Treatment of Melanoma Skin Cancer by Stage

These cancers are typically treated by surgery with a wide excision 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 might 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 the SLNB finds cancer in the lymph nodes, then the cancer is actually stage III (see below). Most often, the other nearby lymph nodes will be watched closely with regular exams and imaging tests, such as ultrasounds. If there’s a higher risk that cancer might have spread to other lymph nodes, a completion lymph node dissection might be recommended to remove the lymph nodes in the area.

After surgery, treatment with either immune checkpoint inhibitors or targeted therapy drugs (if the melanoma has a BRAF gene change) might be an option to try to lower the risk of melanoma coming back. If the risk is already low, it’s not clear how helpful this is, so this is something you might want to discuss with your doctor.

Surgery with wide excision 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 might 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 the SLNB 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, adjuvant treatment after surgery might be an option to help lower the risk of the cancer returning (see below).

If the SLNB finds that the sentinel node contains cancer cells, then the cancer is stage III (see below). Most often, the other nearby lymph nodes will be watched closely with regular exams and imaging tests such as an ultrasound of the nodes. If there’s a higher risk that cancer might have spread to other lymph nodes, a completion lymph node dissection might be recommended to remove the lymph nodes in the area.

Whether or not the lymph nodes are removed, adjuvant treatment after surgery with immune checkpoint inhibitors or targeted therapy drugs (if the melanoma has a BRAF gene change) might be recommended to try to lower the chance the melanoma will come back, depending on the risk.

Your doctor will discuss your options with you based on your situation.

Surgical treatment with wide excision to remove the melanoma and a margin of normal skin around it is the standard treatment for these cancers.

For some stage III melanomas, a lymph node dissection might be recommended to remove nearby lymph nodes. Sometimes other treatments are given before surgery to try to shrink the tumors, known as neoadjuvant treatment.

For melanomas that are stage III because of a positive sentinel lymph node biopsy, just watching the nearby lymph nodes with exams and imaging tests such as ultrasound is often recommended. A lymph node dissection might be advised if there’s a higher risk of the cancer having spread to the nodes.

For melanomas that have spread to the nearby lymph nodes based on exams or imaging tests, a lymph node dissection is typically done. Often, neoadjuvant treatment with immune checkpoint inhibitors or targeted therapy drugs is given first.

For melanomas that have spread to nearby areas in the skin or lymph vessels, known as satellite lesions or in-transit metastasis, the tumors are removed, if possible. Sometimes neoadjuvant treatment with immune checkpoint inhibitors or targeted therapy drugs might be given first.

Other options might include injections of the T-VEC immunotherapy (Imlygic) or interleukin-2 (IL-2) directly into the melanoma, or treatment with immune checkpoint inhibitors or targeted therapy drugs.

For melanomas on an arm or leg that can’t be removed completely, another option might be isolated limb perfusion or isolated limb infusion, where just the limb is infused with chemotherapy.

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

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.

If there are only a few metastases (areas of cancer spread), 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 might be treated with radiation or with injections of the T-VEC immunotherapy (Imlygic) directly into the tumors. In either case, this is often followed by adjuvant treatment with immunotherapy or targeted therapy drugs.

If the melanoma has spread more widely, immunotherapy and targeted drugs are often the main treatment options.

Immune checkpoint inhibitors

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.

Targeted therapy drugs if the cancer cells have certain gene changes

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.

Although immunotherapy is often used before targeted therapy drugs, they might be preferred in cases where shrinking tumors quickly is important. Or they might be used in people who can’t tolerate the side effects of immunotherapy.

A small portion of melanomas have changes in the C-KIT gene. These melanomas might be helped by targeted drugs such as imatinib (Gleevec), dasatinib (Sprycel), or 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 might be helped by treatment with targeted drugs.

Other treatment options

Other immunotherapies might be an option if immune checkpoint inhibitors or other treatments aren’t working. Options might include:

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

IL-2 and lifileucel 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 are the chemo drugs used most often, either by themselves or combined with other drugs. Even when chemo shrinks the cancer or stops its growth, 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 might 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.  

Melanoma might come back in the skin near the site of the original tumor, sometimes even in the scar from the surgery. In general, 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.

If melanoma recurs in nearby lymph vessels in or just under the skin, known as in-transit recurrence, it is typically removed with surgery, if possible.

Other options might include injections of the T-VEC immunotherapy (Imlygic) or interleukin-2 (IL-2) directly into the melanoma; radiation therapy; or applying imiquimod cream.

For melanomas on an arm or leg that can’t be removed, another option might be isolated limb perfusion or isolated limb infusion (infusing just the limb with chemotherapy).

Other treatment options might include targeted therapy (for melanomas with a BRAF or C-KIT gene change), immunotherapy, or chemotherapy.

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, immunotherapy, or targeted therapy (for cancers with BRAF gene changes).

If surgery is not an option, radiation therapy, immunotherapy, targeted therapy, or chemo can be used.

If melanoma comes back in distant parts of the body, most often it occurs in the lungs, bones, liver, or brain.

Treatment for distant recurrences is generally the same as for stage IV melanoma.

Melanomas that recur on an arm or leg might 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) might help as well. Immunotherapy, targeted therapy, or chemo might also be options.

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