Treatment of Melanoma Skin Cancer, by Stage

The type of treatment(s) your doctor recommends will depend mainly 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 after surgery if not all the cancer cells can be removed for some reason, 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 melanomas have grown into deeper layers of the skin, but they haven’t grown beyond the area where they started.

These cancers are typically treated by wide excision (surgery to remove the tumor 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 traits 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 (which changes the cancer stage to stage III – see below), 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 imaging test such as 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

Stage II melanomas have grown deeper into the skin than stage I melanomas, but they still haven’t grown beyond the area in the skin where they started.

Wide excision (surgery to remove the melanoma and a margin of normal skin around it) is the standard treatment for these cancers. 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. Radiation therapy to the area might be another option, especially if the melanoma has features that make it more likely to come back.

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 recommended. Another option might be to watch the lymph nodes closely with an imaging test such as ultrasound of the nodes every few months.

Whether or not the lymph nodes are removed, 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.

Your doctor will discuss the best options with you depending on the details of your situation.

Treating stage III melanoma

These cancers have spread to nearby areas in the skin or lymph vessels, or they have reached the nearby lymph nodes.

Surgical treatment for stage III melanoma usually requires wide excision of the primary tumor as in earlier stages, along with a lymph node dissection (where all the nearby lymph nodes are surgically removed).

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), interleukin-2 (IL-2), or Bacille Calmette-Guerin (BCG) vaccine 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 stage III melanomas might be hard to cure with current treatments, so taking part in a clinical trial of newer treatments might be a good option.

Treating stage IV melanoma

Stage IV melanomas have already spread (metastasized) to other parts of the body, such as distant lymph nodes, areas of skin, or other organs.

Skin tumors or enlarged lymph nodes causing symptoms can often be removed by surgery or treated with radiation therapy.

If there are only a few metastases, surgery to remove them might sometimes be an option, depending on where they are and how likely they are to cause symptoms. Metastases that can’t be removed may be treated with radiation or with injections of the T-VEC vaccine (Imlygic) directly into the tumors. In either case, this is often followed by adjuvant treatment with medicines such as immunotherapy or targeted therapy drugs.

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 often the first treatment. These drugs can shrink tumors for long periods of time in some people. Options might include:

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

Combinations of checkpoint inhibitors seem to be more effective, although they’re also more likely to result in serious side effects, especially if they contain ipilimumab.

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. These melanomas often respond to treatment with targeted therapy drugs – typically a combination of a BRAF inhibitor and a MEK inhibitor. However, the immune checkpoint inhibitors mentioned above are often tried first, as this seems to be more likely to help for longer periods of time. Another option might be a combination of targeted drugs plus the immune checkpoint inhibitor atezolizumab (Tecentriq).

While immunotherapy is often used before targeted therapy, there might be situations where it makes sense to use targeted therapy first. 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.

Rarely, melanomas might have changes in other genes such as NRAS, ROS1, ALK, or the NTRK genes, which can be treated with targeted drugs.

Immunotherapy using other medicines might be an option if immune checkpoint inhibitors or other treatments aren’t working. Options might include:

• Interleukin-2 (IL-2) (also known as aldesleukin)
• Lifileucel (Amtagvi), a type of tumor-infiltrating lymphocyte (TIL) therapy 

These treatments can cause serious side effects in some people, so they are usually given in the hospital.

Chemotherapy (chemo) 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 chemo shrinks these cancers, the cancer usually starts growing again over time.

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, people may want to think about taking part in a clinical trial. Many studies are now looking at new targeted drugs, immunotherapies, 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 where in the body the melanoma is, what treatments a person has already had, the person’s overall health and preferences, 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 with surgery, if possible. Other options might include injections of the T-VEC vaccine (Imlygic), interleukin-2 (IL-2), or Bacille Calmette-Guerin (BCG) vaccine 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 treatments might include targeted therapy (for melanomas with a BRAF or C-KIT gene change), immunotherapy, or chemotherapy.

Recurrence in nearby lymph nodes

If the nearby lymph nodes weren’t removed during the initial treatment, the melanoma might come back in these lymph nodes. Lymph node recurrence is typically 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 might also come back in distant parts of the body. Almost any organ can be affected. Most often, the melanoma comes 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 options.

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