Metastatic Malignant Melanoma

Metastatic melanoma occurs when melanoma, the most serious type of skin cancer, spreads from its original location to other parts of the body, most commonly to the skin, lymph nodes, lungs, liver, bones, or brain.

Table of contents

• What is Metastatic Melanoma
• Causes and Risk Factors
• Symptoms
• Getting a Diagnosis
• Treatment Options
• What to Expect
• Taking Care of Yourself

What is Metastatic Melanoma

Metastatic melanoma is the most serious form of skin cancer because it has spread beyond its original location to other parts of the body. When melanoma spreads, it is called metastatic or advanced melanoma. Healthcare providers may also refer to it as stage IV melanoma.^[1][2]

Melanoma is the third most common skin cancer after basal and squamous cell carcinoma. In 2023, melanoma ranked as the fifth most common cancer in both males and females.^[1] While most melanomas are detected at an early stage with high survival rates approximating 94%, a proportion of patients have metastatic disease at the time of diagnosis or develop it later.^[1]

Metastatic melanoma usually spreads first into nearby lymph nodes (small bean-sized organs that are part of the immune system) before spreading to other organs. The most common sites where melanoma spreads include the skin and tissue just under the skin, followed by the lungs, liver, bones, and brain.^[1][2] Sometimes melanoma is already advanced when it is first diagnosed.^[3]

Causes and Risk Factors

In most cases, melanoma is caused by exposure to ultraviolet (UV) radiation from the sun or tanning beds. This radiation damages the DNA of skin cells, causing them to grow out of control.^[2] An individual’s risk of the cancer spreading is directly related to the depth of invasion and whether there is ulceration (a break in the skin) of the primary tumor.^[1]

You are more likely to develop melanoma if you have fair skin along with lighter hair and eye color, many moles or irregular moles, or a family history of melanoma.^[2][4] The disease can also occur on parts of the body that don’t get sunlight, such as the palms of the hands and the retinas of the eyes.^[2]

Before age 50, rates of melanoma are higher in women than in men. After age 50, rates are much higher in men.^[4] In men, melanoma is often found on the trunk (the area from the shoulders to the hips) or the head and neck. In women, melanoma forms most often on the arms and legs.^[9]

Symptoms

When melanoma has spread to other areas of the body, symptoms depend on where the cancer has traveled. The symptoms can be vague and may include:^[2][5]

• Hardened lumps under the skin
• Swollen or painful lymph nodes, especially in the armpit or groin
• Trouble breathing or a cough that doesn’t go away
• Swelling of the liver (under the lower right ribs) or loss of appetite
• Bone pain or, less often, broken bones
• Headaches, seizures, or weakness or numbness in the arms or legs
• Weight loss
• Feeling very tired (fatigue) and lacking energy most of the time

If you experience any of these symptoms, it is important to tell your doctor or nurse so they can help you get the treatment you need to relieve them.^[13]

Getting a Diagnosis

Before any tests, your doctor will want to know about your symptoms, when you first noticed them, and whether you have been diagnosed with melanoma before. They will also ask about your family history of melanoma and your history of sun exposure or tanning bed use.^[2]

If you haven’t already been diagnosed with melanoma, your doctor will do a skin exam. If they suspect skin cancer, you will need a biopsy to find out. A biopsy removes a sample of tissue to be examined under a microscope to determine how thick the tumor is. Usually, a thicker tumor means there is a higher risk the cancer will spread.^[2]

If you have been diagnosed with melanoma, you may also have blood tests and imaging tests to see if it has spread to other areas. Different types of imaging tests may be used:^[2]

• Chest X-ray: Uses low doses of radiation to make pictures of the inside of the body
• CT scan (computerized tomography): Uses powerful X-rays to get detailed images of what’s happening inside you
• MRI (magnetic resonance imaging): Uses powerful magnets and radio waves to make pictures of organs and structures inside the body
• PET scan: Uses radioactive material to look for signs of cancer

The doctor will also check to see if your lymph nodes are enlarged. They may use a thin needle to remove a sample of cells from a lymph node for examination.^[2]

The location where the cancer has spread affects prognosis. According to research on patients with stage IV melanoma, those with cancer spread to the skin, lymph nodes, or gastrointestinal tract had a median survival of 12.5 months. Those with isolated lung metastases had a median survival of 8.3 months, while those with cancer in the liver, brain, or bone had a median survival of 4.4 months.^[7]

Treatment Options

The treatment of metastatic melanoma has changed dramatically in recent years with the development of immune checkpoint inhibitors and targeted therapies.^[1] While in many cases metastatic melanoma cannot be cured, treatments and support can help you live longer and better.^[2]

Immunotherapy

Immunotherapy helps strengthen or restore the immune system’s ability to fight cancer. It is commonly offered for metastatic melanoma to help shrink and control the growth of the cancer.^[8] Immunotherapy drugs used include nivolumab, pembrolizumab, nivolumab combined with relatlimab, ipilimumab, and lifileucel.^[8]

These drugs are given through a needle into a vein by infusion. How often and how long immunotherapy is given depends on the type of drug used. Immunotherapy drugs may be used alone, or some may be combined with each other.^[8] High-dose interleukin-2 is associated with durable responses in a small percentage of patients.^[7]

For cancer that has spread to nearby areas of skin or lymph vessels that cannot be removed by surgery, localized immunotherapy may be offered. This means the treatment is given directly into or applied to the surface of the tumors.^[8]

Targeted Therapy

Targeted therapy uses drugs to target specific molecules on cancer cells to stop the growth and spread of cancer. It is usually offered for metastatic melanoma with certain gene changes (mutations), including mutations in the BRAF gene.^[8]

A critical question for guiding the choice of treatment is whether the tumor contains a BRAF V600 mutation. For patients with this mutation, targeted combination therapy options include dabrafenib combined with trametinib, vemurafenib combined with cobimetinib, or encorafenib combined with binimetinib.^[8][11] For patients without a BRAF mutation, single-agent immunotherapy with pembrolizumab or nivolumab is recommended.^[11]

Targeted therapy drugs are taken as pills by mouth daily. How long treatment is given depends on the type of drug used and how well the cancer responds to treatment.^[8]

Surgery

Surgery is rarely used to treat metastatic melanoma. You may be offered surgery if cancer is found in only one or a few small areas on or just under the skin, in one group of lymph nodes, or in a single location in the lung, liver, brain, or small intestine.^[8] In patients with solitary or acutely symptomatic brain metastases, surgical management or treatments such as gamma knife radiation may alleviate symptoms and provide local control of disease.^[11]

Radiation Therapy

Radiation therapy uses high-energy rays or particles to destroy cancer cells. It may be offered for metastatic melanoma and is also used as palliative treatment to help relieve symptoms.^[8]

What to Expect

The 10-year survival rate for patients with metastatic melanoma is less than 10%.^[7] However, doctors have therapies that have greatly increased survival rates, and researchers are working to find new medications that can do even more.^[2]

Many factors have been proposed to influence prognosis in patients with metastatic melanoma. In addition to the site of disease, the presence of elevated serum lactate dehydrogenase is an important prognostic factor.^[7]

Treatment may be able to shrink the melanoma or stop it growing for a time. You will need to talk to your specialist to understand what your diagnosis means, what’s likely to happen, what treatments are available, and how treatment can help you.^[3]

For stage IV melanoma, follow-up care is important. This typically involves regular physical exams, imaging tests as needed, and monitoring for any new symptoms or changes in your health. You should report any new symptoms to your healthcare team promptly.^[16]

Taking Care of Yourself

From the moment you learn that you or someone you love has melanoma, you will face challenging decisions and at times overwhelming circumstances. Learning to live and manage this new normal will take time. Throughout your journey with melanoma, it’s important to listen to your body, give yourself some slack, and remember that you are more than any diagnosis.^[14]

Find Support

It’s important to have people you can talk to about your plans, fears, and feelings. You might find it helpful to talk to your family and friends about the cancer, though some people may find this difficult.^[2][3] You can also reach out to a counselor or join a support group, either in person or online, where you can get advice from people going through the same thing.^[15]

Specialist nurses can help if you’re finding it difficult to cope or if you have any problems. They can get you the help you need and provide information about support in your local area.^[13]

Maintain Good Nutrition

Getting the right nutrients can raise your energy levels and help your body fight the cancer. Aim to eat a balanced diet that includes protein from lean sources such as beans, fish, lean meat, chicken, and nuts; carbohydrates from whole grains; plenty of colorful fruits and vegetables for vitamins, minerals, and antioxidants; and healthy fats from vegetable oils, avocados, and nuts.^[15] You need to drink at least eight 8-ounce cups of liquid each day, but have more if you’re vomiting or have diarrhea.^[15]

Stay Active

A workout may be the last thing you feel like doing, but exercise helps you stay strong. It can also boost your energy levels, curbing the fatigue brought on by the disease, and is a good way to ease stress and anxiety.^[15] Before you start an exercise program, talk with your doctor about how much activity and what type of activity is best for you.^[15]

Manage Fatigue

You may experience cancer-related fatigue, a lack of energy caused by various factors including treatment. You’ll need to plan your activities, since you have a limited amount of energy. Prioritize what’s important, ask for help, or say no to other things. Take it easy when you need to.^[15]

Get Adequate Rest

Many people with cancer have trouble sleeping. To help you sleep more soundly, try going to bed and waking up around the same time each day, use your bedroom only for sleep, keep a journal by your bed to jot down distracting thoughts, and keep your bedroom slightly cool if you have night sweats.^[15]

Practice Self-Care

After learning you have melanoma, self-care might look different than before. Making time and space in your life to take care of yourself is more important now than ever. Remember that saying no to invitations or requests is okay when you need time and space to heal, process, and take care of yourself. Do more of what you love, whether that’s reading, spending time with loved ones, or pursuing hobbies.^[14]

Manage Pain and Other Symptoms

It is important that you feel as well as you possibly can. Tell your doctor or nurse if you have any symptoms such as pain. They can help you get the treatment you need to relieve them.^[13]

Get Financial Support

You might have extra expenses due to the cancer. Your specialist nurse or GP can help you get grants for heating costs, holidays, or household expenses related to your illness. Ask to see a social worker who can let you know which benefits or grants you can claim and help with the claiming process.^[13]