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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine.
Melanoma arises from pigment cells; most cases are cured by excision when found early, and it is the skin cancer most likely to spread when it is not. Risk is driven by ultraviolet exposure and fair skin; the tumour carries the highest mutation burden of any common cancer, which is why it became the proving ground for immunotherapy. About half of cutaneous melanomas carry BRAF V600 mutations, a quarter NRAS, and acral and mucosal subtypes carry KIT alterations; uveal melanoma is a distinct disease driven by GNAQ/GNA11 and BAP1.
The treatment revolution began in 2011 with ipilimumab and vemurafenib and accelerated with PD-1 blockade (2014). Nivolumab-ipilimumab now delivers ~50% melanoma-specific survival at ten years in advanced disease (CheckMate 067), pembrolizumab 34% overall survival at ten years (KEYNOTE-006), and nivolumab-relatlimab offers a gentler doublet. For BRAF-mutant disease, DREAMseq settled that immunotherapy should come first. In resectable stage III disease, NADINA and SWOG S1801 moved immunotherapy to before surgery with response-adapted follow-on treatment, and adjuvant PD-1 or BRAF/MEK covers stage IIB-III. After immunotherapy fails, lifileucel TIL therapy (2024) and the oncolytic virus RP1 with nivolumab (2026) are approved; tebentafusp is the first survival-extending drug in metastatic uveal melanoma. Intismeran autogene plus pembrolizumab became the first personalised mRNA vaccine to pass a phase 3 in August 2026.
| Setting | Approach | Guideline |
|---|---|---|
| Stage II-III | Adjuvant pembrolizumab/nivolumab; neoadjuvant IO for resectable stage III. | not mapped |
| Metastatic first line | Nivolumab-ipilimumab or nivolumab-relatlimab; BRAF/MEK if rapid control needed. | not mapped |
| After PD-1 | Lifileucel, RP1 + nivolumab, ipilimumab-based, trials; tebentafusp (uveal). | not mapped |
| Screening and diagnosis | Dermoscopy, total-body photography for high-risk patients, excisional biopsy with Breslow thickness and ulceration reported; AI decision support emerging. | not mapped |
| Stage I-II primary | Wide local excision with margins by thickness (1-2 cm); sentinel lymph node biopsy from ~0.8 mm Breslow or with ulceration; nodal ultrasound surveillance rather than completion dissection if positive (MSLT-II). | NCCN Category 1 for SLNB thresholds |
| Stage IIB-IIC (thick or ulcerated, node-negative) | Adjuvant pembrolizumab or nivolumab for one year (KEYNOTE-716, CheckMate 76K); discuss modest absolute benefit and irAE risk; ctDNA-guided trials. | NCCN 2A, ESMO-MCBS A |
| Resectable stage III (macroscopic nodes) | Neoadjuvant ipilimumab + nivolumab (two cycles) then surgery with response-adapted adjuvant therapy (NADINA), or neoadjuvant pembrolizumab (SWOG S1801); alternative adjuvant-only PD-1 or, if BRAF-mutant, dabrafenib-trametinib. | NCCN Preferred (neoadjuvant IO) |
| Stage III after surgery (adjuvant) | Nivolumab or pembrolizumab for one year; dabrafenib-trametinib for BRAF V600 (COMBI-AD, 10-year RFS 48%); relatlimab adds nothing (RELATIVITY-098). | NCCN 1, ESMO-MCBS A |