Melanoma is a cancer of the skin. It begins when color-producing cells, called melanocytes, become abnormal and begin to grow uncontrollably, forming a mass of cells called a tumor. Melanoma can appear in an area no different from surrounding skin, or it can develop from or near a mole. It is found most frequently on the backs of men and women or on the legs of women, but melanoma can occur anywhere on the body, including the head and neck. This section describes melanoma of the skin. For information on basal cell and squamous cell skin cancers, read the Cancer.Net Guide to Non-Melanoma Skin Cancer. For more information on melanoma of the eye, read the Cancer.Net Guide to Eye Cancer. For information on anorectal melanoma, see the Cancer.Net Guide to Anal Cancer.

The skin, the body's largest organ, protects against infection and injury and helps regulate body temperature. The skin also stores water and fat and produces vitamin D. 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 starts in melanocytes and is the most aggressive type of skin cancer. It can grow deep into the dermis, invading lymph and blood vessels. The initial type of treatment is determined by the size of the tumor as measured in thickness.

People diagnosed with melanoma may face more extensive treatment than those with non-melanoma skin cancer. Treatment of the primary (initial) melanoma usually involves surgery, which often cures early stage or thin melanoma. Chemotherapy, radiation therapy, and/or immunotherapy may also be part of the treatment for more advanced disease. Researchers are also investigating new approaches to treating advanced melanoma, including targeted therapy, gene therapy, and vaccine therapy.

Statistics

In 2008, an estimated 62,480 adults (34,950 men and 27,530 women) in the United States will be diagnosed with melanoma. It is estimated that 8,420 deaths (5,400 men and 3,020 women) from this disease will occur this year.

Melanoma accounts for about 3% of skin cancer cases and a large majority of skin cancer deaths. Melanoma is the sixth most common cancer among men and the seventh most common cancer in women. Sometimes, melanoma is found in children and adolescents. Melanoma rates are more than 10 times higher in white people than black people.

The five-year relative survival rate (percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) of patients with melanoma is 91%. If melanoma is found before it has spread, the five-year relative survival rate is 99%. The five-year relative survival rate if melanoma is found to have regional and distant spread is 65% and 15%, respectively.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of 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 (or sometimes one-year) intervals, they may not represent recent advances made in the treatment or diagnosis of this cancer.

Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2008.

To learn about the cancer terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Basic Oncology Terms.

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A risk factor is anything that increases a person's chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. 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 communicating them to your doctor may help you make more informed lifestyle and health-care choices.

The following factors increase the risk of developing melanoma:

Individual history. People with increased numbers of moles or those with unusual moles called dysplastic nevi (flat, large moles that have irregular color and shape) are at higher risk for developing melanoma. About 50% of melanoma cases occur in people who have dysplastic nevi. Also, people who have weakened immune systems or those who use certain medications that suppress immune function are at higher risk for developing skin cancer. In addition, people who have had one melanoma are at increased risk for developing additional new melanomas; overall, in the general population, 2% of people who develop one melanoma develop other new melanomas. People who have had a non-melanoma skin cancer are also at a somewhat increased risk for developing melanoma.

Family history. Approximately 10% of melanoma occurs in individuals who 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. Alterations in two genes (CDKN2A and CDK4) that may lead to melanoma have been identified. These genes, however, only account for a small proportion of families with melanoma. Genetic testing for these two genes is not currently used in clinical practice. It is likely that other genes and environmental factors also affect risk of melanoma. For more information, please read The Genetics of Melanoma.

Exposure to ultraviolet (UV) radiation. Ultraviolet B (UVB) radiation from the sun produces sunburn and plays a role in the development of both melanoma and non-melanoma skin cancer. Ultraviolet A (UVA) radiation penetrates skin more deeply and may also play a role in the development of both melanoma and non-melanoma skin cancer. 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 significant time outside during midday hours. People who use tanning beds, tanning parlors, or sun lamps are also at increased risk for skin cancer. Even people who tan well increase their risk of melanoma with more sun exposure.

Fair skin. Less pigment (melanin) in skin offers poorer protection against UV radiation. People with light hair and light-colored eyes who have skin that tans poorly or freckles, or those who burn easily, are two to three times more likely to develop melanoma.

Sunburn. According to many scientific studies, multiple, severe, blistering sunburns increase the risk of developing melanoma.

Prevention

Reducing exposure to UV radiation, particularly through sun exposure, lowers the risk of melanoma. This is important for all age groups, and it is especially important for people who have risk factors for melanoma. Sun damage is cumulative, meaning it builds up over time. Steps to reduce sun exposure, avoid sunburn, and help prevent many cases of melanoma include:

• Limiting or avoiding sun exposure between 10:00 AM and 4:00 PM
  
  
• 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 often, especially after heavy perspiration or being in the water
  
  
• Examining skin regularly (examinations by a health-care professional and self-examinations)
  
  
• Avoiding use of sun lamps, tanning beds, and tanning salons

People with melanoma may experience the following symptoms. Sometimes, people with melanoma do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. The skin features that frequently occur in melanoma are listed below. If you are concerned about a symptom or skin feature on this list, please talk with your doctor.

Changes in the skin are often the first warning sign of melanoma. An accurate diagnosis by a doctor or other health-care professional is critical. Often, the diagnosis can only accurately be made after a lesion is removed and examined. Melanoma can appear anywhere on the body, even on areas that are not exposed to the sun, and can appear in a number of different ways:

• A new, possibly large, irregularly shaped, dark brownish spot with darker or black areas
  
  
• A simple mole that changes in color (particularly turning darker), size (growing), or texture (becoming firmer), and/or flakes or bleeds
  
  
• A lesion with an irregular border and red, white, blue, gray, or bluish-black areas or spots
  
  
• Shiny, firm, dome-shaped bumps anywhere on the body
  
  
• Dark lesions under the fingernails or toenails, on the palms, soles, tips of fingers and toes, or on mucous membranes (skin that lines the mouth, nose, vagina, and anus)

Early detection of melanoma

The earlier melanoma is detected, the better the chance for successful treatment. Periodic self-examinations may help find melanoma early.

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.

A doctor should be consulted for:

• A growth on the skin that matches any feature on the above list
  
  
• 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
  
  
• A sore that doesn't heal within two weeks

Often, the first sign of melanoma is a change in the size, shape, or color of an existing mole. It also may appear as a new or abnormal-looking mole. The "ABCDE" rule can be used to help remember what to watch for:

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

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

Color: The color is often uneven. 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) (the size of a pencil eraser) or has grown in size.

Evolving: The mole has been changing in size, shape, color, 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, lumpy, or scaly. Although the skin may feel different and may itch, ooze, or bleed, melanoma usually does not cause pain.

Doctors use many tests to diagnose cancer and determine if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For melanoma, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

• Age and medical condition
• The type of cancer
• Severity of symptoms
• Previous test results

If a person shows signs of melanoma, the doctor will take a complete medical history, noting the symptoms and risk factors. The doctor may order various tests to confirm a diagnosis of melanoma and/or determine if or where the disease has spread.

Physical examination. A physical examination should include examining the person's skin for lesions.

Biopsy. A doctor who suspects a skin spot is melanoma will perform a biopsy. In this procedure (usually performed with a local anesthetic to numb the area), the doctor removes the suspect lesion using techniques that preserve the entire lesion so that the thickness of the potential cancer and its margins (healthy tissue around the lesion that is removed to make sure no cancer cells remain) can be carefully examined. The tissue is sent to 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.

Sentinel lymph node biopsy. This type of biopsy is a surgical procedure and is used to determine if cancer cells have spread to the regional lymph nodes. (See Treatment.)

X-ray. An x-ray is a picture of the inside of the body. For instance, a chest x-ray can help doctors determine if the cancer has spread to the lungs.

Blood tests. The patient's blood may be tested to help determine if the cancer has spread.

Occasionally, the following tests may be performed to diagnose melanoma and/or help determine the extent of the disease:

Ultrasound. An ultrasound uses sound waves to create pictures of the internal parts of the body, including collections of lymph nodes (called 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.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body.

Positron emission tomography (PET) scan. In a PET scan, radioactive sugar molecules are injected into the body. Cancer cells usually absorb sugar more quickly than normal cells, so they may light up on the PET scan. PET scans are often used to complement information gathered from CT scan, MRI, and physical examination.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Newly Diagnosed.

To learn more about what to expect during common diagnostic tests, read Cancer.Net: Tests and Procedures.

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine a cancer's stage, so staging may not be complete until all 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 properly stage melanoma, the lesion and some surrounding normal tissue are surgically removed and analyzed using a microscope. Doctors use the melanoma's thickness, measured in millimeters (mm), to help determine the disease's stage. 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 uses three criteria to judge the stage of the cancer: the tumor itself, the regional lymph nodes around the tumor, and if the tumor has spread to the rest of the body. The results are combined to determine the stage of cancer for each person. There are five stages: 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 large 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 the first of three factors that doctors use to determine the overall stage of the melanoma. The T classification is used to describe the primary melanoma, particularly its size.

If the outer layer of skin (the epidermis) does not appear under a microscope to be overlying the melanoma, that is referred to as ulceration. In addition, the doctor may also refer to the Clark's level of the tumor, which is a specific classification to describe how deep the melanoma has grown into the layers of skin. The Clark's level also uses Roman numerals (I, II, III, IV,V; one to five) in its description.

Based on the size, ulceration, and Clark's level, some T classifications are subdivided into smaller groups that describe more details about a patient's condition. This helps the doctor develop the best treatment plan for each patient. Tumor classification information is listed below.

TX: The tumor cannot be evaluated.

T0: There is no evidence of cancer.

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 have not showed 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 Clark's level II or III.

T1b: The primary tumor has ulceration or Clark's level IV or V.

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 second of three factors to determine the stage, the "N" in the TNM system stands for regional lymph nodes, the normally small, bean-shaped organs that are located throughout the body. The lymph nodes normally help the body fight infection and cancer and are an important part of the body's immune system. In addition, the "N" classification includes whether small deposits of melanoma are found between the primary tumor and the regional lymph nodes (in-transit metastases or satellites).

NX: The regional lymph nodes cannot be evaluated.

N0: There is no evidence of cancer spread to 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 under a microscope (microscopic metastasis).

N1b: The doctor can feel the cancer in the lymph nodes, or see it on a scan (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 under a microscope (microscopic metastasis).

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

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.



• Two or more lymph nodes appear joined together (called matted lymph nodes).



• In-transit metastases or satellites are present, with any number of affected lymph nodes.

Metastasis. The "M" in the TNM system describes melanoma that has spread beyond the primary melanoma site and the regional lymph nodes. In melanoma, metastasis can be identified 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. This is the third of the three factors used to determine the overall stage of the melanoma.

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 parts of the skin, 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 marker called LDH is classified as MIc. A serum tumor marker 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.

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 is Clark's level II or III.

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Stage IB: Describes either of these conditions:

• The melanoma is 1.0 mm or smaller, and either has ulceration or Clark's level IV or V invasion.
  
  
• The melanoma is between 1.0 mm and 2.0 mm and has no ulceration.

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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.

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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.

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

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Stage III: The melanoma is of any thickness and 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.

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Stage IIIB: Describes any of these conditions:

• The melanoma has spread to up to three regional lymph nodes in clinically apparent form (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.

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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.

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Stage IV: The primary melanoma has spread to other, distant parts of the body beyond the regional lymph nodes (called distant metastasis). 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.

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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, Sixth Edition (2002) published by Springer-Verlag New York, www.springer-ny.com.

The treatment of melanoma depends on the size and location of the tumor, whether the cancer has spread, and the person's overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan. The team may include such specialists as a surgical oncologist, medical oncologist, radiation oncologist, dermatologist (a doctor who specializes in diseases and conditions of the skin), and a pathologist.

Surgery

Melanoma can be successfully treated in almost all cases if it is diagnosed and treated when the tumor is relatively thin. Surgery to remove the tumor is the standard treatment.

Most melanomas are found when they are thin (less than 1.0 mm), when outpatient surgery is often all the treatment required. A doctor will remove the tumor and some healthy tissue around it to make sure no cancer cells remain; the amount of normal tissue that should be removed depends on the thickness of the melanoma. If the melanoma has grown deep into the skin, lymph nodes near the tumor may be removed and examined for cancer cells. In some cases, the doctor may recommend a sentinel lymph node biopsy (see below); this may be an outpatient procedure or require an overnight stay in the hospital.

Typically, the complete excision (surgical removal) of the melanoma requires the removal of 1.0 centimeters (cm) (3/8 of an inch) to 2.0 cm (3/4 of an inch) of normal-appearing skin surrounding the melanoma in all directions, called the margin. In addition, the underlying fat tissue is removed. The specific size of the margin taken depends on the size, stage, and potential aggressiveness of the melanoma. If it is staged as melanoma in situ (Stage 0), a margin of between 0.5 cm to 1.0 cm may be recommended. In general, a thin melanoma (measuring 1.0 mm or smaller in thickness) can be safely excised with a 1.0 cm margin of skin, while a thicker melanoma requires a 2.0 cm margin of skin.

Depending on the site of the surgery, a skin graft (using the skin from another part of the body to both close the wound and reduce scarring) may be necessary. Since melanoma surgery for primary melanoma is usually limited to the removal of the skin and subcutaneous tissues, rehabilitation is rarely necessary for this procedure.

To determine if the melanoma has spread to regional lymph nodes, the doctor may perform a procedure known as lymphatic mapping and sentinel lymph node biopsy. In this surgical procedure, the doctor removes one or a few sentinel lymph nodes to check for cancer cells. A sentinel lymph node is the first node into which the lymph system drains from the primary melanoma site. If cancer cells are detected in the sentinel lymph node, it means that the disease has spread to the regional lymph node basin. Other lymph nodes in the region are also at risk for spread.

When melanoma has spread to lymph nodes, surgical removal of the remaining lymph nodes in that region is usually recommended. This is called a lymph node dissection. The number of lymph nodes removed varies depending on the area of the body while the likelihood of finding additional affected lymph nodes that contain metastatic melanoma is due in part on the stage of the melanoma. People who have had a lymph node dissection around an arm or leg are at 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 (distant metastasis) is greater in patients who have involved lymph nodes than in patients whose lymph nodes do not contain disease.

If the melanoma has spread to distant organs (Stage IV) or recurs (comes back after treatment), surgery may be a treatment option to help control the disease.

After surgery, the surgeon or medical oncologist may also recommend adjuvant treatment (treatment given after the primary treatment) based on what information was learned about the disease during surgery. This may include immunotherapy, chemotherapy, and/or radiation therapy; see more information below on each treatment.

Immunotherapy

Immunotherapy (also called biologic therapy) works by helping the body's immune system find and attack cancer cells. It uses materials either made by the body or in a laboratory to boost, target, or restore immune function. Immunotherapy works well in treating melanoma, particularly in reducing the risk that the melanoma will recur. Immunotherapy may be used in combination with surgery and/or chemotherapy, or as part of a clinical trial. Many immunotherapies are being evaluated for melanoma in clinical trials.

Only one adjuvant therapy has been shown to consistently reduce the likelihood of a recurrence of melanoma, and this treatment is called high-dose interferon alfa-2b. This treatment, given intravenously (injected into a vein) in the doctor's office 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, has been shown to reduce recurrence and, in two clinical trials, has prolonged survival significantly. This is the only therapy that is currently approved as adjuvant therapy, except as part of a clinical trial. Adjuvant therapy for melanoma is often recommended when the primary melanoma is found at a later stage or if there is involvement of lymph nodes.

Interleukin-2 (IL-2) is another immunotherapy used to treat melanoma. High-dose IL-2 treatment is used with patients when cancer has spread beyond the scope of surgery. In clinical trials, the therapy does not significantly increase a patient's life span, but it delays the time it takes for cancer to reappear after treatment. A few patients have had long-term disappearance of detectable melanoma with this approach.

Some cancer centers offer an experimental treatment for melanoma in the form of a therapeutic vaccine. Certain proteins that are unique to melanoma tumors are given as an injection. The person's immune system then recognizes these proteins and destroys the cancerous cells. Vaccines may be given to patients as part of a clinical trial. Another type of experimental immunotherapy involves altering the patient's lymphocytes (white blood cells) in the laboratory to enhance 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 only available as part of a clinical trial.

Side effects of these treatments vary widely. They can include fatigue, fever, chills, headache and some memory difficulties, muscle ache, and skin irritation. Occasionally, side effects from immunotherapy can include a change in blood pressure or cause increased fluid in the lungs. Side effects of immunotherapy can be greater than or less than side effects from other types of treatment. Patients should discuss with their doctors the benefits and risks of each treatment option.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. For melanoma, this is typically used when there is a high risk that the melanoma may spread or to control advanced disease, although cure of widespread melanoma is rare. There are several combinations of chemotherapy that are currently being tested in clinical trials.

In addition to systemic chemotherapy, there are also chemotherapy techniques to focus on a specific region, if melanoma has spread but not beyond a limb (an arm or a leg). Isolated limb perfusion (ILP) is an approach that involves both surgery and chemotherapy. First, a surgeon separates the limb's blood circulation from the rest of the body. Then, a high dose of chemotherapy is injected to the limb's bloodstream to kill cancer cells. Isolated limb infusion (ILI) is similar to ILP, but in order to isolate the limb's blood circulation from the rest of the body, pressure is applied above the area using a tourniquet; a high dose of chemotherapy is then injected into the bloodstream of the limb to kill cancer cells via catheters inserted into the major blood vessels entering and leaving the limb.

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

Common systemic chemotherapy used for melanoma include dacarbazine (DTIC), carboplatin (Paraplatin), cisplatin (Platinol), and temozolamide (Temodar). ILP/ILI may use melphalan (Alkeran). The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body.

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 to the brain and bones. It may also be used when cancer has spread to the lymph nodes, following a lymph node dissection (see above). Radiation therapy is also used when the extent of surgery for a larger melanoma is limited by the location of the tumor. And, research is being done to test the effectiveness of chemoradiation, a combination of radiation therapy and chemotherapy, to treat melanoma.

Radiation therapy can cause skin irritation, nausea, and fatigue. 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 altered taste and dry mouth, may occur. These side effects usually go away once treatment is finished. If lymph nodes near an arm or leg were affected, the person may be at higher risk of fluid build-up in that limb, a side effect called lymphedema (see Side Effects). Lymphedema can be a long-term, ongoing side effect.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.

Doctors and scientists are always looking for better ways to treat patients with melanoma. A clinical trial is a way to test a new treatment in order to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy drugs, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

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 finding new drugs and other therapies 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.

To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient's options, so 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 than 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.

Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below are some of the side effects that are potentially associated with treatments for melanoma. For more detailed information on managing these and other side effects of cancer and cancer treatment, visit the Cancer.Net Managing Side Effects section.

Diarrhea. Diarrhea is frequent, loose, or watery bowel movements. It is a common side effect of certain chemotherapy or of radiation therapy to the pelvis, such as in women with uterine, cervical, or ovarian cancers. It can also be caused by certain tumors, such as pancreatic cancer.

Dry mouth (xerostomia). Xerostomia occurs when the salivary glands do not make enough saliva (spit) to keep the mouth moist. Because saliva is needed for chewing, swallowing, tasting, and talking, these activities may be more difficult with a dry mouth. Dry mouth can be caused by chemotherapy or radiation treatment, which can damage the salivary glands. Dry mouth caused by chemotherapy is usually temporary and normally clears up about two to eight weeks after treatment ends. Radiation treatment to the head, face, or neck can cause dry mouth and is most common with radiation treatment to the oral cavity to treat head and neck cancer. It can take six months or longer for the salivary glands to start producing saliva again after the end of treatment.

Fatigue. Fatigue is extreme exhaustion or tiredness and is the most common problem patients with cancer experience. More than half of patients experience fatigue during chemotherapy or radiation therapy, and up to 70% of patients with advanced cancer experience fatigue. Patients who feel fatigue often say that even a small effort, such as walking across a room, can seem like too much. Fatigue can seriously affect family and other daily activities, can make patients avoid or skip cancer treatments, and may even affect the will to live.

Flu-like symptoms. Interferon alfa-2b and interleukin-2 are immunologic and biologic therapies and are associated with many symptoms that are commonly associated with flu or a cold, such as fever, chills, and malaise. These symptoms diminish with repetitive treatments and differ from the side effects commonly associated with cancer chemotherapy drugs that are not biologics. Supportive treatment of these symptoms is as important as the support of other side effects of cancer treatment, and your doctor may stress the important of taking adequate fluids, rest, and medications that reduce fever, chills, and flu-like symptoms for this reason.

Hair loss (alopecia). A potential side effect of radiation therapy and chemotherapy is hair loss. Radiation therapy and chemotherapy cause hair loss by damaging the hair follicles responsible for hair growth. Hair loss may occur throughout the body, including the head, face, arms, legs, underarms, and pubic area. The hair may fall out entirely, gradually, or in sections. In some cases, the hair will simply thin-sometimes unnoticeably-and may become duller and dryer. Losing one's hair can be a psychologically and emotionally challenging experience and can affect a patient's self-image and quality of life. However, the hair loss is usually temporary, and the hair often grows back.

Infection. An infection occurs when harmful bacteria, viruses, or fungi (such as yeast) invade the body and the immune system is not able to destroy them quickly enough. Patients with cancer are more likely to develop infections because both cancer and cancer treatments (particularly chemotherapy and radiation therapy to the bones or extensive areas of the body) can weaken the immune system. Symptoms of infection include fever (temperature of 100.5°F or higher); chills or sweating; sore throat or sores in the mouth; abdominal pain; pain or burning when urinating or frequent urination; diarrhea or sores around the anus; cough or breathlessness; redness, swelling, or pain, particularly around a cut or wound; and unusual vaginal discharge or itching.

Fluid in the arms or legs (lymphedema). Lymphedema is the abnormal buildup of fluid in the lymphatic system, the series of channels and nodes (small sacs that hold fluid) that carries lymph through the body and helps fight infection and disease. Lymph is a clear liquid that carries protein and cells that fight infection. When cancers metastasize (spread), cells first go to the lymph nodes and then are carried to other parts of the body. Lymphedema can develop immediately after cancer surgery or radiation therapy, or it can develop months or years later. The most common causes of lymphedema include surgery to remove the lymph nodes, especially for breast cancer, prostate cancer, or melanoma; radiation therapy to the lymph nodes; metastatic cancer (cancer that has spread from its primary location); bacterial or fungal infection; injury to the lymph nodes; and other diseases involving the lymph system.

Mouth sores (mucositis). Mucositis is an inflammation of the inside of the mouth and throat, leading to painful ulcers and mouth sores. It occurs in up to 40% of patients receiving chemotherapy treatments. Mucositis can be caused by a chemotherapeutic drug directly, the reduced immunity brought on by chemotherapy, or radiation treatment to the head and neck area.

Nausea and vomiting. Vomiting, also called emesis or throwing up, is the act of expelling the contents of the stomach through the mouth. It is a natural way for the body to rid itself of harmful substances. Nausea is the urge to vomit. Nausea and vomiting are common in patients receiving chemotherapy for cancer and in some patients receiving radiation therapy. Many patients with cancer say they fear nausea and vomiting more than any other side effects of treatment. When it is minor and treated quickly, nausea and vomiting can be quite uncomfortable but cause no serious problems. Persistent vomiting can cause dehydration, electrolyte imbalance, weight loss, depression, and avoidance of chemotherapy.

Nervous system disturbances. Nervous system disturbances can be caused by many different factors, including cancer, cancer treatments, medications, or other disorders. Symptoms that result from a disruption or damage to the nerves caused by cancer treatment (such as surgery, radiation treatment, or chemotherapy) can appear soon after treatment or many years later. See Managing Side Effects: Nervous System Disturbances for the most common symptoms.

Skin problems. The skin is an organ system that contains many nerves. Because of this, skin problems can be very painful. Many patients find skin problems especially difficult to cope with because the skin is on the outside of the body and visible to others. Because the skin protects the inside of the body from infection, skin problems can often lead to other serious problems. As with other side effects, prevention or early treatment is best. In other cases, treatment and wound care can often improve pain and quality of life. Skin problems can have many different causes, including chemotherapeutic drugs leaking out of the intravenous (IV) tube, which can cause pain or burning; peeling or burned skin caused by radiation therapy; pressure ulcers (bed sores) caused by constant pressure on one area of the body; and pruritis (itching) in patients with cancer, most often caused by leukemia, lymphoma, myeloma, or other cancers.

Taste changes. Dysgeusia refers to a change in the way foods taste. Some foods may taste different than they used to, foods may not have much taste at all, or everything may taste the same. Bitter, sweet, and salty foods may taste different than they did before, and some patients experience a metallic or chemical taste in their mouth, especially after eating meat or other high-protein foods. Taste changes can lead to food aversions (dislikes), loss of appetite, and weight loss. Taste changes are a common side effect of chemotherapy. About 50% of patients receiving chemotherapy experience taste changes. Radiation therapy to the head and neck can cause taste changes because of damage to the taste buds. Radiation therapy can also cause changes to the sense of smell. Since smell and taste are closely linked, changes to the sense of smell can affect how foods taste.

After treatment for melanoma ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years.

Routine screening for new additional melanoma (and non-melanoma skin cancer) is necessary as part of follow-up care, as is use of sun-protective measures. Screening measures 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 essential to help prevent second malignancies, either melanoma or non-melanoma skin cancers. Many people who are treated for melanoma lead an active, outdoor lifestyle, but it is essential to take steps to protect themselves from further skin damage. Participating in outdoor activities before 10:00 AM or after 4:00 PM and wearing long sleeves, pants, sunscreen, and a hat will protect against further skin damage. A major consideration following diagnosis and treatment of melanoma is adjusting a person's lifestyle to use sun protective 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.

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 services.

If the person's treatment included lymph node dissection and/or radiation therapy to the axillary (under the arm) or inguinal areas (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 the person treated for melanoma is experiencing pain from surgery, he or she should speak with the surgeon or other health-care team member. Although rare, some individuals have post surgical long-term pain. If needed, a pain management specialist can also help find ways to manage pain.

People recovering from melanoma are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, 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 Healthy Living After Cancer.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: After Treatment.

Research for melanoma is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Always discuss all prevention, diagnostic, and treatment options with your doctor.

Enhanced prevention and early detection methods. Both primary prevention (keeping melanoma from developing) and secondary prevention (early detection of melanomas) are important. One promising avenue of intervention is in screening of high-risk populations. A melanoma risk calculator has been developed for use by health-care professionals to estimate an individual's five-year cumulative risk of melanoma; the validity of the risk calculator needs to be tested in other groups of patients. Other tools being used for early detection of melanoma include epilluminescence microscopy or dermoscopy, which evaluates patterns of size, shape, and pigmentation in pigmented skin lesions. Among trained, experienced examiners, use of dermoscopy may reduce the number of biopsies of pigmented lesions to rule out melanoma, although more research is needed. Another new technology to visualize melanocytic lesions is confocal scanning laser microscopy, but this is only available in a few major facilities.

New and enhanced treatments. New approaches to treating melanoma are being investigated, including combinations of traditionally used treatments, new immunotherapeutic and chemotherapeutic agents, therapeutic vaccines, gene therapy, and targeted therapies. Vaccines aim to stimulate the body's own defenses to destroy melanoma cancer cells. Evidence is mounting that vaccination can cause immune responses to melanoma, even in advanced disease, but these therapies are still considered experimental. In addition, there are several new chemotherapy drugs and combinations being evaluated in clinical trials. Gene therapy is a targeted form of treatment that uses biologic gene manipulation to change bits of genetic code in a person's cells. Although gene therapy is relatively new, it shows promising 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. Also, treatments based on what is known about genetics and how changes in genes cause cancer to develop are already available for some cancers. These are called targeted treatments because they can pick out one signal, or target, in the process of cancer formation and repair it without killing healthy cells. Research is underway to determine how this approach may be useful in treating melanoma.

Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:

For patients with primary melanoma (initial diagnosis of a skin lesion):

• What stage of melanoma do I have? What is the size, in millimeters, of the melanoma? Is the melanoma ulcerated? What is the depth of the melanoma (the Clark's level)?



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



• What stage of melanoma do I have?



• What are my treatment options? What treatment plan do you recommend? Why?



• What are the goals of this treatment?



• 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?



• Should I have another type(s) of treatment following surgery?



• Is the cancer likely to recur (come back)?



• What is my prognosis?



• What follow-up care is necessary? What steps can I take to reduce the risk of additional new melanomas?



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

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):

• Will the remainder of the lymph nodes be removed?



• What are the potential complications of lymph node surgery?



• How many lymph nodes are affected?



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



• Is radiation therapy recommended after surgery?



• Do recommend other types of treatment after surgery? What are the risks and benefits of each treatment?



• What are the goals of treatment?



• What are the side effects of each treatment?



• What clinical trials are open to me?



• What is my prognosis?



• What follow-up care is necessary?

For patients with stage IV (advanced) melanoma:

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



• What are the treatment options?



• What are the goals of treatment?



• 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 clinical trials are open to me?



• What is my prognosis?

American Academy of Dermatology
P.O. Box 4014
Schaumburg, IL  60618-4014
Toll Free: 866-503-SKIN (7546)
Phone: 847-330-0230
www.aad.org

Melanoma Center
www.melanomacenter.org

Melanoma International Foundation
250 Mapleflower Rd.
Glenmoore, PA  19343
Toll Free (Patient and Family Hotline): 866-463-6663
Phone: 610-942-3432
www.melanomaintl.org

Melanoma Patients' Information Page
The Pattersons
P.O. Box 389
Cloverdale, CA  95425
www.mpip.org

National Council on Skin Cancer Prevention
c/o Michelle Baker
5800 Wilson Lane
Bethesda, MD  20817
www.skincancerprevention.org

Skin Cancer Foundation
149 Madison Ave., Ste. 901
New York, NY  10016
Phone: 800-SKIN-490
www.skincancer.org

SunWise School Program
U.S. Environmental Protection Agency
1200 Pennsylvania Ave., NW (6205J)
Washington, DC  20460
www.epa.gov/sunwise

View all of Cancer.Net's Patient Information Resources.