Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma may also appear as a new mole. It may be black, abnormal, or "ugly looking."

Thinking of "ABCDE" can help you remember what to watch for:

• Asymmetry - the shape of one half does not match the other
• Border - the edges are ragged, blurred or irregular
• Color - the color is uneven and may include shades of black, brown and tan
• Diameter - there is a change in size, usually an increase
• Evolving - the mole has changed over the past few weeks or months

Surgery is the first treatment of all stages of melanoma. Other treatments include chemotherapy and radiation, biologic, and targeted therapies. Biologic therapy boosts your body's own ability to fight cancer. Targeted therapy uses substances that attack cancer cells without harming normal cells.

• The skin is a vital organ that covers the entire outside of the body, forming a protective barrier against pathogens and injuries from the environment. The skin is the body's largest organ; covering the entire outside of the body, it is about 2 mm thick and weighs approximately six pounds.
• The skin helps regulate body temperature, gathers sensory information from the environment, stores water, fat, and vitamin D, and plays a role in the immune system protecting us from disease.
• The color, thickness and texture of skin vary over the body. There are two general types of skin; thin and hairy, which is more prevalent on the body, and thick and hairless, which is found on parts of the body that are used heavily and endure a large amount friction, like the palms of the hands or the soles of the feet.
• Basically, the skin is comprised of two layers that cover a third fatty layer. These three layers differ in function, thickness, and strength.
• The outer layer is called the epidermis; it is a tough protective layer that is made up of five sublayers that work together to continually rebuild the surface of the skin.
• The second layer of the skin (located under the epidermis) is called the dermis; it contains collagen and elastin, blood vessels, lymph vessels, nerve endings, sweat glands, sebaceous (oil) glands, and hair follicles.
• The innermost layer of the skin is a fatty layer of subcutaneous tissue consisting of a network of fat and collagen cells and is known as the subcutis or hypodermis.
• The basal cell layer of the epidermis contains melanocytes. Melanoma develops when melanocytes undergo malignant transformation.
• The stratum corneum is the outermost layer of the epidermis, and is made up of thin layers of continually shedding, dead keratinocytes. The stratum corneum is also known as the "horny layer," because its cells are toughened like an animal's horn. As the outermost cells age and wear down, they are replaced by new layers of strong, long-wearing cells.
• Regional lymph nodes for melanoma of the skin vary by primary site, and are bilateral or contralateral for the primary sites of head, neck and trunk.

Melanoma is a disease in which malignant (cancer) cells form in melanocytes (cells that color the skin).

The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. Skin also helps control body temperature and stores water, fat, and vitamin D. The skin has several layers, but the two main layers are the epidermis (upper or outer layer) and the dermis (lower or inner layer). Skin cancer begins in the epidermis, which is made up of three kinds of cells:

• Squamous cells: Thin, flat cells that form the top layer of the epidermis.
• Basal cells: Round cells under the squamous cells.
• Melanocytes: Cells that make melanin and are found in the lower part of the epidermis. Melanin is the pigment that gives skin its natural color. When skin is exposed to the sun or artificial light, melanocytes make more pigment and cause the skin to darken.

From 2010 to 2019, the number of new cases of melanoma increased by about 1% per year, though the number of deaths each year from melanoma continues to decrease. Melanoma is most common in adults, but it is sometimes found in children and adolescents.

There are different types of cancer that start in the skin.

There are two main forms of skin cancer: melanoma and nonmelanoma.

Melanoma is a rare form of skin cancer. It is more likely to invade nearby tissues and spread to other parts of the body than other types of skin cancer. When melanoma starts in the skin, it is called cutaneous melanoma. Melanoma may also occur in mucous membranes (thin, moist layers of tissue that cover surfaces such as the lips). This summary is about cutaneous (skin) melanoma and melanoma that affects the mucous membranes.

The most common types of skin cancer are basal cell carcinoma and squamous cell carcinoma. They are nonmelanoma skin cancers. Nonmelanoma skin cancers rarely spread to other parts of the body.

Melanoma can occur anywhere on the skin.

In men,melanoma is often found on the trunk (the area from the shoulders to the hips)or the head and neck. In women, melanoma forms most often on the arms and legs.

When melanoma occurs in the eye, it is called intraocular or ocular melanoma.

The appearance and growth of melanoma will differ depending on the morphologic type:

Superficial spreading melanoma

Superficial spreading melanoma is the most common type of melanoma, representing approximately 70% of all melanomas. This melanoma goes through a prolonged (years) horizontal growth pattern on the skin before becoming invasive. Superficial spreading melanomas are flat or slightly elevated brown lesions with black, blue or pink discoloration which are typically greater than 6 mm in diameter and have irregular asymmetric borders. These melanomas may be found on any body surface, especially the head, neck, and trunk of males and the lower extremities of females.

Nodular melanoma

Nodular melanoma represents about 15% of all melanomas and becomes invasive soon after first appearing. A nodular melanoma typically looks similar to a blood vessel growth, presenting as a dark brown-to-black papule or dome-shaped nodule; however, 5% of nodular melanomas are amelanotic (see below). These melanomas are commonly found on all body surfaces, especially the trunk of males.

Acral-lentiginous melanoma

Acral-lentiginous melanoma represents approximately 8% of all melanomas and is the most common melanoma in dark-skinned people. Acral-lentiginous melanomas represent up to 70% of melanomas in blacks and up to 46% in Asians. This type can occur on the palms, soles and nail beds (subungual). Like nodular melanoma, acral-lentiginous melanoma is extremely aggressive, with rapid progression from the horizontal to vertical growth phase.

Lentigo maligna melanoma

Lentigo maligna melanoma accounts for approximately 5% of melanomas. Lentigo maligna melanomas are typically found on sun-exposed areas of the skin in adults and are clearly linked to exposure to the sun. Often many years pass between the first appearance of this melanoma and when it becomes invasive. The precursor lesion is typically greater than 3 cm in diameter, and, upon becoming invasive, develops a dark brown-to-black color or raised blue-black nodule.

Amelanotic melanoma

Amelanotic melanoma is rare and challenging to diagnose because there is an absence of pigmentation (color). However, hallmark traits of melanoma, such as changes in size, borders, and symmetry, are present in this melanoma.

Desmoplastic melanoma

Desmoplastic melanoma is rare, representing approximately 1.7% of all melanomas. This type of melanoma is locally aggressive and difficult to diagnose both clinically and microscopically. The majority of these tumors occur on the head and neck of elderly patients and one half are amelanotic.

Unusual moles, exposure to sunlight, and health history can affect the risk of melanoma.

Anything that increases a person's chance of getting a disease is called a risk factor. Not every person with one or more of these risk factors will develop melanoma, and it will develop in some people who don't have any known risk factors. Talk with your doctor if you think you may be at risk.

Risk factors for melanoma include the following:

• Having a fair complexion, which includes the following:
  • Fair skin that freckles and burns easily, does not tan, or tans poorly.
  • Blue or green or other light-colored eyes.
  • Red or blond hair.
• Being exposed to natural sunlight or artificial sunlight (such as from tanning beds).
• Being exposed to certain factors in the environment (in the air, your home or workplace, and your food and water). Some of the environmental risk factors for melanoma are radiation, solvents, vinyl chloride, and PCBs.
• Having a history of many blistering sunburns, especially as a child or teenager.
• Having several large or many small moles.
• Having a family history of unusual moles (atypical nevus syndrome).
• Having a family or personal history of melanoma.
• Being White.
• Having a weakened immune system.
• Having certain changes in the genes that are linked to melanoma.

Being White or having a fair complexion increases the risk of melanoma, but anyone can have melanoma, including people with dark skin.

Signs of melanoma include a change in the way a mole or pigmented area looks.

These and other signs and symptoms may be caused by melanoma or by other conditions. Check with your doctor if you have any of the following:

• A mole that:
  • changes in size, shape, or color.
  • has irregular edges or borders.
  • is more than one color.
  • is asymmetrical (if the mole is divided in half, the 2 halves are different in size or shape).
  • itches.
  • oozes, bleeds, or is ulcerated (a hole forms in the skin when the top layer of cells breaks down and the tissue below shows through).
• A change in pigmented (colored) skin.
• Satellite moles (new moles that grow near an existing mole).

A common mole (nevus) is a small growth on the skin that is usually pink, tan, or brown and has a distinct edge.

A dysplastic nevus is often large and does not have a round or oval shape or a distinct edge. It may have a mixture of pink, tan, or brown shades. People who have many dysplastic nevi have a greater chance than others of developing melanoma, a dangerous form of skin cancer. However, most dysplastic nevi do not turn into melanoma.

If the color, size, shape, or height of a mole changes or if it starts to itch, bleed, or ooze, people should tell their doctor. People should also tell their doctor if they see a new mole that doesn't look like their other moles.

The photos below show the difference between common moles and dysplastic nevi.

Photos of Moles

Melanoma is a type of cancer that begins in melanocytes (cells that make the pigment melanin). Below are photos of melanoma that formed on the skin. Melanoma can also start in the eye, the intestines, or other areas of the body with pigmented tissues.

Often the first sign of melanoma is a change in the shape, color, size, or feel of an existing mole. However, melanoma may also appear as a new mole. People should tell their doctor if they notice any changes on the skin. The only way to diagnose melanoma is to remove tissue and check it for cancer cells.

Thinking of "ABCDE" can help you remember what to look for:

• Asymmetry: The shape of one half does not match the other half.
• Border that is irregular: The edges are often ragged, notched, or blurred in outline. The pigment may spread into the surrounding skin.
• Color that is uneven: Shades of black, brown, and tan may be present. Areas of white, gray, red, pink, or blue may also be seen.
• Diameter: There is a change in size, usually an increase. Melanomas can be tiny, but most are larger than the size of a pea (larger than 6 millimeters or about 1/4 inch).
• Evolving: The mole has changed over the past few weeks or months.

Melanomas can vary greatly in how they look. Many show all of the ABCDE features. However, some may show changes or abnormal areas in only one or two of the ABCDE features.

In more advanced melanoma, the texture of the mole may change. The skin on the surface may break down and look scraped. It may become hard or lumpy. The surface may ooze or bleed. Sometimes the melanoma is itchy, tender, or painful.

Photos of Melanoma

Tests that examine the skin are used to diagnose melanoma.

In addition to asking about your personal and family health history and doing a physical exam, your doctor may perform the following tests and procedures to find and diagnose melanoma:

• Skin exam: A doctor or nurse checks the skin for moles, birthmarks, or other pigmented areas that look abnormal in color, size, shape, or texture.
• Biopsy: A procedure to remove the abnormal tissue and a small amount of normal tissue around it. A pathologist looks at the tissue under a microscope to check for cancer cells. It can be hard to tell the difference between a colored mole and an early melanoma lesion. Patients may want to have the sample of tissue checked by a second pathologist. If the abnormal mole or lesion is cancer, the sample of tissue may also be tested for certain gene changes.

  There are four main types of skin biopsies. The type of biopsy done depends on where the abnormal area formed and the size of the area.

  • Shave biopsy: A sterile razor blade is used to “shave-off” the abnormal-looking growth.
  • Punch biopsy: A special instrument called a punch or a trephine is used to remove a circle of tissue from the abnormal-looking growth.

  • Incisional biopsy: A scalpel is used to remove part of a growth.
  • Excisional biopsy: A scalpel is used to remove the entire growth.

After melanoma has been diagnosed, tests may be 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.

For melanoma that is not likely to spread to other parts of the body or recur, more tests may not be needed. For melanoma that is likely to spread to other parts of the body or recur, the following tests and procedures may be done after surgery to remove the melanoma:

• Lymph node mapping and sentinel lymph node biopsy: The removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node in a group of lymph nodes to receive lymphatic drainage from the primary tumor. It is the first lymph node the cancer is likely to spread to from the primary tumor. 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. Sometimes, a sentinel lymph node is found in more than one group of nodes.
• 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 neck, chest, abdomen, and pelvis.
• 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.
• MRI (magnetic resonance imaging) with gadolinium: 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. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues, such as lymph nodes, or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.
• 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). High LDH levels may predict a poor response to treatment in patients with metastatic disease.

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

KEY POINTS

• After melanoma has been diagnosed, tests may be 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.
• Cancer may spread from where it began to other parts of the body.
• The stage of melanoma depends on the thickness of the tumor, whether cancer has spread to lymph nodes or other parts of the body, and other factors.
• The following stages are used for melanoma:
  • Stage 0 (Melanoma in Situ)
  • Stage I
  • Stage II
  • Stage III
  • Stage IV
• Melanoma can recur (come back) after it has been treated.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if melanoma spreads to the lung, the cancer cells in the lung are actually melanoma cells. The disease is metastatic melanoma, not lung cancer.

The stage of melanoma depends on the thickness of the tumor, whether cancer has spread to lymph nodes or other parts of the body, and other factors.

To find out the stage of melanoma, the tumor is completely removed and nearby lymph nodes are checked for signs of cancer. The stage of the cancer is used to determine which treatment is best. Check with your doctor to find out which stage of cancer you have.

The stage of melanoma depends on the following:

• The thickness of the tumor. The thickness of the tumor is measured from the surface of the skin to the deepest part of the tumor.

• Whether the tumor is ulcerated (has broken through the skin).

• Whether cancer is found in lymph nodes by a physical exam, imaging tests, or a sentinel lymph node biopsy.

• Whether the lymph nodes are matted (joined together).

• Whether there are:
  • Satellite tumors: Small groups of tumor cells that have spread within 2 centimeters of the primary tumor.
  • Microsatellite tumors: Small groups of tumor cells that have spread to an area right beside or below the primary tumor.
  • In-transit metastases: Tumors that have spread to lymph vessels in the skin more than 2 centimeters away from the primary tumor, but not to the lymph nodes.

• Whether the cancer has spread to other parts of the body, such as the lung, liver, brain, soft tissue (including muscle), gastrointestinal tract, and/or distant lymph nodes. Cancer may have spread to places in the skin far away from where it first formed.

The following stages are used for melanoma:

Stage 0 (Melanoma in Situ)

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.

Stage I

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

• Stage IA: The tumor is not more than 1 millimeter thick, with or without ulceration.
• Stage IB: The tumor is more than 1 but not more than 2 millimeters thick, without ulceration.

Stage II

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

• 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, without ulceration.

• Stage IIB: The tumor is either:
  • more than 2 but not more than 4 millimeters thick, with ulceration; or
  • more than 4 millimeters thick, without ulceration.

• Stage IIC: The tumor is more than 4 millimeters thick, with ulceration.

Stage III

Stage III is divided into stages IIIA, IIIB, IIIC, and IIID.

• Stage IIIA: The tumor is not more than 1 millimeter thick, with ulceration, or not more than 2 millimeters thick, without ulceration. Cancer is found in 1 to 3 lymph nodes by sentinel lymph node biopsy.
• Stage IIIB:
  • (1) It is not known where the cancer began or the primary tumor can no longer be seen, and one of the following is true:
    • cancer is found in 1 lymph node by physical exam or imaging tests; or
    • there are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.

      or

  • (2) The tumor is not more than 1 millimeter thick, with ulceration, or not more than 2 millimeters thick, without ulceration, and one of the following is true:
    • cancer is found in 1 to 3 lymph nodes by physical exam or imaging tests; or
    • there are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.

      or

  • (3) The tumor is more than 1 but not more than 2 millimeters thick, with ulceration, or more than 2 but not more than 4 millimeters thick, without ulceration, and one of the following is true:
    • cancer is found in 1 to 3 lymph nodes; or
    • there are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.
• Stage IIIC:
  • (1) It is not known where the cancer began, or the primary tumor can no longer be seen. Cancer is found:
    • in 2 or 3 lymph nodes; or
    • in 1 lymph node and there are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin; or
    • in 4 or more lymph nodes, or in any number of lymph nodes that are matted together; or
    • in 2 or more lymph nodes and/or in any number of lymph nodes that are matted together. There are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.

      or

  • (2) The tumor is not more than 2 millimeters thick, with or without ulceration, or not more than 4 millimeters thick, without ulceration. Cancer is found:
    • in 1 lymph node and there are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin; or
    • in 4 or more lymph nodes, or in any number of lymph nodes that are matted together; or
    • in 2 or more lymph nodes and/or in any number of lymph nodes that are matted together. There are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.

      or

  • (3) The tumor is more than 2 but not more than 4 millimeters thick, with ulceration, or more than 4 millimeters thick, without ulceration. Cancer is found in 1 or more lymph nodes and/or in any number of lymph nodes that are matted together. There may be microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.

    or

  • (4) The tumor is more than 4 millimeters thick, with ulceration. Cancer is found in 1 or more lymph nodes and/or there are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.
• Stage IIID: The tumor is more than 4 millimeters thick, with ulceration. Cancer is found:
  • in 4 or more lymph nodes, or in any number of lymph nodes that are matted together; or
  • in 2 or more lymph nodes and/or in any number of lymph nodes that are matted together. There are microsatellite tumors, satellite tumors, and/or in-transit metastases on or under the skin.

Stage IV

In stage IV, the cancer has spread to other parts of the body, such as the lung, liver, brain, spinal cord, bone, soft tissue (including muscle), gastrointestinal (GI) tract, and/or distant lymph nodes. Cancer may have spread to places in the skin far away from where it first started.

Melanoma can recur (come back) after it has been treated.

The cancer may come back in the area where it first started or in other parts of the body, such as the lungs or liver.

Treatment Option Overview

KEY POINTS

• There are different types of treatment for patients with melanoma.
• The following types of treatment are used:
  • Surgery
  • Chemotherapy
  • Radiation therapy
  • Immunotherapy
  • Targeted therapy
• New types of treatment are being tested in clinical trials.
  • Vaccine therapy
• Treatment for melanoma may cause side effects.
• 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.

The following types of treatment are used:

Surgery

Surgery to remove the tumor is the primary treatment of all stages of melanoma. A wide local excision is used to remove the melanoma and some of the normal tissue around it. 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.

Sometimes, it is important to know whether cancer has spread to the lymph nodes. Lymph node mapping and sentinel lymph node biopsy are done to check for cancer in the sentinel lymph node (the first lymph node in a group of lymph nodes to receive lymphatic drainage from the primary tumor). It is the first lymph node the cancer is likely to spread to from the primary tumor. 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 found, more lymph nodes will be removed and tissue samples will be checked for signs of cancer. This is called a lymphadenectomy. Sometimes, a sentinel lymph node is found in more than one group of nodes.

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

Surgery to remove cancer that has spread to the lymph nodes, lung, gastrointestinal (GI) tract, bone, or brain may be done to improve the patient’s quality of life by controlling symptoms.

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 drug 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.

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. External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer. External radiation therapy is used to treat melanoma and may also be used as palliative therapy to relieve symptoms and improve quality of life.

Immunotherapy

Immunotherapy 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.

The following types of immunotherapy are being used in the treatment of melanoma:

• Immune checkpoint inhibitor therapy: Immune checkpoint inhibitors block proteins called checkpoints that are made by some types of immune system cells, such as T cells, and some cancer cells. These checkpoints help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells. When these checkpoints are blocked, T cells can kill cancer cells better. They are used to treat some patients with advanced melanoma or tumors that cannot be removed by surgery.

  There are two types of immune checkpoint inhibitor therapy:

  • CTLA-4 inhibitor therapy: CTLA-4 is a protein on the surface of T cells that helps keep the body’s immune responses in check. When CTLA-4 attaches to another protein called B7 on a cancer cell, it stops the T cell from killing the cancer cell. CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill cancer cells. Ipilimumab is a type of CTLA-4 inhibitor.

  • PD-1 and PD-L1 inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. PD-L1 is a protein found on some types of cancer cells. When PD-1 attaches to PD-L1, it stops the T cell from killing the cancer cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. This allows the T cells to kill cancer cells. Pembrolizumab and nivolumab are types of PD-1 inhibitors. Atezolizumab is a PD-L1 inhibitor that is being studied in combination with cobimetinib and vemurafenib (types of targeted therapy).

• Interleukin-2 (IL-2): 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: TNF is a protein made by white blood cells in response to an antigen or infection. TNF is made in the laboratory and used as a treatment to kill cancer cells. It is being studied in the treatment of melanoma.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. The following types of targeted therapy are used or being studied in the treatment of melanoma:

• Signal transduction inhibitor therapy: Signal transduction inhibitors block signals that are passed from one molecule to another inside a cell. Blocking these signals may kill cancer cells. They are used to treat some patients with advanced melanoma or tumors that cannot be removed by surgery. Signal transduction inhibitors include:
  • BRAF inhibitors (dabrafenib, vemurafenib, encorafenib) that block the activity of proteins made by mutant BRAF genes; and
  • MEK inhibitors (trametinib, cobimetinib, binimetinib) that block proteins called MEK1 and MEK2 which affect the growth and survival of cancer cells.

  Combinations of BRAF inhibitors and MEK inhibitors used to treat melanoma include:

  • Dabrafenib plus trametinib.
  • Vemurafenib plus cobimetinib.
  • Encorafenib plus binimetinib.
• Oncolytic virus therapy: A type of targeted therapy that is used 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. Talimogene laherparepvec is a type of oncolytic virus therapy made with a form of the herpesvirus that has been changed in the laboratory. It is injected directly into tumors in the skin and lymph nodes.
• 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.

For patients with melanoma who are at high risk of the cancer coming back after it has been treated, there is a growing number of adjuvant therapy options which may be given to lower the risk. Adjuvant therapy may include immune checkpoint inhibitors and combinations of signal transduction inhibitors.

New targeted therapies and combinations of therapies are being studied in the treatment of melanoma.

Vaccine therapy

Vaccine therapy is a cancer treatment that uses a substance or group of substances to stimulate the immune system to find the tumor and kill it. Vaccine therapy is being studied in the treatment of stage III melanoma that can be removed by surgery.

Treatment for melanoma may cause side effects.

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. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

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.

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.

Treatment of Stage 0 (Melanoma in Situ)

Treatment of stage 0 is usually surgery to remove the area of abnormal cells and a small amount of normal tissue around it.

Treatment of Stage I Melanoma

Treatment of stage I melanoma may include the following:

• Surgery to remove the tumor and some of the normal tissue around it. Sometimes lymph node mapping and removal of lymph nodes is also done.
• A clinical trial of new ways to find cancer cells in the lymph nodes.

Treatment of Stage II Melanoma

Treatment of stage II melanoma may include the following:

• Surgery to remove the tumor and some of the normal tissue around it. Sometimes lymph node mapping and sentinel lymph node biopsy are done to check for cancer in the lymph nodes at the same time as the surgery to remove the tumor. If cancer is found in the sentinel lymph node, more lymph nodes may be removed.
• A clinical trial of new types of treatment to be used after surgery.

Treatment of Stage III Melanoma That Can Be Removed By Surgery

Treatment of stage III melanoma that can be removed by surgery may include the following:

• Surgery to remove the tumor and some of the normal tissue around it. Skin grafting may be done to cover the wound caused by surgery. Sometimes lymph node mapping and sentinel lymph node biopsy are done to check for cancer in the lymph nodes at the same time as the surgery to remove the tumor. If cancer is found in the sentinel lymph node, more lymph nodes may be removed.
• Surgery followed by immunotherapy with immune checkpoint inhibitors (nivolumab, pembrolizumab, or ipilimumab) if there is a high risk that the cancer will come back.
• Surgery followed by targeted therapy with signal transduction inhibitors (dabrafenib and trametinib) if there is a high risk that the cancer will come back.
• A clinical trial of immunotherapy with or without vaccine therapy.
• A clinical trial of surgery followed by therapies that target specific gene changes.

Treatment of Stage III Melanoma That Cannot Be Removed By Surgery, Stage IV Melanoma, and Recurrent Melanoma

Treatment of stage III melanoma that cannot be removed by surgery, stage IV melanoma, and recurrent melanoma may include the following:

• Oncolytic virus therapy (talimogene laherparepvec) injected into the tumor.
• Immunotherapy with ipilimumab, pembrolizumab, nivolumab, or interleukin-2 (IL-2). Sometimes ipilimumab and nivolumab are given together.
• Targeted therapy with signal transduction inhibitors (dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib, binimetinib). These may be given alone or in combination.
• Chemotherapy.
• Palliative therapy to relieve symptoms and improve the quality of life. This may include:
  • Surgery to remove lymph nodes or tumors in the lung, gastrointestinal (GI) tract, bone, or brain.
  • Radiation therapy to the brain, spinal cord, or bone.

Treatments that are being studied in clinical trials for stage III melanoma that cannot be removed by surgery, stage IV melanoma, and recurrent melanoma include the following:

• Immunotherapy alone or in combination with other therapies such as targeted therapy.
• For melanoma that has spread to the brain, immunotherapy with nivolumab plus ipilimumab.
• Targeted therapy, such as signal transduction inhibitors, angiogenesis inhibitors, oncolytic virus therapy, or drugs that target certain gene mutations. These may be given alone or in combination.
• Surgery to remove all known cancer.
• Regional chemotherapy (hyperthermic isolated limb perfusion). Some patients may also have immunotherapy with tumor necrosis factor.
• Systemic chemotherapy.