A full skin assessment should be considered as a preliminary treatment option for assessing the risk of further melanomas, surveillance planning and for detecting synchronous primaries and/or other keratinocytic skin cancers that may require intervention.

The definitive treatment of a primary melanoma involves an adequate margin of skin and subcutaneous fat. For a melanoma in situ, this is 5–10 mm. For an invasive melanoma, the margins of 10 mm or 20 mm will be considered depending on its thickness and specific type of melanoma (Cancer Council Australia Melanoma Guidelines Working Party 2019).

Surgery in a primary care or dermatology centre

Surgery under local anaesthetic with direct primary closure for excision biopsy and selected re-excision for in situ and early-stage melanomas can be undertaken in the primacy care setting by a dermatologist or a general practitioner with adequate training and experience.

Surgery by a specialist team

Surgery for all other excisions (including sentinel lymph node biopsy and regional lymphadenectomy) should be undertaken by a surgeon with adequate training and experience.

Resection of regional and distant metastatic melanoma may be appropriate in selected cases.

Timeframe for starting treatment

Surgery in a primary care setting should occur within two weeks of the decision that it is necessary.

Training and experience required of the surgeon

Fellow of the Royal Australian College of Surgeons, or equivalent, with adequate training and experience that enables institutional credentialing and agreed scope of practice in melanoma (ACSQHC 2015).

Documented evidence of the surgeon’s training and experience, including their specific (sub-specialty) experience with melanoma and procedures to be undertaken, should be available.

Health service characteristics

To provide safe and quality care for patients having more advanced surgery, health services should have these features:

• critical care support
• 24-hour medical staff availability
• 24-hour operating room access and intensive care unit
• diagnostic imaging
• pathology
• nuclear medicine imaging

Radiation therapy may benefit patients in the following circumstances:

• definitive treatment for in situ melanoma in special circumstances such as, where surgery needs to be avoided for medical reasons, and sites on the body where complete resection would be prohibitively morbid
• adjuvant radiation therapy following surgical resection for invasive melanoma at high risk of recurrence if potentially effective systemic therapy is not available – at primary sites this includes recurrent disease, desmoplastic melanoma specifically with neurotropism and where adequate margins cannot be attained; at regional sites depending on the location, size and number of nodes specifically when extra-nodal extension is present
• palliative treatment for life prolongation (stereotactic radiotherapy for oligometastatic disease) and symptom relief/prevention, particularly for brain and spinal disease.

Timeframe for starting treatment

If not urgent, radiation therapy should begin within four weeks of the MDM. Some patients will require urgent treatment.

Training and experience required of the appropriate specialists

The radiation oncologist should be a Fellow of the Royal Australian and New Zealand College of Radiologists, or equivalent, with adequate training and experience that enables institutional credentialing and agreed scope of practice in melanoma.

The training and experience of the radiation oncologist should be documented.

Health service unit characteristics

To provide safe and quality care for patients having radiation therapy, health services should have these features:

• linear accelerator (LINAC) capable of image-guided radiation therapy (IGRT)
• dedicated CT planning
• access to MRI and PET imaging
• automatic record-verify of all radiation treatments delivered
• a treatment planning system
• trained medical physicists, radiation therapists and nurses with radiation therapy experience
• coordination for combined therapy with systemic therapy, especially where facilities are not co-located
• participation in Australian Clinical Dosimetry Service audits
• an incident management system linked with a quality management system

Patients with stage III melanoma (confined to regional lymph nodes) and all advanced melanoma (stage IV) should be considered for systemic treatment, given their potential for improvement in progression-free survival and overall survival. Options include immunotherapy and targeted therapy.

Systemic therapy should be prescribed and conducted under the supervision of a medical oncologist.

Timeframes for starting treatment

If systemic therapy is to be given as adjuvant therapy, this should occur within 12 weeks of the definitive surgery.

If systemic therapy is to be given to treat stage IV disease, therapy should begin as soon as clinically relevant (as soon as possible), ideally within four weeks.

Training and experience required of the appropriate specialists

Medical oncologists must have training and experience of this standard:

• Fellow of the Royal Australian College of Physicians (or equivalent)
• adequate training and experience that enables institutional credentialing and agreed scope of practice within this area (ACSQHC 2015).

Cancer nurses should have accredited training in these areas:

• anti-cancer treatment administration
• specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
• the handling and disposal of cytotoxic waste (ACSQHC 2020).

Systemic therapy should be prepared by a pharmacist whose background includes this experience:

• adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.

In a setting where no medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner or nurse with training and experience that enables credentialing and agreed scope of practice within this area. This should be in accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist or as clinically required.

The training and experience of the appropriate specialist should be documented.

Health service characteristics

To provide safe and quality care for patients having systemic therapy, health services should have these features:

• a clearly defined path to emergency care and advice after hours
• access to diagnostic pathology including basic haematology and biochemistry, and imaging
• cytotoxic drugs prepared in a pharmacy with appropriate facilities
• occupational health and safety guidelines regarding handling of cytotoxic drugs, including preparation, waste procedures and spill kits (eviQ 2019)
• guidelines and protocols to deliver treatment safely (including dealing with extravasation of drugs)
• coordination for combined therapy with radiation therapy, especially where facilities are not co-located
• appropriate molecular pathology access

Stage III melanoma

Patients with resected stage IIIB/C/D melanoma should be considered for adjuvant systemic therapy. The prognosis for patients with stage IIIA melanoma is good and adjuvant systemic therapy is not recommended for this sub-group. For patients with a BRAF V600 mutant melanoma, targeted therapy (combination BRAF and MEK inhibitors) or adjuvant immunotherapy (single agent anti PD-1) can be recommended. For patients without a BRAF mutation, adjuvant immunotherapy should be used. Therapy is given for up to a year.

Currently, there is strong evidence for clinically significant improvements in relapse-free survival with the adjuvant use of targeted therapy or anti-PD1 immunotherapy; however, improvements in overall survival from these treatments have not yet been demonstrated. These may emerge with further follow-up. The decision to recommend adjuvant treatment should be taken by a suitably experienced oncologist and consider the health status and preferences of the individual patient.

Unresectable stage III and stage IV melanoma

All patients with unresectable stage III or stage IV melanoma should be considered for systemic therapy. Enrolment into clinical trials is encouraged where possible.

Immunotherapy, with either anti-PD-1 agents (pembrolizumab or nivolumab) alone or with nivolumab in combination with the anti-CTLA-4 agent ipilimumab can be given as the first line of therapy for metastatic melanoma. Combination immunotherapy results in higher response rates and longer progression-free survival but has significantly greater toxicity, necessitating careful patient selection. Immunotherapy should be continued until disease progression, unacceptable toxicity or completion of two years of treatment. Immunotherapy can cause a unique set of side effects, referred to as immune-related adverse events (irAEs). These toxicities result in inflammation occurring in normal tissues and can affect any part of the body. The most common irAEs are rash, itch, thyroid dysfunction, hypophysitis, hepatitis, colitis, arthritis and pneumonitis. Patients with pre-existing autoimmune conditions are at risk of exacerbation of their autoimmune disease. Clinically significant irAEs require interruption of the immunotherapy and, usually, immunosuppressive doses of corticosteroids. As these are a unique set of toxicities very distinct from traditional chemotherapy side effects, practitioners involved in managing these patients should seek expert advice from the patient’s treating unit if toxicity is suspected.

Patients with BRAF V600 mutant melanoma are also candidates for targeted therapy. Combination therapy with both a BRAF and a MEK inhibitor should be used in preference to treatment with single-agent BRAF inhibition. Treatment with targeted therapy should continue until the development of disease progression or intolerable toxicity. There is no randomised data to suggest a superior sequence of treatment (targeted therapy followed by immunotherapy or vice versa) for metastatic BRAT-mutant melanoma.