Melanoma
Malignant Melanoma · Cutaneous Melanoma · Skin Cancer (Melanoma)
~325,000 new cases/year — incidence rising globally
Melanoma arises from melanocytes and is the most lethal form of skin cancer. The two major therapeutic breakthroughs — BRAF/MEK targeted therapy and checkpoint immunotherapy — have transformed Stage IV melanoma from median OS of 6–9 months to >3 years in some populations. BRAF V600E mutation (present in ~50% of cutaneous melanoma) is the key biomarker determining treatment choice. Immunotherapy (anti-PD1 ± anti-CTLA4) benefits both BRAF-mutant and wild-type tumours.
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Subtypes
9
Diagnostic Tests
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Treatment Options
For Informational Purposes Only
Content on this page is for educational purposes only and does not constitute medical advice.
🗺 What Do I Do Next? — Your Roadmap
Just diagnosed with Melanoma? Here are your essential next steps.
Get the Full Diagnostic Workup
Before any treatment begins, you need 9 key tests — imaging, blood markers, biopsy, and molecular profiling. See the Diagnostic Workup section below. Do NOT start treatment without molecular testing — it determines which therapies work for your specific subtype.
Know Your Molecular Subtype
Melanoma is not one disease — it has 4 distinct subtypes defined by biomarkers (BRAF V600E, BRAF V600K, NRAS, C-KIT, and more). Your subtype determines which treatments apply to you. See Subtypes & Mutations below.
Assemble Your Care Team
You need a multidisciplinary team: oncologist (medical, surgical, radiation), pathologist, radiologist, and ideally a molecular tumour board review. Seek a second opinion at a major cancer centre for any Stage III-IV diagnosis.
Review All Treatment Options
Treatment for Melanoma spans Surgery, Radiation, Targeted Therapy, Immunotherapy. See the full Treatment Options section below. Ask your oncologist which options apply to your specific subtype and stage.
Ask About Clinical Trials
Many of the most effective treatments started as clinical trials. Ask your oncologist about eligibility. Search clinicaltrials.gov with your cancer type + molecular profile. Academic centres have the most trials.
Key Biomarkers & Mutations
Subtypes & Molecular Profiles
Most common targetable alteration in melanoma. Combination BRAF + MEK inhibition (dabrafenib + trametinib, vemurafenib + cobimetinib, encorafenib + binimetinib) produces high response rates (>60%) and rapid disease control. Resistance almost universally develops within 12–18 months. Choice between targeted therapy and immunotherapy first depends on pace of disease, LDH, and tumour burden.
KEY THERAPIES FOR THIS SUBTYPE
Diagnostic Workup
9 testsBIOPSY & PATHOLOGY
Excisional Biopsy of Primary Lesion
At diagnosisFull-thickness excision for Breslow thickness, Clark level, ulceration, mitotic rate, microsatellitosis — all determine T-stage and SLNB indication.
ENDOSCOPY & PROCEDURE
Sentinel Lymph Node Biopsy (SLNB)
At primary surgeryRegional lymph node staging for Breslow thickness ≥ 0.8 mm or < 0.8 mm with ulceration or high mitotic rate.
IMAGING
CT Chest / Abdomen / Pelvis
Stage III-IV or symptomaticDistant metastasis staging for Stage III-IV. Brain, liver, lung, adrenal, soft tissue.
Brain MRI with contrast
Stage IV or neurological symptomsBrain metastases — melanoma has high neurotropism. Mandatory at Stage IV staging.
PET-CT
Stage III-IV stagingWhole-body metastatic survey — superior to CT for soft tissue, lymph node, and skin metastases.
GENETIC & MOLECULAR
BRAF V600 Mutation Testing
At metastatic diagnosisMandatory for all advanced/metastatic melanoma — determines BRAF/MEK inhibitor eligibility.
Extended Melanoma Panel (NRAS, C-KIT, NF1, TMB)
At metastatic diagnosisNRAS mutation, C-KIT in acral/mucosal melanoma, NF1 mutation, TMB — guides clinical trial eligibility and immunotherapy prediction.
BLOOD & TUMOUR MARKERS
LDH (Lactate Dehydrogenase)
At diagnosis and every 6–8 weeks during treatmentStrong independent prognostic marker in Stage IV melanoma — elevated LDH is associated with poor prognosis and is incorporated into AJCC staging.
S100B
At diagnosis and during follow-upSensitive melanoma marker for monitoring response and detecting early recurrence. More sensitive than LDH for early-stage recurrence.
Treatment Options
11 optionsSURGERY
Wide Local Excision (WLE)
Primary melanoma resection with adequate margins (0.5–2 cm depending on Breslow thickness). Standard surgical treatment.
Therapeutic Lymph Node Dissection
Clinically or radiologically involved regional lymph nodes. Completion dissection after positive SLNB is now optional (DeCOG/MSLT-II trials).
RADIATION
Stereotactic Radiosurgery (SRS)
Brain metastases — SRS for limited brain mets (1–4 lesions). Whole-brain radiation reserved for multiple/large brain mets.
TARGETED THERAPY
Dabrafenib + Trametinib (Tafinlar + Mekinist)
BRAF V600E/K mutant unresectable Stage III or Stage IV melanoma. Also adjuvant for resected Stage III BRAF V600E/K (COMBI-AD — 5-year RFS benefit).
Encorafenib + Binimetinib (COLUMBUS)
BRAF V600E mutant metastatic melanoma — COLUMBUS trial. Better tolerability profile than dabrafenib/trametinib.
Imatinib / Sunitinib
C-KIT mutant/amplified acral or mucosal melanoma — response rates ~20–30%.
IMMUNOTHERAPY
Pembrolizumab (Keytruda)
Unresectable or metastatic melanoma regardless of BRAF status — KEYNOTE-006. Also adjuvant Stage IIB-IV resected (KEYNOTE-716).
Nivolumab + Ipilimumab (CheckMate 067)
High-risk metastatic melanoma — highest long-term OS (~50% at 5 years). Greater toxicity than monotherapy — grade 3–4 AEs in 55%. Used when rapid disease control needed.
Relatlimab + Nivolumab (Opdualag)
Unresectable or metastatic melanoma — LAG-3 + PD-1 dual blockade. RELATIVITY-047: superior PFS to nivolumab alone with less toxicity than ipilimumab combo.
Ipilimumab (Yervoy)
Anti-CTLA4 — earlier approval, now usually used in combination with nivolumab rather than as monotherapy. Adjuvant after resected Stage III.
T-VEC (Talimogene Laherparepvec — Imlygic)
Intralesional oncolytic viral therapy for injectable Stage IIIB-IVM1a melanoma. Activates local and systemic anti-tumour immune response.