Dermoscopy and other visualisation techniques

1.3.1.

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. [2015]

1.3.2.

Do not routinely use confocal microscopy or computer assisted diagnostic tools to assess pigmented skin lesions. [2015]

Photography

1.3.3.

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. [2015]

Assessing and managing atypical Spitzoid lesions

1.3.4.

Discuss all suspected atypical Spitzoid lesions at the specialist skin cancer multidisciplinary team meeting. [2015]

1.3.5.

Make the diagnosis of a Spitzoid lesion of uncertain malignant potential on the basis of the histology, clinical features and behaviour. [2015]

1.3.6.

Manage a Spitzoid lesion of uncertain malignant potential as melanoma. [2015]

Taking tumour samples for genetic testing

1.3.7.

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. [2015]

BRAF analysis of primary melanoma tissue samples

1.3.8.

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. [2022]

1.3.9.

Consider BRAF analysis of melanoma tissue samples from people with stage IIA or IIB primary melanoma. [2022]

1.3.10.

Carry out BRAF analysis of melanoma tissue samples from people with stage IIC to IV primary melanoma. [2022]

1.3.11.

Local skin multidisciplinary teams should arrange BRAF analysis of melanoma tissue samples and state the preferred tissue block for analysis. [2022]

1.3.12.

When doing BRAF analysis, consider immunohistochemistry as the first test for BRAF V600E, if available. [2022]

1.3.13.

If BRAF V600E immunohistochemistry is negative or inconclusive, use a different BRAF genetic test. [2022]

1.3.14.

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. [2022]

Excision for stages 0 to II melanoma

1.5.1.

Consider a clinical margin of at least 0.5 cm when excising stage 0 melanoma. [2022]

1.5.2.

If excision for stage 0 melanoma does not achieve an adequate histological margin, discuss further management with the specialist skin cancer multidisciplinary team. [2022]

1.5.3.

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. [2022]

Imiquimod for stage 0 melanoma

1.5.4.

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. [2015]

1.5.5.

Consider a repeat skin biopsy for histopathological assessment after treatment with topical imiquimod for stage 0 melanoma, to check whether it has been effective. [2015]

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.

Completion lymph node dissection for stage III melanoma

1.6.1.

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. [2022]

Therapeutic lymph node dissection for stage III melanoma

1.6.2.

Offer therapeutic lymph node dissection to people with palpable stage IIIB to IIID melanoma, or cytologically or histologically confirmed nodal disease detected by imaging. [2015]

Adjuvant treatments for resected stage III melanoma

Non-curative treatment for superficial skin metastases in stage III melanoma

1.6.5.

Consider topical imiquimod to palliate superficial melanoma skin metastases. [2015]

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.

Genomic biomarker-based treatment for stage III melanoma

The point at which to use genomic biomarker-based therapy in solid tumour treatment pathways is uncertain. See NICE’s topic page on genomic biomarker-based cancer treatments for guidance on specific treatments.

Management of oligometastatic stage IV melanoma

1.8.1.

Refer the care of people who appear to have oligometastatic melanoma to the specialist skin cancer multidisciplinary team for recommendations about staging and management. [2015]

1.8.2.

Consider surgery or other ablative treatments to prevent or control symptoms of oligometastatic stage IV melanoma in consultation with other site specific multidisciplinary teams. [2015, amended 2022]

Brain metastases

1.8.3.

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. [2022]

1.8.4.

Discuss the care of people with melanoma and brain metastases with the specialist skin cancer multidisciplinary team. [2015]

1.8.5.

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. [2015, amended 2022]

Systemic anticancer treatments for untreated stage IV and unresectable stage III melanoma

1.8.6.

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. [2022]

1.8.7.

Offer treatment with immunotherapy to people with untreated stage IV or unresectable stage III melanoma, as set out in recommendations 1.8.8 to 1.8.9. If immunotherapy is contraindicated or unsuitable, based on the factors in recommendation 1.8.6, follow recommendations 1.8.10 to 1.8.12 for alternative treatments based on BRAF type. [2022]

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

Referral to specialist palliative care services

1.8.16.

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. [2022]

Genomic biomarker-based treatment

The point at which to use genomic biomarker-based therapy in solid tumour treatment pathways is uncertain. See NICE’s topic page on genomic biomarker-based cancer treatments for guidance on specific treatments.

Information and support for people who have had melanoma

1.9.1.

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. [2022]

1.9.2.

Offer psychosocial support to the person and their family or carers at all follow-up appointments. [2022]

1.9.3.

Ensure that local follow-up policies:

• are in line with recommendations 1.1.1 to 1.1.3 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). [2022]

Exceptions to routine follow-up

1.9.4.

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 recommendation 1.9.3. [2022]

1.9.5.

Offer personalised follow-up to people with unresectable stage III or IV melanoma. [2022]

1.9.6.

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). [2022]

1.9.7.

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. [2022]

1.9.8.

Offer whole-body and brain MRI, instead of CE-CT, to women who are pregnant and having imaging as part of follow-up. [2022]

1.9.9.

Offer brain MRI for follow-up imaging, instead of brain CE-CT, to people with known or resected brain metastases. [2022]

1.9.10.

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. [2022]

Planning routine follow-up

1.9.11.

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. [2022]

1.9.12.

For people having both CE-CT and ultrasound scans, alternate between the 2 types of scan. [2022]

1.9.13.

Do not routinely use PET-CT during follow-up of people with melanoma. [2022]

1.9.14.

Continue to follow the recommendations on managing concurrent drug treatment. [2022]

1.9.15.

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 the table on follow-up after stages I to IV melanoma. [2022]

Table

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).

This table 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 recommendations 1.9.5 to 1.9.10.

1. Monitoring and response biomarkers

Can biomarkers accurately classify recurrence, progression and response to treatment? [2022]

2. Safety, prognostic and predictive biomarkers

Can biomarkers be used for risk stratification and treatment planning for people with melanoma? [2022]

3. Effectiveness of localised treatments

What is the effectiveness of localised treatment for people with stages III and IV melanoma? [2022]

4. Histological margins

What is the optimal histological excision margin in stage 0 melanoma? [2022]

5. Surveillance strategies

How frequently should surveillance imaging be conducted, and which imaging modality should be used for people with stage IIB to IIIC melanoma? [2022]

Survivorship

What are the experiences of people who are living with, through and beyond a melanoma diagnosis in terms of survivorship and their disease journey? [2022]

Techniques for confirming a diagnosis in people with suspected atypical Spitzoid melanocytic lesions

In people with reported atypical Spitzoid lesions, how effective are fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) and tests to detect driver mutations compared with histopathological examination alone in predicting disease specific survival?

This should be investigated in a prospective diagnostic study. Secondary outcomes should include sensitivity, specificity, accuracy, positive predictive value, disease specific survival and progression free survival. [2015]

Surgical excision for people with lentigo maligna

For people with lentigo maligna (stage 0 in sun damaged skin, usually on the face) how effective is Mohs micrographic surgery, compared with excision with a 0.5 cm clinical margin, in preventing biopsy proven local recurrence at 5 years?

This should be investigated in a randomised controlled trial. Secondary outcomes should include cosmetic and functional outcomes. [2015]

Vitamin D supplementation

In people with stage I to III melanoma does vitamin D supplementation improve overall survival?

This should be investigated in a placebo controlled randomised trial. Secondary outcomes should include disease specific survival and toxicity, including the development of renal stones and hypercalcaemia. [2015]

The effect of drug therapy for concurrent conditions on melanoma survival

In people diagnosed with melanoma what is the effect of drug therapy to treat concurrent conditions on disease specific survival?

This should be investigated in a national prospective cohort study. Secondary outcomes should include overall survival and quality of life. [2015]

Why the committee made the recommendations

How the recommendations might affect practice

The recommendations might increase the use of genetic testing. They are expected to increase immunohistochemistry with BRAF V600E analysis as a means of genetic testing and reduce variations in genetic testing practice.

Return to recommendations

Why the committee made the recommendations

How the recommendations might affect practice

In current practice SLNB is commonly offered to people with melanoma and a Breslow thickness of 0.8 mm to 1.0 mm. The recommendations are expected to reduce SLNB in this group by targeting it specifically to those with risk factors for a positive SLNB. Ulceration is the most common risk factor and is therefore likely to be the main reason for offering SLNBs.

Variation in the use of imaging during staging is expected to be reduced, with an increase in the use of CE-CT.

Return to recommendations

Why the committee made the recommendations

The committee agreed to retain the 2015 recommendations on clinical margins for excision.

The 2015 committee found no evidence on the optimal clinical margin for stage 0 melanoma. They made the recommendation on the basis of clinical experience suggesting that local recurrence may be seen when margins smaller than 0.5 cm are used. The 2022 committee found no further evidence so retained the recommendation.

Evidence supported the 2015 recommendations to use minimum clinical margins of 1 cm in stage I melanoma and 2 cm in stage II melanoma. The margin should be around the histological biopsy scar and take into account the primary melanoma margins. The committee acknowledged that smaller margins may be needed for cosmetic reasons on sites such as the face, head and digits. However, the use of smaller margins should be discussed within the specialist skin cancer multidisciplinary team. The reasoning for a smaller margin should be justified and the person should have clinical surveillance. The evidence confirmed that larger margins of 4 cm to 5 cm are associated with more adverse events and no improvement in outcomes.

The committee acknowledged continuing uncertainty about optimal excision margins, particularly in stage 0 disease, and made a recommendation for research on histological margins.

How the recommendations might affect practice

The recommendations are unchanged and are not expected to change current practice.

Return to recommendations

Why the committee made the recommendation

How the recommendation might affect practice

Completion lymph node dissection is no longer standard practice and the recommendations will not change this.

Return to recommendation

Why the committee made the recommendations

Good quality evidence on localised treatments is lacking. The committee agreed that several treatment options can be considered but that in the absence of good evidence, this decision should be based on treatment suitability for the person with melanoma. They also agreed to remove the option of CO2 laser listed in the 2015 guideline because it is no longer used in standard practice.

The committee concurred that there is uncertainty about the best option for people with different clinical characteristics and made a recommendation for research on effectiveness of localised treatments.

How the recommendations might affect practice

Treatments for in-transit metastases are rarely used. The recommendations may help to target these treatments but will not lead to substantial changes in practice.

Return to recommendations

Why the committee made the recommendations

The committee looked at evidence on immunotherapies (ipilimumab, nivolumab, pembrolizumab, and nivolumab plus ipilimumab) and targeted therapies (encorafenib plus binimetinib, trametinib plus dabrafenib, dabrafenib monotherapy and vemurafenib monotherapy). These therapies were also compared in a health economic model.

The committee noted the complexities and nuances in the treatment pathway. They identified a number of factors that should be taken into account when considering treatment choices to allow appropriate and individualised treatment decisions.

The evidence showed that, overall, the immunotherapies are more clinically effective than the targeted therapies. Within the immunotherapies, nivolumab plus ipilimumab was the most clinically effective. The health economic model demonstrated that it is also the most cost effective.

However, the committee noted evidence showing that the risk of toxicity with immunotherapies is higher than with targeted therapies, and that this risk increases when immunotherapies are used in combination. They therefore agreed that monotherapy should be an option if combination immunotherapy is deemed unsuitable for people, for example those with poor performance status or comorbidities who are less likely to tolerate toxicity. The evidence showed that nivolumab and pembrolizumab have similar clinical effectiveness and cost effectiveness when used as monotherapies so the committee agreed that either of these options should be offered.

The committee noted NICE technology appraisal guidance recommending ipilimumab monotherapy for untreated advanced (unresectable or metastatic) melanoma, but did not include this option in their recommendation because it is not commonly used as first-line treatment and monotherapy with either nivolumab or pembrolizumab is more cost effective in this population. The committee also acknowledged that ipilimumab is licensed for use as monotherapy in adults and young people aged 12 and over. However, based on their clinical experience, its use as a monotherapy is considered to be the same as in adults.

If immunotherapy, either in combination or as monotherapy, is unsuitable, the committee agreed that targeted therapies based on BRAF status are an option. The committee noted that someone with symptomatic brain metastases will usually need steroids, which excludes treatment with immunotherapy. In addition, for people with a high disease burden or rapid progression there may not be enough time to generate the necessary immune response that is associated with immunotherapy. Within the targeted therapies, evidence showed that encorafenib plus binimetinib, or trametinib plus dabrafenib, had similar clinical effectiveness. The health economic model did not demonstrate clear differences in cost effectiveness between these 2 options. Therefore, the committee agreed that either of these options for combination treatment could be recommended. If both of these options are unsuitable, the committee agreed that monotherapy with dabrafenib or vemurafenib should be offered.

If targeted treatment for BRAF-mutated melanoma is unsuitable, or if the melanoma is BRAF-wild type, the committee agreed that the options are limited to chemotherapy with dacarbazine or best supportive care.

The committee made recommendations on treatments for previously treated stage IV or unresectable stage III melanoma. The evidence for the clinical and cost effectiveness of treatment in this area was limited. Therefore, the committee preferred to list the available treatment options, and to highlight the factors that should be taken into account when considering treatment choices for previously treated melanoma.

No evidence was found for the effectiveness of systemic cancer therapies specific to children and young people. However, the committee agreed that treatment should not differ between children and adults, and that recommendations also apply to children and young people. When treating children and young people, healthcare professionals should refer to the individual summary of product characteristics for the treatment being considered. This is because most of the treatments recommended in this guideline are not licensed for use in the UK in children and young people under 18, but there are differences in their licensed populations.

The committee noted that people with incurable melanoma have a high symptom burden which should be managed at an early stage, and recommended referral to specialist palliative care services.

How the recommendations might affect practice

The recommendations are expected to increase the proportion of people who are offered nivolumab plus ipilimumab as systemic treatment for stage IV and unresectable stage III melanoma.

The recommendations for previously treated melanoma are not expected to have an impact on practice, as all available treatments are listed alongside the factors that should be considered when making treatment recommendations.

Return to recommendations

Why the committee made the recommendations

How the recommendations might affect practice

Current practice varies and it is expected that these recommendations will help to standardise practice across centres. Clinic visits for people with stages I to IIC melanoma may be reduced, especially for people with stage IA melanoma. It is therefore important that people are given contact details for the specialist skin cancer multidisciplinary team. The use of ultrasound, CE-CT or MRI scanning is expected to increase, but the use of PET-CT is expected to decrease.

Return to recommendations