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- Material and Methods
This study investigated time trends and latitude differentials in the thickness distributions of invasive melanomas diagnosed in Australia between 1990 and 2006 using data from population-based cancer registries. Trends in incidence rates were calculated by sex, age group, thickness, year at diagnosis and latitude. For thin (<1.00mm) melanomas the increase was very pronounced during the early 1990s (1990–1996, annual percentage change and 95% confidence interval: males +5.6(+3.5,+7.7); females +4.1(+1.7,+6.5), but then incidence rates became stable among both males (+0.6(−0.1,+1.4)) and females (−0.0(−0.9,+0.9)) of all ages between 1996 and 2006. In contrast, incidence of thick (>4.00 mm) melanomas continued to increase over the entire period (males +2.6(+1.9,+3.4); females +1.6(+0.6,+2.6)). Recent reductions in the incidence of thin melanomas were observed among young (<50 years) males and females, contrasted by an increase in thin melanomas among older people, and increases in thick melanomas among most age groups for males and elderly (75+) females. A strong latitude gradient in incidence rates was observed, with rates being highest in northern, more tropical areas and lowest in the most southern regions. However, the magnitude of the increase in thick melanomas was most pronounced in southern parts of Australia. The observed trends in thin melanomas can most likely be attributed to the impact of early detection and skin awareness campaigns. However, these efforts have not impacted on the continued increase in the incidence of thick melanomas, although some increase may be due to earlier detection of metastasising melanomas. This highlights the need for continued vigilance in early detection processes.
With its high rates of ultraviolet radiation, outdoor lifestyle and predominately Caucasian population, Australia continues to have the highest incidence rates of cutaneous melanoma in the world, with an estimated age-standardised incidence rate (World 2000 population) of 40.2 cases per 100,000 population in 2008, similar to New Zealand (40.1).1, 2 Rates in other countries are substantially lower, with Switzerland (20.8), Denmark (19.9) and Norway (19.1) on the second tier of melanoma risk, and the USA (15.6), UK (11.6) and Germany (13.2) having lower incidence rates.1, 2 While melanoma has been the most rapidly increasing cancer among fair-skinned populations worldwide,3 studies from Europe, Canada, the United States and Australia have reported slowing or stabilizing rates of increase in incidence rates starting from the mid-1980s onwards.3–7 Much of the observed increase in melanoma incidence has been in thinner melanomas, with the incidence rates for thicker melanomas either increasing at a reduced rate or stabilizing.4, 6, 8, 9 With the strong association between tumour thickness and survival,8, 10–13 any increase in the incidence of thick melanomas has important implications for the mortality burden caused by melanoma.
Although other Australian studies have reported patterns of melanoma incidence over time by thickness4, 6, 8, 9 these have all been state-specific and have used varying analytical and reporting methods. To our knowledge, national trends on melanoma incidence by thickness have not been previously reported. In addition, the pooling of state-specific incidence data enables us to directly examine the association between incidence trends and geographical latitude, as has been recently reported for Norway.14
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- Material and Methods
This large study, utilising data from almost 140,000 Australians diagnosed with melanoma, demonstrated that the previously sharp rate of increase in thin melanomas has plateaued. However, rates of thick melanoma have continued to increase among both males and females, particularly in areas of higher latitude.
In contrast to these national results, a recent Queensland study4 examining trends between 1991 and 2002 found no evidence to suggest that the increasing trends for thin melanomas were levelling off. Similarly, ongoing increasing trends have been reported previously in the United Kingdom (1993–2003),8, 19 the United States (1988–1994),20 New South Wales (1989–1996)6 and (1993–2003),8 Puerto Rico (1987–2002),21 Southern Germany (1976–2003),22 and Northern Ireland (1984–2006).23 However the short time periods and analytical methods used in some of these studies may not have allowed changes in trends to be detected.
It has been suggested that widespread increases in thin melanomas during the 1990s were predominately due to heightened levels of melanoma awareness and improved early detection, rather than a real increase in the underlying melanoma incidence.4, 24 The recent levelling off of this increase observed in the Australian context is consistent with this hypothesis—improved detection leads to an initial large increase in the incidence of early disease after which incidence rates plateau, albeit at a higher level than previously, as the pool of undetected lesions diminishes.25, 26 It remains to be seen whether this stabilization in the incidence of thin melanomas continues, or even whether incidence trends will eventually start to decrease across the whole population.
To the extent that the apparent increased detection of thin melanomas observed here is explained by earlier diagnosis (as opposed to over-diagnosis of non-progressive lesions), it would be expected to be followed in time by a reduced incidence of thick melanomas. These Australian results suggest the opposite has occurred. That is, the improvements in early diagnostic methods have not been sufficient to counter an increase in the incidence in the underlying incidence of thicker tumours. One explanation is that some tumours grow rapidly and are thus less likely to be detected before they become thick. Therefore advances in early detection activities such as skin screening may be less likely to have an impact on the incidence rates of these types of tumours.27
Increased tumour thickness has been consistently shown to be the strongest predictor of poorer survival prognosis, both internationally8, 10–13 and in Australia.28–30 When combined with the limited effectiveness of treatment for thick melanomas,31 it would be expected that any trends in thick melanomas, after allowing for some lead time, would be reflected in melanoma mortality outcomes. Therefore, the consistently increasing incidence of thick melanomas observed in this study should be accompanied by increasing mortality rates of melanoma. This has not been observed. A previous study reporting on Australian melanoma mortality rates since 1950, found that, following consistent increases, melanoma mortality rates stabilized among males between 1989 and 2002 and decreased among females.31 Additional analyses (results not shown) suggest these patterns have continued up to 2006.
One possible explanation is that trends in the proportion (9%) of melanomas with unknown thickness, nearly twice as common as thick melanomas (5%), could compromise the reported trends in thick melanomas, particularly since the percentage of melanomas with unknown thickness has decreased over time, from 12% in 1990 to 8% in 2006. Reductions in the percentage of melanomas with unknown thickness have also been reported in the United States.24 Although we were unable to obtain national data, unpublished data from the Queensland Cancer Registry showed that over well over half (60%) of the melanomas with unknown thickness were diagnosed on the basis of histology of metastasis. If previously metastasising melanomas are now being detected earlier, most likely as thick melanomas, then this would increase the number of thick melanomas being detected, and hence directly impact on observed incidence trends by thickness. However the relationship between thick melanomas and melanomas with unknown thickness is not consistent by latitude; the rates of thick melanomas have increased in each of the 3 regions whereas the rates of melanomas with unknown thickness has either decreased (Northern), remained stable (Central) or increased (Southern). Also the trends in melanomas of unknown thickness are highly variable, suggesting against a consistent improvement in detection practices. Therefore the possible implications of changes in the rates of melanomas with unknown thickness on the observed incidence trends by thickness can only be speculative. Although some of the observed increase in thick melanomas may be due to improved detection of previously metastasising melanomas, it would be presumptuous to suggest that a real increase has not occurred. Clearly further investigation is required.
Our finding that the incidence of thin melanoma is decreasing among younger people is promising. The importance of early life sun exposure and the generally long latency period for the development of melanoma is well established.32 Public primary prevention campaigns directed at reducing sun exposure have been ongoing in Australia since the early 1980s.4, 33 The observed reduction in thin melanomas in younger age groups, and a similar stabilising of rates of non-melanoma skin cancer,34 could lend cautious support to the success of these campaigns, particularly if these lower rates continue into the future.4, 34, 35
As suggested by others,24 the current analysis highlights a need for new early detection strategies to be developed, particularly for segments of the population previously shown to be at higher risk of thick melanomas, including men, older people and those with low education.36 These strategies should include identification of the clinical features of melanomas that are more likely to have a rapid growth phase, and encouraging regular clinical skin examinations among high risk individuals. A recent case-control study of melanoma screening demonstrated that having a whole-body clinical skin examination in the 3 years prior to a diagnosis of melanoma was associated with a 40% reduction in the incidence of melanoma ≥3.00mm thick.37 Therefore, more research is needed to understand differences in the development between thin and thick melanoma which would then allow specific targeting of the various underlying factors in future public health campaigns.
We found a strong association between melanoma incidence and latitude, with overall incidence risks being significantly lower in the Central and Southern regions compared with the Northern region. A similar pattern was observed for thin melanomas, but for thick melanomas there was only a significant differential between the Southern and Northern regions. We also found strong evidence that the changes in incidence over time varied by latitude, with the increase in incidence of thick melanomas over time particularly pronounced in Southern states. Reasons for this differential increase are unclear. The authors of a European study38 suggested possible reasons for an observed differential in the incidence of thick melanoma by latitude were variations in overall awareness of melanoma and frequency of campaigns aimed at early detection. However, it is unlikely that factors such as lower prevalence of melanoma, impacting on clinical diagnostic abilities,39 or lower community awareness of melanoma, are explanations for the observed Australian trends. Per capita expenditure on sun protection programs is reportedly much higher in Victoria (Southern region) than Queensland (Northern region),40 however the increased incidence of non-melanoma skin cancer in Northern Australia34 may indirectly increase awareness through greater utilisation of doctors for treatment.
The strengths of this study include the use of data from population-based cancer registries providing a complete enumeration of all Australians diagnosed with invasive melanoma between 1990 and 2006, including information about melanoma thickness at diagnosis. All information used in this study has been collected prospectively for administrative purposes independently of the study hypotheses, thus removing recall or information bias. In contrast to other research studies that have considered constant linear changes over their entire study period, the use of Joinpoint regression enabled us to detect changes in the magnitude and direction of trends over time. Since the selection of joinpoints can be influenced by random fluctuations in rates, particularly those at the end points, we chose conservative parameters to reduce the chance of detecting spurious changes in trends. We were unable to obtain region-specific data by calendar year due to confidentiality restrictions, so the aggregating of incidence data across year groups may have influenced our ability to recognise trends over time by latitude.
There are encouraging trends in the incidence of thin melanomas; however, the continued increase in the incidence of thick melanomas, more pronounced in regions of high latitude, is cause for concern. Although improvements in early detection could mean that some melanomas that may previously have metastasised are now being diagnosed as thick melanomas, there is still a strong need to develop new early detection strategies, ideally with an emphasis on those groups known to have greater risk of being diagnosed with thick melanomas, to improve the efficacy of detecting melanoma early and address this increasing trend of thick melanomas.