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Advanced Melanoma

When melanoma has spread to lymph nodes or beyond

Medically reviewed by Dr. Steven Q. Wang, MDLast reviewed

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What Is Advanced Melanoma?

Most melanomas are found early, removed with surgery, and never come back. A minority behave differently — reaching the lymph nodes, appearing in the skin between the original spot and the nearest nodes, or spreading to distant organs such as the lung, liver, bone, or brain. Doctors call this "advanced" melanoma, and it is managed with a different set of tools — usually systemic medication and a team of specialists rather than a single surgeon.

"Advanced melanoma" is an umbrella term for two broad situations:

Regionally advanced melanoma (stage III)

The melanoma has spread to nearby lymph nodes, or has formed satellite or in-transit deposits in the skin and lymphatic channels between the original tumor and those nodes. It has not reached distant organs. Many stage III melanomas can still be removed with surgery, and treatment increasingly includes medication given before and/or after that surgery.

Metastatic melanoma (stage IV)

The melanoma has spread beyond the regional lymph nodes to distant sites — most often distant skin and lymph nodes, the lungs, liver, bone, or brain. It is treated primarily with systemic therapy. When distant spread is limited to one or a few spots (oligometastatic disease), surgery or focused radiation may still play a role alongside medication.

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Key Topics

Explore these topics to understand what advanced melanoma means, how it is staged and evaluated, and the treatment options available:

What does "advanced" melanoma mean?
Regionally advanced (stage III) vs. metastatic (stage IV) disease, and what each one means
How is advanced melanoma staged and worked up?
LDH, PET/CT, brain MRI, BRAF testing, and the multidisciplinary team
How does immunotherapy treat advanced melanoma?
Checkpoint inhibitors — anti–PD-1, ipilimumab plus nivolumab, and nivolumab plus relatlimab
When is BRAF/MEK targeted therapy used?
Testing for a BRAF V600 mutation and the oral drug combinations that target it
What is adjuvant therapy, and do I need it after surgery?
Medication after complete removal of stage III (or high-risk stage II) melanoma to lower the chance of recurrence
Can immunotherapy be given before surgery?
Neoadjuvant therapy for resectable stage III melanoma, and why timing matters
How are the side effects of immunotherapy managed?
Immune-related side effects, monitoring, steroids, and when treatment is paused
What if melanoma has spread to the brain?
How brain metastases are found and treated with systemic therapy, radiosurgery, and surgery
TIL therapy and other newer options
Tumor-infiltrating lymphocyte (TIL) cell therapy, oncolytic virus therapy, and what comes after first-line treatment
How do I find a clinical trial for advanced melanoma?
Where to look, what the phases mean, and questions to ask
What should I ask my care team about advanced melanoma?
Questions for your surgical oncologist, medical oncologist, and radiation oncologist
What is the outlook, and what support is available?
Prognosis, follow-up, survivorship, and supportive care for advanced disease

Signs Melanoma May Be Advanced

Most melanomas are caught while still confined to the skin. Findings that prompt a doctor to look for advanced disease include:

  • •A firm or enlarging lymph node near a known or previously treated melanoma (in the neck, armpit, or groin)
  • •New pigmented or pink bumps in the skin between the original melanoma and the nearest lymph nodes (satellite or in-transit lesions)
  • •A positive sentinel lymph node biopsy at the time the primary melanoma was removed
  • •A thick primary melanoma, or one that was ulcerated or had a high mitotic rate on pathology
  • •Persistent cough, bone pain, headaches, unexplained weight loss, or fatigue in someone with a melanoma history
  • •A rising blood LDH level or new spots on a CT, PET/CT, or brain MRI

Who Develops Advanced Melanoma

  • •People whose primary melanoma was thick, ulcerated, or had spread to a sentinel lymph node
  • •People whose melanoma was found late, or in a hard-to-see spot such as the scalp, back, or sole of the foot
  • •People with a melanoma that has recurred at or near the original site despite treatment
  • •People on long-term immunosuppression, including organ transplant recipients
  • •Less commonly, people with acral, mucosal, or uveal (eye) melanoma, which behave differently from sun-related skin melanoma

Why Early Detection Still Matters

Melanoma found while it is thin and confined to the skin is cured with surgery alone the large majority of the time. The same melanoma left to grow can reach the lymph nodes or distant organs, at which point treatment means months to years of systemic medication and closer monitoring.

Advanced melanoma is also far more treatable than it was a decade ago. Immunotherapy and targeted therapy have turned stage IV melanoma from a disease measured in months into one where many people live for years, and some appear to be cured. If you have a melanoma history and notice a new lump, a changing scar, or symptoms that will not settle, tell your oncology team promptly.

Systemic Treatment Overview

When surgery alone cannot control the disease, advanced melanoma is treated with medication that works throughout the body, sometimes alongside surgery or radiation. Every option below is individualized and carries meaningful side effects that are weighed against its benefits.

  • •Immunotherapy (checkpoint inhibitors): Drugs such as pembrolizumab, nivolumab, the ipilimumab-plus-nivolumab combination, and nivolumab plus relatlimab release the brakes on the immune system so it can attack the melanoma. This is the backbone of treatment for most people with advanced melanoma.
  • •Targeted therapy (BRAF/MEK inhibitors): For the roughly 40–50% of melanomas with a BRAF V600 mutation, oral drug pairs such as dabrafenib plus trametinib, encorafenib plus binimetinib, or vemurafenib plus cobimetinib block the signal driving tumor growth, often working quickly.
  • •Adjuvant and neoadjuvant therapy: For stage III (and some high-risk stage II) melanoma, immunotherapy or targeted therapy given after surgery — and, increasingly, immunotherapy given before surgery — lowers the chance the melanoma returns.
  • •Cellular therapy, oncolytic virus therapy, and clinical trials: Tumor-infiltrating lymphocyte (TIL) therapy, injectable oncolytic virus therapy, and trial drugs offer additional options, particularly when first-line treatment stops working.

Sources

Clinical Guidelines & Peer-Reviewed Literature

  • Amaral T, Ottaviano M, Arance A, et al. Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025;36(1):10-30. PubMed
  • Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-492. PubMed
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535-1546. PubMed
  • Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381(7):626-636. PubMed

Patient Resources

Disclaimer: This page is for educational purposes only and is not a substitute for professional medical advice. Always consult a qualified dermatologist or oncologist about your diagnosis and treatment plan.

Printable Discussion Guide

Every question from the topics above, collected into one printable checklist — with a checkbox and space for notes beside each, and header fields for your appointment date and doctor's name.

Download complete advanced melanoma discussion guide (PDF)

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