Oncologist-approved cancer information from the American Society of Clinical Oncology

Melanoma


Last Updated: August 26, 2011

This section has been reviewed and approved by the Cancer.Net Editorial Board,  08/11

Overview

The skin is the body’s largest organ. It protects against infection and injury, and it helps regulate body temperature. The skin also stores water and fat and produces vitamin D. Melanoma is the most serious form of skin cancer.

Melanoma starts from pigment-producing (color-producing) cells called melanocytes. Frequently, melanoma develops from a pre-existing mole. Melanoma occurs most commonly on the skin of men’s backs or on women’s legs, but melanoma can occur anywhere on the body, including the head and neck, the skin under the fingernails, and even the soles of the feet or palms of the hands.

The median age at which people are diagnosed with melanoma is just above 50 years old. Still, melanoma occurs in young adults with greater frequency than many other cancer types.

Skin is made up of two main layers: the epidermis (outer layer of skin) and the dermis (inner layer of skin). The deeper layer of the epidermis contains melanocytes. Melanoma can grow deep into the dermis, invading lymph and blood vessels. The initial type of treatment is determined by the thickness of the tumor, and more broadly, by whether the disease has spread (called metastasis) to nearby (regional) lymph nodes or to other parts of the body at the time of diagnosis.

Treatment of the primary (initial) melanoma generally involves surgery, which usually cures early-stage or thin melanoma. Additional surgery may be needed to make sure that the melanoma has been entirely removed and to find out if the melanoma has spread to nearby lymph nodes (tiny, bean-shaped organs that help fight infection). After surgery, the doctor will evaluate whether additional (adjuvant) therapy—such as immunotherapy, chemotherapy, radiation therapy, or further surgery—is necessary. Researchers are also investigating new ways to treat advanced melanoma, including targeted therapies, additional immunotherapies, and vaccine therapy. More details can be found in the Treatment and the Current Research sections.

This section focuses on cutaneous melanoma, which is melanoma that arises on the skin’s surface. Melanoma can also develop in the mucous membranes which lines the mouth, gastrointestinal tract, and other locations on the body. Learn more about melanoma diagnosed elsewhere in the body, such as melanoma of the eye, melanoma of the anus, and melanoma of the vagina. For information on non-melanoma skin cancer, review the section on basal cell and squamous cell skin cancers.

Find out more about basic cancer terms used in this section.

Looking for More of an Overview?

If you would like additional introductory information, explore these related items on Cancer.Net:

  • ASCO Answers Fact Sheet: Read a one-page fact sheet (available in PDF) that offers an easy-to-print introduction for this type of cancer.

  • Cancer.Net Patient Education Video: View a short video led by an ASCO expert in this type of cancer that provides basic information and areas of research.

Or, choose “Next” (below, right) to continue reading this detailed section.

Statistics

This year, an estimated 70,230 adults (40,010 men and 30,220 women) in the United States will be diagnosed with melanoma. It is estimated that 8,790 deaths (5,750 men and 3,040 women) from melanoma will occur this year.

Melanoma accounts for less than 5% of skin cancer cases but a majority of skin cancer deaths, as it is the most serious form of skin cancer. Melanoma is the fifth most common cancer among men and the seventh most common cancer in women. Sometimes, melanoma is found in children and teenagers. Melanoma rates are more than 10 times higher in white people than black people, and are similar for men and women younger than 65. However, men older than 65 are more than twice as likely to be diagnosed with melanoma as women older than 65.

The vast majority of people diagnosed with melanoma are cured by their initial surgery. The five-year survival rate (percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases) is 91%. Overall survival depends upon thickness of the primary melanoma, whether or not lymph nodes are involved, or whether there is spread of melanoma to distant sites. For melanoma that is only located near where it started, the five-year survival rate is 98%. The five-year survival rates for melanoma that has spread to the nearby lymph nodes or to other parts of the body are 62% and 16%. The factors that affect survival are explained in detail in the Diagnosis and Staging sections.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of people with this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with melanoma. Because the survival statistics are measured in five-year intervals, they may not represent recent advances made in the treatment or diagnosis of this cancer. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2011.

Medical Illustrations

Anatomy of the Skin

Larger image

Our staging illustrations are currently being updated to comply with the new 2010 American Joint Committee on Cancer staging guidelines. We apologize for the inconvenience.

Risk Factors and Prevention

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them to your doctor may help you make more informed lifestyle and health care choices.

The following factors may raise a person’s risk of developing melanoma:

Sun exposure. Exposure to ultraviolet (UV) radiation from the sun can cause melanoma. Ultraviolet B (UVB) radiation from the sun appears more closely associated with melanoma, but newer information suggests that ultraviolet A (UVA) may also play a role in the development of melanoma, as well as basal and squamous cell skin cancers.

People who live in areas with bright sunlight year-round or at high altitudes have a higher risk of developing skin cancer, as do those who spend a lot of time outside during the midday hours. Risk of melanoma is higher in people whose skin has a tendency to burn rather than tan and who have had multiple, severe, blistering sunburns, particularly in childhood. Melanoma has also been linked to intermittent recreational exposure to UV, whether from the sun or from indoor tanning facilities.

Artificial tanning. People who use tanning beds, tanning parlors, or sun lamps have an increased risk of melanoma and other types of skin cancer. Recreational sun tanning should be avoided.

Moles. People with many moles or unusual moles called dysplastic nevi or atypical moles (flat, large moles that have irregular color and shape) have a higher risk of developing melanoma.

Fair skin. People with fair complexion, blond or red hair, blue eyes, and freckles are at increased risk for developing melanoma.

Family history. Approximately 10% of people with melanoma have a family history of melanoma. Therefore, it is recommended that close relatives (parents, brothers and sisters, and children) of a person with melanoma routinely have their skin examined. Changes in two genes (CDKN2A and CDK4)that may lead to melanoma have been identified. However, only a small number of families with melanoma have changes in these genes. It is likely that other genes and environmental factors also affect risk of melanoma. Learn more about the genetics of melanoma.

Personal history of skin cancer. People who have had one melanoma have an increased risk of developing additional new melanomas. People who have had basal cell or squamous cell skin cancer also have an increased risk of developing melanoma.

Race or ethnicity. Melanoma rates are more than 10 times higher in white people than black people; however, it is important to note that melanoma can occur in a person of any race or ethnicity. In fact, the rates of melanoma among Hispanics are rising.

Immune system. People who have weakened immune systems or use certain medications that suppress immune function have a higher risk of developing skin cancer.

Prevention

Reducing exposure to UV radiation, particularly through reducing sun exposure, lowers the risk of melanoma. This is important for people of all ages and is especially important for people who have an increased risk of melanoma. Sun damage builds up over time. Steps to reduce sun exposure, avoid sunburn, and help prevent melanoma include:

  • Limiting or avoiding sun exposure between 10:00 AM and 4:00 PM, as well as avoiding recreational sunbathing.

  • Wearing sun-protective clothing, including a hat that shades the face, neck, and ears. Clothes made of fabric labeled with UPF (UV protection factor) may provide better protection. UV-protective sunglasses are also recommended.

  • Using sunscreen with a sun protection factor (SPF) of 15 or higher throughout the year and reapplying it at least every two hours, especially after heavy perspiration or being in the water.

  • Examining the skin regularly (including examinations by a health care professional and self-examinations). Learn more about the signs and symptoms of melanoma.

  • Avoiding use of sun lamps, tanning beds, and tanning salons.

Learn more about protecting your skin from the sun.

It is important to note that limiting your sun exposure reduces your body’s production of vitamin D. Therefore, people with limited sun exposure should talk with their doctor about how to include good sources of vitamin D in their diet, including the use of supplements.

Symptoms

Change in size, shape, color, or feel in a mole is often the first warning sign of melanoma. Melanoma can appear anywhere on the body, even on areas that are not exposed to the sun. The most frequent locations for melanoma are the trunk (torso), legs, and arms. Melanoma can also develop under the fingernails or toenails; on the palms, soles, or tips of fingers and toes; or on mucous membranes (such as skin that lines the mouth, nose, vagina, and anus).

Melanoma can appear in a number of different ways. Most melanomas are dark brown/black and are often described as “ugly looking.” Bleeding is a sign of more advanced melanoma.

Changes can occur in an existing mole, or melanoma may appear as a new or abnormal-looking mole. The "ABCDE" rule can be used to help remember the warning signs:

Asymmetry: The shape of one half of the mole does not match the other.

Border: The edges are ragged, notched, uneven, or blurred.

Color: Shades of black, brown, and tan may be present. Areas of white, gray, red, or blue may also be seen.

Diameter: The diameter is usually larger than 6 millimeters (mm) (1/4 inch; the size of a pencil eraser) or has grown in size. Melanoma may be smaller when first detected.

Evolving: The mole has been changing in size, shape, color, or appearance, or growing in an area of previously normal skin. Also, when melanoma develops in an existing mole, the texture of the mole may change and become hard or lumpy. Although the skin may feel different and may itch, ooze, or bleed, melanoma usually does not cause pain.

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you’ve been experiencing the symptom(s) and how often.

If cancer is diagnosed, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

Early detection of melanoma

Earlier detection and recognition of melanoma is the key to improving the chance for successful treatment and overall survival. Recognizing early warning signs of melanoma and doing regular self-examinations of a person’s skin will help find melanoma early when the disease is highly curable.

Self-examination of skin. Self-examinations should be performed in front of a full-length mirror in a brightly lit room. It helps to have another person check the scalp and back of the neck. Include the following steps in a skin self-examination:

  • Examine the front and back of the entire body in a mirror, then the right and left sides, with arms raised.

  • Bend the elbows and look carefully at the outer and inner forearms, upper arms (especially the hard-to-see back portion), and hands.

  • Look at the front, sides, and back of the legs and feet, including the soles and the spaces between the toes.

  • Part the hair to lift it, and examine the back of the neck and scalp with a hand mirror.

  • Check the back, genital area, and buttocks with a hand mirror.

Talk with your doctor if you find any of the following:

  • A growth on the skin that matches any feature on the ABCDE rule list, see above

  • New growth on the skin

  • A suspicious change in an existing mole or spot

  • An unusual sensation in a mole, such as itching or tingling
Medical tests for early detection. A medical technique being used for early detection of melanoma is epiluminescence microscopy, or dermoscopy, which evaluates patterns of size, shape, and pigmentation in pigmented skin lesions. Among trained, experienced medical professionals, the use of dermoscopy may reduce the number of biopsies (see Diagnosis) of pigmented lesions to rule out melanoma, although more research is needed. Meanwhile, confocal scanning laser microscopy is another new technology to better examine possible melanoma lesions, but it is only available in a few major facilities.

Melanoma risk calculator. As noted above, melanoma that is found early has a much higher chance of being cured. A melanoma risk calculator has been developed and piloted by the American Joint Committee on Cancer Melanoma Task Force for use by health care professionals to estimate a person’s prognosis (chance of recovery) at the time of diagnosis of melanoma that has not yet spread to other parts of the body (see Staging). Your doctor can help you understand this tool, which is available at www.melanomaprognosis.org.

Diagnosis

Doctors use many tests to diagnose cancer and find out if it has metastasized (spread). For melanoma, a biopsy of the suspicious skin area, called a lesion, is the only way to make a definitive diagnosis. The doctor may suggest other tests that will help make a diagnosis and determine the overall stage of the melanoma. Imaging tests may be used to find out whether the cancer has metastasized.

A biopsy and pathologic examination of a skin lesion for melanoma

A biopsy is the removal of a small amount of tissue (usually performed with a local anesthetic to numb the area) for examination under a microscope. The suspected skin lesion is removed using techniques that preserve the entire lesion so that the thickness of the potential cancer and its margin (healthy tissue around the lesion that is removed) can be carefully examined. The tissue sample is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease), who determines if it is a melanoma.

After a biopsy, the pathologist will write a report (called a pathology report) that should include the following information. Each of these items is described in detail below:

  • Type/subtype of melanoma

  • Thickness of melanoma

  • Presence or absence of ulceration

  • Mitotic rate

  • Margin status

There are four types of skin melanoma:

  • Superficial Spreading Melanoma: This is the most common type, accounting for 70% of melanomas. It usually develops from an existing mole.

  • Lentigo Maligna Melanoma: This type tends to occur in older people. It most commonly begins on the face, ears, and arms on skin that is chronically exposed to the sun.

  • Nodular Melanoma: This type accounts for about 15% of melanoma, often appears rapidly as a bump on skin. It is often black, but it may also be pink or red.

  • Acral Lentiginous Melanoma: This type develops on palms, soles, or under the nail bed. It sometimes occurs on people with darker skin. Acral lentiginous melanoma is not related to sun exposure.

Subtyping

Recent information has shown that melanoma can also be classified into molecular subtypes based upon distinct genetic alterations in the melanoma rather than histologic types. The most common mutation or broken gene in melanoma is the BRAF (V600E) gene which is mutated in about 50% of melanomas. Another common mutation is the C-kit mutation. This occurs more commonly in melanomas that arise from the mucosal lining, acral lentiginous melanoma, or melanoma that arises from chronically sun damaged skin (such as lentigo maligna melanoma). The classification of melanoma into different subtypes based upon genetic alterations can have a major effect on treatment options, as targeting specific mutated genes is an important new way of treating advanced melanoma. Learn more about this approach, called targeted therapy, in the Treatment and Current Research sections.

The pathologist will measure the “thickness” of the melanoma in millimeters (or fraction of a millimeter) from the top of the skin down to the underlying skin because it is the most reliable feature reflecting the risk of spread. Other features include the mitotic rate (an estimate of the speed at which tumor cells are dividing), measured as the number of mitoses per millimeter squared (mm2). In addition, the presence or absence of ulceration of the primary melanoma is defined in the pathology report. If there is ulceration, research has shown it significantly increases the risk of the melanoma coming back after treatment (called recurrence or relapse), and it may predict whether adjuvant treatment with an immunotherapy called interferon will be beneficial after surgery (see Treatment).

The thickness, ulceration, and mitotic rate of the melanoma also determine the stage, treatment approach, and prognosis (see below). A thin melanoma, which means the tumor is less than 1 mm thick, is associated with low risk of spread to regional lymph nodes or to distant sites. An intermediate-thickness melanoma is between 1 mm and 4 mm. A thicker melanoma, greater than 4 mm thick, is associated with a greater chance of recurrence.

Additional patient evaluation after a diagnosis of melanoma

After the initial diagnosis of melanoma, you will be referred to a specialist. The doctor will take a complete medical history, noting any symptoms or signs, and perform a complete physical examination, including a total skin examination and an examination of regional (draining) lymph nodes. The focus of these examinations is to identify risk factors and signs or symptoms that may indicate melanoma has spread beyond the original site.

The extent of the initial evaluation is based upon the risk of recurrence associated with the primary (original) melanoma. In general, for most low-risk melanomas (such as those less than 1 mm), no further search for metastases or spread is necessary. In patients with higher-risk melanoma, more extensive testing (as described below) may be considered. Therefore, the extent of the initial evaluation for a patient with newly diagnosed melanoma depends upon on the stage and discussion with the team of doctors.

Depending on the results of the evaluation, including the pathology report of the primary melanoma tumor, testing may include the following blood tests and/or imaging studies.

Blood tests. The patient’s blood may be tested to help determine if the cancer has spread. For melanoma, this may include a complete blood count and chemistry panel, which is a test that evaluates blood electrolytes (minerals in your body, such as potassium and calcium) and enzymes (specialized proteins) that can be abnormal if cancer has spread. In addition, the doctor may test to check the blood’s level of lactate dehydrogenase (LDH; an enzyme that can help signal tissue damage) level. LDH is a tumor marker, which is a substance found in a patient’s blood that is produced either by the tumor itself or by the body in response to the cancer.

X-ray. An x-ray is a way to create a picture of the structures inside your body, using a small amount of radiation.

Ultrasound. An ultrasound uses sound waves to create pictures of the internal organs, including collections of lymph nodes (called lymph node basins) and soft tissue.

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a patient’s vein to provide better detail.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A contrast medium may be injected into a patient’s vein to create a clearer picture.

Positron emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.

Learn more about what to expect when having common tests, procedures, and scans.

After these diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is cancer, these results also help the doctor describe the cancer; this is called staging. Learn more about the first steps to take after a diagnosis of cancer.

Staging

Our staging illustrations are currently being updated to comply with the new 2010 American Joint Committee on Cancer staging guidelines. We apologize for the inconvenience.

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and whether it is affecting the functions of other organs in the body. Doctors may use diagnostic tests (see Diagnosis)to determine a cancer's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis (chance of recovery). There are different stage descriptions for different types of cancer.

To determine the stage of a melanoma, the lesion and some surrounding normal tissue needs to be surgically removed and analyzed using a microscope. Doctors use the melanoma’s thickness, measured in millimeters (mm), and other characteristics to help determine the disease’s stage. (These factors are explained in the Diagnosis section.) The original melanoma is often called the primary melanoma or primary tumor.

One tool that doctors use to describe the stage is the TNM system. This system judges three factors: the tumor itself, the regional lymph nodes near the tumor, and if the tumor has spread to other parts of the body. The results are combined to determine the stage of cancer for each person. There are five stages of melanoma: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

  • How thick is the primary tumor and where is it located? (T)

  • Has the tumor spread to the regional lymph nodes, or is there evidence of in-transit metastases or satellites (defined below)? (N)

  • Has the cancer metastasized to other (distant) parts of the body? (M)

Tumor. Using the TNM system, the "T" plus a letter and/or number (0 to 4) is used to describe the primary melanoma, particularly its size.

The pathologist will measure the thickness of the melanoma in millimeters. Other important features of the melanoma include the mitotic rate (the speed at which tumor cells are dividing) per millimeter squared (mm2) and the presence or absence of ulceration (see Diagnosis). “a” and “b” T- subcategories are assigned based on ulceration and number of mitosis per mm2.

The T classifications are based on the thickness, the presence or absence of ulceration, and the mitotic rate. Tumor classification information is listed below:

TX: The tumor cannot be evaluated.

T0: There is no evidence of a primary tumor.

Tis: Called melanoma in situ, which means that cancer cells are found in only the outer layer of skin (epidermis) and has not grown into any other layers. The cancer cells do not show signs of spreading.

T1: The primary tumor is 1.0 mm or thinner, and one of the following:

T1a: The primary tumor has no ulceration and a mitotic rate less than 1/mm2.

T1b: The primary tumor has ulceration and/or a mitotic rate equal to or greater than 1/mm2.

T2: The primary tumor’s thickness is between 1.0 mm and 2.0 mm, and one of the following:

T2a: The primary tumor has no ulceration.

T2b: The primary tumor has ulceration.

T3: The primary tumor’s thickness is between 2.0 mm and 4.0 mm, and one of the following:

T3a: The primary tumor has no ulceration.

T3b: The primary tumor has ulceration.

T4: The primary tumor is thicker than 4.0 mm, and one of the following:

T4a: The primary tumor has no ulceration.

T4b: The primary tumor has ulceration.

Node. The "N" in the TNM system stands for regional lymph nodes. In addition, the N classification includes whether small deposits of melanoma are found in the lymph channels between the primary tumor and the regional lymph nodes (called in-transit metastases or satellites), either on the skin (cutaneous) or under the skin (subcutaneous).

NX: The regional lymph nodes cannot be evaluated.

N0: There is no evidence of cancer in the lymph nodes.

N1: The cancer has spread to one lymph node, and one of the following:

N1a: The doctor cannot feel cancer in the lymph nodes but can detect cancer cells in a lymph

node sample when viewed under a microscope (called microscopic metastasis).

N1b: The doctor can feel the cancer in the lymph nodes or see it on a scan (called macroscopic metastasis).

N2: Cancer has spread to two or three lymph nodes, and one of the following:

N2a: The doctor cannot feel cancer in the lymph nodes but can detect cancer cells in a lymph node sample when viewed under a microscope.

N2b: The doctor can feel the cancer in the lymph nodes or see it on a scan.

N2c: The doctor finds in-transit metastases or satellites.

N3: Any of the following conditions:

  • The cancer has spread to four or more lymph nodes.

  • Multiple lymph nodes appear joined together (called matted lymph nodes).

  • In-transit metastases or satellites are present, with at least one affected lymph nodes.

Distant metastasis. The "M" in the TNM system indicates whether melanoma has spread to other parts of the body, beyond the primary melanoma site and the regional lymph nodes. In melanoma, metastasis may be found in the skin, subcutaneous tissue (under the skin), or in other organs such as the lung, liver or brain. Lymph nodes beyond the primary tumor region are called distant lymph nodes.

MX: Distant metastasis cannot be evaluated.

M0: The melanoma has not spread to distant sites.

M1a: The cancer has spread outside the region where it first started to other distant parts of the skin, distant locations under the skin, or any distant lymph nodes.

M1b: The cancer has spread to the lungs.

M1c: The cancer has spread to any other internal organ in the body. Also, any distant metastasis combined with a blood test result showing an elevated level of a tumor marker called LDH (see Diagnosis) is classified as MIc.

Melanoma stage grouping

Doctors determine the stage of the melanoma by combining the T, N, and M classifications.

Stage 0: Refers to melanoma in situ (melanoma cells are found only in the outer layer of skin).

Stage IA: The melanoma is 1.0 mm or thinner, has no ulceration, and has a mitotic rate less than 1/mm2.

Stage IB: Describes either of these conditions:

  • The melanoma is 1.0 mm or thinner and has ulceration and a mitotic rate equal to or greater than 1/mm2.

  • The melanoma is between 1.0 mm and 2.0 mm and has no ulceration.

Stage IIA: Describes either of these conditions:

  • The melanoma is between 1.0 mm and 2.0 mm and has ulceration.

  • The melanoma is between 2.0 mm and 4.0 mm and has no ulceration.

Stage IIB: Describes either of these conditions:

  • The melanoma is between 2.0 mm and 4.0 mm and has ulceration.

  • The melanoma is larger than 4.0 mm and has no ulceration.

Stage IIC: The melanoma is larger than 4.0 mm and has ulceration.

Stage III: The melanoma is of any thickness, and melanoma has spread to one or more regional lymph nodes and/or there is in-transit or satellite involvement. However, the melanoma has not spread to distant parts of the body.

Stage IIIA: The primary melanoma has no ulceration and has spread to up to three lymph nodes in the form of micrometastases.

Stage IIIB: Describes any of these conditions:

  • The melanoma has spread to up to three regional lymph nodes in the form of macrometastases and the primary melanoma has no ulceration.

  • The melanoma has spread to up to three regional lymph nodes, but is still microscopic and the primary melanoma has ulceration.

  • There is in-transit or satellite involvement without regional lymph node spread.

Stage IIIC: Describes any of these conditions:

  • The melanoma has spread to up to three regional lymph nodes, the lymph nodes show macrometastases, and the primary tumor has ulceration.

  • The melanoma has spread to four or more regional lymph nodes.

  • The melanoma has in-transit or satellite involvement and has spread to any of the lymph nodes.

  • The location of the primary tumor is unknown, and there are isolated metastases in lymph nodes, skin, and tissues under the skin.

Stage IV: The primary melanoma has spread to other, distant parts of the body beyond the regional lymph nodes. This is regardless of the primary tumor’s thickness and whether it has spread to any of lymph nodes or satellite or in-transit sites.

Recurrent: Recurrent melanoma is melanoma that comes back after treatment. If there is a recurrence, the cancer may need to be staged again (re-staging) using the system above.

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer-Verlag New York, www.cancerstaging.net.

Treatment

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.

Targeted Therapies

This section is the result of a collaboration between ASCO and Cancer Commons – Melanoma and is updated dynamically.

As mentioned in the Treatment section, a patient’s treatment plan can be tailored or personalized based upon known subtypes of melanoma. This approach, known as targeted therapy, is designed to target or inhibit specific genes or pathways that contribute to melanoma cell growth. This is a major focus of research for melanoma.

Patients can learn more about these genes and pathways by using the Targeted Therapy Finder, a search tool that provides information on possible therapies and diagnostic tests based upon a patient’s melanoma diagnosis. Patients are encouraged to use this tool and share the results with their doctor when making treatment decisions.

The information provided through this resource is maintained by the Cancer Commons – Melanoma editorial board.

Use the Targeted Therapy Finder – Melanoma.

About Clinical Trials

Doctors and scientists are always looking for better ways to treat patients with melanoma. To make scientific advances, doctors create research studies involving people, called clinical trials.

Many clinical trials are focused on new treatments, evaluating whether a new treatment is safe, effective, and possibly better than the current (standard) treatment. These types of studies evaluate new drugs, different combinations of existing treatments, new approaches to radiation therapy or surgery, and new methods of treatment. Patients who participate in clinical trials are often among the first to receive new treatments before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

There are also clinical trials that study new ways to ease symptoms and side effects during treatment and manage the late effects that may occur after treatment. Talk with your doctor about clinical trials regarding side effects. In addition, there are ongoing studies about ways to prevent the disease.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that it is the only way to make progress in treating melanoma. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with melanoma.

Sometimes people have concerns that, by participating in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill.” The use of placebos in cancer clinical trials is rare. When a placebo is used in a study, it is done with the full knowledge of the participants. Find out more about placebos in cancer clinical trials.

To join a clinical trial, patients must participate in a process known as informed consent. During informed consent, the doctor should list all of the patient’s options so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.

For specific topics being studied for melanoma, learn more in the Current Research section.

Patients who participate in a clinical trial may stop participating at any time for any personal or medical reason. This may include that the new treatment is not working or there are serious side effects. It is important that patients participating in a clinical trial talk with their doctor and researchers about who will be providing their treatment and care during the clinical trial, after the clinical trials ends, and/or if the patient chooses to leave the clinical trial before it ends.

Side Effects

Cancer and its treatment can cause a variety of side effects. However, doctors have made major strides in recent years in reducing pain, nausea and vomiting, and other physical side effects of cancer treatments. Many treatments used today are less intensive but as effective as treatments used in the past. Doctors also have many ways to provide relief to patients when such side effects do occur.

Fear of treatment side effects is common after a diagnosis of cancer, but it may be helpful to know that preventing and controlling side effects is a major focus of your health care team. Before treatment begins, talk with your doctor about possible side effects of the specific treatment you will be receiving. The specific side effects that can occur depend on a variety of factors, including the type of melanoma, its location and stage, the individual treatment plan (including the length and dosage of treatment), and your overall health. Common side effects for each treatment option are described in detail within the Treatment section.

If the person’s treatment included lymph node dissection and/or radiation therapy under the arm or in the groin, fluid build-up in the affected limb, called lymphedema, is possible. Graduated support garments and other therapies may help manage the condition.

If you have pain from surgery, he or she should speak with the surgeon or another health care team member. Although rare, some individuals have post-surgical long-term pain, called chronic pain. If needed, a pain management specialist can also help find ways to manage pain.

Ask your doctor which side effects are most likely to happen (and which are not), when side effects are likely to occur, and how they will be addressed by the health care team. Also, be sure to communicate with the doctor about side effects you experience during and after treatment. Care of a patient’s symptoms and side effects is an important part of a person’s overall treatment plan; this is called palliative or supportive care. It helps people with cancer at any stage of illness be as comfortable as possible. Learn more about the most common side effects of cancer and different treatments, along with ways to prevent or control them.

Be sure to talk with your doctor about the level of caregiving you may need during treatment and recovery, as family members and friends often play an important role in the care of a person with melanoma. Learn more about caregiving.

In addition to physical side effects, there may be psychosocial (emotional and social) effects are well. For many patients, a diagnosis of melanoma is stressful and can bring difficult emotions. Patients and their families are encouraged to share their feelings with a member of their health care team who can help with coping strategies. Learn more about the importance of addressing such needs, including concerns about managing the cost of your cancer care.

A side effect that occurs more than five years after treatment is called a late effect. Treatment of late effects is an important part of survivorship care. Learn more about late effects or long-term effects by reading the After Treatment section or talking with your doctor.

After Treatment

After active treatment for melanoma ends, talk with your doctor about developing a follow-up care plan, called surveillance and monitoring. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years. The purpose of monitoring is to detect a recurrence or spread of the disease, as well as a new primary melanoma. The most important parts of surveillance are your medical history and physical exams.

The follow-up and surveillance program for a person with a history of melanoma is based upon a person’s risk of recurrence, is highly individualized, and can vary from person to person. ASCO offers cancer treatment summary forms to help keep track of the cancer treatment you received and develop a survivorship care plan once treatment is completed. In general, history and physical examinations are performed every 3-6 months for the first 2-3 years and then annually thereafter, based on the doctor’s recommendations. A chest x-ray, CT scan, MRI, and/or PET/CT scan can be considered for screening of patients with higher risk melanoma. For early-stage disease, scans are not generally recommended for routine surveillance.

Routine screening with a skin examination for new melanoma (and non-melanoma skin cancer) is necessary as part of follow-up care, as is sun protection and sun avoidance. Screening for melanoma and other skin cancers may include mole mapping (photography of the moles) by a doctor. If possible, the patient should receive copies of their photographs and education in skin self-examination. There is growing evidence that individuals followed using photographs have melanomas diagnosed at an earlier stage.

Sun protection is important to help prevent second skin cancers, either melanoma or non-melanoma skin cancer. Many people who are treated for melanoma lead an active, outdoor lifestyle, but it is important to take steps to protect yourself from further skin damage. Participating in outdoor activities before 10:00 AM or after 4:00 PM and wearing long sleeves, pants, sunscreen, UV-protective sunglasses, and a hat help protect against further skin damage. A major consideration following diagnosis and treatment of melanoma is adjusting a person’s lifestyle to use sun protective or sun avoidance measures at all times. In addition, if a person is working in an area where there is high UV exposure, there may be occupation-related issues. Learn more about protecting your skin from the sun.

For an early-stage, thin melanoma, the surgery is most often outpatient surgery, with little need for rehabilitation. With a thicker melanoma and possible skin grafts, depending on the location, there may be some need for rehabilitation following treatment. As explained in Side Effects, some patients experience lymphedema or chronic pain; talk with your doctor about how these can be managed.

People recovering from melanoma are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, not smoking, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about the next steps to take in survivorship, including making positive lifestyle changes.

Find out more about common terms used after cancer treatment is complete.

Current Research

Doctors are working to learn more about melanoma, ways to prevent it, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trial. Always talk with your doctor about the diagnostic and treatment options best for you.

Enhanced prevention and early detection methods. There is ongoing research on better prevention and early detection strategies for melanoma. Both primary prevention (keeping melanoma from developing) and secondary prevention (early detection of melanoma) are important. One promising area is the screening of people with a high risk of developing melanoma.

Targeted therapy. As discussed in the Treatment section, targeted therapy is a treatment that targets specific genes or proteins. It is a major area of research for melanoma. Ongoing research has identified a number of molecular pathways and activated or mutated genes in melanoma. This includes the most commonly mutated gene BRAF as well as activation of the MAP kinase pathway. Ongoing laboratory and clinical research confirms the importance of these genes and pathways in melanoma.

There are several drugs being researched that target BRAF and the MAP kinase pathway. This includes BRAF inhibitors (such as the recently approved vemurafenib; see Treatment), GSK BRAF inhibitors, and MEK inhibitors. There are many ongoing clinical trials exploring these new approaches in phase I, phase II, and phase III clinical trials. Ongoing clinical trials are evaluating the optimum dose and schedule and combining targeted therapies with other pathway inhibitors, as well as combining these therapies with immunotherapy. Other studies will be focused on the development of new drugs which target the AKT/PI3K pathway. Another important focus is the development of agents which target the C-kit gene, which is mutated or associated with extra copies of the gene in certain subtypes of melanoma including lentigo maligna melanoma, mucosal melanoma, and acral lentiginous melanoma (melanoma of the palms, soles, and nail beds).

In summary, recent advances in medical understanding of the genetic abnormalities that occur in melanoma will allow for the selection of tailored and targeted treatment that matches the patient’s type/subtype of melanoma.

Immunotherapy. Immunotherapy, in which the immune system is activated to fight cancer, is also a major focus in melanoma research. Ongoing clinical trials are evaluating several different approaches, including those discussed in Treatment.

Currently, melanoma peptide vaccines are being intensely evaluated in clinical trials for patients with both localized and advanced melanoma. Research has shown that vaccination can cause the immune system to fight melanoma, even in advanced disease, but these therapies are still considered experimental. The vaccines are made using certain proteins found only on a melanoma tumor and are given as an injection; the person’s immune system then recognizes the proteins and destroys melanoma cancer cells. Learn more about vaccines.

In addition, as explained in the Treatment section, ipiluminab is a promising new immunotherapy for the treatment of patients with melanoma.

Ipiluminab is a monoclonal antibody directed against CTLA-4 (cytotoxic T-lymphocyte associated molecule-4). This new approach works by taking the brakes off the immune system. Ongoing clinical trials of ipiluminab will provide further guidance regarding the role of this drug in the treatment of patients with melanoma. This medicine does have unique side effects. Because it activates the immune system, it can trigger “autoimmune” side effects in which the patient’s own immune system attacks normal cells in their body. Patients are monitored closely for diarrhea and other side effects.

Another type of experimental immunotherapy involves altering the patient’s lymphocytes (white blood cells) in the laboratory to increase their ability to fight the tumor. The changed cells are given back to the patient, often in combination with chemotherapy. These types of treatments are known as adoptive cell transfer (ACT).

Chemotherapy. There are several new types of chemotherapy and combinations of drugs being evaluated in clinical trials. In addition, the combination of chemotherapy and anti-angiogenesis inhibitors (substances that prevent the formation of new blood vessels that tumors need to grow and spread) or immunotherapy is also being explored. In addition, the combination of chemotherapy and drugs that may alter melanoma resistance to chemotherapy drugs are currently being explored.

Gene therapy. Gene therapy is a targeted form of treatment that is able to change bits of genetic code in a person's cells. Although gene therapy is relatively new, it shows potential for treating melanoma. Although there are several approaches to gene therapy, one goal is to make the cancer cells "look" different, so the immune system can recognize them as cancer and attack them.

Supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current melanoma treatments in order to improve patients’ comfort and quality of life.

Learn more about common statistical terms used in cancer research.

Looking for More about Current Research?

If you would like additional information about the latest areas of research regarding melanoma, explore these related items:

Or, choose “Next” (below, right) to continue reading this detailed section.

Questions to Ask the Doctor

Talking often with the doctor is important to make informed decisions about your health care. These suggested questions are a starting point to help you learn more about your cancer care and treatment. You are also encouraged to ask additional questions that are important to you.

For patients with newly diagnosed skin melanoma:

  • Can you explain my pathology report to me?

  • What stage of melanoma do I have? What is the depth, in millimeters, of the melanoma? Is the melanoma ulcerated? Does my melanoma have mitotic activity?

  • Is it likely the melanoma has spread? Why or why not?

  • What are my treatment options?  What clinical trials are open to me?

  • What are the possible side effects of each treatment option, both in the short term and the long term?

  • How will each treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?

  • What are the goals of each treatment option? What is my prognosis?

  • Will surgery be able to remove all of the cancer? Do I need additional surgery?

  • After the surgical removal of the melanoma, will I need a skin graft?

  • Should I have a sentinel lymph node biopsy to find out if there is spread to the lymph nodes?

  • What treatment plan do you recommend? Why?

  • Is the cancer likely to recur following treatment? What steps can I take to reduce the risk of additional new melanomas?

  • What follow-up tests will I need, and how often will I need them?

  • If I’m worried about managing the costs related to my cancer care, who can help me with these concerns?

  • What support services are available to me? To my family?

  • Are my family members at a higher risk of melanoma?

Additional questions for patients with stage III melanoma (when the sentinel lymph node biopsy indicates cancer is present or when cancer is found in the lymph nodes):

  • How many lymph nodes are affected with melanoma?

  • Will the remainder of the lymph nodes be removed? If yes, what are the potential complications of lymph node surgery?

  • Is there any extracapsular extension of the melanoma (that is, has the melanoma spilled out of the lymph node)? What does this mean?

  • What are my treatment options? What clinical trials are open to me?

  • What are the side effects of each treatment?

  • What are the goals of each treatment option? What is my prognosis?

  • What are the risks and benefits of each treatment option?

  • Is radiation therapy or other therapy recommended after surgery?

  • What treatment plan do you recommend? Why?

  • What follow-up care is necessary?

Additional questions for patients with stage IV (metastatic) melanoma:

  • Where has the melanoma spread? Is a brain scan or PET scan necessary to determine where it has spread?

  • What are my treatment options? What clinical trials are open to me?

  • How will side effects and symptoms be managed, to reduce my discomfort and increase my quality of life?

  • What are the goals of each treatment? What is my prognosis?

  • Is surgical removal of the metastases an option (especially if one or two tumors are present)? If so, what are the benefits and risks?

  • What treatment plan do you recommend? Why?

  • What support services are available to me? To my family?

Patient Information Resources

In addition to Cancer.Net, there are other sources of information about this type of cancer available online. Cancer.Net maintains a list of national, not-for-profit organizations that may be helpful in finding additional information, services, and support. As always, be sure to talk with your doctor about questions you may have about information you find about this disease.

View organizations that offer information on this specific type of cancer.