Melanoma

This section outlines treatments that are the standard of care (the best proven treatments available) for this specific type of cancer. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study to test a new treatment to evaluate whether it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, see the Clinical Trials and Current Research sections.

Treatment overview

In cancer care, different types of doctors often work together to create a patient's overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. For a person with melanoma, that team may include a surgical oncologist (a doctor who specializes in treating cancer with surgery), a medical oncologist (a doctor who specializes in treating cancer with medication), a radiation oncologist (a doctor who specializes in giving radiation therapy to treat cancer), a dermatologist (a doctor who specializes in diseases and conditions of the skin), and a pathologist (see Diagnosis).

Treatment recommendations depend on the thickness of the primary melanoma, whether the cancer has spread and the stage of the melanoma. Descriptions of the most common treatment options for melanoma are listed below, classified by stage of melanoma:

Stage I and Stage II (confined to the skin; called local), Stage III (spread to lymph nodes or in-transits, or satellites; called regional), and Stage IV (spread to another part of the body; called metastatic.). Other factors included in treatment decisionmaking include possible side effects, as well as the patient's preferences and overall health. Learn more about making treatment decisions.

Treatment options for local and regional melanoma (Stage I, Stage II, and Stage III)

Surgery

Surgery is the removal of the tumor and surrounding tissue during an operation. It is the primary treatment for people with local melanoma and most patients with regional melanoma, and sometimes it is the only treatment necessary. Other times, people will need additional treatment following surgery, called adjuvant treatment. In recommending a specific treatment plan, doctors will consider the stage of the disease, as well as the patient's individual risk of recurrence (the chance the cancer will return following initial treatment).

Types of surgery for local and regional melanoma are:

Wide excision. The primary treatment for melanoma is excision (surgical removal) of the primary melanoma on the skin. The extent of the surgery depends on the thickness of the melanoma. Most melanomas are found when they are thin (less than 1.0 mm), when outpatient surgery is often the only treatment needed. A doctor removes the tumor, underlying subcutaneous (under the skin) tissue, and some surrounding healthy tissue (called a margin) to ensure that no cancer cells remain. This surgery is called a wide excision.

If the melanoma is staged as in situ (Stage 0), the doctor may remove a margin of skin between 0.5 cm and 1.0 cm. The width of the margin increases with the thickness of the melanoma, ranging from a 1.0 cm margin for melanoma measuring 1.0 mm or thinner to a 2.0 cm margin for melanoma measuring between 2.01 mm and 4.0 mm in thickness. The recommended margin for a melanoma thicker than 4.0 mm is at least 2.0 cm.

Depending on the site and extent of the surgery, a skin graft (a procedure using the skin from another part of the body to both close the wound and reduce scarring) may be necessary.

Lymphatic mapping and sentinel lymph node biopsy. This surgical procedure helps determine whether the melanoma has spread to regional lymph nodes. It is generally used for patients with melanomas that are more than 1 mm thick.

For melanomas that are less than 1 mm thick, the likelihood that the cancer has spread to the lymph nodes is so low that, in most cases, sentinel lymph node mapping is not necessary. However, sometimes the doctor will recommend this procedure for a person with a thin melanoma if there are other indications the melanoma is more aggressive, such as ulceration or higher mitotic rate (see Diagnosis). If the melanoma is less than 1 mm, your doctor will discuss whether this approach is recommended based on other features of the primary melanoma and other factors.

During the procedure, the doctor removes one or a few sentinel lymph nodes to check for melanoma cancer cells. A sentinel lymph node is the first node into which the lymph system drains from the primary melanoma site. If melanoma cancer cells are not detected in the sentinel lymph node, no further lymph node surgery is required. However, if the sentinel lymph node does contain melanoma, the disease has spread to regional lymph nodes, and lymph node dissection (see below) is typically recommended. Sentinel lymph node mapping should be performed during the same operative procedure as the wide excision because such surgery can change the lymphatic drainage pattern, which may affect the reliability of the procedure in some situations.

Lymph node dissection. If melanoma has spread to nearby lymph nodes, surgical removal of the remaining lymph nodes in that region is usually recommended. The number of lymph nodes removed depends on the area of the body. People who have had a lymph node dissection around an arm or leg have higher risk for fluid build-up in that limb, a side effect called lymphedema (see Side Effects). In general, the risk of spread to areas of the body beyond the regional lymph nodes is greater for patients who have lymph nodes containing melanoma than when lymph nodes do not contain disease.

Learn more about cancer surgery.

Adjuvant therapy (Stage II and Stage III)

After surgery, the surgeon or medical oncologist may also recommend adjuvant treatment for patients who are at higher risk for recurrence of melanoma. Adjuvant therapy is treatment given after the initial treatment (surgery) in order to reduce the risk of melanoma recurrence. People who might consider adjuvant therapy are those whose melanomas are more than 4 mm thick (Stage IIB) or have spread to regional lymph nodes (Stage III). Treatment options include interferon, radiation therapy, participation in a clinical trial (see Current Research section), or observation/active surveillance, which includes regular check-ups with your doctor.

On the other hand, if the melanoma is thinner and no lymph nodes are involved, your doctor may not recommend adjuvant therapy.

Adjuvant therapy: Immunotherapy

An approved adjuvant systemic therapy for this stage of melanoma is high-dose interferon alfa-2 b, which is a type of immunotherapy. Immunotherapy (also called biologic therapy) is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to bolster, target, or restore immune function. Learn more about immunotherapy.

High-dose interferon alfa-2b has been shown to consistently reduce the likelihood of a recurrence of melanoma. While treatment with the FDA-approved regimen of one year at high dosage has been shown to improve the chances of remaining recurrence-free, the increase in overall survival has been more modest, demonstrated in some, but not all, studies of high-dose interferon. Interferon is given intravenously (injected into a vein) for 20 doses (five days a week, for four weeks) in the first month, and then under the skin three times a week at home for 11 months. However, there are substantial side effects to this treatment, including flu-like symptoms—such as fatigue, fever, chills, nausea, vomiting, and headache—and depression. As a result, patients should have a thorough conversation with their doctor about the risks and benefits of this treatment.

In addition, FDA approved a therapy called ipilimumab that targets CTLA-4 antibodies for Stage III melanoma that cannot be surgically removed (unresectable) as well as for Stage IV melanoma; see below, under Stage IV, for more details.

Additional clinical trials with interferon are currently ongoing and are designed to evaluate the benefit of low dose interferon, shorter duration of interferon, or alternative formulations of interferon, such as pegylated interferon. In addition, clinical trials with vaccine approaches or other anti-CTLA4 antibodies, are being evaluated for treatment of Stage II and Stage III melanoma. In addition, vaccines that may improve the specific immune resistance to melanoma have been the focus of multiple trials and are currently being explored as adjuvant therapy for melanoma (see the Current Research section for additional details).

Adjuvant therapy: Targeted therapy

Targeted therapy is a treatment that targets the cancer's specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. In 2011, FDA approved a targeted therapy called vemurafenib for people with both Stage IV and Stage III melanoma that cannot be surgically removed when a specific genetic mutation BRAF (V600) is present (see Diagnosis). For more details about this treatment option, read below under the section entitled Stage IV: Targeted Therapy.

Adjuvant therapy: Radiation therapy

An additional type of adjuvant treatment, called adjuvant radiation therapy, may also be recommended in some situations, including, for example, after lymph node dissection reveals extensive regional tumor involvement.

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells.
There are two types of radiation therapy. The first is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation treatment is given using implants, it is called internal radiation therapy or brachytherapy. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Learn more about radiation therapy.

Adjuvant therapy: Regional chemotherapy

Chemotherapy is the use of drugs to kill cancer cells, usually by stopping the cancer cells' ability to grow and divide. It is given by a medical oncologist.

For stage III melanoma, the doctor may recommend a chemotherapy technique that focuses on a specific region, called regional chemotherapy.

If melanoma has spread only on one limb (spread from a primary melanoma arising on an arm or a leg known as satellite or in-transit metastases), isolated limb perfusion (ILP) is an approach that uses surgery and chemotherapy. First, under general anesthesia, a surgeon separates the limb's blood circulation from the rest of the body. Then, while still in the operating room, a high dose of chemotherapy is immediately injected into the limb's bloodstream to kill cancer cells. Isolated limb infusion (ILI) is similar to ILP; however, to isolate the limb's blood circulation from the rest of the body, tubes called catheters are first inserted by radiologists, and pressure is applied above the area using a tourniquet. Then, a high dose of chemotherapy is injected into the major blood vessels entering and leaving the limb using these catheters in the operating room. The drug most commonly used for ILP/ILI is melphalan (Alkeran), which is used together with hyperthermia (maintaining a warm extremity temperature). These treatments can control the regional disease, but do not appear to routinely alter the overall survival of patients with melanoma, since patients with in-transit or satellite metastases are also at risk for distant spread of the melanoma. Since the chemotherapy is delivered to the limb in these situations, side effects are mostly limited to the limb involved, although some systemic side effects (see below, under Chemotherapy) are possible.

Treatment options for Stage IV metastatic melanoma

Melanoma that has metastasized or spread beyond draining lymph nodes is considered Stage IV melanoma (see Staging). The most common sites of spread beyond the skin include the lung, liver, and brain.

At this stage, eliminating the disease entirely is difficult. In addition to extending survival time, an important part of cancer care is relieving a person's symptoms and side effects. It includes supporting the patient with his or her physical, emotional, and social needs, an approach called palliative or supportive care. People often receive disease-directed therapy and treatment to ease symptoms at the same time.

Patients with this diagnosis are encouraged to talk with doctors who are experienced in treating this stage of cancer, because there can be different opinions about the best treatment plan. Learn more about seeking a second opinion before starting treatment, so you are comfortable with the treatment plan chosen. It is important to note that there are a number of new approaches for the treatment of metastatic melanoma, including new molecularly targeted therapies and new immunotherapies, which appear extremely promising. Participation in a clinical trial is the preferred option for patients with stage IV melanoma. Some of the treatments described below are available only through clinical trials.

Treatment recommendations for patients with metastatic melanoma depends on multiple factors, including the patient's age and overall health, the locations and number of metastases, how fast the disease is spreading, and the patient's wishes for treatment. Treatment options include chemotherapy, immunotherapy, biochemotherapy (the combination of immunotherapy with chemotherapy), targeted therapy, radiation therapy, surgery for isolated and/or limited metastases, and participation in a clinical trial.

Patients with metastatic melanoma have a high risk for brain metastases. Surgery or radiation therapy (see below) may be considered for brain metastases based upon symptoms, number of lesions, and location of metastases in the brain.

Common treatment options for Stage IV metastatic melanoma are described below.

Stage IV: Chemotherapy

As explained above, chemotherapy is the use of drugs to kill cancer cells. A chemotherapy regimen (schedule) usually consists of a set number of cycles given over a specific time. A patient may receive one drug at a time or combinations of different drugs at the same time.

Systemic chemotherapy is delivered through the bloodstream (by vein; called an “IV”) or as a pill to reach cancer cells throughout the body. Systemic chemotherapy used for melanoma includes dacarbazine (DTIC-Dome), which is the only FDA approved chemotherapy for melanoma. Temozolomide (Methazolastone, Temodar) is essentially an oral version of DTIC, and it is frequently used for the treatment of Stage IV melanoma. Other chemotherapies used to treat melanoma include cisplatin (Platinol), the taxanes (a group of drugs that includes paclitaxel [Taxol] and docetaxel [Taxotere]), carmustine (BiCNU), fotemustine (Muphoran), lomustine (CeeNU), and vinblastine (Velban, Velsar). Combinations of chemotherapy drugs, such as paclitaxel and carboplatin, also may be given to patients with Stage IV melanoma. Combinations of new drugs that may reduce melanoma resistance to chemotherapy are now under exploration.

The side effects of chemotherapy depend on the individual and the dose used but they can include fatigue, risk of infection, nausea and vomiting, loss of appetite, diarrhea, some nerve damage causing changes in sensation, and hair loss. These side effects usually go away once treatment is finished.

Learn more about chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Stage IV: Immunotherapy

As explained above, immunotherapy is aimed at boosting the body's natural defenses to fight the cancer.

Interleukin-2 (IL-2, aldesleukin, Proleukin) is a type of immunotherapy used to treat melanoma. IL-2 strongly activates T-cells and is used for patients with advanced melanoma.  The current FDA-approved IL-2 regimen consists of two 5-day courses of IL-2, separated by a rest period of 7 to 10 days.  Typically, two or three courses are given when the melanoma responds well to treatment. The most common side effects are low blood pressure, fever, chills, and a condition known as “capillary leak syndrome,” when fluids and proteins leak from blood vessels, which can cause very low blood pressure and other dangerous effects. Patients being treated with high dose IL-2 require intensive monitoring, and IL-2 should be given by an experienced health care team familiar with the side effects of IL-2 treatment.

Ipilimumab (Yervoy) is another type of immunotherapy that was approved by the FDA in March 2011 as a treatment for patients with unresectable Stage III and Stage IV (metastatic) melanoma as a first treatment or following previous therapy. It is the first of two drugs approved in 2011 that have been shown to extend survival for such patients (the second is a targeted therapy called vemurafenib, described below). Ipilimumab is an anti-CTLA-4 monoclonal antibody that is given through an infusion into a vein, given every three weeks for a total of four doses.

There can be serious, even life-threatening, side effects based upon the body's reaction to ipilimumab, called an autoimmune response.  Such side effects can include significant colon inflammation (colitis), liver problems, skin reactions, nerve and hormone gland inflammation, and eye problems. Due to these potential, significant side effects, the drug's manufacturer has created a FDA-approved wallet card for patients (PDF) being given this therapy, to carry with them for emergency reference. Learn more about this medication and its side effects in a Cancer.Net podcast.

Before treatment begins, be sure to talk to your doctor about potential side effects, and let your doctor know right away about any side effects you experience during treatment. It is also important to tell your doctor about all other medications you are taking, including over-the-counter drugs and dietary or herbal supplements, to avoid possible side effects from drug interactions with ipilimumab.

Doctors are also looking into combining immunotherapy and chemotherapy as a way to treat metastatic melanoma; this approach is called biochemotherapy. However, there are many side effects and evidence has not yet shown survival benefit over standard treatment.

Other clinical trials are investigating newer immunotherapy approaches, including adoptive immunotherapy, vaccine studies, Leukine or GM-CSF or treatment with other anti-CTLA-4 monoclonal antibodies (such as trememlimumab). See the Current Research section for further discussion of some of these new approaches.

Stage IV: Targeted therapy

As explained above and in the Diagnosis section, ongoing research has identified several key pathways and genes involved in melanoma. These advances now allow doctors to begin to classify melanoma into specific subtypes (see Diagnosis) based upon the melanoma's genetic abnormalities or mutations. As a result, a patient's treatment plan can be tailored or personalized based upon each subtype of melanoma. This approach, known as targeted therapy, is designed to target or inhibit specific genes or pathways that contribute to melanoma cell growth. Therefore, a major research focus is the development of new drugs that target specific molecular pathways and genes that are abnormal or activated in melanoma.

The discovery that approximately 50% of melanomas have a mutated or broken BRAF gene has provided an important new direction in the treatment of melanoma. Targeted therapies put the brake on the growing cells by inhibiting the activated gene. In August 2011, the FDA approved a new BRAF inhibitor called vemurafenib (Zelboraf, previously known as PLX4032 or RO5185426). The drug, which is taken as a pill, is specifically indicated for patients with melanoma whose tumors have V600E mutation in the BRAF gene. An estimated 50% of patients with melanoma have this type of BRAF mutation, which does not occur in normal cells. The drug is not indicated for use in patients without the mutation.  In a recent clinical trial for patients with metastatic melanoma whose tumors had the mutated BRAF gene, vemurafenib resulted in tumor shrinkage in the majority of those patients and it extended patients' survival. Based on those findings, it is now approved for standard use for patients with locally advanced Stage III melanoma that cannot be removed by surgery or for patients with Stage IV melanoma, provided their melanoma has the mutated BRAF gene. Side effects of vemurafenib included skin problems, including rashes, sun sensitivity, and a less aggressive form of skin cancer called squamous cell carcinoma that can often be treated with minor surgery. Other side effects included joint pain, fatigue, nausea, and hair loss. Talk with your doctor about what side effects may affect you before treatment begins.

There are several other drugs in development which target BRAF in clinical trials. See Current Research section for additional information.

Activating mutations in the C-kit gene may occur in lentigo maligna melanoma, acral lentiginous melanoma, and mucosal melanoma. Drugs in development for mutated C-kit melanoma include imatinib (Gleevec), nilotinib (Tasigna), and dasatinib (Sprycel) for patients with Stage IV melanoma.

Learn more about the basic approach of targeted therapy.

Stage IV: Radiation therapy

As described above, radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells.

Radiation therapy for melanoma can be used in several ways. Radiation therapy is most commonly used to relieve symptoms caused by melanoma that has spread, especially if it has spread to the brain and bones. It may be given to the entire area (whole brain) or through stereotactic radiosurgery, which involves delivering a single, high dose of radiation directly to the tumor and not healthy tissues. This works best for a tumor that is only in one area or a few areas of the brain.

It may also be used when cancer has extensive spread to the lymph nodes, following a lymph node dissection (see above, under Adjuvant therapy). Radiation therapy is also used when the amount of melanoma that can be removed with surgery is limited by the location of the tumor. In addition, researchers are testing the effectiveness of chemoradiation, a combination of radiation therapy and chemotherapy.

Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. A patient may experience hair loss if radiation therapy is used on the scalp. If radiation therapy is used around the head and neck, side effects, such as a change in taste and dry mouth, may occur. Most side effects go away soon after treatment is finished. If lymph nodes near an arm or leg were affected, the person may have higher risk of fluid build-up in that limb, a side effect called lymphedema. Lymphedema can be a long-term, ongoing side effect. Learn more about radiation therapy and managing side effects.

If the melanoma has spread to a single distant organ (Stage IV) or has recurred (come back after treatment), the surgical removal of cancer that has spread to an internal organ may help control the disease.

Recurrent melanoma

Once your treatment is complete and there is a remission (absence of cancer symptoms; also called “no evidence of disease” or NED), talk with your doctor about the possibility of the cancer returning. Many survivors feel worried or anxious that the cancer will come back. Learn more about coping with this fear.

If the melanoma does return after the original treatment, it is called recurrent cancer. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence).

When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. After testing is done, you and your doctor will talk about your treatment options. Often the treatment plan will include the therapies described above (such as surgery, chemotherapy, immunotherapy, targeted therapy, and radiation therapy) but may be used in a different combination or given at a different pace. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent cancer.

People with recurrent cancer often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.

If treatment fails

If disease-directed treatment is not successful, this may also be called advanced cancer. This diagnosis is stressful, and it may be difficult to discuss. However, it is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Learn more about advanced cancer care planning.

Find out more about common terms used during cancer treatment.