MELANOMA TREATMENT: STAGES,
OPTIONS, AND OUTCOMES

Melanoma starts in melanocytes, the pigment-producing cells of the skin. Most melanomas develop on sun-exposed skin (cutaneous melanoma), but the disease can also arise in the eye (uveal melanoma), in mucosal surfaces such as the mouth, nasal passages, or genital area (mucosal melanoma), and on palms, soles, or under nails (acral melanoma). These subtypes behave differently and may need different treatment approaches. Genetic profiling matters. Around half of cutaneous melanomas carry BRAF mutations (most often BRAF V600E), and roughly 15 to 25 per cent carry NRAS mutations. KIT mutations are more common in mucosal and acral melanoma, while uveal melanoma has its own driver pattern (GNAQ, GNA11). Mutation testing helps select the most appropriate systemic therapy.

Melanoma staging is based on the AJCC system, which considers tumour thickness (Breslow), ulceration, lymph node involvement, and distant spread. Sentinel lymph node biopsy is often used in stage I–II melanoma above 1 mm thickness to confirm whether disease has reached regional nodes.

• Stage 0 (in situ) — confined to the top layer of the skin, w

  Stage 0 (in situ) — confined to the top layer of the skin, with very high cure rates after surgery.

• Stage I — thin tumours (typically up to 2 mm) without spread

  Stage I — thin tumours (typically up to 2 mm) without spread to lymph nodes or distant sites.

• Stage II — thicker tumours, sometimes ulcerated, but still w

  Stage II — thicker tumours, sometimes ulcerated, but still without lymph node or distant spread.

• Stage III — regional spread to nearby lymph nodes or in-tran

  Stage III — regional spread to nearby lymph nodes or in-transit/satellite lesions.

• Stage IV — distant metastases, most commonly to lung, liver,

  Stage IV — distant metastases, most commonly to lung, liver, brain, bone, or distant skin and lymph nodes. LDH level is part of stage IV substaging.

Stage 0 to Stage II Treatment is primarily surgical: wide local excision with margins guided by tumour thickness, sometimes combined with sentinel lymph node biopsy. Adjuvant systemic therapy is generally not required for low-risk early-stage disease, though selected high-risk stage IIB/IIC patients are now offered adjuvant immunotherapy. Stage III (Resectable) Standard treatment combines surgery with adjuvant therapy for one year. Options include adjuvant PD-1 immunotherapy (pembrolizumab or nivolumab) regardless of BRAF status, or adjuvant BRAF/MEK inhibitor combinations (dabrafenib plus trametinib) for BRAF V600-mutant disease. Neoadjuvant immunotherapy — giving immunotherapy before surgery — is increasingly used and has shown promising outcomes. Stage IV and Unresectable Disease Systemic therapy is the cornerstone, with several established options: Brain metastases require dedicated planning. Stereotactic radiosurgery, neurosurgery, and systemic therapy with good central nervous system activity (combination immunotherapy or BRAF/MEK in BRAF-mutant disease) are commonly used together.

• PD-1 monotherapy — pembrolizumab or nivolumab, a common firs

  PD-1 monotherapy — pembrolizumab or nivolumab, a common first-line option.

• PD-1 plus CTLA-4 combination — nivolumab plus ipilimumab, mo

  PD-1 plus CTLA-4 combination — nivolumab plus ipilimumab, more effective in many patients but with higher toxicity.

• PD-1 plus LAG-3 combination — nivolumab plus relatlimab (Opd

  PD-1 plus LAG-3 combination — nivolumab plus relatlimab (Opdualag), an alternative with a different toxicity profile.

• BRAF/MEK targeted therapy — dabrafenib plus trametinib, vemu

  BRAF/MEK targeted therapy — dabrafenib plus trametinib, vemurafenib plus cobimetinib, or encorafenib plus binimetinib for BRAF V600-mutant melanoma.

• TIL therapy — lifileucel, an FDA-approved tumour-infiltratin

  TIL therapy — lifileucel, an FDA-approved tumour-infiltrating lymphocyte therapy for selected patients after immunotherapy failure.

• Clinical trials — neoantigen mRNA vaccines, novel checkpoint

  Clinical trials — neoantigen mRNA vaccines, novel checkpoint targets (TIGIT, others), and combination strategies.

CancerFax supports melanoma patients through a structured pathway:

• Case review — stage, mutation status, prior treatments, and

  Case review — stage, mutation status, prior treatments, and current disease status are reviewed to clarify what options are realistic.

• Treatment mapping — appropriate immunotherapy, targeted ther

  Treatment mapping — appropriate immunotherapy, targeted therapy, TIL therapy, and clinical trial options are identified across countries.

• Hospital and trial matching — reports are shared with approp

  Hospital and trial matching — reports are shared with appropriate melanoma specialists, multidisciplinary teams, or trial centres.

• Cost and logistics planning — patients receive guidance on d

  Cost and logistics planning — patients receive guidance on drug pricing, expected cycles, surgery timing, brain-metastasis management, and stay duration.

• Coordination and follow-up — CancerFax supports admission, i

  Coordination and follow-up — CancerFax supports admission, interpreter needs, monitoring schedules, and continuity after returning home.

Standard surgery, immunotherapy, and BRAF/MEK targeted therapy are available in major cancer centres globally, with cost and access varying significantly by country. TIL therapy is currently delivered in selected United States centres and through clinical trials elsewhere; neoantigen vaccine trials run in the United States, Germany, the United Kingdom, China, and others. Specialised programmes for uveal melanoma, mucosal melanoma, and brain-metastasis management are concentrated in fewer high-volume centres. CancerFax helps patients identify the right centre and protocol for their subtype, mutation, and disease pattern rather than choosing by hospital name alone.

Frequently Asked Questions

Answers to common questions from patients and families.