Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Key guideline recommendations

1. Sentinel lymph node biopsy is recommended for all patients without clinical nodal involvement with a T2a or higher tumour (Breslow thickness more than 1.0 mm).

   I, A

2. Testing for targetable mutations is recommended in patients with stage III or IV melanoma (resectable or unresectable); BRAF V600 testing is mandatory.

   I, A

3. In previously untreated resectable stage III melanoma, neoadjuvant nivolumab–ipilimumab followed by adjuvant treatment based on pathological response and BRAF status can be offered (not EMA or FDA approved at the time of publication).

   I, A; ESMO-MCBS: A

4. Neoadjuvant plus adjuvant pembrolizumab is also recommended for these patients (not EMA or FDA approved).

   II, A

5. In patients with a major pathological response (per INMC criteria) after neoadjuvant treatment, adjuvant treatment can be omitted; in the absence of a major response, further treatment should be considered.

   I, A

6. Adjuvant systemic treatment options: anti-PD-1 (nivolumab for resected stage IIIB to IV with no evidence of disease, or pembrolizumab for resected stage III) or dabrafenib–trametinib for resected stage III melanoma with a BRAF V600E mutation; these treatments should be started within 12 weeks of complete surgery.

   I, A

7. Adjuvant targeted therapy should not be offered to patients with a BRAF V600K mutation, because of the potential detrimental effect on overall survival reported in the COMBI-AD trial.

   II, D

8. In stage IIIA with a tumour burden of less than 1 mm, adjuvant systemic treatment is generally not recommended; adjuvant nivolumab–ipilimumab is not recommended for resected stage III.

   I, D

9. In unresectable disease, first-line ipilimumab–nivolumab is the preferred option for all patients regardless of BRAF status, provided it can be given safely during the first few months (i.e. when a rapid response is not needed because of aggressive or symptomatic disease). Single-agent nivolumab or pembrolizumab is also recommended in first line.

   I, A; ESMO-MCBS: A/4

10. Nivolumab–relatlimab can be offered as first-line treatment, but EMA approval is only for tumours with PD-L1 expression below 1% (FDA approval regardless of PD-L1).

    I, B; ESMO-MCBS: 3

11. TIL therapy is an intensive option for selected patients (young, stage IV M1a–c, performance status ≤1, LDH less than twice the upper limit of normal and 1 to 3 prior therapies) who can tolerate its toxicity (not EMA or FDA approved).

    II, B

12. Patients with asymptomatic brain metastases should preferably be treated initially with nivolumab–ipilimumab.

    II, A

Study population

Clinical significance and place in guidelines

Limitations