How Stage 4 Melanoma Is Diagnosed (and What to Expect After)

by Krista Bennett DeMaio Health Writer

The journey to a stage 4 diagnosis may not feel that different from being diagnosed with an earlier stage of melanoma. It starts with a skin check, a biopsy, and lab work determining that your spot is, in fact, cancer. But, of course, stage 4 is the most serious stage of melanoma, cancer that develops in pigment-producing cells known as melanocytes. It means that your cancer has spread to other areas such as the lungs or brain. So, what comes next is quite different from other stages—the doctors you’ll see, your treatment plan, your prognosis, all of it. Deep breath. Here’s what to expect.

suspicious mole

It Usually Starts With Suspicious Spot

Maybe you noticed a mole that stood out from the rest (an “ugly duckling,” as melanoma experts call it). Its edges were irregular, maybe it was asymmetrical in shape, unevenly pigmented, noticeably large (bigger than a pencil eraser), or rapidly changing (itching, bleeding, oozing). These are the spots that concern dermatologists. If you had one, your doc did a biopsy on your own ugly duckling. During this in-office procedure, your doctor either shaved off a layer of your mole, punched it out with a hole-punch-like tool, or removed it with surgical excision, along with a margin of healthy skin to check for wandering cancer cells.

counting moles

It May Not Be Your First Run-In With Melanoma

“Many people with stage 4 melanoma have a history of primary melanoma,” says Philip Friedlander, M.D., a medical oncologist specializing in melanoma at Mount Sinai Hospital in New York City. Earlier-stage melanoma that was considered high risk (having characteristics that make it more likely to spread) may return at some point as stage 4, he says. In fact, 13.4% of those with a high-risk melanoma had a recurrence, research in JAMA Dermatology showed. Seventy percent of those recurred in a local area, while 29% had a recurrence somewhere else on their body.

senior headache

Another Symptom Might Have Tipped Your Doctor Off

“Sometimes we find a stage 4 melanoma diagnosis because the patient has a symptom or abnormality somewhere else in the body,” says Dr. Friedlander. That could mean shortness of breath or a lingering cough due to a lung metastasis, or severe headaches due to your melanoma spreading to the brain. In these cases, doctors have to work backward to find melanoma is the root cause.

CT scan

After a Skin Biopsy, More Tests Are in Store

If a biopsy reveals melanoma, you’ll have additional tests to determine its spread, including a lymph node biopsy and some imaging tests. “We routinely do either a PET scan or CT scan of the chest, abdomen, and the pelvis,” says Allison Betof Warner, M.D., a medical oncologist at Memorial Sloan Cancer Center in New York City. “And all patients with stage 4 disease should have an MRI of the brain.” Your doctor may also order a blood test to measure your levels of an enzyme called lactate dehydrogenase. Elevated levels indicate a more extensive spread.

genetic testing

You May Have a Genetic Mutation

It’s very likely that your melanoma tumor will have a DNA mutation. These mutations turn off tumor-suppressor genes, allowing cancers to grow out of control, according to the American Cancer Society. Discovering which mutation you have through genetic profiling can help your doctor determine the best course of treatment. Research has shown that about 50% of melanomas contain the BRAF mutation, while others may contain MEK mutations or the less common C-KIT mutation. Most people will only have only one of these mutations.

 Surgeon giving instruction to medical team.

You’ll Have a Team on Your Side

Once your physician finds out where your stage 4 melanoma has spread, you’ll be referred to more doctors for treatment. If your tumors are operable, you’ll be referred to a surgical oncologist, who will perform the surgery. You’ll also have a medical oncologist, who will determine your ideal type of treatment, or combination of treatments. Treatments for stage 4 melanoma include immunotherapy, targeted drugs, chemotherapy, and radiation.

targeted therapy

Drugs Can Target Your Type of Tumor

If your melanoma tumor has one of the gene mutations we mentioned, your oncologist may start with a drug that targets specific proteins in the mutation. Depending on which mutation your melanoma tested positive for, your oral drug options include: BRAF inhibitors including Zelboraf (venemurafenib), Tafinlar (dabrafenib), and Braftovi (encorafenib); MEK inhibitors such as Mekinist (trametinib), Cotellic (cobimetinib), and Mektovi (binimetib); and C-KIT inhibitors, which include Gleevac (imatinib) and Tasigna (nilotinib). Because BRAF and MEK mutations are closely associated, research has shown that combining the two types of drugs may yield better results.


Immunotherapy May Be Part of Your Treatment

“All stage 4 melanoma patients are eligible for immunotherapy,” says Dr. Friedlander. This class of intravenous drugs work by boosting your immune cells so they can find and kill cancer cells. There are a few different types. Checkpoint inhibitors release a “checkpoint” on immune cells that stops them from attacking cancer cells, giving them free to seek and destroy. The three available are Yervoy (ipilmumab), Opdivo (nivolumab), and Keytruda (pembrolizumab). IV drugs (interleukin-2 and interferon) behave like cancer-fighting proteins the body already makes. Melanoma vaccines are often immunotherapy as well. T-VEC, for instance, works by stimulating your immune system.


Your May Experience Side Effects

“The vast majority of patients who receive immunotherapy will have little to no side effects,” says Dr. Betof Warner. “It’s a huge change from the days when patients were on chemotherapy and were profoundly nauseous, vomiting, and had suppressed immune systems.” Still, side effects can occur, including flu-like fever, aches, fatigue, and nausea. The risk of side effects with targeted therapy is a bit higher, but Dr. Betof Warner says they tend to disappear faster. These can include rashes, headaches, joint pain. And more seriously, kidney failure, bleeding, and heart and liver problems.

scary Internet

Don’t Google Survival Rates

“Not only because it’s not helpful, but because they’re not even accurate,” says Dr. Betof Warner. “The survival statistics for stage 4 melanoma are still evolving because most of the drugs we use were approved about five years ago, so the numbers are literally just coming out.” And they’re more promising. Recent research in the New England Journal of Medicine showed that 52% of patients on a combination of two checkpoint inhibitors were alive after five years. In 2018, the survival rate for stage 4 melanoma was listed as just 22.5%. Stay focused on your own treatment rather than searching stats.

Krista Bennett DeMaio
Meet Our Writer
Krista Bennett DeMaio

Krista Bennett DeMaio has well over a decade of editorial experience. The former magazine-editor-turned-freelance writer regularly covers skincare, health, beauty, and lifestyle topics. Her work has appeared in national publications and websites including Oprah, Women’s Health, Redbook, Shape, Dr. Oz The Good Life,, and She lives in Huntington, New York with her husband and three daughters.