Melanoma treatment overview: what happens after diagnosis?

Education and decision-support only — not a medical device or personalised advice. Always discuss your specific situation with your specialist team.

If you or a family member has recently been diagnosed with melanoma, the sheer volume of clinical terminology can feel overwhelming. This article explains, in plain language, what melanoma staging means, what the main treatment options are, and what the typical journey looks like after a diagnosis. It draws on the four leading international guidelines [1–4].

What is melanoma?

Melanoma is a cancer that develops from melanocytes — the pigment-producing cells in the skin. It accounts for only about 1–2% of all skin cancers but causes the large majority of skin-cancer deaths, because of its potential to spread (metastasise) to lymph nodes and distant organs if caught late.

The good news: melanoma caught at an early stage (Stage I–II) is highly treatable, with 5-year survival rates above 90% for thin, localised tumours [1]. Even Stage III disease (spread to nearby lymph nodes) now has substantially improved outcomes thanks to effective adjuvant therapies [3].

How melanoma is staged (Stage I to IV)

Staging tells you and your team how far the cancer has progressed. The current standard is the AJCC 8th Edition staging system [1], which considers:

Stage	What it means
Stage I	Melanoma is thin and confined to the skin. Sub-stages IA (≤0.8 mm, no ulceration) and IB (0.8–2.0 mm, or any ulcerated thin lesion). Excellent outlook.
Stage II	Thicker melanoma (>2 mm) or with ulceration, still confined to the primary site. Sub-stages IIA, IIB, IIC.
Stage III	Melanoma has spread to nearby lymph nodes or in-transit deposits in the skin, but not to distant organs. Wide range of sub-stages (IIIA–IIID). Adjuvant treatment is now standard for most patients.
Stage IV	Distant metastases — most commonly to lungs, liver, brain, or other skin sites. Systemic therapy is the mainstay; outcomes have improved dramatically since 2011.

Staging also depends on tumour thickness (Breslow depth, in millimetres), ulceration (whether the skin surface over the tumour is broken), and mitotic rate.

The main treatment pathways

1. Surgery — the foundation for most melanomas

For Stage I and II melanoma, surgery alone is often curative. Two procedures are standard:

Wide Local Excision (WLE): After the initial biopsy confirms melanoma, a surgeon removes a margin of normal-looking skin around the scar. The required margin depends on tumour thickness — typically 0.5–2 cm [2, 3].

Sentinel Lymph Node Biopsy (SLNB): For melanomas ≥0.8 mm (or thinner with high-risk features), the surgeon maps and removes the first ("sentinel") lymph node that drains the tumour area. If melanoma cells are found in the sentinel node, this upstages the diagnosis to Stage III and informs the adjuvant therapy decision. SLNB is a staging tool — it helps your team plan next steps, but its direct survival benefit is still debated [2].

2. Adjuvant immunotherapy — reducing recurrence after surgery

"Adjuvant" means given after surgery to reduce the risk of recurrence. For Stage IIB/IIC and Stage III patients who have had all detectable melanoma surgically removed, international guidelines now recommend:

• Pembrolizumab (Keytruda®) — an anti-PD-1 checkpoint inhibitor, approved for high-risk Stage IIB/IIC (KEYNOTE-716 trial) and Stage III (KEYNOTE-054) [3, 4]
• Nivolumab (Opdivo®) — another anti-PD-1 agent, approved for Stage III (CheckMate 238 trial) [3]

These are immunotherapy drugs: they release the brakes on your immune system so it can recognise and attack residual melanoma cells. They are given by intravenous infusion, typically every 3–6 weeks for 12 months. Side effects — called immune-related adverse events — can affect any organ, most commonly the thyroid, skin, or gut. Your team monitors you closely for these.

3. Targeted therapy — for BRAF-mutant melanoma

About 40–50% of melanomas carry a BRAF V600 mutation [4]. If yours does, targeted therapy is an option:

• BRAF + MEK inhibitor combinations: dabrafenib/trametinib (Tafinlar®/Mekinist®), vemurafenib/cobimetinib (Zelboraf®/Cotellic®), or encorafenib/binimetinib (Braftovi®/Mektovi®)
• These drugs block the signals that drive BRAF-mutant cells to divide uncontrollably
• They work very quickly (response often seen within weeks) and are taken orally (tablets)
• They are used both as adjuvant therapy (for resected Stage III, BRAF-mutant disease) and as first-line systemic therapy for Stage IV [3, 4]

Your tumour will be tested for BRAF status as part of routine diagnostic work-up. Ask your oncologist for the result.

4. Systemic immunotherapy for Stage IV

For advanced (Stage IV) melanoma, the treatment landscape has transformed since 2011. The main options are:

• Anti-PD-1 monotherapy (pembrolizumab or nivolumab) — often the first-line choice for BRAF wild-type Stage IV disease
• Ipilimumab + nivolumab combination — a dual checkpoint blockade regimen; higher response rates but also more immune-related side effects [3]
• BRAF + MEK inhibitors — for BRAF-mutant Stage IV; choice between immunotherapy and targeted therapy is guided by disease tempo, mutation load, and patient factors
• TIL therapy (lifileucel / Amtagvi®) — a cellular therapy using tumour-infiltrating lymphocytes (immune cells harvested from the patient's own tumour, expanded, and re-infused); approved in the US for advanced melanoma refractory to anti-PD-1 [4]; availability in the UK is evolving

5. Radiation (rare in melanoma)

Radiotherapy is not a first-line treatment for most melanomas. It is occasionally used:

• After lymph node dissection in high-risk Stage III patients
• For brain metastases (stereotactic radiosurgery)
• For palliation of painful bone or other metastatic deposits

What happens after diagnosis — the typical journey

1. Diagnosis confirmed by a dermatologist or GP biopsy → report includes Breslow depth, ulceration, mitotic rate, BRAF status
2. Staging workup — CT scan (chest/abdomen/pelvis), possibly PET-CT or brain MRI depending on stage
3. MDT (multidisciplinary team) meeting — a team of surgeons, oncologists, radiologists and pathologists review your case and agree a plan
4. Surgery — WLE ± SLNB within a few weeks of diagnosis for Stage I–III
5. Adjuvant therapy discussion — if Stage IIB–III, your oncologist will discuss whether immunotherapy or targeted therapy (for BRAF+) is appropriate
6. Surveillance — regular follow-up appointments and imaging for at least 5 years

Finding out more and next steps

💡 Before starting any systemic therapy, ask your oncologist whether an open clinical trial is available at your centre. Some trials require that you have not yet received certain treatments. See our Clinical Trial Finder and the Patient resources on the About page for links to Melanoma Focus UK, NIHR Be Part of Research, and ClinicalTrials.gov.

Specialist melanoma care in the UK is coordinated through skin MDTs within cancer networks. If you feel you have not received a specialist opinion, you are entitled to ask for a referral or a second opinion.

References

[1] Gershenwald JE, Scolyer RA, Hess KR et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer 8th Edition Cancer Staging Manual. CA Cancer J Clin. 2017;67(6):472–492. PMID 28961944 (Grade A, Tier 1)

[2] Wernham AGH, Tagliaferri L, Payne M et al. UK guidelines for the management of cutaneous melanoma. Br J Dermatol. 2024. PMID 38078653 (Grade A, Tier 1)

[3] Michielin O, Ascierto PA, Atkins MB et al. (ESMO) Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(1):11–40. PMID 38530680 (Grade A, Tier 1)

[4] NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Current version. nccn.org/guidelines (requires free registration) (Grade A, Tier 1)

Education and decision-support only — not a medical device. Does not diagnose, screen, predict, or provide personalised medical advice. Discuss all treatment decisions with your specialist team.

Emerging therapies on the horizon

The melanoma treatment landscape continues to evolve rapidly. Two agents in late-stage clinical development are worth knowing about:

Fianlimab + cemiplimab (anti-LAG-3 + anti-PD-1) [TRIAL ACTIVE]

Fianlimab (REGN3767) is an anti-LAG-3 antibody being evaluated in combination with cemiplimab (anti-PD-1) as a first-line treatment for advanced (Stage III/IV) melanoma. Phase 2 data published in 2024 showed strong overall response rates — comparable to or exceeding existing first-line dual-checkpoint combinations — with a manageable side-effect profile [5].

A registrational Phase 3 trial is ongoing. As of early 2026, fianlimab is not yet approved by the FDA or EMA. It is listed as [TRIAL ACTIVE] here, meaning the pivotal trial is open and enrolling. Patients interested in this option should ask their oncologist whether they are eligible for the trial or an expanded access programme. Use our Clinical Trial Finder or search ClinicalTrials.gov for "fianlimab".

TIL therapy (lifileucel / Amtagvi) — additional evidence

Since the main body of this article was written, a Phase 3 randomised trial (the TILL study) confirmed TIL therapy produces superior progression-free survival versus ipilimumab in patients with advanced melanoma who progressed on anti-PD-1 [6]. This trial underpins the FDA approval of lifileucel (Amtagvi®) in February 2024 as the first TIL therapy approved anywhere in the world.

Additional references for this section:

[5] Chesney JA et al. Fianlimab plus cemiplimab in unresectable or metastatic melanoma. J Clin Oncol. 2024. PMID 37881489

[6] Rohaan MW, Borch TH, van den Berg JH et al. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma. N Engl J Med. 2022;387(23):2113–2125. PMID 36477031

[Also see] Sarnaik AN et al. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. J Clin Oncol. 2021;39(24):2656–2666. PMID 34181447

Questions to ask your specialist

Bring this list to your next appointment — your oncologist or dermatologist can help you work through each one:

1. What is my exact stage? (Breslow depth, ulceration, lymph node status, AJCC 8th edition T/N/M classification)
2. Has my tumour been tested for a BRAF V600 mutation? If not, please request this test — it affects which treatments are available to me.
3. Would I benefit from adjuvant (post-surgery) therapy? (Most relevant if I am Stage IIB, IIC, or III — ask about pembrolizumab or BRAF-targeted therapy if applicable.)
4. Is there a clinical trial I should consider before starting standard treatment? Some trials require that I have not yet had certain therapies — it is important to ask early. Our Clinical Trial Finder lists known studies.
5. What does my follow-up schedule look like? (frequency of imaging, dermoscopy, blood tests, and when to contact the team between appointments)
6. Will I be discussed at an MDT (multidisciplinary team) meeting? If not, I can request one.

See our Getting specialist care section on the About page if you need guidance on accessing a melanoma specialist or MDT.