Key Points for This Section

After melanoma has been diagnosed, tests are done to find out if cancer cells have spread within the skin or to other parts of the body. There are three ways that cancer spreads in the body. The method used to stage melanoma is based mainly on the thickness of the tumor and whether cancer has spread to lymph nodes or other parts of the body. The following stages are used for melanoma: Stage 0 (Melanoma in Situ) Stage I Stage II Stage III Stage IV

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

The process used to find out whether cancer has spread within the skin 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. Talk with your doctor about what the stage of your cancer is.

The following tests and procedures may be used in the staging process:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Wide local excision: A surgical procedure to remove some of the normal tissue around the area where abnormal tissue was removed. A pathologist then looks at the tissue under a microscope to check for cancer cells.
• Lymph node mapping and sentinel lymph node biopsy: Procedures in which a radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through lymph ducts to the sentinel node or nodes (the first lymph node or nodes where cancer cells are likely to have spread). The surgeon removes only the nodes with the radioactive substance or dye. A pathologist views a sample of tissue under a microscope to check for cancer cells. If no cancer cells are found, it may not be necessary to remove more nodes.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, 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. For melanoma, pictures may be taken of the chest, abdomen, and pelvis.
• 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. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• 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.
• Laboratory tests: Medical procedures that test samples of tissue, blood, urine, or other substances in the body. These tests help to diagnose disease, plan and check treatment, or monitor the disease over time.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. For melanoma, the blood is checked for an enzyme called lactate dehydrogenase (LDH). LDH levels that are higher than normal may be a sign of melanoma.

The results of these tests are viewed together with the results of the tumor biopsy to find out the stage of the melanoma.

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 method used to stage melanoma is based mainly on the thickness of the tumor and whether cancer has spread to lymph nodes or other parts of the body.

The staging system is based on the following:

• The thickness of the tumor. The thickness is described using the Breslow scale.
• Whether the tumor is ulcerated (has broken the skin).
• Whether the tumor has spread to the lymph nodes and if the lymph nodes are joined together (matted).
• Whether the tumor has spread to other parts of the body.

The following stages are used for melanoma:

Stage 0 (Melanoma in Situ)

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Stage 0 melanoma in situ. Abnormal melanocytes are in the epidermis (outer layer of the skin).

In stage 0, abnormal melanocytes are found in the epidermis. These abnormal melanocytes may become cancer and spread into nearby normal tissue. Stage 0 is also called melanoma in situ.

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Millimeters (mm). A sharp pencil point is about 1 mm, a new crayon point is about 2 mm, and a new pencil eraser is about 5 mm.

Stage I

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Stage I melanoma. In stage IA, the tumor is not more than 1 millimeter thick, with no ulceration (break in the skin). In stage IB, the tumor is either not more than 1 millimeter thick, with ulceration, OR more than 1 but not more than 2 millimeters thick, with no ulceration. Skin thickness is different on different parts of the body.

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

• Stage IA: In stage IA, the tumor is not more than 1 millimeter thick, with no ulceration.
• Stage IB: In stage IB, the tumor is either:
  • not more than 1 millimeter thick and it has ulceration; or
  • more than 1 but not more than 2 millimeters thick, with no ulceration.

Stage II

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Stage II melanoma. In stage IIA, the tumor is either more than 1 but not more than 2 millimeters thick, with ulceration (break in the skin), OR it is more than 2 but not more than 4 millimeters thick, with no ulceration. In stage IIB, the tumor is either more than 2 but not more than 4 millimeters thick, with ulceration, OR it is more than 4 millimeters thick, with no ulceration. In stage IIC, the tumor is more than 4 millimeters thick, with ulceration. Skin thickness is different on different parts of the body.

Stage II is divided into stages IIA, IIB, and IIC.

• Stage IIA: In stage IIA, the tumor is either:
  • more than 1 but not more than 2 millimeters thick, with ulceration; or
  • more than 2 but not more than 4 millimeters thick, with no ulceration.
• Stage IIB: In stage IIB, the tumor is either:
  • more than 2 but not more than 4 millimeters thick, with ulceration; or
  • more than 4 millimeters thick, with no ulceration.
• Stage IIC: In stage IIC, the tumor is more than 4 millimeters thick, with ulceration.

Stage III

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Stage III melanoma. The tumor may be any thickness, with or without ulceration (a break in the skin), and (a) cancer has spread to one or more lymph nodes; (b) lymph nodes with cancer may be joined together (matted); (c) cancer may be in a lymph vessel between the primary tumor and nearby lymph nodes; and/or (d) very small tumors may be found on or under the skin, not more than 2 centimeters away from the primary tumor.

In stage III, the tumor may be any thickness, with or without ulceration. One or more of the following is true:

• Cancer has spread to one or more lymph nodes.
• Lymph nodes may be joined together (matted).
• Cancer may be in a lymph vessel between the primary tumor and nearby lymph nodes.
• Very small tumors may be found on or under the skin, not more than 2 centimeters away from where the cancer first started.

Stage IV

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Stage IV melanoma. The tumor has spread to other parts of the body.

In stage IV, the cancer has spread to other places in the body, such as the lung, liver, brain, bone, soft tissue, or gastrointestinal (GI) tract. Cancer may have spread to places in the skin far away from where it first started.

Key Points for This Section

There are different types of treatment for patients with melanoma. Five types of standard treatment are used: Surgery Chemotherapy Radiation therapy Biologic therapy Targeted therapy New types of treatment are being tested in clinical trials. 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 melanoma.

Different types of treatment are available for patients with melanoma. 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.

Five types of standard treatment are used:

Surgery

Surgery to remove the tumor is the primary treatment of all stages of melanoma. The doctor may remove the tumor using the following operations:

• Wide local excision: Surgery to remove the melanoma and some of the normal tissue around it. Some of the lymph nodes may also be removed.
• Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and a sample of tissue is checked under a microscope for signs of cancer.
• Sentinel lymph node biopsy: The removal of the sentinel lymph node (the first lymph node the cancer is likely to spread to from the tumor) during surgery. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes.
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  Sentinel lymph node biopsy of the skin. A radioactive substance and/or blue dye is injected near the tumor (first panel). The injected material is detected visually and/or with a probe that detects radioactivity (middle panel). The sentinel nodes (the first lymph nodes to take up the material) are removed and checked for cancer cells (last panel).

Skin grafting (taking skin from another part of the body to replace the skin that is removed) may be done to cover the wound caused by surgery.

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

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).

One type of regional chemotherapy is hyperthermic isolated limb perfusion. With this method, anticancer drugs go directly to the arm or leg the cancer is in. The flow of blood to and from the limb is temporarily stopped with a tourniquet. A warm solution with the anticancer drugs is put directly into the blood of the limb. This gives a high dose of drugs to the area where the cancer is.

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

See Drugs Approved for Melanoma ¹³ for more information.

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

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Interferon and interleukin-2 (IL-2) are types of biologic therapy used to treat melanoma. Interferon affects the division of cancer cells and can slow tumor growth. IL-2 boosts the growth and activity of many immune cells, especially lymphocytes (a type of white blood cell). Lymphocytes can attack and kill cancer cells.

Tumor necrosis factor (TNF) therapy is a type of biologic therapy used with other treatments for melanoma. TNF is a protein made by white blood cells in response to an antigen or infection. Tumor necrosis factor can be made in the laboratory and used as a treatment to kill cancer cells.

See Drugs Approved for Melanoma ¹³ 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. The following types of targeted therapy are being used in the treatment of melanoma:

• Monoclonal antibody therapy: 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 may be used with chemotherapy as adjuvant therapy. Ipilimumab is a monoclonal antibody used to treat melanoma.
• Signal transduction inhibitors: A substance that blocks signals that are passed from one molecule to another inside a cell. Blocking these signals may kill cancer cells. Vemurafenib is a signal transduction inhibitor used to treat advanced melanoma or tumors that cannot be removed by surgery.
• Oncolytic virus therapy: A type of targeted therapy that is being studied in the treatment of melanoma. Oncolytic virus therapy uses a virus that infects and breaks down cancer cells but not normal cells. Radiation therapy or chemotherapy may be given after oncolytic virus therapy to kill more cancer cells.
• Angiogenesis inhibitors: A type of targeted therapy that is being studied in the treatment of melanoma. Angiogenesis inhibitors block the growth of new blood vessels. In cancer treatment, they may be given to prevent the growth of new blood vessels that tumors need to grow.

See Drugs Approved for Melanoma ¹³ for more information.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site ¹⁴

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.