Treating Metastatic Melanoma: How New Methods Are Improving Outcomes
If melanoma spreads beyond the skin, here’s what doctors suggest.

Catching melanoma early is crucial. Early melanoma is often thin and can be surgically removed relatively simply. If treated early, melanoma has a lower risk of recurring or metastasizing (or spreading to lymph nodes or other organs). However, once melanoma spreads, treatment becomes a bit more complicated.
Metastatic melanoma, also known as advanced melanoma or stage IV melanoma, is more difficult to treat because the melanoma is now “no longer surgically removable,” according to Jeffrey Weber, MD, PhD, medical oncologist and melanoma researcher at Perlmutter Cancer Center at NYU Langone Health.
To attack the cancer cells that have spread to other organs, doctors use adjuvant therapies—secondary treatments that help rid the entire body of melanoma.
Surgical Excision for Melanoma
The first step to treat any stage of melanoma is always to remove the melanoma from the skin. Typically, after removing the melanoma, doctors study the skin sample under the microscope to check for cancer cells.
Doctors continue to remove thin layers of skin at a time and studying them under the microscope. The surgery is considered complete once no cancer cells appear in the sample. This method allows for the most minimal amount of skin to be removed, to prevent scarring and damage.
How much skin is removed surrounding the melanoma—which is called the margins—depends on the severity of the melanoma and how likely it is to recur. The more advanced the melanoma, the more likely a wider margin will be required.
Adjuvant Therapies for Metastatic Melanoma
Excision cannot treat metastatic melanoma by itself because the cancer cells have spread to distant lymph nodes and other internal organs. The second treatment step is called adjuvant therapy, which helps reduce the likelihood of melanoma recurrence.
The adjuvant therapies used to treat metastatic melanoma often include checkpoint inhibitors, targeted therapy, and (less frequently) chemotherapy and radiation therapy.
Checkpoint inhibitors are a type of immunotherapy that utilizes the body’s natural “checkpoint” system. Immune cells have proteins that can be turned on or off to activate the immune response. Melanoma cells can manipulate this system and use those checkpoints to tell the immune response *not* to attack. This is what makes cancer cells able to reproduce so rapidly.
Checkpoint inhibitors block those proteins to ensure the body recognizes the melanoma cell and attacks. Learn more about how immunotherapy revolutionized melanoma treatment here.
Targeted therapy helps the body attack cells that carry specific proteins as a result of cancerous gene mutations. For melanoma, targeted therapy may target BRAF, MEK, or C-KIT genes, as these mutations are linked to melanoma.
Not all people with melanoma will have these specific gene mutations, and the individual must have one of them to qualify for targeted therapy. If a biopsy reveals they do have the presence of one of these gene mutations, targeted therapy may be a more precise and effective option than chemotherapy or radiation therapy.
Chemotherapy attacks rapidly dividing cells in the body. This is one way of targeting cancer cells, but it’s not very precise since many types of cells reproduce quickly, such as hair cells (which is why chemo often results in hair loss and other side effects).
Now that doctors have immunotherapy and targeted therapy, this option is no longer commonly used to treat melanoma. It may be used if other adjuvant therapies for melanoma have been unsuccessful, or it might be used in combination with another method, like immunotherapy.
Radiation therapy uses X-rays to kill cancer cells. While it’s uncommon to use as an adjuvant therapy, it is helpful for a rare type of melanoma called desmoplastic melanoma.
“Fifteen years ago, the average survival of a patient with metastatic melanoma was about 10 months,” says Dr. Weber. “Today, it’s probably around 40 to 50 months. That’s a big difference, and in the future it’s only going to get better.”
Dr. Weber is a medical oncologist, melanoma researcher, and the deputy director of the Perlmutter Cancer Center at NYU Langone Health.
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Advanced or metastatic melanoma means
melanoma that has not only started in
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the skin, or in the lymph nodes, or
what we call the local regional area, but
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has spread and
is no longer surgically removable.
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That is,
it can no longer be removed by the surgeon
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to render the patients free of disease.
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That usually means it has
spread to the distant organs.
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And that's the scenario where the medical
oncologist now calls upon all of the drugs
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in our armamentarium to try to
treat it and put it into remission.
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The drugs we most commonly use fall
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into categories, either immunologic drugs,
which are the ones used most commonly.
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And those immunotherapies are drugs that
in general disinhibit the immune system,
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which is highly suppressed in melanoma and
many other cancers.
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There is also targeted therapy.
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Targeted therapies are usually oral
drugs that are deliberately developed to
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target genetic changes in the melanoma,
not in the patient, but in the melanoma.
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So about 40-50% of melanomas
have a genetic change or
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a mutation called BRAF, or B-Raf.
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And if you have a drug that
can specifically block it,
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it will cause the tumor to shrink and
cause benefit for the patient.
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We will often use those
oral drugs in combinations,
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we call them the BRAF and MEK drugs.
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And there are three combinations
that are FDA approved.
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We will use that if the patient's
tumor has the mutation.
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Otherwise, the patients tend to get
treated with immunologic therapy.
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And there are multiple possible
immunologic therapies alone or
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in combination that we use in
the clinic to, in my view,
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fairly successfully treat
metastatic melanoma.
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15 years ago,
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the average survival of a patient with
metastatic melanoma was about 10 months.
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Today, it's probably
around 40 to 50 months.
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That's a big difference.
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And in the future,
it's only gonna get better.
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Patient education: melanoma treatment; advanced or metastatic melanoma (beyond the basics). Waltham, MA: UpToDate, 2018. (Accessed on December 15,2021 at https://www.uptodate.com/contents/melanoma-treatment-advanced-or-metastatic-melanoma-beyond-the-basics.)
Treatment of melanoma skin cancer, by stage. Atlanta, GA: Centers for Disease Control and Prevention, 2018. (Accessed on December 15,2021 at https://www.cancer.org/cancer/melanoma-skin-cancer/treating/by-stage.html.)
Treatment of metastatic melanoma: a new world opens. New York, NY: Skin Cancer Foundation. (Accessed on December 15,2021 at https://www.skincancer.org/skin-cancer-information/melanoma/melanoma-treatments/treatment-of-metastatic-melanoma.)