2.1 Introduction

Melanoma, especially when diagnosed at an advanced stage, can cause serious morbidity and may be fatal despite treatment. Prevention of the disease, or failing that, minimising its consequences by early detection, are key goals.

2.2 Causation

A comprehensive review of evidence by the International Agency for Research on Cancer (IARC) has concluded that solar radiation is a cause of melanoma.² Evidence level 2++

Two more recent systematic reviews focussed on the relationship between patterns of sun exposure and risk of melanoma. The first was a high quality review of case control studies which concluded that intermittent unaccustomed exposure was more important than age at sunburn.³ The second study was a review of ecological and case control studies and concluded that exposure to high levels of sunlight in childhood is a strong determinant of risk, but that exposure in adulthood also plays a part.⁴ Evidence level 2++

The contribution of specific wavelength bands and the action spectrum for melanoma induction are unknown.³ Sunburn is mainly due to UVB (280 to 320 nm) radiation, implicating UVB as a contributing factor to the pathogenesis of melanoma. There is accumulating evidence for the role of UVA (and sunbeds) in the pathogenesis of melanoma.⁵ Evidence level 2++

2.3 Primary prevention

Primary prevention is defined as prevention targeted towards the general population.

There is indirect evidence that sun avoidance and other sun-protective measures (eg clothing, hats and opaque sunscreens) are likely to reduce the risk of melanoma. Sunscreen effectiveness is difficult to demonstrate for a number of reasons. High risk individuals are more likely to use sunscreen, although sunscreen use may be associated with greater sun exposure.^{6, 7} It may be that sunscreens offer a false sense of security and lead to increased time spent in the sun.^{6, 7} Most sunscreens offer greater protection from UVB, reducing the risk of sunburn, but not of exposure to UVA. ^{6, 7} Some ingredients found in sunscreens may be carcinogenic.^{6, 7} Case control studies and clinical trials have shown no reduction or increase in melanoma incidence with broad spectrum sunscreen use. Little is known about the potential long term effects of sunscreen use.^{6, 7} Given these potentially adverse effects of sunscreens in relation to risk of melanoma, physical protection measures should be regarded as more important than sunscreen use.^{6, 7} Evidence level 2++

There may be theoretical risks associated with sun avoidance,⁸ eg a lack of vitamin D, but the balance of evidence in terms of risks and benefits favours a cautious approach to sun exposure. In the absence of evidence to support recommendations about specific aspects of protection measures in Scotland, the advice below is based on the Australian guidelines on melanoma, interpreted in the light of the Scottish climate.⁹ Evidence level 4

Table 1 : Prevention of Melanoma

2.3.1 PUBLIC EDUCATION TO PROMOTE PRIMARY PREVENTION

As melanoma is potentially preventable, educating the general public might be an important preventive measure. Six randomised controlled trials (RCTs) of interventions aimed at a variety of target groups including the general public, employees and school children were identified.^{10, 11, 12, 13, 14, 15} All interventions were in some part reliant on brochures and leaflets to deliver preventive information. Leaflets significantly increased short term user-knowledge of sun awareness measures, and assisted in the early detection of melanoma (see also section 2.4.4). The tone of a leaflet or educational brochure is important when delivering health promotion messages relating to sun awareness and should be non-alarmist.¹¹ Evidence level 1+

Two observational studies suggest that interactive computer-based educational packages may result in higher short term knowledge gain (sun awareness) when compared to non-interactive packages.^{16, 17} A retrospective cohort study of French primary school children found that health education programmes could improve the knowledge, attitude and behaviour of young children. Children with a fair complexion (the target of this campaign) showed the best improvement in their responses.¹⁸ Evidence level 2+

Leaflets, brochures and educational packages can significantly influence increased short term user-knowledge of sun awareness measures, and can assist in the early detection of melanoma (see also section 2.4.4).

nsufficient evidence was identified to enable recommendations to be made about the style or content of leaflets and brochures.

Brochures and leaflets should be used to deliver preventive information on melanoma to the general public.

Leaflets and brochures used in melanoma prevention work should be non-alarmist.

If computer-based learning programmes are used they should be interactive in nature.

2.4 Screening and surveillance

2.4.1 IDENTIFICATION OF INDIVIDUALS AT HIGHER RISK

A review of the literature on the reliability and usefulness of risk-assessment tools suggests that patients can count the number of moles 5 mm or larger in reasonable agreement with physicians, but that they cannot accurately distinguish atypical moles from others.¹⁹ No longitudinal studies of the use of risk-assessment tools in primary care were identified. Evidence level 2++

A cross-sectional study that sent postal questionnaires to a random sample of households from a general practice population found that self assessment of risk was generally poor compared with the assessment of a dermatologist, suggesting that it might be very difficult to identify systematically a high risk population suitable for screening.²⁰ Evidence level 3

An RCT carried out in 11 communities in Western Australia showed that targeted advertising can increase the yield of individuals with a higher prevalence of risk factors.²¹ This may not be immediately transferable to Scotland, where disease prevalence is lower and baseline awareness may be lower. Evidence level 1+

2.4.2 RISK FACTORS

Risk factors for melanoma have been identified mainly from case control studies (see Table 2). The strength of a risk factor is usually expressed in terms of an “odds ratio” (OR). In the context of this guideline, the OR is the ratio of the odds in favour of exposure to a risk factor in people with melanoma to the odds in favour of exposure to the same risk factor among people who have not developed melanoma. For relatively rare diseases such as melanoma, the OR can be thought of as being equivalent to the relative risk, that is, the ratio of the incidence rate of melanoma among exposed individuals to the incidence rate among unexposed individuals. The higher the OR (or relative risk), the stronger the association between the risk factor and melanoma. This is important from the perspective of an individual, but from a public health perspective a lower OR for a commonly occurring risk factor may be more important than a higher OR for a risk factor which occurs rarely in the population.

Table 2: Established risk factors for cutaneous melanoma

2.4.3 SURVEILLANCE OF INDIVIDUALS AT HIGHER RISK

Results from a Scottish cohort study suggest that surveillance of individuals at higher risk, once identified, can lead to early diagnosis of thin lesions. The cost effectiveness of this approach is unclear.²⁸ Evidence level 2+

2.4.4 PUBLIC EDUCATION TO PROMOTE EARLY DETECTION

A study in the west of Scotland suggested that a public education campaign and rapid referral system to encourage earlier detection of melanoma could result in sustained decreases in the rate of diagnosis of thick melanomas (>3.5mm) and mortality in females, but not in males.²⁹ This contrasts with the results of the Cancer Research Campaign Mole Watcher Study that did not find lower cumulative mortality from melanoma in regions exposed to a health education intervention compared to non-intervention regions.³⁰ Evidence level 3

The available evidence is insufficient to recommend for or against the routine screening of individuals at higher risk of melanoma. Interventions to promote the awareness of risk factors and skin self awareness are probably warranted.

Healthcare professionals and members of the public should be aware of the risk factors for melanoma.

Individuals identified as being at higher risk should be advised about appropriate methods of sun protection educated about the diagnostic features of cutaneous melanoma encouraged to perform self examination of the skin.

2.4.5 MASS SCREENING

No randomised controlled trials on mass screening were identified. Two American systematic reviews of screening for melanoma (and other skin cancers) have identified observational data to suggest that screening in high risk groups might be effective. ^{19, 31} Evidence level 2++

A formal programme of mass screening for melanoma in Scotland is not recommended.

2.5 Genetics

A recent consensus document estimated that one to two percent of melanomas were attributable to the inheritance of melanoma susceptibility genes.³² The document also estimates that a similar percentage of melanoma patients come from “melanoma prone” families with three or more first degree relatives with melanoma. Evidence level 4

Members of such families are at significantly increased risk of developing melanomas. Many more melanoma patients have only one relative who also has melanoma.³³ An intensive search for putative melanoma susceptibility genes has identified mutations in the CDKN2A gene in 20-30% of melanoma prone families in Scotland, reflecting rates reported in other parts of the world.^{34, 35, 36, 37} This mutation is less frequently found in families with only two affected members. Mutations in the CDK4 gene have been found in only three families and it is likely that there are as yet unidentified melanoma susceptibility genes. Current expert consensus recommends that genetic testing in familial or sporadic melanoma is not appropriate in a routine clinical setting and should only be undertaken in the context of appropriate research studies and when appropriate counselling services are available.³⁸ Evidence level 4

Genetic testing in familial or sporadic melanoma is not appropriate in a routine clinical setting and should only be undertaken in the context of appropriate research studies.