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. But other factors can be important as well, such as the risk of the cancer returning after treatment, if the cancer cells have certain gene changes, and your overall health.

Treating stage 0 melanoma

Stage 0 melanoma (melanoma in situ) has not grown deeper than the top layer of the skin (the epidermis). It is usually treated by surgery (wide excision) to remove the melanoma and a small margin of normal skin around it. The removed sample is then sent to a lab to be looked at with a microscope. If cancer cells are seen at the edges of the sample, a second, wider excision of the area may be done.

Some doctors may consider the use of imiquimod cream (Zyclara) or radiation therapy instead of surgery, although not all doctors agree with this.

For melanomas in sensitive areas on the face, some doctors may use Mohs surgery or even imiquimod cream if surgery might be disfiguring, although not all doctors agree with these uses.

Treating stage I melanoma

Stage I melanoma is typically treated by wide excision (surgery to remove the melanoma as well as a margin of normal skin around it). The width of the margin depends on the thickness and location of the melanoma. Most often, no other treatment is needed.

Some doctors may recommend a sentinel lymph node biopsy (SLNB) to look for cancer in nearby lymph nodes, especially if the melanoma is stage IB or has other characteristics that make it more likely to have spread. You and your doctor should discuss this option.

If the SLNB does not find cancer cells in the lymph nodes, then no further treatment is needed, although close follow-up is still important.

If cancer cells are found on the SLNB, a lymph node dissection (removal of all lymph nodes near the cancer) might be recommended. Another option might be to watch the lymph nodes closely by getting an ultrasound of the nodes every few months.

If the SLNB found cancer, adjuvant (additional) treatment with immune checkpoint inhibitors or targeted therapy drugs (if the melanoma has a BRAF gene mutation) might be recommended to try to lower the chance the melanoma will come back. Other drugs or perhaps vaccines might also be options as part of a clinical trial.

Treating stage II melanoma

Wide excision (surgery to remove the melanoma and a margin of normal skin around it) is the standard treatment for stage II melanoma. The width of the margin depends on the thickness and location of the melanoma.

Because the melanoma may have spread to nearby lymph nodes, many doctors recommend a sentinel lymph node biopsy (SLNB) as well. This is an option that you and your doctor should discuss.

If a SLNB is done and does not find cancer cells in the lymph nodes, then sometimes no further treatment is needed, but close follow-up is still important.

For certain stage II melanomas, the immune checkpoint inhibitor pembrolizumab (Keytruda) might be given after surgery to help reduce the risk of the cancer returning.

If the SLNB finds that the sentinel node contains cancer cells (which changes the cancer stage to stage III – see below), then a lymph node dissection (where all the lymph nodes in that area are surgically removed) might be done right away. Adjuvant (additional) treatment with immune checkpoint inhibitors or targeted therapy drugs (if the melanoma has a BRAF gene mutation) might be recommended to try to lower the chance the melanoma will come back. Other drugs or perhaps vaccines might also be options as well as part of a clinical trial.

In other cases where the SLNB finds cancer, the lymph nodes might be watched closely with an ultrasound of the nodes every few months, instead of doing a lymph node dissection right then. Your doctor will discuss the best options with you depending on the details of your situation.

Treating stage III melanoma

These cancers have already reached the lymph nodes when the melanoma is first diagnosed. Surgical treatment for stage III melanoma usually requires wide excision of the primary tumor as in earlier stages, along with lymph node dissection.

After surgery, (additional) adjuvant treatment with immune checkpoint inhibitors or with targeted therapy drugs (for cancers with BRAF gene changes) may help lower the risk of the melanoma coming back. 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. Another option is to give radiation therapy to the areas where the lymph nodes were removed, especially if many of the nodes contain cancer.

If melanoma tumors are found in nearby lymph vessels in or just under the skin (known as in-transit tumors), they are removed, if possible. Other options might include injections of the T-VEC vaccine (Imlygic), Bacille Calmette-Guerin (BCG) vaccine, or interleukin-2 (IL-2) directly into the melanoma; radiation therapy; or applying imiquimod cream. For melanomas on an arm or leg, another option might be isolated limb perfusion or isolated limb infusion (infusing just the limb with chemotherapy). Other possible treatments might include targeted therapy drugs (for melanomas with a BRAF or C-KIT gene change), immunotherapy, or chemotherapy.

Some people with stage III melanoma might not be cured with current treatments, so they may want to think about taking part in a clinical trial of newer treatments.

Treating stage IV melanoma

Stage IV melanomas have already spread (metastasized) to distant lymph nodes or other areas of the body. Skin tumors or enlarged lymph nodes causing symptoms can often be removed by surgery or treated with radiation therapy.

Metastases in internal organs are sometimes removed, depending on how many there are, where they are, and how likely they are to cause symptoms. Metastases that cause symptoms but cannot be removed may be treated with radiation, immunotherapy, targeted therapy, or chemotherapy.

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

Immunotherapy drugs called checkpoint inhibitors are typically the first drugs tried, especially in people whose cancer cells do not have BRAF gene changes. These drugs can shrink tumors for long periods of time in some people. Options might include:

• Pembrolizumab (Keytruda) or nivolumab (Opdivo) 
• Nivolumab combined with relatlimab (Opdualag)
• Nivolumab or pembrolizumab, plus ipilimumab (Yervoy)

Combinations of checkpoint inhibitors might be more effective, although they're also more likely to result in serious side effects.

People who get any of these drugs need to be watched closely for serious side effects..

In about half of all melanomas, the cancer cells have BRAF gene changes. If a BRAF gene change is found, treatment with newer targeted therapy drugs – typically a combination of a BRAF inhibitor and a MEK inhibitor – might be a good option. Immune checkpoint inhibitors such as pembrolizumab or nivolumab might be another option, as well as a combination of targeted drugs plus the immune checkpoint inhibitor atezolizumab (Tecentriq).

Doctors are now studying if targeted therapy or immunotherapy is better as the first treatment. But there might be situations where it makes sense to use one instead of the other. For example, the targeted drugs are more likely to shrink tumors quickly, so they might be preferred in cases where this is important. In either case, if one type of treatment isn’t working, the other can be tried.

A small portion of melanomas have changes in the C-KIT gene. These melanomas might be helped by targeted drugs such as imatinib (Gleevec) and nilotinib (Tasigna), although these drugs often stop working eventually.

Immunotherapy using interleukin-2 (IL-2) can help a small number of people with stage IV melanoma live longer, and it might be tried if immune checkpoint inhibitors aren’t working. Higher doses of IL-2 seem to be more effective, but they can also have more severe side effects, so they might need to be given in the hospital.

Chemotherapy can help some people with stage IV melanoma, but other treatments are usually tried first. Dacarbazine (DTIC) and temozolomide (Temodar) are the chemo drugs used most often, either by themselves or combined with other drugs. Even when chemotherapy shrinks these cancers, the cancer usually starts growing again within several months.

It’s important to carefully consider the possible benefits and side effects of any recommended treatment before starting it.

Because stage IV melanoma is often hard to cure with current treatments, patients may want to think about taking part in a clinical trial. Many studies are now looking at new targeted drugs, immunotherapies, chemotherapy drugs, and combinations of different types of treatments. (See What’s New in Melanoma Skin Cancer Research?)

Treating recurrent melanoma

Treatment of melanoma that comes back after initial treatment depends on the stage of the original melanoma, what treatments a person has already had, where the melanoma comes back, and other factors.

Local recurrence

Melanoma might come back in the skin near the site of the original tumor, sometimes even in the scar from the surgery. In general, these local (skin) recurrences are treated with surgery similar to what would be recommended for a primary melanoma. This might include a sentinel lymph node biopsy (SLNB). Depending on the results of the SLNB, other treatments might be recommended as well.

In-transit recurrence

If melanoma recurs in nearby lymph vessels in or just under the skin (known as in-transit recurrence), it should be removed, if possible. Other options include injections of the T-VEC vaccine (Imlygic), Bacille Calmette-Guerin (BCG) vaccine, or interleukin-2 (IL-2) directly into the melanoma; radiation therapy; or applying imiquimod cream. For melanomas on an arm or leg, another option might be isolated limb perfusion or isolated limb infusion (infusing just the limb with chemotherapy). Other possible treatments might include targeted therapy (for melanomas with a BRAF or C-KIT gene change), immunotherapy, or chemotherapy.

Recurrence in nearby lymph nodes

If nearby lymph nodes weren’t all removed during the initial treatment, the melanoma might come back in these lymph nodes. Lymph node recurrence is treated by lymph node dissection if it can be done, sometimes followed by adjuvant (additional) treatments such as radiation therapy and/or immunotherapy or targeted therapy (for cancers with BRAF gene changes). If surgery is not an option, radiation therapy or systemic treatment (immunotherapy, targeted therapy, or chemo) can be used.

Recurrence in other parts of the body

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 lungs, bones, 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/infusion chemotherapy.

Melanoma that comes back in the brain can be hard to treat. Single tumors can sometimes be removed by surgery. Radiation therapy to the brain (stereotactic radiosurgery or whole brain radiation therapy) may help as well. Systemic treatments (immunotherapy, targeted therapy, or chemo) might also be tried.

As with other stages of melanoma, people with recurrent melanoma may want to think about taking part in a clinical trial.