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Practice Guideline
. 2025 Jan;36(1):10-30.
doi: 10.1016/j.annonc.2024.11.006. Epub 2024 Nov 14.

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

T Amaral  1 , M Ottaviano  2 , A Arance  3 , C Blank  4 , V Chiarion-Sileni  5 , M Donia  6 , R Dummer  7 , C Garbe  8 , J E Gershenwald  9 , H Gogas  10 , M Guckenberger  11 , J Haanen  12 , O Hamid  13 , A Hauschild  14 , C Höller  15 , C Lebbé  16 , R J Lee  17 , G V Long  18 , P Lorigan  17 , E Muñoz Couselo  19 , P Nathan  20 , C Robert  21 , E Romano  22 , D Schadendorf  23 , V Sondak  24 , K P M Suijkerbuijk  25 , A C J van Akkooi  26 , O Michielin  27 , P A Ascierto  28 ; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org
Affiliations
Practice Guideline

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

T Amaral et al. Ann Oncol. 2025 Jan.
No abstract available

Keywords: ESMO Clinical Practice Guideline; cutaneous melanoma; diagnosis; prognosis; risk assessment; treatment.

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Figures

Figure 1
Figure 1. Proposed algorithm for the management of patients with pT1b-pT4b cN0 cM0 melanoma.
Purple: algorithm title; blue: systemic anticancer therapy; orange: surgery; white: non-treatment aspects. c, clinical; DMFS, distant metastasis-free survival; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; ESMO, European Society for Medical Oncology; FDA, Food and Drug Administration; LM, lentigo maligna; M, metastasis; MCBS, ESMO-Magnitude of Clinical Benefit Scale; N, node; NEB, no evaluable benefit; OS, overall survival; p, pathological; PD-1, programmed cell death protein 1; R1, microscopic tumour at the margin; RFS, recurrence-free survival; RT, radiotherapy; SLNB, sentinel lymph node biopsy; T, tumour; WG, working group; WLE, wide local excision. aRT can be considered for local tumour control in cases of inadequate resection margins of LM [III, B] and could be discussed for patients with an R1 resection [III, C]. Adjuvant RT to the primary excision site should be considered for patients with desmoplastic or neurotropic melanoma for whom adequate (≥8 mm) pathological resection margins cannot be achieved [IV, C]. bTreatment discussions with the patient should include consideration of the RFS benefit but lack of mature OS data [I, A]. cTreatment discussions with the patient should consider the DMFS and RFS benefits but lack of mature OS data compared with placebo [I, A]. dESMO-MCBS v1.1 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS WG and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). eTreatment discussions with the patient should consider the DMFS and RFS benefits and potential OS benefit for patients with BRAF V600E-mutated melanoma [I, A]. fESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group.
Figure 2
Figure 2. Proposed algorithm for the management of patients with stage III melanoma and clinically positive LNs or resectable stage IV melanoma.
Purple: algorithm title; turquoise: combination of treatments and treatment modalities; white: non-treatment aspects. DMFS, distant metastasis-free survival; EMA, European Medicines Agency; ESMO, European Society for Medical Oncology; FDA, Food and Drug Administration; LN, lymph node; MCBS, ESMO-Magnitude of Clinical Benefit Scale; OS, overall survival; PD-1, programmed cell death protein 1; RFS, recurrence-free survival; RT, radiotherapy; WG, working group. aRT could be discussed for patients after resection of bulky LN metastases, especially if further surgical clearance is not feasible [III, C]. bTreatment discussions with the patient regarding adjuvant anti-PD-1 therapy should consider the DMFS and RFS benefits but lack of mature OS data compared with placebo [I, A]. cTreatment discussions with the patient regarding adjuvant targeted therapy should consider the DMFS and RFS benefits and potential OS benefit for patients with BRAF V600E-mutated melanoma [I, A]. dNot EMA or FDA approved as neoadjuvant therapy. eTreatment discussions with the patient regarding neoadjuvant therapy should consider the EFS, DMFS and RFS benefits but lack of mature OS data [I, A]. fESMO-MCBS v1.1 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS WG and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).
Figure 3
Figure 3. Proposed algorithm for the management of patients with ITMs.
Purple: algorithm title; turquoise: combination of treatments and treatment modalities; white: non-treatment aspects. DFI, disease-free interval; DMFS, distant metastasis-free survival; ECT, electrochemotherapy; EMA, European Medicines Agency; ESMO, European Society for Medical Oncology; FDA, Food and Drug Administration; ILI, isolated limb infusion; ILP, isolate limb perfusion; ITM, in-transit metastasis; MCBS, ESMO-Magnitude of Clinical Benefit Scale; OS, overall survival; PD-1, programmed cell death protein 1; RFS, recurrence-free survival; RT, radiotherapy; T-VEC, talimogene laherparepvec; WG, working group. aFor anti-PD-1-based therapy, treatment discussions with the patient should consider the DMFS and RFS benefits but lack of mature OS data compared with placebo [I, A]. For dabrafenibetrametinib, these discussions should also consider the DMFS and RFS benefits and potential OS benefit for patients with BRAF V600E-mutated melanoma [I, A]. bNot EMA or FDA approved as neoadjuvant therapy. cESMO-MCBS v1.1 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS WG and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).
Figure 4
Figure 4. Proposed algorithm for the management of patients with stage III/IV melanoma according to prior adjuvant treatment received.
Purple: algorithm title; blue: systemic anticancer therapy; turquoise: combination of treatments and treatment modalities; white: non-treatment aspects. BM, brain metastasis; BRAFi, BRAF inhibitor; ChT, chemotherapy; ctDNA, circulating tumour DNA; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; ESMO, European Society for Medical Oncology; FDA, Food and Drug Administration; ICI, immune checkpoint inhibitor; LDH, lactate dehydrogenase; M, metastasis; MCBS, ESMO-Magnitude of Clinical Benefit Scale; MEKi, MEK inhibitor; NGS, next-generation sequencing; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PS, performance status; RT, radiotherapy; TIL, tumour-infiltrating lymphocyte; T-VEC, talimogene laherparepvec; WG, working group; WT, wild type. aPatients with metastatic melanoma should have metastases (preferably) or the primary tumour screened for the detection of BRAF V600 mutation [IV, A; ESCAT score: I-A]. If no tumour tissue is available, ctDNA may be an alternative [III, C]. bEnrolment into a clinical trial is preferred wherever possible [V, A]. cAdditional treatment options include palliative resection [IV, C], RT [IV, B] and/or T-VEC [I, C] for patients with symptomatic extracranial disease; and best supportive and palliative care for all patients [V, A]. Local therapies should also be considered for all patients throughout the disease course, including for resectable recurrence after (neo)adjuvant therapy and, where needed, to achieve local control, with access to tissue for NGS analysis providing the potential for personalised therapy. dImmediate contraindications to ICI include rapid progression, elevated LDH levels, comorbidities and any symptoms that preclude ICI use. In these situations, ICI therapy should be reconsidered as soon as the contraindications are resolved and ICI becomes a viable therapy option. eAbsolute contraindications to ICI should be based on a multidisciplinary assessment. fESMO-MCBS v1.1 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS WG and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). gEMA approved for PD-L1 expression <1%, FDA approval is regardless of PD-L1 expression. hFor patients in whom the decision to treat with targeted therapy has been made, those who cannot receive a MEKi (e.g. due to cardiovascular comorbidities, a recent BM bleeding event, history of retinal detachment or other ophthalmological contraindications) can be offered encorafenib as monotherapy [II, B; not FDA or EMA approved]. iESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group. jInduction targeted therapy followed by anti-PD-1 therapy is not EMA or FDA approved. The optimal duration of induction targeted therapy is currently unknown. kFor patients who do not require a rapid tumour response to therapy due to aggressive disease. lNot EMA or FDA approved for second-line use. mAn option for selected young, fit patients with stage IV M1a-c melanoma, PS 0, normal LDH, 1-3 prior treatments and who are able to tolerate TIL-related side-effects. nNot EMA or FDA approved.
Figure 5
Figure 5. Proposed algorithm for the management of patients with MBMs.
Purple: algorithm title; blue: systemic anticancer therapy; turquoise: combination of treatments and treatment modalities; dark green, RT; white: non-treatment aspects. BRAFi, BRAF inhibitor; ChT, chemotherapy; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; ESMO, European Society for Medical Oncology; FDA, Food and Drug Administration; LMD, leptomeningeal disease; MBM, melanoma brain metastasis; MEKi, MEK inhibitor; MRI, magnetic resonance imaging; RT, radiotherapy; SRS, stereotactic radiosurgery; WT, wild-type. aEnrolment into a clinical trial wherever possible is preferred [V, A]. bNone of the systemic treatment options listed are EMA or FDA approved to treat MBMs. cIn patients where local treatment has been discounted due to the number and/or volume of MBMs, evaluate for the possibility of resection of dominant lesion(s). dEarly concurrent SRS may be preferred over late SRS as salvage treatment [IV, C]. Close monitoring with MRI is recommended so that SRS can be added when indicated [IV, B]. eESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group.
Figure 6
Figure 6. Proposed algorithm for the follow-up of patients with melanoma.
Purple: algorithm title; white: non-treatment aspects. CR, complete response; CT, computed tomography; ICI, immune checkpoint inhibitor; LN, lymph node; MDT, multidisciplinary team; mo, month; MRI, magnetic resonance imaging; NA, not applicable; NED, no evidence of disease; PET, positron emission tomography; Q, every; US, ultrasound; UV, ultraviolet; yr, year. aThe follow-up schedule should be tailored to each individual patient, considering the disease stage, individual risk and personal needs of the patient, and may include clinical–dermatological examination, LN US, laboratory examinations and imaging [V, B].
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