Management of advanced malignant melanoma

In 2003, just over 8,100 people in the UK were diagnosed with MM. The male to female ratio is 2:3. There has been a general increase in incidence during the past five years. Some of this may be due to increased surveillance and early detection, but most is thought to be due to changes in sun behaviour. Mortality rates have not increased at the same rate as incidence, because of earlier diagnosis and intervention.1

Risk factors include exposure to UV radiation, excessive childhood sun exposure, use of sunbeds, fair skin, light hair, blue/green eye colour, multiple naevi, dysplastic naevus syndrome and a family history (10 per cent of cases).1,2 Damage to the ozone layer is also contributing.3

Those at higher risk than the general population include people with a history of melanoma/atypical mole syndrome, a damaged immune system4 or giant congenital pigmented naevi.5 Patients with a family history of three or more cases should be referred to clinical genetics for counselling. Those with two or more cases, where one of these had multiple primary melanomas or atypical mole syndrome, should also be referred in this way.6

Pathology, symptoms, investigations
Cutaneous melanomas are classified as one of four common subtypes, which make up 90 per cent of all diagnosed cases. A few very rare types make up the other 10 per cent, including ocular melanoma and mucosal lentiginous melanoma (vulva, anus, oral cavity, and conjunctiva).

Superficial spreading melanoma (70 per cent) is commonly found in middle-aged people, on sun-exposed skin, often on the back of the legs in women and the back in men. Owing to an extended radial growth phase, it is often identified and removed before deep invasion and potential lymph node involvement.

Nodular melanoma (10-15 per cent) is usually found on the trunk and limbs of patients in the fifth or sixth decade. Often raised with relatively well-defined borders, they are usually darkly pigmented, appearing blue or dark brownish-black.

Lentigo MM (10 per cent) is most common in older people with extensive sun exposure, usually found on the scalp and face. Acral lentiginous (5 per cent) can be found on the soles of the feet, or around the big toenail, on the palm or on the subungual region. This type is thought to be unrelated to sun exposure.1,5,7

The ABCD rule (see Box 1) can help to identify lesions that need further investigation.4 It is essential for dermatologists to provide a rapid access service to diagnose and manage MM.6 Patients with a potential MM should be seen within two weeks of referral.8 If a GP removes a lesion found to be a melanoma, the patient should be referred immediately to a specialist. All patients with ulcerated lesions with a Breslow thickness of 1-2 mm (T2b, see Box 2) and all other lesions with a thickness of >2mm (T3a) need referral to a specialist multidisciplinary team.

UK guidelines6 state that only those at intermediate or high risk of recurrent disease (stage IIB or over) should undergo staging. However, there is some debate regarding those staged at IIA, because the five-year survival rates are significantly lower.

Surgical treatment
All patients with primary melanoma should see a dermatologist or plastic surgeon for a surgical resection with a view to cure. Excision biopsies have no place in the radical treatment of MM in view of the high risk of local relapse.

The excision margin depends on the thickness of the tumour, with a 1cm margin adequate for tumours <1mm, increasing to 2cm for tumours >4mm thick.6

Management of stage 3 disease
The most important prognostic factor for MM is the presence or absence of lymph node metastases.9 Their presence reduces five-year survival by approximately 40 per cent, compared with people who have no evidence of nodal metastases (see Box 3).10

Sentinel lymph node (SLN) biopsy allows accurate staging of regional lymph node fields by surgical removal and targeted histological examination of those lymph nodes receiving direct lymph drainage from the tumour site (sentinel nodes). On average, only one or two nodes need to be removed to achieve this.11

The procedure, which involves injecting blue dye and/or radiolabelled colloid into the skin around the primary lesion, can identify the sentinel node in up to 97 per cent of cases.12 Postoperative complications occur in about 40 per cent of patients after elective dissection of a nodal field, while SLN biopsy causes postoperative complications in only 10 per cent. Severe complications, such as lymphoedema, are also much less common.11 There is continuing debate about the role of SLN biopsy in MM. There is no role for elective lymph node dissection.12 Those with confirmed lymph node disease should undergo lymph node dissection. Failure rates after nodal dissection alone are well documented and there is a need for effective adjuvant local therapy, because local recurrences are difficult to treat and often accompanied by substantial morbidity, such as ulceration and disfigurement.13

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