SKIN CANCER August 2013

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1 2.4 Life risk 5 Risk facrs SUMMARY There are two types of : malignant melanoma of the, and non-melanoma (NMSC). Malignant melanoma is the less common but most serious type of. In in 21, around 12,8 people were diagnosed with malignant melanoma, and in in 211 around 2,2 people died from the disease. NMSC is much more common, with more than 99,5 recorded in in 21; registration of the disease is known be incomplete, however. The vast majority of NMSC are detected early and are not life-threatening. In in 211, there were around 59 deaths from NMSC. Malignant melanoma is the fifth most common in, but only the 18 th most common cause of death, reflecting high from the disease. More than eight in ten malignant melanoma are estimated be caused by UV radiation from the sun and sunbeds. Incidence rates have more than quadrupled since the mid-197s in Great Britain. Most of the increase is considered be real and linked changes in sunrelated behaviour, such as an increase in frequency of holidays abroad over. The age distribution for malignant melanoma is unusual compared with other s, with a relatively high proportion of in younger people; but still 45% of are diagnosed in the over-65s. Whilst malignant melanoma is more common in females than males in the younger age groups, this pattern reverses in older people. 1 INTRODUCTION There are two types of : malignant melanoma of the a and non-melanoma (NMSC). Malignant melanoma is the most serious type of. NMSC is much more common than malignant melanoma, and in the vast majority of it is detected early and is not lifethreatening. Malignant melanoma is a that develops from melanocytes (cells found in the deep layers of the epidermis). Melanocytes produce the ultraviolet (UV)-protective pigment melanin, which is responsible for the colour of. NMSC most commonly develops from the epidermal cells keratinocytes, which produce the waxy -strengthening substance keratin. There are several different types of NMSC: basal cell carcinoma (BCC) develops in keratinocytes at the botm of the epidermis, whilst squamous cell carcinoma (SCC) develops in keratinocytes elsewhere in the epidermis; other cells in the can also undergo malignant transformation, resulting in rarer NMSC types such as Merkel cell carcinoma, Kaposi sarcoma, and T-cell lymphoma of the. This Cancer report summarises the most recent statistical and epidemiological information for in and rest of the world. The registration of NMSC is known be incomplete (Section 9) and so this report mainly focuses on malignant melanoma, but NMSC is presented where available. a Cancer More on : Visit cruk.org/ stats for more : Skin key facts on sunbed use Also see: NCIN lead registration office for - Public Health England's Knowledge and Intelligence team (South West) SunSmart, 's national prevention campaign Survival from malignant melanoma has improved markedly in recent decades and is now amongst the highest for any, largely thanks increased awareness, earlier and better s. Today eight in ten malignant melanoma patients are predicted survive for at least ten years after their. But there is still room for improvement, particularly among men. Skin is an extremely preventable disease. With rates high, the main focus of research and practice continues be on prevention and earlier. Called malignant melanoma hereafter. Malignant melanoma (C43) 2 INCIDENCE Malignant melanoma is the fifth most common in the UK (21), accounting for 4% of all new. In males and females separately, malignant melanoma is the sixth most common (4% each of the male and female tal). 1-4 In 21, there were 12,818 new of malignant melanoma in (Table 1): 6,21 (48%) in men and 6,617 (52%) in women, giving a male: female ratio of around 1: Table 1: Sex England Wales Scotland Northern Ireland Number of new UK Males 5, ,21 Females 5, ,617 Persons 1, , ,818 Crude rate per 1, Males Females Persons European age-standardised rate per 1, 1-4 With 95% confidence limits 21 Males Females Persons Malignant Melanoma Incidence by Country of 2 cruk.org/stats

2 2.4 Life risk 5 Risk facrs The crude incidence rate b shows that there are 2 new malignant melanoma for every 1, males in, and 21 for every 1, females. The European age-standardised incidence rates (AS rates) c are significantly higher in Wales compared with England, Scotland and Northern Ireland (males only). They are also significantly lower in Northern Ireland compared with Wales, England and Scotland (males only) (Table 1). 1-4 The rates do not differ significantly between the constituent countries of for females. The Cancer Atlas for and Ireland , which analysed rates at local authority and health board level, showed that male and female malignant melanoma incidence rates have a very similar geographical distribution. The highest rates for both sexes occur in south west England and in the densely populated belt of Scotland, from Glasgow in the west Edinburgh in the east. 5 Similarly the latest analysis of malignant melanoma incidence rates across the former networks throughout reports significantly higher rates in the south and south west regions of England, whilst the incidence rates for areas of London are significantly lower than all other networks. 6,7 Malignant melanoma incidence is related age, but it has an unusual pattern when compared with most other sites. In between 28 and 21, an average of 27% of were diagnosed in those aged under 5 years, and an average of 45% of were diagnosed in the 65s and over (Figure 1). 1-4 This is in contrast all s combined (excluding nonmelanoma ), where 11% of were diagnosed in those aged under 5 during the same period, and 63% of were diagnosed in those aged 65 years and over. Age-specific incidence rates increase steadily from around age 2-24 years, reaching a peak at age 85+ years for both sexes (with the increase being sharper for males from age years onwards). Figure 1: Malignant Melanoma Incidence by Age 1, Incidence Incidence rates are higher for females than for males in the younger age groups, with a male:female incidence ratio of age-specific incidence rates ( account for the different proportions of males females in each age group) of 4:1 in 2-24 year-olds. However, males have higher incidence rates from age years onwards; the male:female ratio of agespecific rates increases with age more prominently in older age groups, from around 11:1 at age 6-64 years, around 16:1 at age 85+ years. Malignant melanoma incidence rates have increased overall in Great Britain since the mid-197s (Figure 2). 1-3 For males, European AS incidence rates were around seven s higher in than in For females, the increase is smaller but rates have still quadrupled between and Since the mid-197s in Great Britain, malignant melanoma incidence rates have increased more rapidly than any of the current ten most common s in males and females. Figure 2: Malignant Melanoma Incidence Over Time, Great Britain Rate per 1, Males Females Persons Year of 2 25 Malignant melanoma (C43), European age-standardised incidence rates, Great Britain, Some of the increase may be due increased surveillance and early detection as well as changes in diagnostic criteria, but most is considered be real and linked changes in sunrelated behaviour such as an increase in frequency of holidays abroad over A study published in December 211 estimated that around 86% of malignant melanomas in in 21 were linked exposure UV radiation from the sun and sunbeds (Section 5) Average number 2 of per year Males Females Age at Rate per 1, Males Females Malignant melanoma (C43), average number of new per year and age-specific incidence rates, UK, b c Crude rates are calculated using a simple formula in which the number of is divided by the corresponding population and multiplied by 1, Age standardisation takes account of age differences in the underlying populations, and hence provides unbiased comparisons of incidence rates with respect age (for example, over, between sexes, or between geographical areas). Age-standardised rates are calculated by multiplying individual age-specific rates by corresponding proportions (or weights) in a standard population and then summing create an overall rate per 1,. 2 of 2 cruk.org/stats

3 2.4 Life risk 5 Risk facrs Malignant melanoma incidence trends for are shown in Figure Over the last decade (between and 28-21) the European AS incidence rates have increased by 65% and 46% in males and females, respectively. Figure 3: Malignant Melanoma Incidence Over Time, UK Rate per 1, Males Females Persons Year of Malignant melanoma incidence rates have increased overall for all of the broad age groups for males in Great Britain since the mid-197s (Figure 4). 1-4 The largest overall increase has been for males aged 6-79 years, with European AS incidence rates increasing around ten-fold between and Malignant melanoma (C43), European age-standardised incidence rates, UK, Figure 4: Malignant Melanoma Incidence Over Time by Age, Males Rate per 1, Year of Malignant melanoma (C43), European age-standardised incidence rates, by age, males, Great Britain, Malignant melanoma incidence rates have also increased overall for all of the broad age groups for females in Great Britain since the mid-197s (Figure 5). 1-3 Following a similar pattern males, the largest overall increase has also been for females aged 6-79 years, with European AS incidence rates increasing around five-fold between and For each of these age groups, the increase has been faster for males than for females. Incidence Figure 5: Malignant Melanoma Incidence Over Time by Age, Females Rate per 1, Year of Malignant melanoma (C43), European age-standardised incidence rates, by age, females, Great Britain, Malignant melanoma incidence rates in males and females combined have also increased overall for all of the broad age groups in Great Britain since the mid-197s (Figure 6). 1-3 As indicated by the separate male and female rates, the largest overall increase has been for people aged 6-79 years, with European AS incidence rates increasing around seven-fold between and Incidence rates for those aged 5-59 years have also more than tripled over the same period. Figure 6: Malignant Melanoma Incidence Over Time by Age, Persons Rate per 1, Year of Malignant melanoma (C43), European age-standardised incidence rates, by age, persons, Great Britain, Life risk Life risk is an estimation of the risk that a newborn child has of being diagnosed with at some point during their life. It is a summary of risk in the population but genetic and lifestyle facrs affect the risk of and so the risk for every individual is different. In 21, in, the life risk of developing malignant melanoma is 1 in 55 for men and 1 in 56 for women of 2 cruk.org/stats

4 2.4 Life risk 5 Risk facrs The life risk for malignant melanoma has been calculated by the Statistical Information Team using the Adjusted for Multiple Primaries (AMP) method; this accounts for the possibility that someone can have more than one of malignant melanoma over the course of their life. 14 Figure 7 shows the percentage distribution of malignant melanoma on parts of the body. These vary by sex, with more than four in ten in males arising on the trunk of the body, particularly on the back, while the most common site for females is on the legs. 1-3 Figure 7: Malignant Melanoma Cases by Body Site Head & neck Trunk Arm Leg Not specified / overlapping Males 22% 41% 19% 13% 4% Head & neck Trunk Arm Malignant melanoma (C43), percentage distribution of diagnosed on parts of the body, by sex, Great Britain, Percentages may not add 1 due rounding. Staging for malignant melanoma describes how deeply the tumour has grown in the, and whether it has spread. Data by stage are not yet routinely available for due inconsistencies in the collecting and recording of staging data in the past; this is improving, however, and plans for a nationally consistent dataset in England are underway. 15 In the mean, by stage is available for the former Anglia Cancer Network in the east of England for the period Anglia covers around 5% of the population of England and may not be representative of the country as a whole due differences in underlying demographic facrs (such as age, deprivation or ethnicity), as well as in local healthcare provision standards and policies. Nonetheless, the Anglia data enable valuable comparisons between stage and malignant melanoma be made. Leg Not specified / overlapping Females 14% 2% 24% 39% 3% Incidence The majority (66%) of men and women diagnosed with malignant melanoma present at stage I (Table 2), 16 with the proportion being higher in women (71%) than in men (61%). Just 1% of men and women present with metastases (stage IV). Table 2: Stage at Malignant Melanoma Cases by Stage Men Women Adults Stage I 61.4% 71.3% 66.4% Stage II 21.% 17.1% 19.1% Stage III 13.7% 8.5% 11.1% Stage IV 2.%.7% 1.3% Stage not known 1.9% 2.4% 2.1% All stages 1.% 1.% 1.% Malignant melanoma (C43), proportion of diagnosed at each stage, adults (aged 15-99), former Anglia Cancer Network, A study using data from three English registries for showed that around half of malignant melanoma (45% in males and 53% in females) are diagnosed when the tumour is less than 1mm thick. 17 Only 14% of males and 1% of females are diagnosed when their tumour is more than 4mm thick. 17 Although registration has a long hisry in many countries of the world, particularly in the more affluent regions such as, nearly 8% of the world s populations live in regions that are not covered by such systems. 18 Nonetheless, with a view characterising the global burden of the disease, the International Agency for Research on Cancer (IARC) routinely uses the available data estimate incidence. 19 Malignant melanoma is the 19 th most common, estimated be responsible for almost 2, new of in 28 (more than 1% of the tal). Malignant melanoma incidence rates are highest in Australia/ New Zealand and lowest in South-Central Asia, with around a 2-fold in World AS incidence rates between the regions of the world for males, and around a 16-fold for females (Figure 8, see next page). 19 The majority of malignant melanomas are caused by heavy sun exposure in white-ned populations. 2,21 Incidence rates are highest by far in Australia/New Zealand, where it is the third most common in both males and females, accounting for one in nine (around 11% in 28) of the tal. 19 Incidence rates are increasing rapidly in many countries, including in the Nordic countries, where the increase has been attributed excessive sun exposure during holidays at lower latitudes. 2 4 of 2 cruk.org/stats

5 2.4 Life risk 5 Risk facrs Figure 8: Malignant Melanoma Incidence Worldwide Australia/ New Zealand Northern America Northern Europe Western Europe Southern Europe Southern Africa Central and Eastern Europe World South America Eastern Africa Middle Africa Central America Western Asia Western Africa Caribbean South -Eastern Asia Northern Africa Eastern Asia South -Central Asia Within the 27 countries of the European Union (EU-27), the highest malignant melanoma European AS incidence rates are estimated be in Sweden for males (around 22 per 1,) and Denmark for females (around 26 per 1,), and the lowest rates are estimated be in Greece for both sexes (more than 3 male per 1,, and around 3 female per 1,) (Figure 9) Socio-economic Rate per 1, Males Females Malignant melanoma (C43), World age-standardised incidence rates, world regions, 28 estimates. 19 Malignant melanoma incidence is strongly inversely related deprivation in ; it is one of the few s where incidence rates are lower for more deprived men and women and there is a clear trend of decreasing rates from the least the most deprived The most recent England-wide data for 2-24 show European AS incidence rates are 122% higher for men living in the least deprived areas compared with the most deprived, and 116% higher for women. 23 It has been estimated that there would have been an additional 2, new malignant melanoma each year in England during 2-24 if all men and women had experienced the same incidence rates as the most affluent. 23 Incidence Figure 9: Malignant Melanoma Incidence in Europe Denmark Sweden The Netherlands Slovenia Czech Republic Ireland UK Germany Finland Luxembourg Belgium Slovakia EU-27 Italy Hungary France (Metropolitan) Austria Esnia Malta Spain Lithuania Latvia Portugal Poland Bulgaria Cyprus Romania Greece Rate per 1, Males Females Malignant melanoma (C43), European age-standardised incidence rates, EU-27 countries, 28 estimates. 22 UK malignant melanoma incidence rates are estimated be the seventh and sixth highest in males and females, respectively, in Europe (EU-27). 22 A study in Scotland for showed that the gap in malignant melanoma incidence by deprivation is slightly smaller, with the least deprived people having 81% higher rates, compared with the most deprived. 24 Comparable associations with deprivation have also been reported in Wales and Northern Ireland. 25,26 5 of 2 cruk.org/stats

6 2.4 Life risk 5 Risk facrs Prevalence refers the number of people who have previously received a of and who are still alive at a given point. Some patients will have been cured of their disease and others will not. The latest estimates for (Table 3) show that nearly 6, men and women were still alive at the end of 26, up ten years after being diagnosed with malignant melanoma. 27 Worldwide, it is estimated that there were around 756, patients still alive in 28, up five years after their. 19 Table 3: Malignant Melanoma Prevalence Sex One-year Five-year Ten-year Males 4,278 16,118 24,617 Females 5,132 21,23 34,53 Persons 9,41 37,321 59,147 Malignant melanoma (C43), one-, five- and prevalence, UK, 31 st December Non-melanoma Non-melanoma s (NMSC) are extremely common, but relatively few deaths (see Section 4.5) are caused by them. In 21, there were 99,549 of NMSC registered in the UK: 56% in men and 44% in women, giving a male:female ratio of 13: The majority of NMSCs are BCCs (74%) or SCCs (23%). 28 The remainder comprises a mixed group of rare s; almost three in ten of these are Merkel cell carcinoma, which has a very poor prognosis. 29 Both BCC and SCC are more common in males than females, though the sex difference is wider for SCC than BCC. 28 The recorded incidence of BCC increased by around a third (36% in males and 32% in females) between 2-22 and in England, Scotland, Northern Ireland and Ireland combined. 28 SCC incidence increased by a similar amount (34% in males and 39% in females) over the same period. 28 Whilst improved registration may partly explain these increases, some of the increase is probably genuine, reflecting increased UV exposure from the sun or sunbeds. 28 NMSCs constitute a substantial burden the national health services across because of the large number of diagnosed each year, however NMSC incidence figures are under-estimates because the recording of NMSC is known be incomplete. 27 Many registries record only the first NMSC of each hislogical type (e.g. BCC or SCC) per person, and small NMSCs treated in primary care or the private secr may never reach the registries. 29 An estimated 3-5% of BCC and around 3% of SCC goes unrecorded, though this may vary by registry Incidence Survival 3 SURVIVAL 3.1 One-, five- and Age-standardised relative d for malignant melanoma in England during shows that 96% of men survive their disease for at least one year, falling 84% surviving for five years or more (Table 4). 36,37 Survival for women is slightly higher, with 98% surviving for one year or more, and 92% surviving for at least five years. Broadly similar has been reported for Wales, Scotland and Northern Ireland Survival continues fall slightly beyond five years after, with 8% of men and 9% of women predicted survive for at least ten years (Table 4). 37 Five-year for malignant melanoma is amongst the highest of the 21 most common s in England. 36 However, with an absolute difference e of 8%, malignant melanoma shows one of the largest disparities in five-year between the sexes. Differences in the thickness of tumours between men and women may explain some of the, as well as diverse attitudes health-related behaviour. 41,42 Table 4: Malignant Melanoma One-, Five- and Ten- Year Survival Sex One-year Five-year Ten-year Men 95.7% 83.6% 79.7% Women 97.7% 91.6% 9.1% Malignant melanoma (C43), one-, five- and age-standardised relative, adults aged 15-99, England, Ten-year has been predicted for patients diagnosed in 29 (using the hybrid approach). 37 Like with most s, for malignant melanoma is much more effective when the disease is caught at an early stage (see Section 3.4). Survival data for NMSC is not routinely available, and is therefore not shown. However, in the majority of, NMSC is detected early and is not life threatening. Both BCC and SCC are highly treatable and rates for NMSCs are very high. 34 However, if left untreated, these tumours can become destructive, invading local tissues and causing disfigurement. 35 d e Relative takes in account the fact that the person may have died even if they did not have ; it is relative the rest of the population. An absolute change in is the numerical difference when one rate is taken away from another. 6 of 2 cruk.org/stats

7 2.4 Life risk 5 Risk facrs 7 of 2 As with nearly all s, for malignant melanoma is higher in younger men and women, even after taking account of the higher background mortality in older people. The reasons for this are likely include a combination of better general health, more effective response and earlier in younger people overall. In men, five-year relative for malignant melanoma in England during ranges from 9% in yearolds 64% in 8-99 year-olds (Figure 1). 36 Five-year is higher in women than men across all age groups, ranging from 96% in year-olds 85% in 8-99 year-olds. Figure 1: Malignant Melanoma Five-Year Survival by Age Males Females Age at % 25% 5% 75% 1% Malignant melanoma (C43), five-year relative by age at, adults aged 15-99, England, As with the majority of s, for malignant melanoma is improving. This can generally be attributed faster and improvements in. However, there is still scope for improvement and increasing remains a major priority of Improving Outcomes: A Strategy for Cancer. 43 One-year can be used as an indicar of early, since death before one year is likely be due the disease being diagnosed at a late stage. In men, one-year age-standardised relative for malignant melanoma in England increased from 79% during % during (Figure 11). 36,37 In women, one-year increased from 89% 98% over the same periods, respectively. Part of the increase in both sexes will be due increased awareness and earlier of the disease as a result of public heath campaigns such as SunSmart (See Section 7); concomitantly, several studies have reported increasing proportions of thin, early stage tumours in recent years. 41,44,45 Whilst is still influenced by early after five years, it is also strongly dependent on the success of. In men, five-year age-standardised relative for malignant melanoma in England increased from 47% during % during (Figure 11). 36,37 In women, five-year increased from 65% 92% over the same periods, respectively. cruk.org/stats Survival Ten-year age-standardised relative for men diagnosed with malignant melanoma in England increased from 39% during a predicted 8% in 29 (Table 4 and Figure 11). 36,37 In women, increased from 58% a predicted 9% over the same periods, respectively. Figure 11: Malignant Melanoma One-, Five- and Ten- Year Survival Over Time Year of Males Females One-year Five-year Ten-year % 25% 5% 75% 1% Malignant melanoma (C43), age-standardised one-, five- and relative, adults aged 15-99, England, ,37 Survival by stage is not yet routinely available for due inconsistencies in the collecting and recording of staging data in the past; this is improving, however, and plans for a nationally consistent dataset in England are underway. 43 In the mean, by stage is available for the former Anglia Cancer Network in the east of England for the period Anglia covers around 5% of the population of England and may not be representative of the country as a whole due differences in underlying demographic facrs (such as age, deprivation or ethnicity), as well as in local healthcare provision standards and policies. Nonetheless, the Anglia data enable valuable comparisons between stage and be made. Survival for malignant melanoma is strongly related stage of the disease at. 46 The majority (66%) of patients present at stage I (see Section 2.6). Just 1% of patients present with metastases (stage IV).

8 2.4 Life risk 5 Risk facrs One-year relative is highest for patients presenting at stage I, with 11% f of men and women surviving for at least one year (Figure 12). 46 In comparison, one-year is considerably lower for those diagnosed with stage IV disease (1% for men and 35% for women). As very few patients are diagnosed at Stage IV, however, the one-year statistics have wide confidence intervals and should therefore be interpreted with caution. There are no significant sex differences at any of the stages. Figure 12: Malignant Melanoma One-Year Survival by Stage Males Females Stage I Stage II Stage III Stage IV Stage not known All stages % 2% 4% 6% 8% 1% Malignant melanoma (C43), one-year relative by stage, adults aged 15-99, former Anglia Cancer Network, Five-year for malignant melanoma is similarly strongly related the stage of the disease at, but there is a much more gradual decrease in between stages I and IV. Five-year relative ranges from 12% f (for men) and 1% (for women) at Stage I 8% (for men) and 25% (for women) at Stage IV (Figure 13). 46 As expected, five-year is significantly lower than one-year across most known-stage groups within each sex. The exceptions are men and women presenting at Stage I, whose five-year remains at 1%, and men and women presenting at Stage IV, in whom does not differ significantly between one and five years (though, as before, low patient numbers preclude reliable analysis). Figure 13: Malignant Melanoma Five-Year Survival by Stage Males Females Stage I Stage II Stage III Stage IV Stage not known All stages % 2% 4% 6% 8% 1% f Survival Mortality EUROCARE (European Cancer Registry-based study on and care of patients) is a series of registry-based comparisons of by country in Europe. 47 Whilst the studies have some unavoidable limitations and the statistics should be viewed with some caution, EUROCARE is the largest co-ordinated effort at providing comparative statistics across Europe. The most recent study in the series, EUROCARE-4, used data collected from 82 registries in 23 European countries for the analysis of 2.7 million adult patients diagnosed in the period ,53 Malignant melanoma is one of the few s in which fiveyear relative in England is significantly higher than the European average. The study showed there is considerable within, however, with significantly lower fiveyear in Wales (74%) compared with England, Scotland and Northern Ireland (85%, 89% and 93%, respectively). 52,53 Such comparatively low in Wales may be explained by differences in stage at, particularly among the more deprived men and women who seem fare worse compared with their UK counterparts. 54 Differences in public awareness and early initiatives may also play a role. It has been estimated that around 93 deaths could be avoided within five years of if malignant melanoma in Britain equalled the best in Europe. 55 Relative can be greater than 1% because it accounts for background mortality. A relative figure greater than 1 indicates that people diagnosed have a better chance of surviving one or five years after than the general population. 4 MORTALITY Malignant melanoma is the 18 th most common cause of death in (211), accounting for 1% of all deaths from. Malignant melanoma is the 17 th most common cause of death among men in (211), accounting for 2% of all male deaths from. Among women in, malignant melanoma is the 18 th most common cause of death (211), accounting for 1% of all female deaths In 211, there were 2,29 deaths from malignant melanoma in (Table 5, see next page): 1,295 (59%) in men and 914 (41%) in women, giving a male:female ratio of 14: The crude mortality rate b shows that there are 4 malignant melanoma deaths for every 1, males in, and 3 for every 1, females. The European age-standardised mortality rates (AS rates) c do not differ significantly between the constituent countries of (Table 5) The latest analysis of malignant melanoma mortality rates throughout reports only modest between the former networks. 6,7 8 of 2 Malignant melanoma (C43), five-year relative by stage, adults aged 15-99, former Anglia Cancer Network, cruk.org/stats

9 2.4 Life risk 5 Risk facrs Table 5: Sex England Wales Scotland Northern Ireland Number of deaths Malignant melanoma mortality is strongly related age, with the highest mortality rates being in older men and women. In between 29 and 211, an average of 5% of malignant melanoma deaths were in the age group, whilst an average of 38% of deaths were in people aged 75 years and over (Figure 14) Age-specific mortality rates increase sharply from around age 5-54 years in both men and women, reaching a peak at age 85 and over in both sexes. Mortality rates are generally similar between males and females until age 5-54 onwards, when rates are higher for males than for females. This is in contrast incidence rates which are higher for females until the mid- 5s. The widest gap between the ages is for those aged 7-74 years, when the male:female mortality ratio of age-specific rates ( account for the different proportions of males females in each age group) is 2:1. UK Males 1, ,295 Females Persons 1, ,29 Crude rate per 1, Males Females Persons European age-standardised rate per 1, With 95% confidence limits 211 Males Females Persons Figure 14: Malignant Melanoma Mortality by Age 2 15 Malignant Melanoma Mortality by Country Malignant melanoma (C43) 4 3 Mortality Malignant melanoma mortality rates have increased overall in since the early 197s (Figure 15) For males, European AS mortality rates increased by 185% between and The rise is smaller for women, with rates increasing by 55% between and From the late 198s onwards, mortality rates have increased much more quickly in males than in females, causing a divergence of the rates between the sexes. This is in contrast malignant melanoma incidence rates in males and females, which have converged in the last decades (see Section 2.3).Over the last decade (between 2-22 and ), the European AS mortality rates have increased by 22% in males and remained stable in females. The increase in malignant melanoma mortality rates is likely be a reflection of the increase in incidence rates. The increase in mortality rates is much less pronounced, however, due improvements in (as a result of earlier and better ). The lower mortality rates in females since the mid-198s mirror the better rates seen in women (see Section 3). Figure 15: Malignant Melanoma Mortality Over Time Rate per 1, Males Females Persons Year of death Malignant melanoma (C43), European age-standardised mortality rates, UK, Malignant melanoma mortality rates have increased overall for most of the broad age groups in since the early 197s, except those aged and 4-49 years (Figure 16, see next page) The largest increases have been in people aged 75 years and over, with European AS mortality rates more than quadrupling between and of 2 5 Average number of deaths per year Males Females Age at death Rate per 1, Males Females cruk.org/stats Malignant melanoma (C43), average number of deaths per year and age-specific mortality rates, UK,

10 2.4 Life risk 5 Risk facrs Figure 16: Malignant Melanoma Mortality Over Time by Age Rate per 1, Year of death Malignant melanoma (C43), European age-standardised mortality rates, by age, persons, UK, The increase in mortality rates over in the older age groups may be explained in part by late, and figures have recently shown that people aged 65 and over are more likely be diagnosed with malignant melanoma at a late stage compared with younger people. 59 Figure 17: Malignant Melanoma Mortality Worldwide Australia /New Zealand Southern Africa Northern Europe Northern America Western Europe Central and Eastern Europe Southern Europe Eastern Africa Middle Africa South America World Central America Western Africa Western Asia Caribbean South -Eastern Asia Eastern Asia Northern Africa South -Central Asia Rate per 1, Males Females Malignant melanoma (C43), World age-standardised mortality rates, World regions, 28 estimates. 19 Sweden Esnia Denmark Slovakia Slovenia The Netherlands Ireland Austria Hungary Luxembourg Czech Republic Finland Poland UK Latvia EU-27 Germany Malta Lithuania Italy France (Metropolitan) Belgium Bulgaria Spain Portugal Romania Greece Cyprus Mortality Worldwide mortality data are collated and distributed by the World Health Organisation. 6 As with the collation of incidence data, there is wide in the coverage of death registration systems across the world, with two-thirds of the world s populations living in regions that are not covered by mortality statistics, as well as in the quality of the cause of death information itself. 18 IARC routinely uses the available data estimate mortality. 19 Malignant melanoma is the 23 rd most common cause of death, estimated be responsible for more than 46, deaths in 28 (around.6% of the tal). Malignant melanoma mortality rates are highest in Australia and New Zealand and lowest in South Central Asia, with a 49-fold in World AS mortality rates between the regions of the world for males, and a 23-fold for females (Figure 17). 19 Figure 18: Malignant Melanoma Mortality in Europe Rate per 1, Males Females Malignant melanoma (C43), European age-standardised mortality rates, EU-27 countries, 28 estimates of 2 cruk.org/stats

11 Mortality Risk facrs 2.4 Life risk 5 Risk facrs Within the 27 countries of the European Union (EU-27), the highest malignant melanoma European AS mortality rates are estimated be in Sweden for both males (around 5 deaths per 1,) and females (around 3 deaths per 1,), and the lowest rates are estimated be in Cyprus for males (1 male death per 1,), and Greece for females (around 1 female death per 1,) (Figure 18, see previous page). 22 UK malignant melanoma mortality rates are estimated be the 14 th (males) and 13 th (females) highest in Europe (EU-27). 4.5 Non-melanoma NMSC is an extremely common (see Section 2.1), but relatively few deaths are caused by it. In 211, there were 585 deaths from NMSC in ; of which 62% were in males BCCs rarely metastasise (spread) and are unlikely be fatal, though they can cause disfigurement; 35 in contrast SCCs somes spread and can therefore lead death RISK FACTORS The main risk facr for malignant melanoma and NMSC are UV radiation (from sun exposure and sunbeds). Skin type and hair and eye colour, sunscreen use, family hisry, previous, and other medical conditions also impact on risk. In the sections which follow, meta-analyses and systematic reviews are cited where available, as they provide the best overview of all available research and often take study quality in account. Individual case-control and cohort studies are reported where good quality aggregated data are lacking. 5.1 Ultraviolet radiation from sun exposure Excess exposure UV radiation is the main preventable risk facr for. 62,63 The sun is the principal source of natural UV radiation, whilst sunbeds produce artificial UV radiation. UVA and UVB are the two types of solar radiation which reach us on Earth. Both types are linked. UVB is predominantly responsible for burning, whilst UVA penetrates deeper in the and is linked with premature ageing. It is also expected that climate change will cause more in the future, as more UV radiation reaches us on Earth, and warmer temperatures encourage people spend more in direct sunlight. 64 There is sufficient evidence that o much exposure solar UV radiation is the main cause of both malignant melanoma and NMSC, according IARC. 65,66 It is estimated that around 11,1 (86%) malignant melanoma in in 21 were linked UV radiation exposure. 62 Among NMSCs, an estimated 5-7% of SCCs and 5-9% of BCCs in fair-ned people are caused by UV radiation Intermittent sun exposure and sunburn Risk of malignant melanoma is most strongly linked intermittent exposure high-intensity sunlight (for example from sunbathing, doing watersports or holidaying in a place where the sun is strong), a meta-analysis has shown. 68 Intermittent sun exposure was associated with a 6% increased risk of malignant melanoma, though this effect was smaller and not significant in studies of UK, US, Canadian or Australian populations. 68 Intermittent exposure high-intensity sunlight often results in sunburn, 68 and a hisry of sunburn doubles the risk of malignant melanoma. 68,69 Having had 26 or more episodes of painful or severe sunburn during your life increases the risk of malignant melanoma by two three s in women, a pooled analysis showed. 7 Malignant melanoma risk is increased regardless of whether sunburn occurred in childhood or adulthood. 68,71 Sunburn, especially in childhood, or intermittent exposure sunlight, also increases the risk of BCC. 72,73 Sunburn and intermittent sunlight exposure is believed have less of an effect on SCC risk Exposure UV radiation has increased in recent decades in population, as people have increasingly sought a suntan by holidaying abroad Chronic sun exposure Chronic or more continuous sunlight exposure, for example that received by people with outdoor occupations, did not appear increase malignant melanoma risk in a recent meta-analysis, though the review authors commented that occupational sun exposure still probably increases risk over no sun exposure at all. 68 There is evidence that chronic sun exposure increases the risk of NMSC. People who work outdoors are at 43% higher risk of BCC, 77 and 77% higher risk of SCC, 78 and these effects are stronger in countries nearer the equar, two meta-analyses have found. 77,78 11 of 2 cruk.org/stats

12 Risk facrs 5.2 Ultraviolet radiation from sunbeds Table 6: People Who Should Not Use Sunbeds 2.4 Life risk 5 Risk facrs 12 of 2 There is sufficient evidence that use of sunbeds causes malignant melanoma, IARC states. 66 IARC also states there is limited evidence that sunbed use causes SCC. 66 There is currently no IARC statement on sunbeds and BCC. Use of a sunbed for the first before age 35 increases the risk of malignant melanoma by 59%, and use at any age increases malignant melanoma risk by 2-25%, the most recent meta-analysis showed. 79,8 Women using a sunbed once a month or more in their 3s increase their malignant melanoma risk by 49%, and those doing so in their 4s face a 61% increased risk, one large study included in that analysis showed. 81 Another cohort study showed women aged who use a sunbed more than 1 s a year have two-anda-half s the malignant melanoma risk compared with women who do not use sunbeds. 82 Sunbed use is estimated cause around one hundred deaths a year from malignant melanoma in. 79,83 Sunbed use at any age increases the risk of SCC by 67%, and increases BCC risk by 29%, according the most recent meta-analysis. 84 Risk increases for both types of NMSC in relation sunbed use were also shown in an earlier metaanalysis. 79 Exposure before age 25 appears confer even greater risk increases, though in meta-analysis the effect was significant only for BCC (4% risk increase). 84 Women who used a sunbed more than six s a year during high school increased their BCC risk by 73% in comparison with those who didn t use a sunbed, a US cohort study showed. 85 And both SCC and BCC risk were increased by 15% for every four sunbed sessions a year during high school or at age Using a sunbed without ever burning appears be no safer it can increase the risk of malignant melanoma and early-onset BCC (diagnosed in people under 4 years old) by more than 6%, recent case-control studies have shown. 86, Prevalence of sunbed use In 1999 a quarter of men and a third of women in Britain reported trying get a tan in the previous six months. There were even higher rates amongst younger people. Overall, 2% of adults trying get a tan did so using a sunbed or tanning machine only. 88 In 28 and 29, 6% of year-olds in England reported they had used a sunbed, 89 and in 28, 5% of under-25s in Northern Ireland reported currently using sunbeds. 9 Use of sunbeds by under-18s is now banned across the UK, with legislation passed in 28 in Scotland, and 211 in England, Wales and Northern Ireland. The possibility that younger people and those with highrisk types are at greatest risk of due sunbed use is widely recognised. In 23 the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the World Health Organisation (WHO) recommended that certain categories of people should not use sunbeds (Table 6). 91,92 ICNIRP also concluded that anyone using suntanning appliances is likely raise their risk of, eye damage, phodermasis, phosensitivity and premature ageing. 91 Cancer Research UK recommends that people do not use sunbeds. cruk.org/stats People who have photypes I or II (See Table 7 for definition) Children (i.e. less than 18 years of age) People who have large numbers of naevi (moles) People who tend freckle People who have a hisry of frequent childhood sunburn People who have pre-malignant or malignant lesions People who have sun-damaged People who are wearing cosmetics - these may enhance their sensitivity UV exposure People taking medications which make them UV-sensitive. Categories of people who should not use sunbeds, as recommended by ICNIRP and WHO. 5.3 Skin type, hair and eye colour People with light eyes, or hair, or with that sunburns easily or does not tan, have an increased risk of. 72,75,93,94 These facrs in combination are used define the photype (Table 7). This classification is used in most studies exploring pigmentary characteristics and risk. 93 Table 7: Skin Photypes Photype Typical Features Tanning Ability Type I Type II Type III Type IV Type V Type VI Tends have freckles, red or fair hair, and blue or green eyes. Tends have light hair, and blue or brown eyes. Tends have brown hair and eyes. Tends have dark brown eyes and hair. Naturally black-brown. Often has dark brown eyes and hair. Naturally black-brown. Usually has black-brown eyes and hair. Based on: Fitzpatrick T. Soleil et peau. J Med Esthet 1975;2:33-4. Often burns, rarely tans. Usually burns, somes tans. Somes burns, usually tans. Rarely burns, often tans. In comparison with people with photype IV, those with photype I are at more than double (2.27 s) the malignant melanoma risk, photype II at double (1.99 s) the risk, and photype III at 35% increased risk, a recent metaanalysis reported. 93 In comparison with dark-eyed people, those with blue/bluegrey eyes have a 57% higher malignant melanoma risk, and those with green/grey/hazel eyes have a 51% increased risk. 93

13 2.4 Life risk 5 Risk facrs In comparison with dark-haired people, those with red/redblonde hair were shown be at up triple the malignant melanoma risk. 93,95 Blondes are at double the risk, and people with light brown hair are at 46% increased risk. 93 People with freckles were found have around double (1.99 s) the risk of malignant melanoma, versus people without freckles. 93 People with freckles have increased malignant melanoma risk, regardless of the number of moles they have. 96 People with blue/green-blue/green-grey eyes are at increased risk of BCC. 97 People with red and light-coloured hair are at increased risk of BCC and SCC Moles (naevi) Meta-analyses show people with any unusually shaped or large moles (also called atypical naevi; these are usually larger than common naevi, with a more variegated appearance, poorly-defined border, and some areas slightly raised) have around four ten s increased risk of malignant melanoma, 11,12 and the risk increases with the number of atypical moles. 11 People with very high numbers (1+) of common moles on their bodies have nearly seven s the risk compared people with very few (-15 moles), 11 and every additional common mole increases the risk of malignant melanoma by around 2%. 12 People with dysplastic mole syndrome (also known as Familial Atypical Multiple Mole-Melanoma Syndrome or FAMMM; characterised by multiple atypical moles that continue appear in adulthood) and a family hisry of malignant melanoma have a 5-fold increased risk of developing malignant melanoma; 13 however this is very rare and accounts for less than 5% of malignant melanoma. 11 Most moles are genetically determined (inherited), though sun exposure can increase the number of moles. Most moles appear during childhood. 96,14 The emergence of moles in adolescents is under strong genetic control, a UK study of moles in twins concluded. 15 Chronic sun exposure rather than number of sunburn episodes is the most important environmental facr determining mole development Sunscreen use The impact of sunscreen use on risk remains unclear, due largely methodological limitations. 16,17 Sunscreen should be used gether with clothing and shade protect the from sun damage, and should never be used spend longer in the sun. Research shows sunscreen users may counteract the protective effect of sunscreens by: spending longer in the sun than non-users; applying their sunscreen incorrectly; or failing use protective clothing Vitamin D The only established benefit of exposure solar UV radiation is the synthesis of vitamin D, which is vital for bone health. Higher circulating levels of vitamin D in the blood are associated with lower risk of bowel, although it is unclear whether this is a causal relationship Risk facrs However, sunbathing, tanning or burning should not be necessary make sufficient vitamin D obtain health benefits. In fair-ned people, the taken make enough vitamin D is short, and less than the taken for redden or burn. 117 Once sufficient vitamin D is made, any extra is turned in inactive substances. 118 So more sun exposure does not equate greater health benefits, and excessive exposure solar UV radiation is not a means of reducing the incidence or mortality of. 5.7 Family hisry People with a family hisry of malignant melanoma have roughly double the risk of developing the disease, compared people without a family hisry. 119,12 A small percentage of malignant melanoma (around 1%) are attributable inherited risk. 121,122 FAMMM is one of several rare hereditary syndromes associated with an increased risk of malignant melanoma. 123 FAMMM is associated with the hereditary susceptibility genes CDKN2A and CDK4. CDKN2A mutation carriers often have three or more family members with malignant melanoma, or have multiple primary malignant melanomas with no family hisry. CDKN2A mutation carriers living in Europe have a 58% risk of developing malignant melanoma by age Malignant melanoma and NMSC have been linked Li Fraumeni syndrome in some studies, although they are not among the core s occurring in Li Fraumeni families. 125 People with a family hisry of SCC have an increased risk of SCC. 126 People with a family hisry of malignant melanoma have an increased risk of BCC Previous Previous malignant melanoma is associated with eight- twelve-fold increased risk of a second malignant melanoma The effect is stronger for women. 128,129 People with a previous malignant melanoma and a parent with malignant melanoma are at more than 3-fold risk of a second malignant melanoma. 131 Malignant melanoma risk is higher among people with a previous of various other s, including female breast, 132,133 non-hodgkin lymphoma, 134,135 renal cell carcinoma, 134 certain childhood s, 136,137 prostate, 132,138 thyroid, 132 and leukaemia. 132 Generally the increase in risk was less than double. Often these associations are bi-directional, 128 supporting shared genetic or environmental facrs. Previous SCC is associated with ten s higher risk of a second BCC or SCC, whilst previous BCC is associated with ten s higher risk of second BCC but a lower increase in second SCC risk Previous malignant melanoma is associated with three-fold increased risk of NMSC. 142 People who have had NMSC are also at increased risk of other second primary s Other medical conditions, s and procedures Organ transplant recipients are at 29-fold increased NMSC risk, and two-fold increased malignant melanoma risk, a metaanalysis shows of 2 cruk.org/stats

14 2.4 Life risk 5 Risk facrs This may be related the use of immunosuppressant drugs called azathioprine and cyclosporine, which IARC states are causes of NMSC. 66 People with Crohn's disease have an 8% increased risk of malignant melanoma, and people with ulcerative colitis have a 23% increased risk, a meta-analysis shows. 147 Treatment for these bowel conditions may include immunosuppressant drugs, but the increase in malignant melanoma risk appears be independent of. 147 People with apic dermatitis (the most common form of eczema) appear have an increased risk of NMSC, but the association between apic dermatitis and malignant melanoma remains unclear. 148,149 Contact allergy may reduce the risk of NMSC very slightly. 15 A drug called methoxsalen is used in conjunction with exposure UVA treat eczema, and IARC classifies this as a cause of NMSC. 66 Patients with severe psoriasis may have seven s the NMSC risk of the general population, and eleven s the malignant melanoma risk, a cohort study showed. 151 Malignant melanoma risk is apparently doubled in men with Parkinson s disease, but there is no significant association for women, a meta-analysis showed. 152 A Danish cohort study found a smaller effect (41% increase in men and women combined) with similar magnitude in both sexes. 153 NMSC risk was 29% higher in Parkinson s disease patients in that cohort study, but the meta-analysis found no significant association. 152,153 Rheumaid arthritis patients taking tumour necrosis facr inhibirs (anti-tnf-α) may have increased NMSC risk, but the evidence remains unclear: a meta-analysis of randomised controlled trials found the effect was not significant, 154 but a meta-analysis of observational studies found a 45% higher risk of NMSC. 155 Rheumaid arthritis patients taking anti-tnf-α do not have a higher NMSC risk than patients taking other diseasemodifiying anti-rheumatic drugs, 156 nor does their malignant melanoma risk appear be significantly altered. 155 People with HIV or AIDS have been shown have increased malignant melanoma and NMSC risks; 144 presently IARC states that there is limited evidence that HIV type 1 infection causes NMSC Other risk facrs Taller women appear be at increased risk of malignant melanoma and BCC. One study showed women taller than 5 feet 3 inches were at 28-64% higher BCC risk than shorter women; there was no effect of height for men. 97 Malignant melanoma risk increased by 32%-51% for every 1cm increase in height, according recent large studies. 157,158 Malignant melanoma risk is 31% higher in overweight (body mass index BMI ) and obese (BMI 3+) men, compared with men whose BMI is lower than 25, a metaanalysis reported. 159 This analysis showed the risk appears plateau in overweight men rather than continuing increase with higher BMI, 159 however a previous meta-analysis found a 17% risk increase per 5-unit BMI increment. 16 Risk facrs Case-control studies show that women with higher BMI or body surface area have an increased malignant melanoma risk, when results are adjusted for the amount of sun exposure, suggesting mutual confounding between body size and sun exposure (e.g. larger women self-limit their public sun exposure). 15ever, most studies have not adjusted for amount of sun exposure and have not found an association between overweight and malignant melanoma risk in women Obesity is associated with decreased NMSC risk, perhaps due less UV exposure in larger people. 162,163 Women with BMI lower than 25kg/m2 were at 26-43% higher BCC risk and 2-41% higher SCC risk than women with a higher BMI, US cohort studies have shown. 97,162 For men in these analyses, the difference in BCC risk was only significant for people with BMI versus BMI under 25, and there was no significant effect of BMI on SCC risk. 97,162 Babies with a higher birthweight have a higher risk of early-onset malignant melanoma, a Northern Ireland cohort study showed; those weighing 4.5-6kg at birth had more than twice the malignant melanoma risk compared with those weighing 3-3.5kg at birth. 164 There is sufficient evidence that X-radiation and gamma radiation (both types of ionising radiation) cause NMSC, according IARC. 66 Radiotherapy for a previous is estimated have caused 17.9% of second primary malignant melanoma in women and 2.8% of second primary malignant melanoma in men in Exposure cosmic radiation has been posited as an explanation for the higher rates of malignant melanoma in airline staff, but recent evidence suggests that excessive UV exposure and sunsensitive phenotypes are more likely causes. 166,167 People who receive at least one computed mography (CT) scan of the brain before age 2 have a 14% higher risk of malignant melanoma or NMSC, with no significant effect of CT scans other anamical sites, a large Australian cohort study showed. 168 Some chemical exposures that can take place in certain occupations cause NMSC, IARC states. 66 These include coal tar pitch, soot, mineral oils and shale oils. It has been estimated that around 7% of NMSCs in men and around 1% in women in Britain are due occupational exposures (including solar radiation). 169 People diagnosed with genital warts (associated with infection with HPV types 6 and 11) have a 3% increased risk of BCC Facrs shown have no effect on risk Use of oral contraceptives (OCs) or hormone replacement therapy (HRT) does not significantly impact on malignant melanoma risk in women, a meta-analysis shows. 171 Other reproductive facrs (age at birth of first child, number of children) show small effects on malignant melanoma risk, though these effects are largely explained by socio-economic facrs. 171 SCC risk increased by 35% for every five years of HRT use in a cohort study, and BCC risk was 15% higher in women who had ever used HRT compared those who had never used it. 172 OC use did not impact on BCC or SCC risk in this cohort study of 2 cruk.org/stats

15 Risk facrs Diagnosis and 2.4 Life risk 5 Risk facrs 15 of 2 Unlike for many other s, smoking does not appear increase malignant melanoma risk. 66,173 The relationship between smoking and NMSC risk remains unclear, with effects apparently varying by NMSC type, and patient sex. 173,174 Alcohol consumption does not appear increase malignant melanoma or NMSC risk overall. 66,175 Non-steroidal anti-inflammary drugs (NSAIDs) appear not affect malignant melanoma risk, meta-analyses show. 176,177 Case-control studies indicate aspirin may slightly reduce malignant melanoma risk, but no effect is seen in cohort studies and because of the potential adverse consequences of high intake of aspirin, such as gastrointestinal haemorrhage, it would not be recommended as a prophylactic measure. 176,177 6 DIAGNOSIS AND TREATMENT 6.1 How is diagnosed In in England, 68% of malignant melanoma patients were diagnosed having been seen by a specialist as a result of a GP referral (Figure 19). 181 These were either two week wait referrals (41%), or routine or urgent referrals where the patient was not referred under the two-week wait route (27%). 181 Just 3% of malignant melanoma patients were diagnosed after presenting as an emergency: either via the Accident & Emergency department; other emergency hospital admission, attendance or transfer; or emergency GP/ consultant referral. 181 Figure 19: Malignant Melanoma Routes Diagnosis Two-week wait GP referral Other outpatients Impatient elective Emergency presentation Death certificate only Screen detected Unknown Percentage of Patients % 25% 5% 75% 1% Malignant melanoma (C43), routes, persons, England, Screen detected: Flagged by registry as detected via breast or cervical screening programme. Two Week Wait: Urgent GP referrals with a suspicion of. GP/outpatient referral: Routine and urgent referrals where the patient was not referred under the Two Week Wait referral route. Other outpatient: An elective route starting with an outpatient appointment that is either a consultant consultant referral, other referral, self-referral, dental referral or unknown referral. Inpatient elective: Where no earlier information can be found prior admission from a waiting list, booked or planned. Emergency presentation: An emergency route via A&E, emergency GP referral, emergency consultant outpatient referral, emergency transfer, emergency admission or attendance. Death certificate only: Diagnosis by death certificate only. Unknown: No data available from inpatient or outpatient HES or from waiting s or screening. The National Institute for Health and Clinical Excellence Improving Outcomes Guidance (NICE IOG) for states that patients who present primary care with a possible ous lesion should either be treated by a sufficiently-qualified GP (in the case of low-risk BCC or in situ SCC) or referred a specialist (in the case of SCC or malignant melanoma). 182,183 cruk.org/stats Low-fat diet does not appear affect malignant melanoma risk in women, a US cohort study showed. 178 Folic acid supplements were shown have no effect on malignant melanoma risk in the largest meta-analysis date, 179 Vitamin A and carotenoids intake did not affect malignant melanoma risk in a large cohort study. 18 In the 211/12 Cancer Patient Experience Survey, 89% of malignant melanoma patients reported having seen their GP about the health problem caused by no more than twice before being referred hospital. 184 In 211/12 in England, 95% of patients with a two-week wait GP referral for suspected (excluding BCC) were seen by a specialist within two weeks (14 days) of referral. 185 The majority of men and women diagnosed with malignant melanoma present at stage I (see Section 2.6). Sentinel lymph node biopsy is considered by many specialists be a useful staging ol in melanoma, but less than 1% of malignant melanoma in in England had this procedure, it is estimated Key s Malignant melanoma The first-line for malignant melanoma is surgery (wide local excision), the NICE IOG states. 182,183 Radiotherapy can be used with curative intent for melanoma in situ or palliatively (often alongside chemotherapy) for metastatic malignant melanoma. Some patients may receive supportive care and observation only. 182 In the 211/12 Cancer Patient Experience Survey, 86% of malignant melanoma patients said they were given a choice of different types of, and 76% felt their views were definitely taken in account by the team discussing their Non-melanoma Surgical removal is also the first-line for NMSC, though other surgical and non-surgical techniques may be used instead of, or alongside, including: cautery or electrodessication (electrical or chemical burning of the tumour); cryotherapy/cryosurgery (freezing of the tumour using liquid nitrogen); pical (applying a cream such as Imiquimod or Fluorouracil); phodynamic therapy (PDT, using light therapy in combination with a phosensitising cream destroy cells); and radiotherapy (often using superficial X-ray machines, though linear accelerar s are becoming more common). 182,183

16 6.3 Clinical trials Diagnosis and Acknowledgements 2.4 Life risk 5 Risk facrs In 211/12, 19 trials in the National Institute for Health Research portfolio were open and recruiting in the UK: 13 for melanoma (all types), 5 for NMSC, and 1 for all s. 187 There were also 9 funded trials in the process of being set up: 7 for melanoma, 1 for NMSC, and 1 for all s. 187 Most of these trials focused on first- or second-line s, and include a trial looking at nilotinib treat acral and mucosal melanoma that has spread (NICAM), and a study looking at high blood pressure and pazopanib (HYPAZ). It is difficult calculate the exact proportion of patients participating in trials, because under-registration of 7 THE FUTURE Skin patients day generally have a much better prognosis compared with those diagnosed in previous decades, thanks increased awareness, earlier, and advances in. But much more can be done. Skin is essentially an avoidable disease. Prevention is either primary (through reducing exposure UV radiation) or secondary (by earlier ). At the forefront of prevention efforts in is SunSmart, a national prevention campaign. 19 Launched by Cancer Research UK in 23, SunSmart is a public health campaign made up of four key elements: research, public communication, professional support and policy development. It aims improve knowledge, attitudes, and behaviour around preventing overexposure UV and/or sunburn, as well as promoting the benefits of early. Children, teenagers and young adults, and men are particularly important audiences for the campaign. Other public health organisations and charities promoting sun safety include the British Association of Dermalogists, Skcin and the Teenage Cancer Trust There are also numerous local initiatives in, 194 though one survey in England showed these are often a low priority work area with ad-hoc (usually seasonal) activity rather than sustained intervention. 195 This issue needs be addressed, since evidence from Australia suggests long-term commitment and adequate resources for prevention programmes are required improve outcomes. 196,197 NMSC means the tal number of eligible patients is unclear; however, it is likely that recruitment of patients trials is lower than in trials for in general. In 21/11 up 4% of eligible patients were entered in an NIHR randomised controlled trial (RCT), and up 6% were entered in a non-rct trial. 188 In contrast, in 211/12, an estimated 23.1% of UK patients across all tumour sites participated in an NCRI portfolio clinical trial. 189 The 211/12 Cancer Patient Experience Survey found that taking part in clinical trials was discussed with 27% of patients. 184 Sunbed use, particularly in young people, is a completely avoidable risk facr. In in England, 6% of year olds said they had used a sunbed, and in 28 in Northern Ireland, 5% of under-25s in Northern Ireland reported currently using sunbeds. 89,198 Cancer Research UK has campaigned for ugher legislation on sunbed use by children and adolescents, and since 28 in Scotland, and 211 in England, Wales and Northern Ireland, it has been illegal for under-18s use sunbeds There is now some evidence suggest teenagers sunbed use is decreasing. 22 It is o early see the effects of the legislation on the incidence of in, but this should be seen in the coming years. As well as concentrating efforts on early and prevention of, better s and improved quality of care are also urgently needed. 2 from malignant melanoma is consistently lower in men than women across all age groups, and is especially low in elderly men. 36 Improving the and of older patients, and men in particular, is an ongoing challenge. Late stage disease also remains very difficult treat, and this will be a major focus of research in the future. 8 ACKNOWLEDGEMENTS We would like acknowledge the essential work of the National Cancer Registration Service (part of Public Health England) and the Office for National in England, and the registries in Wales, Scotland and Northern Ireland. Population-based data has been collected in most regions of since the early 196s, and without this registration system there would be no incidence or statistics. Cite this report as Cancer Research UK (213). Cancer Report: Skin Cancer. 16 of 2 cruk.org/stats

17 2.4 Life risk 5 Risk facrs 17 of 2 cruk.org/stats How 9 HOW INFORMATION ON IS RECORDED IN THE UK The UK is widely acknowledged as having one of the most comprehensive registration systems in the world, with population-based data being collected in most regions of since the early 196s. 24 From April 213, the recording of incidence and data in England has been co-ordinated by the National Cancer Registration Service, which is part of Public Health England (an executive agency of the Department of Health). There are eight regional registration offices, with the statistics for England as a whole being collated by the Office for National. 1 Wales, Scotland and Northern Ireland each have one national registry. 2-4 Cancer registration data are collected according a common minimum dataset, which includes hospital details, personal details (such as name, sex, date of birth, NHS number and postcode), diagnostic and tumour details (such as location of the tumour in the body, and for some sites the tumour s stage of advancement at ), and death details (where relevant). Information is obtained on a voluntary basis from a wide variety of sources including hospitals, pathology laboraries, centres, centres, hospices, private hospitals, screening programmes, other registers, general practices, nursing homes, death certificates, Hospital Episode (HES) and Cancer Waiting Time (CWT) data. Most registration systems currently record tumours using the International Classification of Diseases tenth revision 1. Data were provided by the Office for National on request, June 212. Similar data can be found here: ewquery=+registrations 2. Data were provided by ISD Scotland on request, April 212. Similar data can be found here: org/health-topics/cancer/publications/ index.asp 3. Data were provided by the Welsh Cancer Intelligence and Surveillance Unit on request, April 212. Similar data can be found here: sites3/page.cfm?orgid=242&pid= Data were provided by the Northern Ireland Cancer Registry on request, June 212. Similar data can be found here: nicr/cancerdata/online/ 5. Quinn M, Wood H, Cooper N, Rowan S, eds., Cancer Atlas of the United Kingdom and Ireland Studies on Medical and Population Subjects No. 68. London: ONS; NCIN. Cancer Incidence and Mortality by Cancer Network, UK, 25. London: NCIN; NCIN. Cancer e-atlas. European Age-Standardised Mortality Rates, UK (England: former Primary Care Trusts: Wales; Scotland: NHS Health Boards; Northen Ireland: Health and Social Care Trusts), Dennis LK. Analysis of the melanoma epidemic, both apparent and real: data from the 1973 through 1994 surveillance, epidemiology, and end results program registry. Arch Dermal 1999;135(3): de Vries, E. and J. Willem Coebergh., Cutaneous malignant melanoma in Europe. Eur J Cancer 24;4(16): de Vries, E. and J.W. Coebergh., Melanoma incidence has risen in Europe BMJ 25; 331(7518): Office for National Travel Trends 25. A report on the International Passenger Survey. London: ONS; Parkin DM, Mesher D, Sasieni P. Cancers attributable solar (ultraviolet) radiation exposure in in 21. Brit J Cancer 211;15 (S2):S66-S Life risk was calculated by the Statistical Information Team at Cancer Research UK, Sasieni PD, Sheln J, Ormisn- Smith N, et al. What is the life risk of developing?: The effect of adjusting for multiple primaries. Brit J Cancer 211;15(3): Department of Health. Improving outcomes: a strategy for. London: DoH; The National Cancer Registration Service, Eastern Office. Personal communication. 17. National Cancer Intelligence Network (NCIN). Mortality, Incidence and gender - Malignant Melanoma. London: NCIN; Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of burden of in 28: GLOBOCAN 28. Int J Cancer 21;127: Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 28 v1.2. Cancer Incidence and Mortality Worldwide: IARC Cancerbase No.1 [Internet]. Lyon, France: International Agency for Research on Cancer; 21. Available from: Accessed May IARC. World Cancer Report 28. Lyon: IARC; Armstrong BK, Kricker A. How much melanoma is caused by sun exposure? Melanoma Res 1993;3(6): European Age-Standardised rates calculated by the Statistical Information Team at Cancer Research UK, 211 using data from GLOBOCAN 28 v1.2, IARC, version (ICD-1), which assigns codes largely based on pography (location in the body) and behaviour (malignant, in situ, benign, or unknown/uncertain). 25 The ICD-1 codes for malignant melanoma and NMSC are C43 and C44, respectively. Melanomas can also occur in other body organs, such as the eye, but these data are not shown here. In this report the term malignant melanoma refers malignant melanoma of the only. The recording of NMSC at registries is known be incomplete. 28,26 Many registries record only the first NMSC of each hislogical type (e.g. BCC or SCC) per person, and small NMSCs treated in primary care or the private secr may never reach the registries. 29 An estimated 3-5% of BCC and around 3% of SCC goes unrecorded, though this may vary by registry Efforts improve the recording of NMSC are ongoing. 26 Cancer mortality statistics are derived from statury death registrations in England and Wales, Scotland and Northern Ireland Data are reported in ICD-1 according the underlying cause of death, which is determined using information collected on the death certificate. g g Death certificates are set out in two parts: part I records the immediate cause of death and any associated conditions leading up the death; part II records details of any other conditions which contributed the death (but were not part of the main sequence of events leading up it). 23. National Cancer Intelligence Network (NCIN). Cancer incidence by deprivation England, London: NCIN; ISD Scotland. Cancer. Skin Cancer. Accessed June Welsh Cancer Intelligence and Surveillance Unit. Cancer in Wales, : A Comprehensive Report. Cardiff: WCISU; Donnelly, DW, Gavin, AT, Comber H. Cancer in Ireland : A comprehensive report (PDF 7.77MB) Northern Ireland Cancer Registry/National Cancer Registry: Ireland; National Cancer Intelligence Network (NCIN). One, Five and Ten Year Cancer Prevalence by Cancer Network UK, 26 London: NCIN; National Cancer Intelligence Network (NCIN). Non-melanoma in England, Scotland, Northern Ireland, and Ireland. London: NCIN; National Cancer Intelligence Network (NCIN). Rare Skin Cancer in England. London: NCIN; Brewster DH, Bhatti LA, Inglis JH, Nairn ER, Doherty VR. Recent trends in incidence of non-melanoma in the East of Scotland, Brit J Dermal 27;156: de Vries E, Micallef R, Brewster DH, et al. Population-based estimates of the occurrence of multiple vs. first primary basal cell carcinomas in 4 European regions. Arch Dermal 212;148(3): Poirier V, Ives A, Hounsome L, et al. The Role of the South West Public Health Observary as the Lead Cancer Registry for Skin Cancer. Poster presented at The British Association of Dermalogists Non- Melanoma Skin Cancer Update Meeting, London, February South West Public Health Observary. Non-Melanoma Skin Cancer: Estimates of. Brisl: South West Public Health Observary; 21. REFERENCES 34. Madan V, Lear JT, Szeimies RM. Non-melanoma. Lancet 21;375(9715): Miller SJ, Alam M, Andersen J et al. Basal cell and squamous cell s J Natl Compr Canc Netw 21;8(8): Office for National (ONS). Cancer in England: Patients diagnosed and followed up 21. London: ONS; Ten-year predicted estimates were provided by the Cancer Research UK Cancer Survival Group, London School of Hygiene and Tropical Medicine on request, December Welsh Cancer Intelligence and Surveillance Unit (WCISU). Cancer Survival Trends in Wales Cardiff: WCISU; Information Services Division Scotland (ISD Scotland). Cancer. Malignant melanoma of the. Accessed September Northern Ireland Cancer Registry (NICR). Cancer Survival Online. Malignant melanoma. Accessed September MacKie RM, Bray CA, Hole DJ, et al. Incidence of and from malignant melanoma in Scotland: an epidemiological study. Lancet 22;36: National Cancer Intelligence Network. Mortality, Incidence and Gender: Malignant Melanoma - NCIN Data Briefing. London: NCIN; Department of Health. Improving outcomes: a strategy for. London: Department of Health; 211.

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20 CANCER RESEARCH UK CANCER STATISTICS Written for health professionals, we provide statistics for and around the world. We have data for more than 3 common s including: Incidence, and mortality stats Variation by age, ethnicity and socio-economic group Prevalence and life risk estimates Risk facrs evidence Treatment, screening and clinical trials stats Over 65 charts, tables, PowerPoint slides, reports, briefings and Key Facts publications give p-line stats or in-depth analyses and interpretation about statistics in and around the world, and are all free download. cruk.org/stats [email protected] 2 of 2