 centimeters.
  • Cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus.
  • Cancer has spread to the innermost layer of the membrane that covers the lung.
  • Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus.

Stage II

Stage II is divided into stages IIA and IIB. Stage IIA and IIB are each divided into two sections depending on the size of the tumor, where the tumor is found, and whether there is cancer in the lymph nodes.

• Stage IIA:
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  Stage IIA non-small cell lung cancer. Cancer has spread to certain lymph nodes on the same side of the chest as the primary tumor; the cancer is (a) 5 cm or smaller, (b) has spread to the main bronchus, and/or (c) has spread to the innermost layer of the lung lining. OR, cancer has not spread to lymph nodes; the cancer is (d) larger than 5 cm but not larger than 7 cm, (e) has spread to the main bronchus, and/or (f) has spread to the innermost layer of the lung lining. Part of the lung may have collapsed or become inflamed (not shown).

  (1) Cancer has spread to lymph nodes on the same side of the chest as the tumor. The lymph nodes with cancer are within the lung or near the bronchus. Also, one or more of the following is true:

  • The tumor is not larger than 5 centimeters.
  • Cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus.
  • Cancer has spread to the innermost layer of the membrane that covers the lung.
  • Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus.

  or

  (2) Cancer has not spread to lymph nodes and one or more of the following is true:

  • The tumor is larger than 5 centimeters but not larger than 7 centimeters.
  • Cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus.
  • Cancer has spread to the innermost layer of the membrane that covers the lung.
  • Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus.
• Stage IIB:
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  Stage IIB non-small cell lung cancer. Cancer has spread to certain lymph nodes on the same side of the chest as the primary tumor; the cancer is (a) larger than 5 cm but not larger than 7 cm, (b) has spread to the main bronchus, and/or (c) has spread to the innermost layer of the lung lining. Part of the lung may have collapsed or become inflamed (not shown). OR, (d) the cancer is larger than 7 cm; (e) has spread to the main bronchus, (f) the diaphragm, (g) the chest wall or the lining of the chest wall; and/or (h) has spread to the membrane around the heart. There may be one or more separate tumors in the same lobe of the lung; cancer may have spread to the nerve that controls the diaphragm; the whole lung may have collapsed or become inflamed (not shown).

  (1) Cancer has spread to nearby lymph nodes on the same side of the chest as the tumor. The lymph nodes with cancer are within the lung or near the bronchus. Also, one or more of the following is true:

  • The tumor is larger than 5 centimeters but not larger than 7 centimeters.
  • Cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus.
  • Cancer has spread to the innermost layer of the membrane that covers the lung.
  • Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus.

  or

  (2) Cancer has not spread to lymph nodes and one or more of the following is true:

  • The tumor is larger than 7 centimeters.
  • Cancer has spread to the main bronchus (and is less than 2 centimeters below where the trachea joins the bronchus), the chest wall, the diaphragm, or the nerve that controls the diaphragm.
  • Cancer has spread to the membrane around the heart or lining the chest wall.
  • The whole lung has collapsed or developed pneumonitis (inflammation of the lung).
  • There are one or more separate tumors in the same lobe of the lung.
  :

Stage IIIA

Stage IIIA is divided into three sections depending on the size of the tumor, where the tumor is found, and which lymph nodes have cancer (if any).

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Stage IIIA non-small cell lung cancer (1). Cancer has spread to certain lymph nodes on the same side of the chest as the primary tumor. The cancer may have spread to (a) the main bronchus; (b) lung lining, chest wall lining, or chest wall; (c) diaphragm; and/or (d) membrane around the heart; and/or (e) there may be one or more separate tumors in the same lobe of the lung. Cancer may have spread to the nerve that controls the diaphragm, and part or all of the lung may have collapsed or become inflamed (not shown).

(1) Cancer has spread to lymph nodes on the same side of the chest as the tumor. The lymph nodes with cancer are near the sternum (chest bone) or where the bronchus enters the lung. Also:

• The tumor may be any size.
• Part of the lung (where the trachea joins the bronchus) or the whole lung may have collapsed or developed pneumonitis (inflammation of the lung).
• There may be one or more separate tumors in the same lobe of the lung.
• Cancer may have spread to any of the following:
  • Main bronchus, but not the area where the trachea joins the bronchus.
  • Chest wall.
  • Diaphragm and the nerve that controls it.
  • Membrane around the lung or lining the chest wall.
  • Membrane around the heart.

or

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Stage IIIA lung cancer (2). Cancer has spread to certain lymph nodes on the same side of the chest as the primary tumor. The cancer may have spread to (a) the main bronchus; (b) the lung lining, chest wall lining, or chest wall; (c) diaphragm; (d) heart and/or membrane around the it; (e) major blood vessels that lead to or from the heart; (f) trachea; (g) esophagus; (h) sternum; and/or (i) carina; and/or (j) there may be one or more separate tumors in any lobe of the same lung. Cancer may have spread to the nerves that control the diaphragm and larynx, and the whole lung may have collapsed or become inflamed (not shown).

(2) Cancer has spread to lymph nodes on the same side of the chest as the tumor. The lymph nodes with cancer are within the lung or near the bronchus. Also:

• The tumor may be any size.
• The whole lung may have collapsed or developed pneumonitis (inflammation of the lung).
• There may be one or more separate tumors in any of the lobes of the lung with cancer.
• Cancer may have spread to any of the following:
  • Main bronchus, but not the area where the trachea joins the bronchus.
  • Chest wall.
  • Diaphragm and the nerve that controls it.
  • Membrane around the lung or lining the chest wall.
  • Heart or the membrane around it.
  • Major blood vessels that lead to or from the heart.
  • Trachea.
  • Esophagus.
  • Nerve that controls the larynx (voice box).
  • Sternum (chest bone) or backbone.
  • Carina (where the trachea joins the bronchi).

or

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Stage IIIA non-small cell lung cancer (3). Cancer has spread to (a) the heart; (b) major blood vessels that lead to or from the heart; (c) trachea; (d) esophagus; (e) sternum; and/or (f) carina. Cancer may have spread to the nerve that controls the larynx (not shown).

(3) Cancer has not spread to the lymph nodes and the tumor may be any size. Cancer has spread to any of the following:

• Heart.
• Major blood vessels that lead to or from the heart.
• Trachea.
• Esophagus.
• Nerve that controls the larynx (voice box).
• Sternum (chest bone) or backbone.
• Carina (where the trachea joins the bronchi).

Stage IIIB

Stage IIIB is divided into two sections depending on the size of the tumor, where the tumor is found, and which lymph nodes have cancer.

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Stage IIIB non-small cell lung cancer (1). Cancer has spread to lymph nodes above the collarbone or on the opposite side of the chest as the primary tumor. The cancer may have spread to (a) the main bronchus; (b) lung lining, chest wall lining, or chest wall; (c) diaphragm; (d) heart or the membrane around it; (e) major blood vessels that lead to or from the heart; (f) trachea; (g) esophagus; (h) sternum; and/or (i) carina; and/or (j) there may be one or more separate tumors in any of the lobes of the lung. Part or all of the lung may have collapsed or become inflamed and cancer may have spread to the backbone and/or the nerves that control the diaphragm and larynx (not shown).

(1) Cancer has spread to lymph nodes above the collarbone or to lymph nodes on the opposite side of the chest as the tumor. Also:

• The tumor may be any size.
• Part of the lung (where the trachea joins the bronchus) or the whole lung may have collapsed or developed pneumonitis (inflammation of the lung).
• There may be one or more separate tumors in any of the lobes of the lung with cancer.
• Cancer may have spread to any of the following:
  • Main bronchus.
  • Chest wall.
  • Diaphragm and the nerve that controls it.
  • Membrane around the lung or lining the chest wall.
  • Heart or the membrane around it.
  • Major blood vessels that lead to or from the heart.
  • Trachea.
  • Esophagus.
  • Nerve that controls the larynx (voice box).
  • Sternum (chest bone) or backbone.
  • Carina (where the trachea joins the bronchi).

or

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Stage IIIB non-small cell lung cancer (2). Cancer has spread to certain lymph nodes on the same side of the chest as the primary tumor and to (a) the heart; (b) major blood vessels that lead to or from the heart; (c) trachea; (d) esophagus; (e) sternum; and/or (f) carina; and/or (g) there may be separate tumors in different lobes of the same lung. Cancer may have spread to the backbone and/or the nerve that controls the larynx (not shown).

(2) Cancer has spread to lymph nodes on the same side of the chest as the tumor. The lymph nodes with cancer are near the sternum (chest bone) or where the bronchus enters the lung. Also:

• The tumor may be any size.
• There may be separate tumors in different lobes of the same lung.
• Cancer has spread to any of the following:
  • Heart.
  • Major blood vessels that lead to or from the heart.
  • Trachea.
  • Esophagus.
  • Nerve that controls the larynx (voice box).
  • Sternum (chest bone) or backbone.
  • Carina (where the trachea joins the bronchi).

Stage IV

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Stage IV non-small cell lung cancer. The cancer has spread to the other lung, and/or to lymph nodes, fluid around the lungs or heart, and/or other places in the body, such as the brain, liver, adrenal glands, kidneys, or bones.

In stage IV, the tumor may be any size and cancer may have spread to lymph nodes. One or more of the following is true:

• There are one or more tumors in both lungs.
• Cancer is found in fluid around the lungs or the heart.
• Cancer has spread to other parts of the body, such as the brain, liver, adrenal glands, kidneys, or bone.

Key Points for This Section

There are different types of treatment for patients with non-small cell lung cancer. Nine types of standard treatment are used: Surgery Radiation therapy Chemotherapy Targeted therapy Laser therapy Photodynamic therapy (PDT) Cryosurgery Electrocautery Watchful waiting New types of treatment are being tested in clinical trials. Chemoprevention New combinations Patients may want to think about taking part in a clinical trial. Patients can enter clinical trials before, during, or after starting their cancer treatment. Follow-up tests may be needed.

There are different types of treatment for patients with non-small cell lung cancer.

Different types of treatments are available for patients with non-small cell lung cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Nine types of standard treatment are used:

Surgery

Four types of surgery are used:

• Wedge resection: Surgery to remove a tumor and some of the normal tissue around it. When a slightly larger amount of tissue is taken, it is called a segmental resection.
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  Wedge resection of the lung. Part of the lung lobe containing the cancer and a small amount of healthy tissue around it is removed.
• Lobectomy: Surgery to remove a whole lobe (section) of the lung.
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  Lobectomy. A lobe of the lung is removed.
• Pneumonectomy: Surgery to remove one whole lung.
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  Pneumonectomy. The whole lung is removed.
• Sleeve resection: Surgery to remove part of the bronchus.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

Radiosurgery is a method of delivering radiation directly to the tumor with little damage to healthy tissue. It does not involve surgery and may be used to treat certain tumors in patients who cannot have surgery.

The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Non-Small Cell Lung Cancer ²⁶ for more information.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodies and tyrosine kinase inhibitors are two types of targeted therapy being used in the treatment of non-small cell lung cancer.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

Monoclonal antibodies used to treat non-small cell lung cancer include bevacizumab and cetuximab. Bevacizumab binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. Cetuximab binds to epidermal growth factor receptor (EGFR) and works to stop cancer cells from growing and dividing.

Tyrosine kinase inhibitors are targeted therapy drugs that block signals needed for tumors to grow. Tyrosine kinase inhibitors may be used with other anticancer drugs as adjuvant therapy.

Tyrosine kinase inhibitors used to treat non-small cell lung cancer include erlotinib and gefitinib. They are types of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.

See Drugs Approved for Non-Small Cell Lung Cancer ²⁶ for more information.

Laser therapy

Laser therapy is a cancer treatment that uses a laser beam (a narrow beam of intense light) to kill cancer cells.

Photodynamic therapy (PDT)

Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiberoptic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells. Photodynamic therapy causes little damage to healthy tissue. It is used mainly to treat tumors on or just under the skin or in the lining of internal organs.

Cryosurgery

Cryosurgery is a treatment that uses an instrument to freeze and destroy abnormal tissue, such as carcinoma in situ. This type of treatment is also called cryotherapy.

Electrocautery

Electrocautery is a treatment that uses a probe or needle heated by an electric current to destroy abnormal tissue.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change. This may be done in certain rare cases of non-small cell lung cancer.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site ⁹.

Chemoprevention

Chemoprevention is the use of drugs, vitamins, or other substances to reduce the risk of developing cancer or to reduce the risk cancer will recur (come back).

New combinations

New combinations of treatments are being studied in clinical trials.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.