Vasyl V. OstafiichukSurgical Oncologist · National Cancer Institute of Ukraine
MelanomaSkin cancerSarcomaResourcesConsultationУкраїнська
Professional layer

Melanoma for clinicians: decisions that change management

A decision map rather than an encyclopedia: what matters before surgery, when SLNB is indicated, how stage III sequencing has changed, which molecular tests are actionable, and when cutaneous algorithms should not be extrapolated to other melanoma subtypes.

Surgery & SLNBmargins · SLNB · positive nodeSystemic therapyIIB–IV · neo-/adjuvant strategiesMolecular testingBRAF and other actionable alterationsSubtypesacral · mucosal · uveal
Practice-changing

What has already changed practice

Key decisions in 2026 that should not automatically be deferred until after surgery.

ESMO 2025 · NADINA

Macroscopic resectable stage III

Neoadjuvant immunotherapy has become a major international strategy for clinically or radiologically detectable resectable stage III melanoma. NADINA reported approximately 84% versus 57% 12-month event-free survival.

NADINA — N Engl J Med 2024 →
ESMO Living Guideline · 2025

Resected stage IIB–IIC

Adjuvant pembrolizumab or nivolumab for 12 months should be discussed, balancing recurrence-free survival benefit, toxicity and the lack of mature overall-survival data.

ESMO Living Guideline →
EADO/EDF/EORTC · 2025

SLNB is staging, not therapeutic dissection

Offer SLNB at ≥1.0 mm and discuss it for 0.8–1.0 mm or thinner ulcerated tumours. A positive sentinel node no longer mandates routine completion lymph node dissection.

European consensus guideline →
ESMO CPG · 2025

Molecular testing

Actionable mutation testing is recommended in resectable or unresectable stage III–IV melanoma, can be considered in high-risk stage IIB–IIC, and is not routinely recommended in stage I–IIA.

ESMO CPG →
Surgical oncology

Questions to answer before surgery

The correct operation starts with pathology, staging and an understanding of the systemic pathway.

Primary tumourComplete pathology including Breslow thickness, ulceration, margins and other parameters relevant to T category and management.
Wide excisionEuropean guidelines support 1–2 cm clinical margins depending on thickness and anatomy; function-critical sites require individual planning.
SLNBA staging procedure in selected clinically N0 patients, ideally planned with definitive excision before major reconstruction alters lymphatic drainage.
Positive SLNRoutine completion lymph node dissection is no longer standard. Nodal surveillance, systemic risk management and MDT review are required.
Macroscopic stage IIIEvaluate a neoadjuvant strategy before therapeutic nodal dissection or major surgery.
Systemic therapy

Neoadjuvant, adjuvant, metastatic

Define the clinical scenario first; choose the drug second.

Resected IIB–IICDiscuss adjuvant anti-PD-1 after balancing recurrence risk, benefit and immune toxicity.
Resectable macroscopic IIINeoadjuvant immunotherapy is now a major strategy; pathological response can influence subsequent treatment intensity.
Resected IIIAdjuvant anti-PD-1; BRAF/MEK targeted therapy is an option in BRAF V600-positive disease depending on context.
Unresectable / IVChoice among immunotherapy, BRAF/MEK when BRAF V600-positive, local therapy and clinical trials depends on tempo, sites, symptoms, CNS disease and previous treatment.
Molecular diagnostics

Not every genomic result is predictive

Separate prognostic information, classification and biomarkers that actually alter therapy.

BRAF V600
A key predictive biomarker for BRAF/MEK targeted therapy and clinically relevant before selecting systemic strategies in stage III–IV disease.
Acral and mucosal melanoma
The genomic landscape differs from typical UV-associated cutaneous melanoma; KIT and other alterations may matter in selected cases. Trial representation is limited, so extrapolation should be explicit.
Do not merge uveal melanoma into the cutaneous algorithm
GNAQ/GNA11/BAP1/SF3B1 and HLA-A*02:01 belong to a different biology and a dedicated uveal melanoma pathway.
Subtypes

When the general algorithm needs adaptation

Rare melanomas deserve specialist MDT review and explicit acknowledgement of evidence limitations.

CutaneousAcral melanoma

Different aetiology and genomics, anatomically challenging surgery and lower representation in pivotal trials.

Professional overview →Non-cutaneousMucosal melanoma

Site-specific staging, function-conscious local control and lower direct evidence for systemic strategies.

Professional overview →Separate biologyUveal melanoma

GNAQ/GNA11, liver-dominant risk, HLA-A*02:01 and tebentafusp.

Open UM cluster →
Evidence backbone. Amaral T et al. ESMO CPG, Ann Oncol 2025; Garbe C et al. EADO/EDF/EORTC European consensus guideline Parts 1–2, Eur J Cancer 2025; Blank CU et al. NADINA, N Engl J Med 2024; Patel SP et al. SWOG S1801, N Engl J Med 2023; ESMO Living Guideline updates 2025. The ASCO melanoma systemic therapy guideline remains useful but is in the 2025–2026 update cycle.