Melanoma is the most dangerous form of skin cancer — arising from melanocytes (pigment-producing cells) in the skin, eyes and rarely other sites. Although less common than basal cell and squamous cell carcinomas (non-melanoma skin cancers), melanoma accounts for approximately 80% of skin cancer deaths due to its propensity to metastasise. Untreated advanced melanoma was nearly universally fatal within 1-2 years; modern immunotherapy and targeted therapy have transformed this outlook dramatically.

What causes melanoma?

The primary cause is ultraviolet radiation (UVR) — from sunlight (UVA and UVB) and artificial tanning devices. UVR causes characteristic UV-signature mutations in melanocyte DNA — particularly in BRAF and NRAS oncogenes. Risk factors: intermittent intense sun exposure and sunburn (particularly in childhood); total cumulative UV exposure; fair skin (Fitzpatrick types I-II); numerous moles (≥50 common nevi, or atypical nevi); personal or family history of melanoma; immunosuppression; and CDKN2A germline mutations (hereditary melanoma). Sunbed use before age 35 increases risk by approximately 75%.

What does melanoma look like?

The ABCDE criteria help identify suspicious pigmented lesions: Asymmetry; Border irregularity; Colour variation (multiple colours within one lesion); Diameter >6mm; and Evolution (any change). Any pigmented lesion that is changing, bleeding, itching or different from surrounding moles ("ugly duckling sign") should be urgently assessed. Amelanotic melanoma (without pigment) can be pink or skin-coloured — a diagnostic challenge. Dermoscopy significantly improves clinical diagnosis accuracy.

How has melanoma treatment changed?

Metastatic melanoma was essentially untreatable before 2011 — median survival approximately 6-9 months, 5-year survival <5-10%. Two concurrent revolutions transformed outcomes: (1) BRAF/MEK inhibitor combinations (for BRAF V600-mutated melanoma, approximately 50%): dabrafenib + trametinib; encorafenib + binimetinib; vemurafenib + cobimetinib — high response rates (60-80%); 5-year survival approximately 34-40%. (2) Immune checkpoint inhibitors (all melanoma): ipilimumab + nivolumab combination — 5-year survival approximately 52% (CheckMate 067). These therapies have produced genuinely durable responses — potentially curative in a subset of metastatic patients.

How is early melanoma treated?

Wide local excision (WLE) with safety margins determined by Breslow thickness (depth of invasion): 2mm — 2cm margins. For stage IB-IIC (thick, high-risk primary): adjuvant anti-PD-1 therapy (pembrolizumab, nivolumab) or BRAF/MEK inhibitors (if BRAF-mutated) significantly reduce recurrence. Sentinel lymph node biopsy (SLNB) for melanomas >1mm for staging. Stage III (lymph node involvement): adjuvant immunotherapy or targeted therapy dramatically reduce recurrence.

Can skin cancer be prevented?

UV protection is the primary prevention strategy: broad-spectrum SPF 30+ sunscreen applied daily and reapplied every 2 hours; protective clothing (UPF 50+ fabric, wide-brimmed hat, sunglasses); seeking shade during peak UV hours (10am-4pm); and strictly avoiding sunbeds. WHO recommends no children under 18 use sunbeds; many countries have legislated against sunbed use under 18. Regular skin self-examination (monthly) and annual dermatologist examination (for high-risk individuals) enable early diagnosis. Australia's "Slip, Slop, Slap" public health campaign has achieved meaningful melanoma prevention.

How does GMJ News cover melanoma?

GMJ News covers IARC melanoma data, ipilimumab + nivolumab long-term survival, BRAF/MEK inhibitor evidence, sunbed legislation, UV protection guidelines and early detection. Melanoma is an increasing concern in Georgia — relevant to PHIG's cancer prevention programme and the Georgian Medical Journal's oncology coverage.

Home › Topics › Melanoma and Skin Cancer

Melanoma and Skin Cancer

Q: How is early melanoma treated?

Wide local excision (WLE) with safety margins determined by Breslow thickness (depth of invasion): 2mm — 2cm margins. For stage IB-IIC (thick, high-risk primary): adjuvant anti-PD-1 therapy (pembrolizumab, nivolumab) or BRAF/MEK inhibitors (if BRAF-mutated) significantly reduce recurrence. Sentinel lymph node biopsy (SLNB) for melanomas >1mm for staging. Stage III (lymph node involvement): adjuvant immunotherapy or targeted therapy dramatically reduce recurrence.

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Cutaneous melanoma — the most dangerous form of skin cancer — caused an estimated 325,000 new cases and 57,000 deaths in 2020, with incidence rising approximately 1-4% per year in most populations driven by UV exposure and sunbed use; non-melanoma skin cancers (NMSC — basal cell and squamous cell carcinoma) are even more common with an estimated 1.2-1.5 billion cumulative lifetime cases globally (WHO/IARC). Melanoma treatment has been revolutionised by two breakthroughs: BRAF/MEK inhibitor combinations (for the approximately 50% of melanomas with BRAF V600E/K mutations) and immune checkpoint inhibitors (ipilimumab + nivolumab) — transforming stage IV 5-year survival from <10% to approximately 50%.

Key messages

325K cases — but immunotherapy transforms stage IV

Melanoma caused approximately 325,000 new cases and 57,000 deaths in 2020 — but the treatment revolution with immune checkpoint inhibitors (ipilimumab + nivolumab) and BRAF/MEK inhibitors has transformed stage IV 5-year survival from <10% to approximately 50% (IARC GLOBOCAN 2020).

UV radiation is the primary cause

Ultraviolet radiation (UVR) — from sun exposure and artificial tanning devices (sunbeds) — is the primary cause of melanoma. A single episode of severe sunburn more than doubles melanoma risk. Sunbed use before age 35 increases risk by approximately 75%.

BRAF V600E — targeted therapy in 50%

Approximately 50% of cutaneous melanomas carry BRAF V600E/K mutations — targetable with BRAF inhibitors (vemurafenib, dabrafenib) + MEK inhibitors (trametinib, cobimetinib) combinations, achieving high response rates and 5-year survival of approximately 35-40%.

Immunotherapy — durable responses

PD-1 inhibitors (nivolumab, pembrolizumab) and CTLA-4 inhibitor (ipilimumab) — alone and combined (nivolumab + ipilimumab — highest efficacy, 5-year survival approximately 52%) — have produced durable, potentially curative responses in metastatic melanoma.

Sun protection and early detection save lives

Stage I melanoma has >99% 5-year survival; stage IV has approximately 50% (with modern treatment) — but was <10% before immunotherapy. UV protection (SPF 30+ sunscreen, protective clothing, avoiding peak UV hours), skin self-examination and early presentation are the primary prevention strategies.

Non-melanoma skin cancers — massive burden

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin (non-melanoma skin cancers, NMSC) are the most common cancers globally — with estimated 1.2-1.5 billion lifetime cases. While rarely fatal (BCC almost never metastasises), NMSC cause significant morbidity and healthcare burden.

Key statistics

325K

new melanoma cases/year (2020 — significant underreporting)

IARC GLOBOCAN

57K

melanoma deaths/year (2020)

IARC GLOBOCAN

~50%

of melanomas carry BRAF V600E/K mutation

ESMO/Research

~52%

5-year survival with ipilimumab + nivolumab (stage IV)

CheckMate 067

75%

increased melanoma risk from sunbed use before age 35

WHO/IARC

>99%

5-year survival for stage I melanoma

ESMO/ASCO

Melanoma age-standardised incidence (per 100,000) by region — GLOBOCAN 2020

Source: IARC GLOBOCAN 2020. Highest in Australia/NZ and Northern Europe (fair-skinned, UV-exposed populations).

Glossary of key terms

BRAF V600E/K mutation
ESMO/FDAThe most common oncogenic mutation in melanoma — present in approximately 50% of cases. Causes constitutive activation of the MAPK signalling pathway. BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) specifically target this mutation. Combined with MEK inhibitors (trametinib, cobimetinib, binimetinib) to prevent resistance.

Immune checkpoint inhibitors (ICI)
FDA/ESMOMonoclonal antibodies targeting immune checkpoint receptors — releasing the brakes on anti-tumour T-cell responses. For melanoma: anti-CTLA-4 (ipilimumab); anti-PD-1 (nivolumab, pembrolizumab); combination (ipilimumab + nivolumab — highest efficacy, highest toxicity). First oncology indication establishing immunotherapy as curative-intent cancer treatment.

ABCDE criteria
WHO/DermatologyThe clinical criteria for suspicious pigmented lesions: Asymmetry (one half unlike the other); Border irregularity (ragged, notched); Colour variation (multiple shades of brown, black, red, white, blue); Diameter >6mm (eraser-size); Evolution (any change in size, shape, colour or new symptoms). Prompt biopsy indicated for suspicious lesions.

Sentinel lymph node biopsy (SLNB)
ESMOA staging procedure — injecting a tracer near the primary melanoma and identifying the first (sentinel) lymph node(s) draining the tumour. Microscopically examining the SLN determines whether melanoma has metastasised to regional lymph nodes — essential for staging and prognosis. Positive SLNB upstages to stage III.

Basal cell carcinoma (BCC)
WHOThe most common human cancer — primarily caused by UV radiation; almost never metastasises but causes significant local destruction if untreated. Treatment: surgical excision; Mohs micrographic surgery (for high-risk/complex sites); radiotherapy; vismodegib (hedgehog pathway inhibitor for advanced/metastatic BCC).

Tumour mutational burden (TMB)
FDA/ESMOThe number of somatic mutations per megabase of genome in a tumour. Melanoma has among the highest TMB of any cancer (from UV-induced DNA damage) — contributing to its exceptional responsiveness to immune checkpoint inhibitors (high neoantigen load).