When you’ve been diagnosed with melanoma, one of the first questions is likely: How are we going to treat this? When caught early (stages 0-II) and removed through surgery, melanoma carries a 98% cure rate, and typically requires no additional treatment. Experts are also increasingly optimistic about advances in treating metastatic melanoma (that is, melanoma that has spread). Significant strides (thanks, science!) are helping patients live longer even with late-stage melanoma. We're here to help you understand your treatment possibilities.
We went to some of the nation's top melanoma experts to bring you the most scientific and up-to-date information possible.
Philip Friedlander, M.D.Assistant Professor of Hematology and Oncology
Sancy Leachman, M.D.Chair of the Department of Dermatology at Oregon Health & Science University and Director of Melanoma Research Program at Knight Cancer Institute
Steven Q. Wang, M.D.Mohs Surgeon and Director of Dermatological Surgery and Dermatology
What Is Melanoma Again?
Melanoma is one of three main types of skin cancer. It’s less prevalent, yet more dangerous, than basal cell carcinoma and squamous cell carcinoma, because it spreads more easily. How does melanoma develop in the first place? It happens when melanocytes, the cells that give your skin pigment when you freckle or tan, start to rapidly divide and grow out of control. You or your doc might notice a mole that’s large, uneven or somehow doesn’t look like your others.
However, about 5% of melanoma looks completely unassuming and is super easy to miss. Because these amelanotic melanomas are missing melanin, which gives moles their color, they can be clear, flesh-toned, or pinkish in color.
Melanoma can occur anywhere on your skin, from the top of your head to the tip of your toe and most any place in between. Two kinds of melanoma, known as intraocular and ocular melanoma, can also occur in your eye.
Fortunately, when you catch it and start treatment early enough, melanoma is almost always curable — which is why it’s so important to do a monthly self-skin check (set a recurring calendar invite) and to see your dermatologist for an annual exam.
If during a skin exam, your doctor spots a mole, birthmark, or other pigmented area that looks concerning, they’ll want to take a closer look. For that, you may undergo a biopsy: a procedure to remove the tissue in question as well as a teeny bit of normal tissue that surrounds it. A pathologist (and possibly two, if you’d like a second opinion) will check this out under the microscope to see if it contains cancer cells. There are four kinds of biopsies and which you get will depend on the size of your growth and where it is on your body:
Shave biopsy: A razor blade is used to shave off the growth
Punch biopsy: An instrument called a punch is used to take a circle from the growth
Incisional biopsy: A scalpel is used to remove part of the growth
Excisional biopsy: A scalpel is used to remove the entire growth
After a melanoma diagnosis, your doctor will also want to determine its stage. This is determined by the thickness of the tumor, whether it has spread to deeper layers of skin, to lymph nodes (areas in your body that filter fluids), and even to other organs.
How do doctors know if the cancer has spread? That’s often revealed through a sentinel lymph node biopsy (SLNB) when you’re diagnosed. Your surgeon will inject radioactive solution or a blue dye near the tumor which flows to nearby lymph nodes. The lymph node that turns blue (or lights up) with the radioactive solution is known as the sentinel lymph node, the first in a cluster of lymph nodes that cancer would reach. The sentinel lymph node then is removed and tested for cancer cells, indicating whether or not the cancer has spread.
Like most things cancer, there’s no one-size-fits-all treatment for melanoma. Each will be guided by the cancer’s stage. What can you expect? Let’s take a look.
Stage 0-II: Surgery
When cutaneous melanoma (melanoma that starts in the skin) is caught in its earliest form — only appearing on the surface layer of skin or spreading to deeper layers but not to lymph nodes or other organs — surgery is the go-to treatment. Deep breath: This doesn’t necessarily mean a hospital stay and general anesthesia.
A very thin melanoma can often be fully removed with surgical excision during the biopsy itself, under local anesthesia. Occasionally, doctors will perform Mohs micrographic surgery, commonly referred to as Mohs surgery, a technique that involves removing the cancer in very thin layers over the course of days until only healthy skin remains. Mohs is typically reserved for non-melanoma skin cancers, but research in JAMA Dermatology has shown that it can be used for melanoma in situ (melanoma contained to the surface layer of skin) — with no additional risk of recurrence or significant changes in survival rates.
For thicker melanomas and those that may have spread into the lower layers of skin, dermatologists will perform what’s called a wide excision, removing the melanoma plus some surrounding healthy tissue (a.k.a. margins). For example, a melanoma that’s 1-millimeter thick requires a 2-centimeter margin of skin to be removed too, to ensure that lingering cancer cells don’t spread. This can also be done under local anesthesia, or general anesthesia for larger, more extensive melanomas. After the tumor is removed, the skin is sutured back together. For a deeper incision, a plastic surgeon or reconstructive plastic surgeon may close the wound and minimize the risk of scarring; (some scarring is almost inevitable).
What are the side effects of surgery? As with most surgical procedures, there is a risk of:
Stage III: Surgery + Lymph Node Removal + Drugs
Stage III melanoma has spread to nearby lymph nodes. As with earlier stages, your doctor will surgically remove the tumor. However, because melanoma has traveled to nearby lymph nodes, these lymph nodes may need to be removed to prevent further spreading.
Doctors may suggest removing the entire cluster of lymph nodes, a.k.a. a complete lymph node dissection. This can cause discomfort and side effects such as swelling and a build-up of fluid where the lymph nodes used to be. However, new research suggests that removal of all the nodes isn’t necessarily better for patient outcomes than only removing the sentinel lymph node: A study in the New England Journal of Medicine found that those who had the lymph nodes removed didn’t survive any longer than those who did not. Still, some experts prefer to remove as many as possible as it can reduce the risk of cancer recurrence in that area. The latest thinking: Whether or not to dissect is a case-by-case decision only you and your doctor can make.
Your oncologist may also suggest a course of treatment known as adjuvant therapy (therapy given in addition to the primary treatment) to prevent cancer cells from coming back. This can include chemotherapy, radiation, or a drug that’s FDA approved for adjuvant care for melanoma. These include:
Interferon (Intron and Slyatron)
Dabrafenib and Trametinib (Tafinlar + Mekinist)
If stage III melanoma is considered unresectable, meaning it’s large and widely through the lymphatic system, removing all the cancer with surgery isn’t possible. That could be because the melanoma has metastasized (or spread) beyond the lymph nodes, attaching to nearby structures such as blood vessels. There’s also the possibility of many transit metastases, meaning melanoma has scattered more than 2 cm from the primary lesion, making it impossible to remove with surgery. Your doctors will likely take an integrative approach, combining surgery with immunotherapy or targeted therapy drugs. Read on for the details on these approaches.
Stage IV: Immunotherapy and Targeted Therapy
When cancer has metastasized to other organs, such as the liver, lungs, or brain, surgery in these areas typically isn’t an option. At this point, your oncologist will likely use a drug or a cocktail of drugs to stop the melanoma from spreading. Unlike many other types of cancer, chemotherapy isn’t the first line of defense for melanoma that has spread. It’s not as effective as some of the latest other treatments, including immunotherapy and targeted therapy. Thanks to these breakthroughs, research has shown that more than half of patients diagnosed with Stage IV melanoma are still alive three years later. The prognosis before these treatments existed was under one year. Here’s how they work:
Immunotherapy for Melanoma
Cancer cells are stealth. They know how to bypass your immune system without being flagged as invaders. The idea behind immunotherapy is to bolster your immune cells so they can recognize and kill cancer cells. What kinds of immunotherapy drugs are available for melanoma There are a few:
Checkpoint inhibitors: Proteins in your body called checkpoints tell immune cells (T-cells) whether an invader should be attacked or ignored. Cancer cells use these checkpoints to trick T-cells into thinking they’re in the latter group. Checkpoint inhibitors block these proteins, so T-cells can see cancer cells as the threat they are and attack. The latest research on checkpoint inhibitors focuses on combining the different types of drugs for better results. These are the checkpoint inhibitors used for melanoma, all given through intravenous (IV) infusion:
Ipilimumab (Yervoy) works by blocking a specific molecule called CTLA-4
Nivolumab (Opdivo) and pembrolizumab (Keytruda) are programmed cell death protein-1 blockers (also known as PD1-blockers), which means they block PD-1, a checkpoint that acts like an off switch on a T-cell, preventing it from attacking cancer.
Cytokines: These IV drugs or injections mimic proteins the body already makes to fight infections, viruses and diseases. Two examples are Interleukin-2 and Interferon. They’re most effective at high doses, which means they come with more risk of toxicity and side effects (flu-like symptoms, fever, low blood cell count) than newer checkpoint inhibitors. Because of this, these drugs are typically not the first course of treatment, but rather reserved for when other immunotherapy drugs aren’t working or your cancer returns.
Melanoma vaccines: A vaccine for cancer? Yes, it exists: T-VEC, FDA-approved in 2015 for more advanced melanoma. Unlike other vaccines, it doesn’t prevent disease, but it does help fight melanoma, killing cancer cells by stimulating your immune system. T-VEC uses a modified herpes virus injected right into the melanoma tumor to annihilate cancer cells, while sparing the healthy ones. More vaccines will likely soon come down the pipeline. Right now, customized vaccines using a person’s own tumor cells are being tested in clinical trials with promising results.
What are the side effects of immunotherapy? The most common include:
loss of appetite
A larger complication with immunotherapy drugs is stimulating the immune system too much, which can spur it to start attacking other organs in the body, including kidneys, lungs, and liver. If this occurs, you’ll likely need to take steroids or other immune-suppressing drugs.
This class of drugs targets specific mutations in the DNA of the melanoma tumor. The most common mutation is BRAF, which appears in half of all melanoma tumors. Also common is the MEK mutation, which is closely associated with the BRAF gene. A less common mutation is the C-KIT gene, more likely to appear in melanomas on sun-damaged areas, like hands, feet, nails and mucosal areas (mouth, genitals). If a tumor tests positive for these mutations, oral drug options include:
BRAF inhibitors: vemurafenib (Zelboraf), dabrafenib (Tafiniar), and encorafenib (Braftovi)
MEK inhibitors: trametinib (Mekinist), cobimetinib (Cotellic), and binimetib (Mektovi)
C-KIT drugs: imatinib (Gleevac) and nilotinib (Tasigna)
While each of these drugs is FDA-approved for solo use, it’s now known that combining a MEK inhibitor with a BRAF inhibitor can be more effective than using either drug alone. Research in the journal Therapeutic Advances in Medical Oncology has shown that in up to 70 percent of patients, a combo can result in a tumor shrinkage. Response rates of one drug alone ranges from 48 to 59 percent.
What are the side effects of targeted therapy? The most common include:
Skin rashes and itching, fever
Less common, but more serious complications include:
Severe allergic reaction
These drugs also come with a higher risk of squamous cell carcinoma (another type of skin cancer), so careful skin monitoring is a must.
How Are Rare Forms of Melanoma Treated?
In rare cases of melanoma on the skin on your finger, toes, or nails, the surgeon may be able to remove the tumor with surgery — if it’s caught early enough. But with more advanced cases, sometimes the surgical treatment is amputation.
For ocular melanoma, small-to-medium-sized tumors in the eye can be treated with:
photodynamic therapy (combining medication with a wavelength of low-level laser)
Surgery for larger, more advanced-stage eye melanomas may require removing the entire eye and replacing with an eye implant.
How Can I Cope With the Side Effects of Treatment?
If you’re experiencing pain from your cancer or side effects from your treatment, supportive care (also called palliative care) can help you manage these, while also providing support for dealing with your disease. A palliative care team may include doctors, nurses, and psychologists who will work with you to improve your quality of life. This can be done through medication, nutrition/dietary changes, meditation, exercise, and emotional and spiritual support (for family caregivers and children, too). It may also include targeted radiation to help relieve pain in areas such as the bones or brain. Don’t hesitate to tell your healthcare team about any discomfort or side effects as soon as you experience them so they can help.
Palliative treatment does not mean you’re giving up on treating cancer. In fact, you can receive palliative care while undergoing immunotherapy or targeted treatments for melanoma, but the goal is to slow the spread and ease the symptoms, not cure the disease.
What About Clinical Trials for Melanoma?
If the current FDA-approved treatments for Stage III and IV melanoma are not working or the cancer has returned after such treatments, your doctor may suggest a clinical trial (experimental drugs that aim to treat the disease in a new way). Since the development of immunotherapy and targeted therapies, there are more clinical trials being conducted than ever before. Interested in exploring potential opportunities? The National Cancer Institute (NCI) has clinical trials listed at its website; find out about open trials by calling 1-800-4-CANCER (1-800-422-6237).
Frequently Asked QuestionsMelanoma Treatment
What’s more effective: immunotherapy or targeted therapy?
Doctors aren’t so sure as studies haven’t determined which drug is a better starting point. Typically, if your tumor tests positive for a gene mutation, your doctor will start with targeted therapy. If that isn’t working well, they may move on to immunotherapy. If there is no gene mutation present, then the first course of action for metastatic and high-risk melanoma is immunotherapy.
What type of doctors will I see during my treatment?
Because doctors now treat melanoma using an integrative approach (combining treatments such as surgery and immunotherapy or targeted drugs), you’ll have a team of doctors. These may include a dermatopathologist (to pinpoint your specific type of melanoma), a surgical oncologist (to surgically remove the tumors), a radiation oncologist (for radiation, if necessary), and a medical oncologist (for immunotherapy, targeted drugs, and chemotherapy, if warranted).
Will my melanoma recur after treatment?
If treatment has eliminated your cancer, you’ll likely need to follow-up with a dermatologist every 3 to 12 months, depending on your specific case. Once you’ve had melanoma, the risk of developing it again is higher than those who never had one, especially if it was thick, looked like a bleeding ulcer, and/or spread to lymph nodes. Sometimes cancer cells survive the treatment and continue to grow at the original site, or even in a new area. Melanoma most commonly reappears within five years, but studies show it can make a comeback even a decade or two later.
Is Stage IV melanoma curable?
Once melanoma has spread to other areas of the body, it’s very difficult to cure. However, some patients have no detectable cancer even years after treatment. The current 5-year survival rate for Stage IV melanoma is around 23 percent.
Immunology and Stage IV Survival Rate:Surgical Oncology. (2019). "Revolutionizing Treatment of Advanced Melanoma With Immunotherapy." ncbi.nlm.nih.gov/pubmed/30691991
Targeted Therapy:Therapeutic Advances in Medical Oncology. (2016). "Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy." ncbi.nlm.nih.gov/pmc/articles/PMC4699264/
Checkpoint Inhibitors:Frontiers in Medicine. (2019). Combining "Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma." ncbi.nlm.nih.gov/pmc/articles/PMC6435047/
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