Management of advanced (unresectable stage III or IV) melanoma

When choosing systemic anticancer treatment for patients with untreated stage IV or unresectable stage III melanoma, treatment decisions should be based on the following factors:

• comorbidities and performance status
• risk of treatment toxicity
• whether potential treatment toxicity will be tolerated
• presence of symptomatic brain metastases
• tumour biology (for example, high disease burden, rapid progression, LDH level).

Treatment decisions should be made after a full assessment of the risks and benefits for the patient by the treating oncologist.

In patients with untreated stage IV or unresectable stage III melanoma immunotherapy with immune checkpoint inhibitors is recommended as first-line treatment irrespective of BRAF status.

Nivolumab plus ipilimumab should be considered for patients with untreated stage IV or unresectable stage III melanoma (if suitable for the patient). If nivolumab plus ipilimumab is unsuitable or unacceptable (for example, because of potential toxicity or patient choice), pembrolizumab or nivolumab monotherapy should be offered.

Encorafenib plus binimetinib, or dabrafenib plus trametinib should be considered for patients with untreated stage IV or unresectable stage III melanoma with BRAF mutation if nivolumab plus ipilimumab, pembrolizumab or nivolumab monotherapy are contraindicated or it is predicted there is not enough time for an adequate immune response (for example, because of high disease burden or rapid progression).

Carbon dioxide laser ablation can be considered for multiple lesions of trunk or abdomen and for limb disease.

Laser ablation should be undertaken in a specialist setting by clinicians with experience of the technique and who are in a position to undertake appropriate post-treatment care or offer alternative treatments if laser ablation is not appropriate.

Electrochemotherapy should be considered as a treatment option for patients with cutaneous melanoma metastases after multidisciplinary team discussion and careful consideration of alternative systemic therapy options.

Bone metastases

Single dose radiotherapy of a least 8 Gy may be considered for palliation of pain from bone metastases.

Spinal cord compression

Evidence for the use of radiotherapy to alleviate pain and neurological deficit associated with spinal cord compression due to metastatic melanoma is inconclusive.

If a patient presents with spinal cord compression consideration should be given to available medical oncology options ie BRAF testing should be considered if this has not already been done, targeted BRAF therapy should be considered in new cases.

Brain metastases

All patients with brain-limited metastasis should be tested for BRAF mutations and have their management discussed at a neuro-oncology multidisciplinary team to determine optimal choice of treatment including systemic or targeted therapy, surgery or stereotactic radiosurgery.

Patients with good performance status, favourable response to corticosteroid treatment, absence of systemic disease and who have favourable CNS disease should be considered for surgical resection of their CNS disease.

If surgery is not possible, patients should be considered for systemic therapy or stereotactic radiotherapy.

Guidance and a training module is available from the Scottish Palliative Care Guideline

www.palliativecareguidelines.scot.nhs.uk

Patients with advanced melanoma require a co-ordinated multiprofessional approach with input from a specialist palliative care team.

Patients with poorly controlled symptoms should be referred to specialist palliative care at any point in the cancer journey.