Melanoma: Assessment and Management in Secondary Care

This specialist Guidelines summary covers the assessment and management of melanoma in children, young people, and adults. It aims to reduce variation in practice and improve survival.

This summary includes recommendations on:

• communication and support
• managing vitamin D levels and drug treatment for other conditions
• assessing and staging melanoma
• managing stages 0 to II melanoma
• managing stage III melanoma
• treating in-transit metastases in stages III and IV melanoma
• managing stage IV and unresectable stage III melanoma
• follow-up after treatment.

This summary is intended for use in a secondary care setting by oncologists. For the complete set of recommendations, please refer to the full guideline.

Communication and Support

• Give people with melanoma accurate and easy-to-understand information (both written and spoken) in a sensitive and timely manner throughout their care, tailored to their needs and circumstances. Topics to discuss include:
  • melanoma and different types of skin cancer
  • treatment options, including the risks and benefits
  • where the person's appointments will take place
  • which healthcare professionals will undertake the person's care and how to get in touch with them
  • expected waiting times for consultations, investigations and treatments
  • follow-up after treatment (see the section on Follow-up After Treatment for Melanoma)
  • preventing recurrence, and how to protect their skin from damage caused by exposure to the sun, while avoiding vitamin D depletion
  • recognising signs and symptoms of suspicious skin lesions
  • what to do if they have any concerns and how to re-access services local services and how to get in touch with them.

For more guidance on giving information to people and discussing their preferences, follow the recommendations on communication and patient centred care in NICE's guidelines on patient experience in adult NHS services and shared decision making. 

• Discuss the psychological and emotional impact of melanoma with the person, ask whether they have any psychological or support care needs, and offer to carry out a holistic needs assessment. Topics to discuss include:
  • their understanding of melanoma and its prognosis
  • their specific concerns and preferences
  • important values or personal goals for care and treatment
  • risk of recurrence, metastatic spread or new primary cancers
  • whether family members are at risk 
• Explain to people with melanoma that they are welcome to bring a companion with them to appointments
• Ensure that each local skin cancer multidisciplinary team and specialist skin cancer multidisciplinary team has:
  • at least one skin cancer clinical nurse specialist to provide people with information and support
  • access to psychological support services for people with melanoma 
• Ensure that healthcare professionals can support people with melanoma by attending training and being competent in:
  • communicating complex and sensitive information clearly
  • tailoring information and support to the person's individual needs and circumstances. 

Managing Vitamin D Levels and Concurrent Drug Treatment

• Measure vitamin D levels at diagnosis in secondary care in all people with melanoma
• Give people whose vitamin D levels are thought to be suboptimal advice on vitamin D supplementation and monitoring in line with local policies and NICE's guideline on vitamin D 
• Do not withhold or change drug treatment for other conditions, except immunosuppressants and immunomodulators, on the basis of a diagnosis of melanoma. For people on immunosuppressive or immunomodulatory treatments, seek advice from the person's specialist team, aiming to optimise quality of life while minimising the person's risk. 

Assessing Melanoma

Dermoscopy and Other Visualisation Techniques

• Assess all pigmented skin lesions that are either referred for assessment or identified during follow-up in secondary or tertiary care, using dermoscopy carried out by healthcare professionals trained in this technique
• Do not routinely use confocal microscopy or computer assisted diagnostic tools to assess pigmented skin lesions. 

Photography

• For a clinically atypical melanocytic lesion that does not need excision at first presentation in secondary or tertiary care:
  • use baseline photography (preferably dermoscopic) and
  • review the clinical appearance of the lesion, and compare it with the baseline photographic images, 3 months after first presentation to identify early signs of melanoma. 

Assessing and Managing Atypical Spitzoid Lesions

• Discuss all suspected atypical Spitzoid lesions at the specialist skin cancer multidisciplinary team meeting
• Make the diagnosis of a Spitzoid lesion of uncertain malignant potential on the basis of the histology, clinical features and behaviour
• Manage a Spitzoid lesion of uncertain malignant potential as melanoma. 

Taking Tumour Samples for Genetic Testing

• If targeted systemic therapy is a treatment option, offer genetic testing using:
  • a secondary melanoma tissue sample if there is adequate cellularity or
  • a primary melanoma tissue sample if a secondary sample is not available or is of inadequate cellularity. 

BRAF Analysis of Primary Melanoma Tissue Samples

• Do not offer BRAF analysis of melanoma tissue samples from people with stage IA or IB primary melanoma at presentation except as part of a clinical trial
• Consider BRAF analysis of melanoma tissue samples from people with stage IIA or IIB primary melanoma 
• Carry out BRAF analysis of melanoma tissue samples from people with stage IIC to IV primary melanoma 
• Local skin multidisciplinary teams should arrange BRAF analysis of melanoma tissue samples and state the preferred tissue block for analysis
• When doing BRAF analysis, consider immunohistochemistry as the first test for BRAF V600E, if available
• If BRAF V600E immunohistochemistry is negative or inconclusive, use a different BRAF genetic test
• Offer BRAF analysis of melanoma tissue samples to people with melanoma if they are potential candidates for any ongoing clinical trials that require knowledge of genetic status. 

Staging with Sentinel Lymph Node Biopsy

• Do not offer imaging or sentinel lymph node biopsy (SLNB) to people who have stage IA melanoma
• Do not offer imaging before SLNB unless lymph node or distant metastases are suspected
• Consider SLNB for people who have melanoma with a Breslow thickness of 0.8 mm to 1.0 mm and at least one of the following features:
  • ulceration
  • lymphovascular invasion
  • a mitotic index of 2 or more 
• Consider SLNB for people who have melanoma with a Breslow thickness greater than 1.0 mm
• For women who are pregnant, discuss the option of delaying SLNB until after the pregnancy is completed
• Consider staging with whole-body and brain contrast-enhanced computed tomography (CE-CT) for people with stage IIB melanoma 
• Offer staging with whole-body and brain CE-CT to people with stage IIC to IV melanoma
• Consider staging with brain magnetic resonance imaging (MRI), instead of brain CE-CT, if locally available and after discussion and agreement with the specialist skin cancer multidisciplinary team
• Offer staging with whole body and brain MRI, instead of CE-CT, to:
  • children and young adults (from birth to 24 years) with stage IIB to IV melanoma
  • women with stage IIB to IV melanoma who are pregnant 
• Consider staging with brain MRI, instead of brain CE-CT, for people with stage IIIC to IV melanoma and one of the following risk factors:
  • a mitotic index of 5 or more
  • primary melanoma located on the scalp 
• Consider a repeat staging scan before starting adjuvant treatment, unless imaging done within the past 8 weeks is available. 

Managing Stages 0 To II Melanoma

Excision for Stages 0 To II Melanoma

• Consider a clinical margin of at least 0.5 cm when excising stage 0 melanoma 
• If excision for stage 0 melanoma does not achieve an adequate histological margin, discuss further management with the specialist skin cancer multidisciplinary team 
• Use a clinical margin of:
  • 1 cm when excising stage I melanoma or when a 2 cm excision margin would cause unacceptable disfigurement or morbidity
  • 2 cm when excising stage II melanoma.

The clinical margin should be around the histological biopsy scar and take into account the primary melanoma margin. 

Imiquimod for Stage 0 Melanoma

• Consider topical imiquimod to treat stage 0 melanoma in adults if surgery to remove the entire lesion with a 0.5 cm clinical margin would lead to unacceptable disfigurement or morbidity
• Consider a repeat skin biopsy for histopathological assessment after treatment with topical imiquimod for stage 0 melanoma, to check whether it has been effective.

In July 2022, this was an off-label use of topical imiquimod in adults and imiquimod was not licensed for use in the UK in children and young people under 18. See NICE's information on prescribing medicines.

Managing Stage III Melanoma

Completion Lymph Node Dissection for Stage III Melanoma

• Do not routinely offer completion lymph node dissection to people with stage III melanoma and micrometastatic nodal disease detected by SLNB unless:
  • there are factors that might make recurrent nodal disease difficult to manage, and
  • after discussion with the person and the specialist skin cancer multidisciplinary team.

Examples of factors that might make recurrent nodal disease difficult to manage include melanoma of the head and neck, people for whom stage III adjuvant therapies are contraindicated, or when regular follow‑up is not possible. 

Therapeutic Lymph Node Dissection for Stage III Melanoma

• Offer therapeutic lymph node dissection to people with palpable stage IIIB to IIID melanoma, or cytologically or histologically confirmed nodal disease detected by imaging. 

Adjuvant Treatments for Resected Stage III Melanoma

Adjuvant Systemic Anticancer Treatments

For guidance on specific treatments, see NICE's technology appraisal guidance on dabrafenib with trametinib for adjuvant treatment of resected BRAF V600 mutation-positive melanoma, pembrolizumab for adjuvant treatment of completely resected stage 3 melanoma and nivolumab for adjuvant treatment of completely resected melanoma with lymph node involvement or metastatic disease.

Adjuvant Radiotherapy

• Do not offer adjuvant radiotherapy to people with stage IIIA melanoma 
• Do not offer adjuvant radiotherapy to people with resected stage IIIB to IIID melanoma unless a reduction in the risk of local recurrence is estimated to outweigh the risk of significant adverse effects. 

Non-curative Treatment for Superficial Skin Metastases in Stage III Melanoma

• Consider topical imiquimod to palliate superficial melanoma skin metastases.

In July 2022, this was an off-label use of topical imiquimod in adults and imiquimod was not licensed for use in the UK in children and young people under 18. See NICE's information on prescribing medicines.

Treating in-Transit Metastases in Stages III and IV Melanoma

• Discuss management of in-transit metastases, including surgery or treatment in a regional specialist centre, with the specialist skin cancer multidisciplinary team
• Offer surgery as the first option and if surgery is not feasible, or if the person has recurrent in-transit metastases, consider one of the following options based on their suitability for the person:
  • systemic anticancer therapy (see Systemic Anticancer Treatments for Untreated Stage IV and Unresectable Stage III Melanoma)
  • talimogene laherparepvec, in line with NICE's technology appraisal guidance on talimogene laherparepvec
  • isolated limb infusion or perfusion
  • radiotherapy
  • electrochemotherapy, in line with NICE's interventional procedures guidance on electrochemotherapy for metastases in the skin from tumours of non-skin origin and melanoma
  • a topical agent such as imiquimod. 

In July 2022, most of the therapies recommended in this guideline were not licensed for use in the UK in children and young people under 18. See NICE's information on prescribing medicines. Refer to the summary of product characteristics for the individual treatments because there are differences in their licensed populations.

Managing Stage IV and Unresectable Stage III Melanoma

Management of Oligometastatic Stage IV Melanoma

• Refer the care of people who appear to have oligometastatic melanoma to the specialist skin cancer multidisciplinary team for recommendations about staging and management
• Consider surgery or other ablative treatments to prevent or control symptoms of oligometastatic stage IV melanoma in consultation with other site specific multidisciplinary teams. 

Brain Metastases

• For guidance on diagnosing, monitoring and managing brain metastases in people aged 16 or over see NICE's guideline on brain tumours (primary) and brain metastases in over 16s
• Discuss the care of people with melanoma and brain metastases with the specialist skin cancer multidisciplinary team
• Refer people with melanoma and brain metastases that might be suitable for surgery or stereotactic radiotherapy to the neuro-oncology multidisciplinary team for a recommendation about treatment. 

Systemic Anticancer Treatments for Untreated Stage IV and Unresectable Stage III Melanoma

In July 2022, most of the therapies in this section were unlicensed for use in the UK in children and young people under 18. See NICE's information on prescribing medicines. Refer to the summary of product characteristics for the individual treatments because there are differences in their licensed populations.

• When choosing systemic anticancer treatment for untreated stage IV or unresectable stage III melanoma, base treatment decisions 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, lactate dehydrogenase level).

Treatment decisions should be made after a full assessment of the risks and benefits by the treating oncologist and discussion with the person, in line with NICE's guideline on shared decision making. 

• Offer treatment with immunotherapy to people with untreated stage IV or unresectable stage III melanoma, as set out in the recommendations in Immunotherapies. If immunotherapy is contraindicated or unsuitable, based on the factors in the first recommendation in Systemic Anticancer Treatments for Untreated Stage IV and Unresectable Stage III Melanoma, follow recommendations from Targeted Therapies for BRAF V600 Mutation-Positive Melanoma and Alternatives to Immunotherapies for BRAF Wild-Type Melanoma.

For other guidance on treatments for advanced melanoma, see NICE's technology appraisal guidance on the NICE topic page for skin cancer.

Immunotherapies

• Offer nivolumab plus ipilimumab to people with untreated stage IV or unresectable stage III melanoma if suitable for them based on the factors in the first recommendation in Systemic Anticancer Treatments for Untreated Stage IV and Unresectable Stage III Melanoma.

See NICE's technology appraisal guidance on nivolumab in combination with ipilimumab for treating advanced melanoma.

• If nivolumab plus ipilimumab is unsuitable or unacceptable (for example, because of potential toxicity), offer pembrolizumab or nivolumab monotherapy. 

See NICE's technology appraisal guidance on pembrolizumab for advanced melanoma not previously treated with ipilimumab and nivolumab for treating advanced (unresectable or metastatic) melanoma.

Targeted Therapies for BRAF V600 Mutation-Positive Melanoma

• Offer encorafenib plus binimetinib, or dabrafenib plus trametinib, to people with untreated BRAF-mutant stage IV or unresectable stage III melanoma if:
  • nivolumab plus ipilimumab, pembrolizumab, and nivolumab 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). 

See NICE's technology appraisal guidance on encorafenib with binimetinib for unresectable or metastatic BRAF V600 mutation-positive melanoma and trametinib in combination with dabrafenib for treating unresectable or metastatic melanoma.

• If encorafenib plus binimetinib, and dabrafenib plus trametinib, are both unsuitable or unacceptable to the person:
  • offer dabrafenib or vemurafenib to people for whom binimetinib and trametinib are contraindicated or
  • if targeted treatment is contraindicated, consider treatment with chemotherapy (dacarbazine) or best supportive care. 

See NICE's technology appraisal guidance on dabrafenib for treating unresectable or metastatic BRAF V600 mutation-positive melanoma and vemurafenib for treating locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma. For other guidance on targeted therapies see NICE's technology appraisal guidance on the NICE topic page for skin cancer.

Alternatives to Immunotherapies for BRAF Wild-Type Melanoma

• For people with untreated BRAF-wild type stage IV or unresectable stage III melanoma for whom nivolumab plus ipilimumab, pembrolizumab, and nivolumab are contraindicated, consider:
  • treatment with chemotherapy (dacarbazine) or
  • best supportive care. 

Systemic Anticancer Treatments for Previously Treated Stage IV or Unresectable Stage III Melanoma

For guidance on immunotherapies, see NICE's technology appraisal guidance on ipilimumab, nivolumab, nivolumab with ipilimumab and pembrolizumab. For guidance on targeted therapies for BRAF V600 mutation-positive melanoma, see NICE's technology appraisal guidance on encorafenib with binimetinib and trametinib with dabrafenib.

• When making treatment decisions for previously treated melanoma, take into account the factors listed in the first recommendation in Systemic Anticancer Treatments for Untreated Stage IV and Unresectable Stage III Melanoma 
• For people with previously treated melanoma in whom immunotherapies and targeted therapies are contraindicated, unsuitable or unacceptable, consider:
  • treatment with chemotherapy (dacarbazine) or
  • best supportive care 
• Do not routinely offer further cytotoxic chemotherapy to people with stage IV or unresectable stage III melanoma who have had previous treatment with dacarbazine except in the context of a clinical trial. 

Referral to Specialist Palliative Care Services

• Refer people with incurable melanoma to specialist palliative care services for symptom management. See NICE's guideline on end of life care for adults: service delivery. 

Follow-Up After Treatment for Melanoma

Information and Support for People Who Have Had Melanoma

• Ensure that people who have completed treatment for melanoma have been given direct contact details for specialist skin cancer services that can provide advice about problems or concerns related to their melanoma 
• Offer psychosocial support to the person and their family or carers at all follow-up appointments
• Ensure that local follow-up policies:
  • are in line with the first three recommendations in the section on Communication and Support
  • include:
    • reinforcing advice about self-examination
    • health promotion for people with melanoma and their families, including sun awareness and avoiding vitamin D depletion (see NICE's guideline on sunlight exposure: risks and benefits)
    • advice on stopping smoking for people who smoke (see NICE's guideline on tobacco: preventing uptake, promoting quitting and treating dependence). 

Exceptions to Routine Follow-Up

• For people who have had stage 0 melanoma, provide advice at a clinic visit during the first year after treatment has been completed, in line with the previous recommendation
• Offer personalised follow-up to people with unresectable stage III or IV melanoma
• Consider personalised follow-up for people who are at increased risk of further primary melanomas (for example, people with atypical mole syndrome, previous melanoma, multiple in-situ melanomas, or a history of melanoma in first degree relatives or other relevant familial cancer syndromes)
• Offer whole-body and brain MRI, instead of CE-CT, to children and young adults (from birth to 24 years) having imaging as part of follow-up 
• Offer whole-body and brain MRI, instead of CE-CT, to women who are pregnant and having imaging as part of follow-up
• Offer brain MRI for follow-up imaging, instead of brain CE-CT, to people with known or resected brain metastases
• Consider brain MRI for follow-up imaging, instead of brain CE-CT, if preferred locally and after discussion and agreement with the specialist skin cancer multidisciplinary team. 

Planning Routine Follow-Up

• Full examination of the skin and regional lymph nodes at clinic appointments should be done by a healthcare professional who has skills and expertise in skin cancer and lymph node examination. They should have access to dermoscopy and medical photography as part of examinations
• For people having both CE-CT and ultrasound scans, alternate between the 2 types of scan
• Do not routinely use positron emission tomography CT (PET-CT) during follow-up of people with melanoma
• Continue to follow the recommendations on Managing Vitamin D Levels and Concurrent Drug Treatment
• Offer follow-up for 1 year to people who have had stage IA melanoma, and for 5 years to people who have had stages IB to IV melanoma, using Table 1. 

Table 1: Follow-up After Stages I to IV Melanoma

• Whole body CE-CT scans will routinely include the thorax, abdomen and pelvis. However, other sites such as the neck may need including based on the person's individual needs and circumstances (for example, when there is an increased risk of the melanoma spreading or for people who are exempt from routine follow-up)
• Table 1 sets out routine follow-up. Offer personalised follow-up to people with unresectable stage III or IV melanoma, people at increased risk of further primary melanomas, children and young adults, and women who are pregnant, in line with the second to seventh recommendations in the section Exceptions to Routine Follow-up.