Cure of cutaneous melanoma
Authors: J Meirion Thomas, Victoria Giblin
Journal: BMJ (2006)

Melanoma is a deadly but potentially curable disease. Its main cause, and the sole controllable factor, is excessive if intermittent exposure to sunlight, particularly in childhood and adolescence.1,2 The incidence of melanoma is rising faster than for any other cancer and is approximately doubling every decade, although survival rates are improving in developed countries (the United Kingdom, for example, has experienced a 30% improvement since the 1970s). Mortality in general increases with age, especially in men (figure).3



Figure 1

Numbers of deaths and age specific mortality rates by sex, malignant melanoma, United Kingdom, 2004. Reproduced with permission of Cancer Research UK (http://info.cancerresearchuk.org/cancerstats/types/melanoma/mortality/)



The cause for the difference in mortality between men and women may be related to primary tumour site. Melanomas of the back may drain to several lymph node basins; they are more common in men than women and their position makes them difficult for patients to find themselves.

Some recent evidence from Australia, which has the highest incidence in the world, shows that although the overall incidence of melanoma continues to rise, some rates are stabilising. For example, one study shows that the rate of increase of in situ melanoma is falling,4 and the incidence of invasive melanoma in people aged 354 and under 455 seems to be stabilising. Similarly, the incidence of thick melanomas (greater than 3 mm) has stabilised or declined in these groups.5 Mortality from melanoma, especially in women in Australia, may be falling.6 Trends for the United States and United Kingdom are similar; mortality from melanoma seems to have reached a plateau in women but continues to rise in men.7

These reports offer some encouragement that a combined strategy of public education and early diagnosis may be effective. This is important because there is no evidence from randomised controlled trials that any surgical procedure or systemic treatment prolongs overall survival in melanoma.

Primary prevention campaigns highlighting the danger of excessive exposure to sunlight and aiming to reduce the incidence of melanoma were first introduced and intensively studied in Australia. The “Slip [on a shirt], slop [on sunscreen], and slap [on a hat]!” and “SunSmart” campaigns were launched in the 1980s, together with education in schools and elsewhere, sponsorship of sporting events, and multi-media campaigns sometimes backed by legislation. Recent Australian studies suggest that education has altered sun related behaviour—tanning is less eagerly sought and weekend sunburn less frequently reported, and the use of sunscreens and protective clothing in the sun has increased.5 In the United States and Europe, where the threat of skin cancer is lower, there is little evidence to suggest that knowledge of the danger of excess sunlight translates into a change in behaviour,8 rather like the association between knowledge and tobacco smoking habits in young people.

The goal of earlier diagnosis is to identify in situ and early invasive melanoma in order to stabilise and subsequently reverse the trend for increasing mortality once prevalent cases have been detected.4,5 The skin is immediately accessible for observation by the patient or a relative, friend, or health professional and therefore offers us an early diagnostic opportunity that is not available in most cancers.

Almost two thirds (60%) of invasive melanomas are of the superficial spreading variety, where the tumour cells spread radially in the skin, giving characteristic physical signs: a flat, spreading, pigmented lesion with an irregular border, differential pigmentation, and later central de-pigmentation. After a latent period of months or years, during which time an excision biopsy may be curative, the radial growth pattern transforms to vertical growth as tumour cells invade downwards into the dermis, gaining access to the lymphatic and vascular capillaries thereby facilitating metastatic dissemination. This vertical change is signalled clinically by the appearance of a nodule in the tumour as the cells spread upwards into the epidermis. In contrast, the more ominous but less common nodular melanoma does not spread radially and only penetrates vertically. Sometimes the rate of progress and ulceration of a lesion is too rapid to allow early diagnosis and cure. The prognosis of primary invasive melanoma is directly related to its vertical height in the skin (the Breslow thickness), with melanomas in radial and early vertical growth phase offering the best opportunity for early diagnosis and cure.

Awareness of diagnostic criteria is essential for early detection of malignant melanoma and should form the basis of public health campaigns. Friedman and colleagues coined the ABCD(E) mnemonic: Asymmetry, Border irregularity, Colour variation and Diameter of 6 mm or greater.9 (E)—Evolution—was added to improve diagnostic sensitivity by emphasising change and progression within a pigmented lesion and encompasses colour, size, symmetry, surface characteristics, itchiness, bleeding, or pain. Mackie and colleagues have popularised the seven point checklist, which includes three major features (change in size, shape, or colour) together with four minor features (diameter 7 mm or greater, inflammation, oozing, or change in sensation).10 However, early malignant lesions such as melanoma in situ may be indistinguishable from benign lesions, and doctors should have a low threshold for biopsy of unusual lesions which do not show typical benign features. Dermatoscopy, possibly coupled with computer based systems and serial photography, may have a role in selecting lesions for biopsy.​biopsy.



Figure 2

Superficial spreading melanoma



To date no surgical or systemic treatment has been shown to improve overall survival of patients with melanoma, although some patients may be cured by complete excision of the primary tumour and removal of palpable metastatic nodes. Increasing the margin of excision at best improves disease-free survival, and disappointingly the novel procedure of sentinel node biopsy to select patients for “early” lymphadenectomy provides no survival advantage.11 The most promising systemic treatment seemed to be interferon alfa, but this only improves disease-free survival, and at the expense of great toxicity. Trials have not shown vaccines to be effective in saving lives.

Early diagnosis of melanoma currently offers the only hope of reducing mortality. Primary prevention remains essential, emphasising for adults, and children the importance of lifestyle changes such as avoiding the midday sun, protective clothing, and sunscreens. Above all, the risk of sunburning in childhood and adolescence should be emphasised at every opportunity.