Cutaneous Melanoma Clinical Practice Guidelines (ESMO, 2019)

European Society for Medical Oncology

This is a quick summary of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

November 04, 2019

The guidelines on diagnosis, treatment, and follow-up of cutaneous melanoma were released on September 30, 2019 by the European Society for Medical Oncology (ESMO).[1]

Diagnosis and Pathology/Molecular Biology

Diagnosis should be based on a full-thickness excisional biopsy with a small side margin.

The histology report should include at least information on the following:

  • Type of melanoma

  • Actinic damage

  • Maximum vertical thickness in millimeters

  • Information on mitotic rate

  • Presence of ulceration

  • Presence and extent of regression and clearance of the surgical margins.

Mutation testing for actionable mutations is mandatory in patients with resectable or unresectable stage III or stage IV melanoma and is highly recommended in high-risk resected stage IIC but not for stage I or stage IIA-IIB. BRAF testing is mandatory.

Staging and Risk Assessment

Physical examination with special attention to the following is mandatory:

  • Other suspicious pigmented lesions

  • Tumor satellites

  • In-transit metastases

  • Regional lymph node metastases

  • Distant metastases

In higher tumor stages, ultrasound, computed tomography, and/or positron emission tomography scans are recommended to allow proper tumor assessment.


For localized disease, wide local excision of primary tumors is recommended, with safety margins as follows:

  • In situ melanomas: 0.5 cm

  • Tumors ≤2 mm thick: 1 cm

  • Tumors >2 mm thick: 2 cm

For locoregional disease, sentinel lymph node biopsy is recommended for all patients with pT1b or higher according to AJCC 8th edition staging.

Complete lymph node dissection (CLND) is not recommended for patients with positive sentinel nodes. In the case of isolated locoregional clinically detectable (macroscopic, non–sentinel node) lymph node metastases, CLND is indicated; removal of the tumor-bearing lymph node alone is insufficient.

Patients with resected stage III melanomas should be evaluated for adjuvant therapy.

Adjuvant radiation therapy (RT) for local tumor control can be considered in cases of inadequate resection margins of lentigo maligna melanoma, in R1 resections, or after resection of bulky disease. Adjuvant RT is not otherwise recommended in the adjuvant setting.

Anti–programmed death inhibitor 1 (PD1) adjuvant therapy or dabrafenib/trametinib are the preferred treatment options.

For advanced disease (unresectable stage III and IV), surgical removal or stereotactic irradiation of locoregional recurrence or single distant metastasis should be considered in fit patients, as a therapeutic option, offering potential for long-term disease control.

Patients with metastatic melanoma should have the metastasis (preferably) or the primary tumor screened for detection of BRAF V600 mutation. First- and second-line treatment options include anti-PD1 antibodies (pembrolizumab, nivolumab) with or without ipilimumab for all patients, and BRAF inhibitor/MEK inhibitor combination for patients with BRAF-mutated melanoma.

PD-1 blockade or a PD-1 blocker and ipilimumab are now a standard of care for all patients, regardless of their BRAF status, in the first-line setting.

For NRAS-mutated melanoma, first-line immunotherapy options identical to those of wild type melanoma are the first choice, as MEK inhibitors have limited efficacy.

If clinical trials or the approved new compounds are not available, cytotoxic drugs such as dacarbazine or temozolomide may be administered, with modest activity anticipated.

For management of brain metastases, study results suggest combination therapy with ipilimumab plus nivolumab as the preferred first-line treatment, as well as in BRAF-mutated asymptomatic patients. For patients with a small number of asymptomatic metastases (<5-10) and non-bulky disease (<3 cm), stereotactic radiosurgery (SRS) up front is an option. Other patients should be considered for systemic treatment first, keeping SRS for the treatment of non-responding lesions. For patients failing systemic treatment, SRS could be considered as a salvage therapy if the total number of progressing lesions is <5-10 and their maximal size is <3 cm.

Follow-up, Long-term Implications, and Survivorship

Melanoma patients should be instructed in the avoidance of sunburns and extended unprotected solar or artificial ultraviolet light exposure, and in lifelong regular self-examinations of the skin and peripheral lymph nodes.

Patients must be aware that family members have an increased melanoma risk.

During melanoma follow-up, patients are clinically monitored to detect relapse and to recognize additional skin tumors, especially secondary melanomas, as early as possible.

There is no consensus on the optimal schedule of follow-up or the utility of imaging and blood tests for patients with resected melanoma; recommendations vary from follow-up visits every 3 months during the first 3 years and every 6–12 months thereafter, to no organized follow-up at all.

Sentinel node–positive patients should be followed with regular ultrasound examinations.

Serum S100 protein assay, to monitor for rising levels, is the most accurate blood test in the follow-up of melanoma patients, if any blood test is recommended at all.

For more information, see Malignant Melanoma. For more Clinical Practice Guidelines, please go to Guidelines.


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