Stage 4 Melanoma

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Stage 4 melanoma, otherwise known as metastatic melanoma, is the most advanced form of melanoma, a serious form of skin cancer that begins in cells known as melanocytes. At this stage, the cancer has spread to other parts of the body or distant points in the skin. Although melanoma is the rarest type of skin cancer, accounting for only 1% of all skin cancers, it is the deadliest and the main culprit behind most skin cancer deaths.

It is estimated that stage 4 melanoma makes up 4% of all melanoma cases. The relative 5-year survival rate drops from 99% in stages 1 and 2 to 66.2% in stage 3 to only 27.3% in stage 4. Stage 4 melanoma is very difficult to treat and has a low survival rate because it has metastasized, but a small population of people with this stage of melanoma respond well to treatment. Melanoma can often be found early, when it is most likely to be cured. Therefore, early detection can significantly improve melanoma prognosis.

Cases of stage 4 melanoma have been rising by 1.3% each year from 2008 to 2017, but the death rates have lowered by an average of 3.2% each year from 2009 to 2018.

Doctor inspecting mole

Peter Dazeley / Getty Images


Symptoms vary from person to person, but the most common sign of melanoma is a new or changed mole. Any area of the skin that appears off in color, shape, size, or texture could indicate melanoma as well. Typically, the ABCDE rule is used to identify changes in symmetry, shape, color, and size of the skin lesion.

Common Symptoms

Changes in the skin typically occur throughout all stages of melanoma, but at stage 4, the most common symptom is bleeding skin ulcerations. However, this symptom may not appear in everyone with stage 4 melanoma.

A person with advanced melanoma may also experience some of the general symptoms of skin cancer, including:

  • Hard or swollen lymph nodes
  • Hard lump on the skin
  • Fatigue
  • Weight loss
  • Jaundice
  • Fluid buildup in the abdomen
  • Stomach pain

Metastatic melanoma most often spreads to the lymph nodes, brain, bones, liver, or lungs, and the additional symptoms experienced at this stage depend on where the melanoma has spread:

  • Lungs: A persistent cough or shortness of breath
  • Brain: Headaches or seizures
  • Lymph nodes: Swelling of the lymph nodes
  • Liver: Loss of appetite or unexplained weight loss
  • Bone: Bone pain or unusual fractures

Rare Symptoms

Although most cases of melanoma don't result in painful or itchy tumors, they can appear in some cases. The tumor could also ulcerate, which means breaking and bleeding. Ulceration can occur as early as stage 1 melanoma. Those with stage 4 melanoma may or may not experience ulceration.


Typically, healthcare providers will need to perform more than just a physical exam to determine whether someone has melanoma and how advanced their stage 4 melanoma is. Sometimes late-stage melanoma is diagnosed through CT or MRI scans, which can capture the spread of the disease before the person even realizes they have melanoma. Skin lesions rarely disappear on their own after the cancer has spread to other parts of the body, or the melanoma itself can form inside organs.

The BRAF Gene Mutation and Melanoma

Roughly half of all documented melanoma cases present with mutations in the BRAF gene. The melanoma cells that have these changes create a BRAF protein, which aids them in their growth. If a person with the BRAF gene mutation has melanoma, knowing about the mutation is of great benefit for treatment because healthcare providers can use targeted therapy to inhibit the BRAF gene mutation from aiding in the growth of the cancer.

If a diagnosis of melanoma is already established, the healthcare provider will look at two factors to determine how advanced a stage 4 melanoma has become: the location of the distant tumors and an elevated level of serum lactate dehydrogenase (LDH), which is an enzyme responsible for turning sugar into energy. The higher the LDH level in body fluids, the more damage the cancer has done.


When melanoma has spread to other organs, it can sometimes be confused with a cancer starting in that organ. Special lab tests can be done on the biopsy samples to determine whether it is a melanoma or other kind of cancer, including:

  • Skin biopsies: If melanoma is suspected, a healthcare provider will have the spot removed and sent to a lab for further testing. It is typically a painless procedure that can tell if cancer is present so that further testing can be done.
  • Fine needle aspiration (FNA) biopsy: This is used on lymph nodes nearby to detect the presence of melanoma cells and determine the extent of the spread.
  • Surgical lymph node biopsy: This is used to remove an enlarged lymph node, which suggests the melanoma has spread to it. This type of biopsy is often done if a lymph node’s size suggests that the melanoma has spread there, but an FNA biopsy of the node wasn’t done or didn’t find any melanoma cells.
  • Sentinel lymph node biopsy: It can determine if the melanoma has spread to the lymph nodes in cases where melanoma has already been diagnosed. This test can be used to find the lymph nodes that are likely to be the first place where the melanoma would go if it has spread. These lymph nodes are called sentinel nodes.

Lab Tests

If the healthcare provider can’t tell for sure if melanoma cells are in the sample just by looking at it, special lab tests will be done on the cells to try to confirm the diagnosis, including:

  • Immunohistochemistry: This process is done to help identify antigens through specific antibodies. The most common use of immunohistochemistry is to distinguish melanoma from other tumors and confirm through specific markers the melanocytic origin of the lesions. It can also be used to detect the BRAF gene.
  • Fluorescence in situ hybridization: This technique of singling out a specific DNA sequence in a chromosome can help researchers develop a map of genetic material in a person's cells. It looks for abnormalities in genes and chromosomes.
  • Comparative genomic hybridization: This is used to identify deleted or duplicated segments of DNA. It can help diagnose melanoma by determining the DNA copy changes in melanoma cells. It is typically used as a supplemental test to confirm the presence of melanoma.
  • Gene expression profiling: Gene profiling is used to measure the activity of thousands of genes to get a full picture of cellular function. In the case of melanoma, it can help healthcare providers investigate whether the tumor can be treated using a tailored and targeted treatment plan based on a person's genetic makeup.


The diagnostic process will include the staging of melanoma. The staging system used to classify melanoma is the TNM system, which stands for:

  • T refers to tumor thickness, how deep into the skin the tumor has grown, and how big it is. The thicker the tumor, the more likely it is to spread. Ulceration is also determined using the T measurement.
  • N determines whether the melanoma has spread to the lymph nodes. 
  • M refers to metastasis, whether the melanoma has spread to distant lymph nodes or organs.

If the cancer has reached stage 4, it typically presents with a tumor of any thickness that may or may not be ulcerated (any T), with or without spread to the nearby lymph nodes (any N), and with definite spread to distant lymph nodes or organs (M1).

Melanoma can recur because screening tests may not catch every cancer cell within the body and the leftover cells could grow into another tumor. Melanoma has a recurrence rate of around 13.4% in individuals who have had a previous case of the disease. This recurrence rate is 70.2% within two years of initial diagnosis for people in stages 1 through 3 and 29.8% for those at stage 4.  


Although the treatment of stage 4 melanoma is more difficult, there has been a vast improvement in treatment options for those with this stage of melanoma. There are several different types of treatment options, some of which are used in conjunction with other treatments for the best results.


Surgery to remove tumors that have spread throughout the body is used to treat stage 4 melanoma, but in most cases, it is part of an overall treatment plan and combined with both immunotherapy and targeted therapy. Tumors will be found and removed from the body where possible.


Radiation treatment is used for those with advanced melanoma when surgery isn’t possible because a person is at high risk for complications. This type of treatment uses energy rays to destroy tumors throughout the body or cancer cells in the lymph nodes.


Immunotherapy stimulates a person’s immune system to fight off cancer cells. It comes in two types; systemic and local immunotherapy. Systemic immunotherapy for advanced melanoma puts substances designed to set an immune response in motion into the bloodstream, while local immunotherapy is performed by injecting those substances into lesions directly. This form of immunotherapy is designed to target and kill melanoma cells at the source.

Immunotherapy drugs called checkpoint inhibitors are used to help shrink tumors. Immunotherapy can also be used in people with tumors that have BRAF mutations. These types of drugs also come with the risk of serious side effects, so those undergoing treatment using checkpoint inhibitors will need to be monitored closely during the treatment.

In the event that checkpoint inhibitors aren't working for someone with stage 4 melanoma, a different type of immunotherapy drug known as interleukin-2 may sometimes be used to help those with the disease live longer.

Targeted Therapy

Targeted therapy uses medications that target specific molecules within cancer cells. By blocking the abnormal function of those specific molecules, this form of therapy aims to slow both the spread and growth of melanoma. The medications used for melanoma are BRAF inhibitors and MEK inhibitors.

Specifically, a form of therapy that combines target therapy with immunotherapy is used in people with the BRAF gene mutation and advanced melanoma, known as triplet therapy or triplet targeted therapy. It has been shown to lead to increased response rate and progression-free survival.

In some cases of advanced melanoma, there are changes in a different kind of gene known as the c-KIT gene. Targeted therapy is also used to help those with this gene change, although the medications often lose their efficacy over time.


In some instances, chemotherapy may be a course of treatment for those with stage 4 melanoma. This is typically done only after trying other forms of treatment. This is because, although chemotherapy works to shrink this type of cancer, it often ends up recurring within months of the treatment.

Clinical Trials

Stage 4 melanoma is often hard to treat with currently available options. Some people with the disease may want to look into available clinical trials studying new targeted therapy drugs, immunotherapies, and chemotherapies. Some clinical trials may also offer a combination of new treatment therapies that could benefit some people with late-stage disease.

One such clinical trial is investigating the use of a peptide vaccine that may work to help with the overall survival rates of stage 4 melanoma. The trials are in the early stages, but the results so far seem promising.


The survival rate for melanoma is high when it is caught early, but for stage 4 melanoma, the survival rate drops significantly. It's important to remember that survival rates are estimates. Your prognosis is influenced by a number of other factors, including your age and general health. The relative 5-year survival rate does not take these factors into account.

Following the treatment plan laid out by your healthcare providers and staying healthy will ensure your best chance of survival. Be sure to keep up with your appointments and maintain a positive outlook. Typically, follow-up examinations should occur every 3 to 6 months.


Stage 4 melanoma is a difficult diagnosis to cope with emotionally and physically, but there are things you can do to stay positive and deal with challenges that arise during your treatment journey.

Emotional Support

Emotional support can go a long way when dealing with a cancer diagnosis. Joining a support group such as the Melanoma Patient Support Group with Cancer Care or Smart Patients Melanoma Support Group can help you handle the challenges and emotions that come with living with advanced melanoma. The Cancer Support Group also has an online tool to help you search for specific groups in your area for in-person support.

You could also find support in other places such as through therapy. If you are religious, getting in touch with your religious community may also be a great way to obtain support for coping with a late-stage melanoma diagnosis.

Lifestyle Changes

It's also important to stay as healthy as possible in other ways while undergoing treatment for stage 4 melanoma. Eating a healthy diet full of whole foods, fruits, and vegetables can give your body the nutrients it needs to keep it at its healthiest. For many, eating during treatment can be difficult due to the side effects of medications. Supplements may be necessary to keep the body full of nutrients and strong enough to fight the cancer.

Light exercise is also a good habit to adhere to during treatment because it can help aid in your recovery. Exercise increases endurance, enhances immune function, and keeps the body strong. Getting at least 30 minutes of mild movement every day can improve your overall health. You'll always want to eliminate any unhealthy habits you may have while managing and coping with stage 4 melanoma, such as smoking or excessive alcohol consumption.

Melanoma treatment may also reduce the body's ability to fight off further infections, which in turn, could make recovery and treatment more difficult. To reduce your risk of infection, you should practice good hygiene practices such as regular hand-washing, keeping your hands away from your face and eyes, avoiding crowds when possible, and inquiring about flu or pneumonia vaccines.

You will also want to limit exposure to UV light. Since treatment can make the skin more sensitive to sunlight, you should spend less time out in the sun or cover up when you do go outside. You can wear clothing that covers all exposed areas of skin, including a hat, and ensure that you're wearing sunglasses that can block out 99% to 100% of UVA and UVB rays. Always wear a broad-spectrum sunscreen if your skin will be exposed and avoid tanning beds completely.

A Word From Verywell

Getting an advanced cancer diagnosis is never easy, but try to relax and keep stress to a minimum. Stress can take a toll on your health. Remember that in many cases, treatments for melanoma are very effective at curing the disease. Speak to your healthcare provider regularly about treatment options, and ask about the possibility of participating in clinical trials. Advanced therapies are being developed continuously, and you may be a good fit for a new treatment. If you follow treatment protocols, exhaust all options when it comes to clinical trials, and take care of your body and mind during treatment, the outlook for survival can be a lot more positive.

14 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Cancer Society. Key statistics for melanoma skin cancer.

  2. National Cancer Institute SEER Database Program. Cancer stat facts: melanoma of the skin for 2021.

  3. Moffitt Cancer Center. What are the symptoms that melanoma has spread?

  4. Jansen YJL, Willekens I, Seremet T, Awada G, Schwarze JK, De Mey J, Brussaard C, Neyns B. Whole-body MRI for the detection of recurrence in melanoma patients at high risk of relapse. Cancers (Basel). 2021 Jan;13(3):442. doi:10.3390/cancers13030442

  5. Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol. 2018 Jan;31(1):24-38. doi:10.1038/modpathol.2017.104

  6. American Cancer Society. Tests for melanoma skin cancer.

  7. American Cancer Society. Melanoma skin cancer stages.

  8. von Schuckmann LA, Hughes MCB, Ghiasvand R, et al. Risk of melanoma recurrence after diagnosis of a high-risk primary tumor. JAMA Dermatol. 2019 May;155(6):688-693. doi:10.1001/jamadermatol.2019.0440

  9. American Cancer Society. Treatment of melanoma skin cancer by stage.

  10. Smalley KS, Eroglu Z, Sondak VK. Combination therapies for melanoma: a new standard of care? Am J Clin Dermatol. 2016 Apr;17(2):99-105. doi:10.1007/s40257-016-0174-8

  11. Slipicevic A, Herlyn M. KIT in melanoma: many shades of gray. J Invest Dermatol. 2015 Feb;135(2):337-338. doi:10.1038/jid.2014.417

  12. American Cancer Society. What's New In Melanoma Skin Cancer Research?

  13. Slingluff CL Jr, Petroni GR, Chianese-Bullock KA, Wages NA, Olson WC, Smith KT, Haden K, Dengel LT, Dickinson A, Reed C, Gaughan EM, Grosh WW, Kaur V, Varhegyi N, Smolkin M, Galeassi NV, Deacon D, Hall EH. Trial to evaluate the immunogenicity and safety of a melanoma helper peptide vaccine plus incomplete Freund's adjuvant, cyclophosphamide, and polyICLC (Mel63). J Immunother Cancer. 2021 Jan;9(1):e000934. doi:10.1136/jitc-2020-000934

  14. Zhang YB, Pan XF, Chen J, Cao A, Zhang YG, Xia L, Wang J, Li H, Liu G, Pan A. Combined lifestyle factors, incident cancer, and cancer mortality: a systematic review and meta-analysis of prospective cohort studies. Br J Cancer. 2020 Feb;122(7):1085-1093. doi:10.1038/s41416-020-0741-x

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By Angelica Bottaro
Angelica Bottaro is a professional freelance writer with over 5 years of experience. She has been educated in both psychology and journalism, and her dual education has given her the research and writing skills needed to deliver sound and engaging content in the health space.