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Cancer Medicine :: Skin Cancer (Melanoma)Treatment

Skin Cancer (Melanoma)

General treatment information

Once melanoma has been diagnosed and staged, your cancer care team will discuss your treatment options with you. Depending on your situation, you may have different types of doctors on your treatment team. These doctors may include:

A dermatologist: a doctor who treats diseases of the skin.

A surgical oncologist: a doctor who uses surgery to treat cancer.

A medical oncologist: a doctor who treats cancer with medicines such as chemotherapy, immunotherapy, or targeted therapy.

A radiation oncologist: a doctor who treats cancer with radiation therapy.

Many other specialists may be involved in your care as well, including nurse practitioners, nurses, nutrition specialists, social workers, and other health professionals.

Based on the stage of the cancer and other factors, your treatment options may include:

Surgery

Chemotherapy

Immunotherapy

Targeted therapy

Radiation therapy

Early-stage melanomas can often be treated effectively with surgery alone, but more advanced cancers often require other treatments. Sometimes more than one type of treatment is used.

It is important to consider your options carefully. If there is anything you do not understand, ask to have it explained.

The next few sections describe the types of treatments used for melanoma of the skin. This is followed by a description of the most common treatment options based on the stage of the melanoma.

Surgery for melanoma skin cancer

Surgery is the main treatment option for most melanomas, and usually cures early stage melanomas.

Simple excision

Thin melanomas can usually be completely cured by a fairly minor surgery called simple excision. The tumor is cut out, along with a small amount of normal non-cancerous skin at the edges. The normal, healthy skin around the edges of the cancer is referred to as the margin.

Simple excision differs from an excisional biopsy. The margins are wider because the diagnosis is already known. The recommended margins vary depending on the thickness of the tumor. Thicker tumors call for larger margins.

Tumor thickness Recommended Margins
In situ 0.5 cm
1 mm or less 1 cm
1 to 2 mm 1 to 2 cm
2 to 4 mm 2 cm
Over 4 mm 2 cm

These margins may need to be altered based on where the melanoma is on the body and other factors. For example, if the melanoma is on the face, the margins may be smaller to avoid large scars or other problems.

Local anesthesia is injected into the area to numb it before the excision. The wound is carefully stitched back together afterward. This will leave a scar.

Re-excision (wide excision)

When a diagnosis of melanoma is made by biopsy, the site will probably need to be excised again. More skin will be cut away from the melanoma site, and the sample will be viewed under a microscope to make sure that no cancer cells remain in the skin. The size of the margin depends on the thickness of the tumor (see the table above).

In some cases, the surgeon may use Mohs surgery (but not all doctors agree on its use for melanoma). In this procedure, the skin (including the melanoma) is removed in very thin layers. Each layer is then viewed under a microscope for signs of cancer. The operation continues until a layer shows no signs of cancer. In theory, this allows the surgeon to remove the cancer while saving as much of the surrounding normal skin as possible.

If the melanoma is on a finger or toe, the treatment may require amputation of all or part of that digit.

Lymph node dissection

In this operation, the surgeon removes all of the lymph nodes in the region near the primary melanoma. For example, if a skin melanoma is found on a leg, the surgeon would remove the nodes in the groin region on that side of the body, which is where melanoma cells would most likely travel to first.

Once the diagnosis of melanoma is made from the skin biopsy, the doctor will examine the lymph nodes nearest the melanoma. Depending on the thickness and location of the melanoma, this may be done by physical exam, or by imaging tests for nodes that are not near the surface.

If the nearby lymph nodes feel abnormally hard or large, and a fine needle aspiration (FNA) biopsy or excisional biopsy finds melanoma in a node or nodes, a lymph node dissection is usually done.

If the lymph nodes are not enlarged, a sentinel lymph node biopsy may be done, particularly if the melanoma is thicker than 1 mm.  If the sentinel lymph node does not show cancer, then it is unlikely the melanoma has spread to the lymph nodes and there is no need for a lymph node dissection. If the sentinel lymph node contains cancer cells, removing the remaining lymph nodes in that area with a lymph node dissection is usually advised. This is called a completion lymph node dissection.

It is not clear if a lymph node dissection can cure melanomas that have spread to the nodes. This is still being studied. Still, some doctors feel it might prolong a patient’s survival and at least avoid the pain that may be caused by cancer growing in these lymph nodes.

A full lymph node dissection can cause some long-term side effects. One of the most troublesome is called lymphedema. Lymph nodes in the groin or under the arm normally help drain fluid from the limbs. If they are removed, fluid may build up. This can cause limb swelling, which may or may not go away. If severe enough, it can cause skin problems and an increased risk of infections in the limb. Elastic stockings or compression sleeves can help some people with this condition. 

Lymphedema, along with the pain from the surgery itself, is a main reason why lymph node dissection is not done unless it is necessary. Sentinel lymph node biopsy, however, is unlikely to have this effect. It is important to discuss the possible risks of side effects with your doctor before having either of these procedures done.

Surgery for metastatic melanoma

If melanoma has spread from the skin to distant organs such as the lungs or brain, the cancer is very unlikely to be curable by surgery. Even when only 1 or 2 metastases are found by imaging tests such as CT or MRI scans, there are likely to be other areas of metastasis that are too small to be found by these scans.

Surgery is sometimes done in these circumstances, but the goal is usually to try to control the cancer rather than to cure it. If 1 or even a few metastases are present and can be completely removed, this surgery may help some patients live longer. Removing metastases in some places, such as the brain, might also relieve symptoms and help improve the patient's quality of life.

If you have metastatic melanoma and surgery is recommended as a treatment option, talk to your doctor and be sure you understand what the goal of the surgery would be, as well as its possible benefits and risks.

Chemotherapy for melanoma skin cancer

Chemotherapy (chemo) uses drugs that kill cancer cells. The drugs are usually injected into a vein or taken by mouth as a pill. They travel through the bloodstream to all parts of the body and attack cancer cells that have already spread beyond the skin to lymph nodes and other organs. Because the drug reaches all areas of the body, it is called a systemic therapy.

Chemo is often used to treat advanced melanoma. Although it is usually not as effective in melanoma as it is in some other types of cancer, chemo may relieve symptoms or extend survival for some patients.

Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Each chemotherapy cycle typically lasts for a few weeks.

Several chemo drugs may be used to treat melanoma:

Dacarbazine (also called DTIC)

Temozolomide

Paclitaxel

Carmustine (also known as BCNU)

Cisplatin

Carboplatin

Vinblastine

Dacarbazine, temozolomide, and paclitaxel may be given either alone or along with some of the other drugs on the list. It is not clear if using combinations of drugs is more helpful than using a single drug, but it can add to the side effects.

Some studies suggest that combining chemo drugs with immunotherapy drugs such as interferon-alpha and/or interleukin-2 may be more effective than a single chemo drug alone, although it's not clear if this helps people live longer. This type of treatment is also called biochemotherapy or chemoimmunotherapy.

Isolated limb perfusion: This is a type of chemotherapy sometimes used to treat advanced melanomas that are confined to an arm or leg. It is done during a surgical procedure. The blood flow of the arm or leg is separated from the rest of the body, and a high dose of chemotherapy is circulated through the limb for a short period of time.

To do this, a tube is placed into the artery that feeds blood into the limb, and a second tube is placed into the vein that drains blood from it. The tubes are connected to a special machine. A tourniquet is tied around the limb to make sure the chemotherapy does not enter the rest of the body. A high dose of chemotherapy (usually with a drug called melphalan) is then infused into the blood in the limb. During the session, the blood exits the limb through the tube in the vein, is heated by a machine in the operating room, and is then recirculated back into the limb through the tube in the artery. By the end of the treatment the drug is completely washed out of the limb, and the tubes are removed so that the circulation is returned to normal.

Isolated limb perfusion lets doctors give high doses to the area of the tumor without exposing internal organs to these doses, which would otherwise cause severe side effects.

Possible side effects of chemotherapy

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken. These side effects may include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting

Diarrhea

Increased risk of infection (from too few white blood cells)

Easy bruising or bleeding (from too few blood platelets)

Fatigue (from too few red blood cells)

These side effects are usually short-term and go away once treatment is finished. Some drugs may have specific effects that are not listed above, so be sure to talk with your cancer care team about what you might expect in terms of side effects.

There are often ways to lessen side effects. For example, you can be given drugs to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about drugs to help reduce side effects.

You should report any side effects you notice while getting chemo to your medical team so that they can be treated promptly. In some cases, the doses of the chemo drugs may need to be reduced or treatment may need to be delayed or stopped to prevent side effects from getting worse.

Immunotherapy for melanoma skin cancer

Immunotherapy stimulates a patient’s own immune system to recognize and destroy cancer cells more effectively. Several types of immunotherapy can be used to treat patients with advanced melanoma.

Ipilimumab for advanced melanoma

Ipilimumab (Yervoy) is a monoclonal antibody, a man-made version of an immune system protein. It targets CTLA-4, a protein that normally helps keep immune system cells called T cells in check. By blocking the action of CTLA-4, ipilimumab boosts the immune response against melanoma cells in the body.

This drug is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments. In patients with melanomas that can’t be removed by surgery or that have spread to other parts of the body, it has been shown to help people live an average of several months longer, although it does not cure the melanoma. Doctors are now studying its use for earlier-stage melanomas as well.

This drug works by basically removing the brakes on the body’s immune system. This can be helpful against cancer cells, but it can also lead to serious side effects. In some cases the immune system starts to attack other parts of the body, which can cause serious problems in the intestines, liver, hormone-making glands, nerves, skin, eyes, or other organs. In some people these side effects have been fatal.

These immune-related side effects most often occur during treatment, but some have been reported up to a few months after treatment has finished. It is very important to report any new side effects to your health care team promptly. If serious side effects do occur, treatment may need to be stopped and you may get high doses of corticosteroids to suppress your immune system.

Cytokines for advanced melanoma

Cytokines are proteins in the body that boost the immune system in a general way. Man-made versions of cytokines, such as interferon-alpha and interleukin-2 (IL-2), are sometimes used in patients with melanoma. They are given as intravenous (IV) infusions, at least at first. Some patients or caregivers may be able to learn how to give injections under the skin at home. Both drugs can help shrink advanced (stage III and IV) melanomas in about 10% to 20% of patients when used alone. These drugs may also be given along with chemotherapy drugs (known as biochemotherapy) for stage IV melanoma.

Side effects of cytokine therapy may include flu-like symptoms such as fever, chills, aches, severe tiredness, drowsiness, and low blood cell counts. Interleukin-2, particularly in high doses, can cause fluid to build up in the body so that the person swells up and can feel quite sick. Because of this and other possible serious side effects, high-dose IL-2 is given only in centers that have experience with this type of treatment.

Interferon-alpha as adjuvant therapy

Patients with thicker melanomas often have cancer cells that have spread to other parts of the body. Even if all of the cancer seems to have been removed by surgery, some of these cells may remain. Interferon-alpha can be used as an added (adjuvant) therapy after surgery to try to prevent these cells from spreading and growing. This may delay the recurrence of melanoma, but it is not yet clear if it improves survival.

High doses must be used for the interferon to be effective. But many patients cannot tolerate the side effects of high-dose therapy. These can include fever, chills, aches, depression, severe tiredness, and effects on the heart and liver. Patients getting this drug need to be closely watched by a doctor who is experienced with this treatment.

When deciding whether to use adjuvant therapy, patients and their doctors should take into account the potential benefits and side effects of this treatment.

Bacille Calmette-Guerin (BCG) vaccine

BCG is a germ related to the one that causes tuberculosis. BCG does not cause serious disease in humans, but it does activate the immune system. The BCG vaccine works like a cytokine by enhancing the entire immune system. It is not directed specifically at melanoma cells. It is sometimes used to help treat stage III melanomas by injecting it directly into tumors.

Imiquimod cream

Imiquimod (Zyclara) is a drug that, when applied as a cream, stimulates a local immune response against skin cancer cells. For very early (stage 0) melanomas in sensitive areas on the face, some doctors may use imiquimod if surgery might be disfiguring. It can also be used for some melanomas that have spread along the skin. Still, not all doctors agree it should be used for melanoma.

The cream is applied anywhere from once a day to 2 times a week for around 3 months. Some people may have serious skin reactions to this drug. Imiquimod is not used for more advanced melanomas.

Targeted therapy for melanoma skin cancer

As doctors have found some of the gene changes that make melanoma cells different from normal cells, they have begun to develop drugs that attack these changes. These targeted drugs work differently from standard chemotherapy drugs. Sometimes, they work when chemotherapy doesn’t. They can also have less severe side effects. Doctors are still learning the best way to use these drugs to treat melanoma.

Drugs that target changes in the BRAF gene

About half of all melanomas have changes (mutations) in the BRAF gene. These changes cause the gene to make an altered BRAF protein that signals the melanoma cells to grow and divide quickly. Drugs that target this protein are now available. If you have advanced melanoma, a biopsy sample of it might be tested to see if it contains a BRAF mutation. Drugs that target the BRAF protein are not likely to work in patients whose melanomas have a normal BRAF gene.

Vemurafenib (Zelboraf) is a drug that targets melanoma cells with the altered BRAF gene. It causes tumors to shrink in about half of the people whose metastatic melanoma has a BRAF gene change. It also prolongs the time before the tumors start growing again and helps some patients live longer, although the melanoma usually starts growing again eventually.

This drug is taken as a pill, twice a day. The most common side effects are joint pain, fatigue, hair loss, rash, itching, sensitivity to the sun, and nausea. Less common but serious side effects can occur, such as heart rhythm problems, liver problems, severe allergic reactions, and severe skin or eye problems.

Some people treated with vemurafenib develop new skin cancers called squamous cell carcinomas. These cancers are usually not serious and can be treated by removing them. Still, your doctor will want to check your skin often during treatment and for several months afterward. You should also let your doctor know right away if you notice any new growths or abnormal areas on your skin.

Radiation therapy for melanoma skin cancer

Radiation therapy uses high-energy rays or particles to kill cancer cells. External beam radiation therapy focuses radiation from outside the body on the skin tumor. This type of radiation therapy is used to treat some patients with melanoma.

Before treatments start, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. The treatment is much like getting an x-ray, but the radiation is stronger. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time—getting you into place for treatment—usually takes longer.

Radiation therapy is not often used to treat the original melanoma that started on the skin. In some cases, it may be given after surgery (as an adjuvant) in the area where lymph nodes were removed, especially if many of the nodes contained cancer cells. This is to try to reduce the chance that the cancer will come back.

Radiation therapy may also be used to treat melanoma that has come back (recurred) after surgery, either in the skin or lymph nodes, or to treat distant spread of the disease.

Radiation therapy is often used to relieve symptoms caused by the spread of the melanoma, especially to the brain or bones. Treatment with the goal of relieving symptoms is called palliative therapy. Palliative radiation therapy is not expected to cure the cancer, but it might help shrink it for a time to control some of the symptoms.

Side effects of radiation therapy depend on where it is aimed. They might include sunburn-like skin problems and hair loss where the radiation enters the body, fatigue, nausea, and vomiting. Often these go away after treatment.

Treatment of melanoma skin cancer by stage

The type of treatment(s) your doctor recommends will depend on the stage and location of the melanoma and on your overall health. This section lists the options usually considered for each stage of melanoma.

Stage 0

Stage 0 melanomas have not grown deeper than the epidermis. They are usually treated by surgery to remove the melanoma and a margin of about 1/2 cm (about 1/5 inch) of normal skin around it.

For melanomas in sensitive areas on the face, some doctors may use a cream containing the drug imiquimod (Zyclara) if surgery might be disfiguring, although not all doctors agree with this use.

Stage I

Stage I melanoma is treated by wide excision (surgery to remove the melanoma as well as a margin of normal skin around it). The amount of normal skin removed depends on the thickness of the melanoma. When the thickness is 1 mm or less, wide excision with 1 cm (2/5 inch) margins is recommended. For stage I melanomas between 1 mm and 2 mm thick, the tumor and 1 cm to 2 cm (4/5 inch) of surrounding skin are removed. No more than 2 cm of normal skin needs to be removed from all sides of the melanoma in stage I. Wider margins make healing more difficult and have not been found to help people live longer.

Some doctors may recommend a sentinel lymph node biopsy, especially if the melanoma is stage IB or has other characteristics that make it more likely to have spread to the lymph nodes. This is an option that you and your doctor should discuss.

If the sentinel lymph node biopsy is positive, a lymph node dissection (removal of all lymph nodes near the cancer) is often recommended, but it's not clear if it can improve survival. Some doctors may recommend adjuvant (additional) treatment with interferon after the lymph node surgery as well.

Stage II

Wide excision is the standard treatment for stage II melanoma. If the melanoma is between 1 mm and 2 mm thick, a margin of 1 to 2 cm of normal skin will be removed as well. If the melanoma is thicker than 2 mm, about 2 cm of normal skin will be removed from around the tumor site.

Because the melanoma may have spread to lymph nodes near the melanoma, many doctors recommend a sentinel lymph node biopsy as well. This is an option that you and your doctor should discuss. If it is done and the sentinel node contains cancer, then a lymph node dissection (where all the lymph nodes in that area are surgically removed) will be done at a later date.

For some patients (such as those with a tumor more than 4 mm thick or with lymph nodes containing cancer), doctors may advise treatment with interferon after surgery (adjuvant therapy). Other drugs or perhaps vaccines may also be recommended as part of a clinical trial to try to reduce the chance the melanoma will come back.

Stage III

These cancers have already reached the lymph nodes when the melanoma is first diagnosed. Surgical treatment for stage III melanoma usually requires lymph node dissection, along with wide excision of the primary tumor as in stage II. Adjuvant therapy with interferon may help some patients with stage III melanomas fight off recurrence longer. Another option may be to give radiation therapy to the areas where the lymph nodes were removed, especially if many of the nodes contain cancer.

If several melanomas are present, they should all be removed. If this is not possible, options include injections of Bacille Calmette-Guerin (BCG) vaccine or interleukin-2 directly into the melanoma, radiation therapy, or applying the topical immunotherapy imiquimod. For melanomas on an arm or leg, another possible option is isolated limb perfusion (infusing the limb with a heated solution of chemotherapy). Other possible treatments include chemotherapy, immunotherapy with cytokines, or both combined (biochemotherapy).

Some patients might benefit from newer treatments being tested in clinical trials. Many patients with stage III melanoma may not be cured with current treatments, so they may want to think about taking part in a clinical trial.

Stage IV

Stage IV melanomas are very hard to cure, as they have already spread to distant lymph nodes or other areas of the body. Skin tumors or spread to the lymph nodes causing symptoms can often be removed by surgery. Metastases in internal organs are sometimes removed, depending on how many there are, where they are located, and how likely they are to cause symptoms. Metastases that cause symptoms but cannot be removed surgically may be treated with radiation, immunotherapy, targeted therapy, or chemotherapy.

The treatment of stage IV melanomas has changed in recent years as newer forms of immunotherapy and targeted drugs have been shown to be more effective than chemotherapy.

Ipilimumab (Yervoy), a newer immunotherapy drug, has been shown to help some people with advanced melanoma live longer. It can sometimes have severe side effects, but doctors may prefer it over other treatment options, such as chemotherapy or other types of immunotherapy.

Vemurafenib (Zelboraf) is a drug that targets melanoma cells with changes in the BRAF gene. This drug is often the preferred treatment in people with advanced melanomas that test positive for the BRAF gene change. Like ipilimumab, it can help some people live longer.

The chemotherapy drugs now being used are of limited value in most people with stage IV melanoma. Dacarbazine (DTIC) and temozolomide (Temodar) are the ones used most often, either by themselves or combined with other drugs. Even when chemotherapy shrinks these cancers, the effect is often only temporary, with an average of about 3 to 6 months before the cancer starts growing again. In rare cases they work for longer periods of time, however.

Immunotherapy using interferon or interleukin-2 can help a small number of patients with stage IV melanoma live longer. Higher doses of these drugs seem to be more effective, but they can also have more severe side effects.

Some doctors may recommend biochemotherapy: a combination of chemotherapy and either interleukin-2, interferon, or both. For example, some doctors use interferon with temozolomide. The 2 drugs combined cause more tumor shrinkage, which might make patients feel better, although the combination has not been shown to help patients live longer. Another drug combination uses low doses of interferon, interleukin-2, and temozolomide. Each seems to benefit some patients. Patients should carefully consider the possible benefits and side effects of any recommended treatment before starting it.

Because stage IV melanoma is very hard to treat with current therapies, patients may want to think about taking part in a clinical trial. Clinical trials of new chemotherapy drugs, targeted drugs, new methods of immunotherapy such as vaccines, and combinations of different types of treatments may benefit some patients.

Even though the outlook for patients with stage IV melanoma tends to be poor overall, a small number of patients respond very well to treatment and survive for many years after diagnosis.

Recurrent melanoma

Treatment of melanoma that comes back after initial treatment depends on the stage of the original melanoma, the prior treatment, and the site of recurrence.

Melanoma may come back in the skin near the site of the original tumor. In general, these local (skin) recurrences are treated with surgery similar to that recommended for a primary melanoma. This may include a sentinel lymph node biopsy. Depending on the thickness and location of the tumor, other treatments may be considered, such as isolated limb perfusion chemotherapy, systemic chemotherapy, immunotherapy, radiation therapy, or tumor injection with BCG vaccine or interferon.

If nearby lymph nodes weren't removed during the initial treatment, the melanoma may come back in these nearby lymph nodes. This may appear as a swelling or tumor mass. Lymph node recurrence is treated by lymph node dissection, and may include adjuvant therapy such as interferon or radiation therapy.

Melanoma can also come back in distant parts of the body. Almost any organ can be affected. Most often, the melanoma will come back in the lung, bone, liver, or brain. Treatment for these recurrences is generally the same as for stage IV melanoma (see above). Melanomas that recur on an arm or leg may be treated with isolated limb perfusion chemotherapy.

Melanoma that comes back in the brain can be hard to treat. Single sites of recurrence can sometimes be removed by surgery. Most chemotherapy drugs aren't able to reach the brain, although temozolomide may be useful. Radiation therapy to the brain may help as well.

What happens after treatment for melanoma skin cancer?

For many people with melanoma, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about cancer growing or coming back. (When cancer comes back after treatment, it is called recurrent cancer or a recurrence.) This is a very common concern in people who have had cancer.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are leading full lives. 

For others, melanoma may never go away completely. These people may get regular treatment with immunotherapy, targeted therapy, chemotherapy, or other treatments to try to help keep the cancer in check. Learning to live with cancer that does not go away can be difficult and very stressful. It has its own type of uncertainty.

Follow-up care

If you have completed treatment, your doctors will still want to watch you closely. It is very important to keep all follow-up appointments. Follow-up is needed to check for cancer recurrence or spread, as well as possible side effects of certain treatments. This is a good time for you to ask your health care team any questions you need answered and to discuss any concerns you might have.

Your follow-up should include regular skin and lymph node exams by yourself and by your doctor. How often you need follow-up doctor visits depends on the stage of your melanoma when you were diagnosed and other factors. In addition to the exams, imaging tests may be recommended for some patients.

A typical follow-up schedule for melanomas thinner than 1 mm generally calls for physical exams every 3 to 12 months for several years. If these exams are normal, you can return for a checkup once a year. Your doctor may recommend more frequent exams if you have many moles or atypical moles.

For thicker melanomas or those that had spread beyond the skin, a typical schedule might include physical exams every 3 to 6 months for 2 years, then every 3 to 12 months for the next few years. After that, exams are done at least once a year. Some doctors also recommend imaging tests such as chest x-rays or CT scans every 6 to 12 months for the first several years, especially for people who had more advanced stage disease.

It is also important for melanoma skin cancer survivors to do regular self-exams of their skin and lymph nodes (most doctors recommend at least monthly). You should see your doctor if you find any new lump or change in your skin. You should also report any new symptoms (for example, pain, cough, fatigue, loss of appetite) that do not go away. Melanoma can come back many years after it was first treated.

Patients with stage IV melanoma whose cancer has been completely removed or disappeared after treatment usually have the same follow-up schedule as those with thicker melanomas (see above). Patients with stage IV melanoma that does not go away completely will have a follow-up schedule that is based on their specific situation.

A person who has had one melanoma may still be at risk for developing another melanoma or a non-melanoma type of skin cancer. People cured of one melanoma should continue to examine their skin every month for new skin cancers, and should avoid too much sun exposure.

What if treatment for melanoma skin cancer is no longer working?

If cancer keeps growing or comes back after one kind of treatment, it may be possible to try another treatment plan that might still cure the cancer, or at least shrink the tumors enough to help you live longer and feel better. But when a person has tried many different treatments and the cancer has not gotten any better, the cancer tends to become resistant to all treatment. If this happens, it’s important to weigh the possible limited benefits of a new treatment against the possible downsides, including treatment side effects. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer—when you have been through many medical treatments and nothing's working anymore. Your doctor may offer you new options, but at some point you might need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor might say that more treatment might have about a 1 in 100 chance of working. Some people will still be tempted to try this. But it is important to think about and understand your reasons for choosing this plan.

Palliative care

No matter what you decide to do, it is important that you feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose. The main goal of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve bone pain caused by cancer that has spread there. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

Hospice care

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can't have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. You can learn more about hospice in our document called Hospice Care.

Staying hopeful is important, too. Your hope for a cure may not be as bright, but there is still hope for good times with family and friends—times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you’ve always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.

What`s new in research and treatment of melanoma skin cancer?

Research into the causes, prevention, and treatment of melanoma is being done in medical centers throughout the world.

Causes, prevention, and early detection

Sunlight and ultraviolet (UV) radiation

Recent studies suggest there may be 2 general ways that UV exposure is linked to melanoma, but there is likely some overlap.

The first link is to sun exposure to as a child and teenager. People with melanoma often have an early history of sunburns or other intense sun exposures, although not everyone does. This early sun exposure may cause changes in the DNA of skin cells (melanocytes) that starts them on a path to becoming melanoma cells many years later. Some doctors think this might help explain why melanomas often occur on the legs and trunk, areas that generally aren’t exposed to the sun as much in adulthood.

The second link is to melanomas that occur on the arms, neck, and face. These areas are chronically exposed to sun, particularly in men. Tanning booths may encourage either kind of melanoma to develop.

Researchers are looking to see how melanomas that develop as a result of these types of UV exposure may differ. For example, they may have different gene changes that would require them to be treated differently.

Public education

Most skin cancers can be prevented. The best way to reduce the number of skin cancers and the pain and loss of life from this disease is to educate the public, especially parents, about skin cancer risk factors and warning signs. It is important for health care professionals and skin cancer survivors to remind everyone about the dangers of excess UV exposure (from the sun and from man-made sources such as tanning beds) and about how easy it can be to protect your skin against too much UV radiation.

Melanoma can often be detected early, when it is most likely to be completely cured. Monthly skin self-exams and awareness of the warning signs of melanomas may be helpful in finding most melanomas when they are at an early, curable stage.

Melanoma DNA research

Scientists have made a great deal of progress during the past few years in understanding how UV light damages DNA and how changes in DNA cause normal skin cells to become cancerous.

Some people, though, may inherit mutated (damaged) genes from their parents. For example, changes in the CDKN2A (p16) gene cause some melanomas to run in certain families. People who have a strong family history of melanoma should speak with a cancer genetic counselor or a doctor experienced in cancer genetics to discuss the possible benefits, limits, and downsides of testing for changes in this gene.

Molecular staging

Advances in melanoma DNA research are also being applied to molecular staging. In ordinary staging, a lymph node removed from a patient is looked at under a microscope to see if melanoma cells have spread to the lymph node.

In molecular staging, RNA (a chemical related to DNA), is extracted from cells in the lymph node. Certain types of RNA are made by melanoma cells but not by normal lymph node cells. A sophisticated test called reverse transcription polymerase chain reaction (RT-PCR) is used to detect these types of RNA.

Early studies have found that RT-PCR is better than routine microscopic testing at detecting the spread of melanoma to lymph nodes. This test could eventually help identify some patients who might benefit from additional treatment such as immunotherapy after surgery. However, some doctors are concerned that this test may lead to unnecessary treatment for some patients, which is why this test is not currently recommended. Studies are now in progress to learn more about how results should influence choice of treatment.

Treatment

Early-stage melanomas can often be cured with surgery, but more advanced melanomas are often much harder to treat because standard cancer treatments such as chemotherapy are not very effective. Newer types of treatment have shown a great deal of promise in treating more advanced melanomas.

Immunotherapy

This type of treatment includes several approaches for helping the body’s immune system attack melanoma cells more effectively. Some forms of immune therapy, such as ipilimumab (Yervoy), cytokines (interferon-alpha and interleukin-2), and the BCG vaccine are already used to treat some melanomas. These treatments work by generally boosting the immune system.

Ipilimumab targets CTLA-4, a protein that normally suppresses the T-cell immune response, which might help melanoma cells survive. This drug has been shown to help some people with advanced melanomas live longer. Researchers are now trying to determine if it might be useful earlier in the course of the disease. Other drugs that counteract CTLA-4 are now being studied as well.

Drugs that block PD-1 and PD-L1

Melanoma cells may also use other natural pathways in the body to help avoid detection and destruction by the immune system. For example, they often have a protein called PD-L1 on their surface that helps them evade the immune system. New drugs that block the PD-L1 protein, or the corresponding PD-1 protein on immune cells called T cells, can help the immune system recognize the melanoma cells and attack them.

In early studies, an anti-PD-1 drug known as BMS-936558 shrank tumors in about 3 out of 10 people with melanoma, while a drug targeting PD-L1 (known as BMS-936559) shrank tumors in about 2 out of 10 people. Many of the tumor responses have been long-lasting so far. Larger studies of these new drugs are now being done.

Melanoma vaccines

Vaccines directed at melanoma are being studied in clinical trials. They are experimental therapies that do not yet have proven benefit.

These vaccines are, in some ways, similar to the vaccines used to prevent diseases such as polio, measles, and mumps that are caused by viruses. Such vaccines usually contain weakened viruses or parts of a virus that cannot cause the disease. The vaccine stimulates the body's immune system to destroy the more harmful type of virus.

In the same way, killed melanoma cells or parts of cells (antigens) can be injected into a patient as a vaccine to try to stimulate the body's immune system to destroy other melanoma cells in the body. Usually, the cells or antigens are mixed with other substances that help boost the body's immune system as a whole. But unlike vaccines that are meant to prevent infections, these vaccines are meant to treat an existing disease.

Making an effective vaccine against melanoma has proven to be harder than making a vaccine to fight a virus. The results of studies using vaccines to treat melanoma have been mixed so far, but newer vaccines may hold more promise.

In a recent clinical trial of patients with advanced melanoma, adding a vaccine to high-dose interleukin-2 (IL-2) increased the portion of tumors that shrank and the length of time before they started growing again better than just giving IL-2 alone. But it's not yet clear if this vaccine can help people live longer.

Other immunotherapies

Other forms of immunotherapy are also being studied. Some early studies have shown that treating patients with high doses of chemotherapy and radiation therapy and then giving them tumor-infiltrating lymphocytes (TILs), immune system cells found in tumors, can shrink melanoma tumors and possibly prolong life as well. Newer studies are looking at changing certain genes in the TILs before they are given to see if this can make them more effective at fighting the cancer. This approach has looked promising in early studies, but it is complex and is only being done in a few centers. These new treatments are being studied further.

Another potential approach to treatment is to combine different types of immunotherapy, which may be more effective than any single treatment for advanced melanoma.

Targeted drugs

As doctors have discovered some of the gene changes in melanoma cells, they have begun to develop drugs that attack these changes. These targeted drugs work differently from standard chemotherapy drugs. They may work in some cases when chemotherapy doesn't. They may also have less severe side effects.

Drugs that target changes in the BRAF gene: As noted in the section, “Targeted therapy for melanoma skin cancer” about half of all melanomas have changes in the BRAF gene, which helps the cells grow. A drug called vemurafenib (Zelboraf) has been shown to shrink many of these tumors and is now often used in melanomas that test positive for this gene change.

Other drugs that target BRAF gene changes are now being studied as well. A drug called dabrafenib has shown results similar to those for vemurafenib in studies. It may have an added benefit of causing fewer squamous cell carcinomas of the skin, but further testing is needed to be sure. This drug is only available through clinical trials at this time.

The MEK gene is in the same signaling pathway inside cells as the BRAF gene. A drug that blocks MEK, known as trametinib, has been shown to cause some melanomas with BRAF mutations to shrink. It’s not yet clear if this drug will be as effective as the BRAF inhibitors, or if it might work against some melanomas that do not respond to BRAF inhibitors. This drug is also only available through clinical trials.

One approach now being studied is to combine a BRAF inhibitor with a MEK inhibitor in the hope of causing tumors to shrink for longer periods of time. Early results have been promising, showing that some side effects (such as the development of other skin cancers) might actually be less common with the combination, but further research is needed.

Drugs that target changes in the c-kit gene: Certain types of melanomas often have unusual gene changes. This often includes melanomas that start:

On the palms of the hands, soles of the feet, or under fingernails

Inside the mouth or in other mucosal areas

In areas that get chronic sun exposure

About one third of these uncommon melanomas have changes in a gene called c-kit. Some drugs that are already used to treat other cancers, such as imatinib (Gleevec) and nilotinib (Tasigna), are known to target cells with changes in c-kit. Clinical trials are now looking to see if these and other drugs might help people with these types of melanoma.

Drugs that target other gene or protein changes: Several drugs that target other abnormal genes or proteins, such as sorafenib (Nexavar), bevacizumab (Avastin), temsirolimus (Torisel), and everolimus (Afinitor), are now being studied in clinical trials as well.

Researchers are also looking at combining some of these targeted drugs with other types of treatments, such as chemotherapy or immunotherapy.

 

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