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Abstract

Up-to-date melanoma relative survival (RS) estimates and trend analysis facilitate close monitoring of melanoma patients' prognosis. This study aimed to provide recent 5-year and 10-year RS from melanoma, stratified by prognostic factors, and identify latest survival trends. Data from 12 German cancer registries were analysed. We included patients with primary cutaneous malignant melanoma (ICD-10: C43.X) diagnosed in 1997-2013 who were at least 15 years old. Five-year and 10-year RS were estimated by period analysis. For 10-year RS analyses, we excluded patients who were 75 years of age or older. Analyses were stratified by sex, age, histology, tumour stage, and body site. We included 82 901 patients, of whom 51% were women. The median age at diagnosis was 62 years. Five-year and 10-year RS in 2007-2013 were 92.4 and 90.8%, respectively. RS was higher in women. The prognosis worsened with older age and higher stage. In superficial spreading melanoma and lentigo maligna melanoma, RS was high; it was lower in nodular, acral lentiginous and 'other' melanoma. RS was the highest for melanoma on the arms; RS for melanoma on unknown or overlapping sites of the skin was the lowest. Five-year and 10-year RS increased significantly from 2005-2007 and 2008-2010 to 2011-2013, by 3.5 and 3.3 percentage points, respectively. For melanoma of 'other' histology, 5-year and 10-year RS increased significantly. Ten-year RS also increased significantly in men with superficial spreading melanoma and T4 melanoma, and in women with T3 melanoma. Melanoma RS improved, especially in certain subgroups. The reasons for improvements need to be investigated further.

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... Nevertheless, the Asian population has a notably lower risk of MM than Caucasians due to ethnic differences, anatomic distribution, histologic subtypes, and stage at diagnosis [6,7]. Interestingly, Ultraviolet (UV) radiation, race, lifestyle, and genetic differences are the most important reasons for the high mortality rate of melanoma which can be decreased via early-stage detection and prevention [8][9][10][11][12][13]. Dermoscopy and intrinsic molecular subtyping of melanoma have been widely accepted as accurate diagnostic methods with more than 50% accuracy compared with the clinical diagnosis in patients with MM [14,15]. ...
... Interestingly, our results propose VM status as a more promising, accurate biomarker and target for MM diagnosis and therapeutics in Asian patients than in Caucasian patients, with a pooled sensitivity of 91% and specificity of 70.5% vs. Lifestyle factors such as UV radiation exposure and nutrition are synergistically contributing to the prevalence of MM [61,62]. Compared to Caucasians, Asian MM patients are diagnosed at older ages; hence, in Asia we face a large population of old MM patients [4,12]. But considering that our study was limited to a small sample size of cases in the Caucasian group (475 cases), more large-sized studies among the Caucasian MM population should be performed to obtain a comprehensive result [61]. ...
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Background: Vasculogenic mimicry (VM) a microvascular system consisting of non-endothelial cells that is newly formed by aggressive tumors, has been proposed as an important therapeutic target in malignant melanoma (MM). We performed a systematic literature review to evaluate the diagnostic and prognostic accuracy of VM status for overall survival of MM patients. Methods: The quality of the included studies was evaluated using the QUADAS-2 tool. Diagnostic capacity of VM variables, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under summary receiver operating characteristic (SROC), were pooled using Meta-DiSc software. Results: A retrospective observational study was conducted based on twelve clinical studies including 978 clinically confirmed melanoma patients with proportion (P). VM+ melanoma cells were associated with poor prognosis in 38% of MM group (P = 0.35, 95% confidence intervals (CI): 0.27-0.42, p < 0.001). The pooled sensitivity and specificity were 0.82 (95% CI: 0.79-0.84) and 0.69 (95% CI: 0.66-0.71), respectively. Furthermore, the pooled PLR, NLR, and DOR were 2.56 (95% CI: 1.94-3.93), 0.17 (95% CI: 0.07-0.42), and 17.75 (95% CI: 5.30-59.44), respectively. Furthermore, the AUC of SROC was 0.63, indicating high reliability of VM status as a biomarker. Importantly, subgroup results suggested that VM+ status is a significantly accurate prognostic biomarker when diagnosed by the CD31-/PAS+ staining methods in Asian MM samples (p < 0.001). Conclusions: Our findings support the potential of VM status of tumors as a promising prognostic biomarker and emphasize an effective adjuvant therapeutic strategy in the prognosis of Asian MM patients.
... 1,2 Once melanoma has spread into the lymph nodes, or even visceral organs and the brain, it remains a life-threatening disease despite the advent of molecular targeted or immunotherapies. 1,2 Melanoma of unknown primary (MUP) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] represents an unusual subtype of melanoma which was reported to be about 2-9% of melanoma of known primary (MKP) at all stages. 3 Some of the literature in the different geographic regions demonstrated better overall survival of MUP than of MKP. 15 Other publications, however, reported an equal or even worse clinical outcome for patients with MUP when compared to MKP with comparable stage of disease. ...
... 3 Some of the literature in the different geographic regions demonstrated better overall survival of MUP than of MKP. 15 Other publications, however, reported an equal or even worse clinical outcome for patients with MUP when compared to MKP with comparable stage of disease. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Hence, the prognosis of patients with MUP compared to MKP patients is still unclear and likely depends on the clinical scenario investigated. A 5-year overall survival rate of MUP before the era of the immune checkpoint inhibitor was reported to range from 8% to 18% with the most common metastatic sites in lymph nodes and gastrointestinal tract. ...
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Background: Melanoma of unknown primary (MUP) is an uncommon clinical subtype of melanoma of known primary (MKP). Objectives: We aimed to compare treatment outcomes of MUP and MKP patients who had undergone therapy with immune checkpoint inhibitors (ICPI). Methods: We studied 41 metastatic melanoma patients (32 with MKP and 9 with MUP) with an indication for ICPI. Results: Clinical characteristics such as age, gender, stage of disease, etc., did not significantly differ (P < .05) between MUP and MKP patients. 20/32 (62.5%) melanoma-specific deaths (MSD) were observed in the MKP group, whereas 2/9 (22.2%) were detected in the MUP group (P = .035). On logistic regression, the MUP status proved to be an independent predictor for a more favorable outcome under immunotherapy when compared to MKP (P = .030). Conclusion: Our preliminary results indicate that MUP patients show better clinical outcome under ICPI when compared to MKP.
... [20][21][22] A negative correlation between survival and age has also been reported in other studies and is associated with more aggressive tumors caused by a decline in the ability of the immune system. 23,24 Our data show that among the pathological subtypes, the superficial spreading subtype has the best prognosis. This may be due to its superficial spreading growth characteristics, which are less likely to reach skin vessels and lymph nodes. ...
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Background and objectives: Surgery is an essential treatment for non-distant metastatic cutaneous melanoma (NMCM). We aim to construct and validate prognostic nomograms based on surgical approaches and the clinicopathological characteristics of NMCM patients. Methods: Data of patients diagnosed with cutaneous melanoma from 2004 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Two online nomograms were constructed to predict the 3, 5-year melanoma-specific survival (MSS) for NMCM patients based on the surgical approaches. These nomograms were evaluated by the dynamic Harrell's concordance index (C-index), decision curve analysis and clinical impact curve. Both internal and external data verification were conducted. Results: A total of 14,091 NMCM cases were included in this study. The C-index of the nomograms for the excisional surgery group and amputation group were 0.818 and 0.806, respectively, and 0.763 and 0.731, respectively, in our hospital data validation. After internal and bootstrap verification, our two nomograms showed good accuracy and practicality. Conclusion: NMCM patients exhibited equal survival rates independent of resection margin size, while those who needed amputation had worse survival rates. We generated two online nomograms distinguished by surgical approach to predict NMCM patient survival based on clinicopathological characteristics.
... This reduction of relative survival for South Australian males between 1997 and 2001 (90%) and 2007-2011 (85%) appears to be most pronounced in those aged 75 + , those living in the least disadvantaged SEIFA quintiles and for those with a Breslow thickness above 4 millimeters. This decrease in relative survival is a cause for concern when compared with stable or increasing relative survival over time in other jurisdictions and countries [34][35][36] although similar results were found in the Netherlands between 2000 and 2014 where survival increased for females but reduced for men [37]. ...
Article
Given the high incidence of melanoma in Australia alongside high mortality with later stage disease, we investigated the populations and locations most at risk, to optimise public health activities in areas where intervention is most needed. This study examines trends and identifies significant prognostic factors and potential disparities in incidence, mortality and survival between population groups in Victoria, Queensland and South Australia.
... Melanoma is a heterogeneous tumor that can be classified into four major subtypes: superficial spreading melanoma (SSM, frequency 41-57%), nodular melanoma (NM, 14-17%), lentigo maligna melanoma (6-14%), and acral lentiginous melanoma (1-7%) (5)(6)(7)(8). NM represents a considerable proportion of thicker and ultimately fatal melanomas (9) and exhibits aggressive clinicopathological features considered as proxies of increased Breslow thickness, such as ulceration, rapid growth rate, and increased mitotic rate (MR) (6,(10)(11)(12). ...
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Background: Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness. Methods: Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided. Results: In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis). Conclusions: T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.
Article
The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the 4 American Joint Committee on Cancer 8th edition T categories by analyzing Australian registry data for 210 042 melanoma patients diagnosed from 1982 to 2014. The 30-year incidence rates of death due to melanoma and nonmelanoma (with 95% confidence intervals [CIs]) were 7.1% (95% CI = 6.9% to 7.3%) and 32.8% (95% CI = 32.3% to 33.3%), respectively. For T2 melanomas, the corresponding rates were 21.6% (95% CI = 21.0% to 22.3%) and 35.6% (95% CI = 34.7% to 36.6%), for T3 melanomas 34.2% (95% CI = 33.4% to 35.1%) and 39.6% (95% CI = 38.5% to 40.8%), and for T4 melanomas 44.3% (95% CI = 43.2% to 45.3%) and 39.6% (95% CI = 38.3% to 41.0%). A plateau in melanoma-related deaths occurred in T4 patients after 20 years, but there were ongoing melanoma-related deaths for the other T categories beyond 30 years. A progressive rise in the risk of death from other causes occurred across all T categories.
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Besides the broad development of nanotechnological approaches for cancer diagnosis and therapy, currently, there is no significant progress in the treatment of different types of brain tumors. Therapeutic molecules crossing the blood–brain barrier (BBB) and reaching an appropriate targeting ability remain the key challenges. Many invasive and non-invasive methods, and various types of nanocarriers and their hybrids have been widely explored for brain tumor treatment. However, unfortunately, no crucial clinical translations were observed to date. In particular, chemotherapy and surgery remain the main methods for the therapy of brain tumors. Exploring the mechanisms of the BBB penetration in detail and investigating advanced drug delivery platforms are the key factors that could bring us closer to understanding the development of effective therapy against brain tumors. In this review, we discuss the most relevant aspects of the BBB penetration mechanisms, observing both invasive and non-invasive methods of drug delivery. We also review the recent progress in the development of functional drug delivery platforms, from viruses to cell-based vehicles, for brain tumor therapy. The destructive potential of chemotherapeutic drugs delivered to the brain tumor is also considered. This review then summarizes the existing challenges and future prospects in the use of drug delivery platforms for the treatment of brain tumors. Graphical Abstract
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Background: Acral location of melanomas is associated with poor survival. It can be due, at least in part, to the fact that acral lentiginous melanoma, a distinct melanoma subtype, has a particular biological profile and a bad clinical behavior. However, since almost 50% of acral melanomas are not of acral lentiginous melanoma subtype, the worse clinical behavior could also be attributable to the intrinsic characteristics of the location. Objective: This study aimed to investigate if melanomas of the lower limb excluding acral lentiginous melanoma differ by location. Methods: This retrospective, observational study recruited patients from an oncology referral center in Spain. We included 285 patients with superficial spreading and nodular melanomas of the lower limb. We compare melanomas by site, clinical and pathological characteristics, and the differences by location of disease-free and melanoma-specific survival by the Kaplan-Meier method and Cox proportional hazard method. Results: Patients with melanomas on the foot, compared to those on the rest of the limb, were older and reported having suffered less sunburns; the melanoma more frequently appeared in areas that had been rarely sun exposed, were more frequently of nodular type, presented thicker tumors, with more ulceration, less regression, and more advanced stage of the disease. Foot location increased the risk of relapse and decreased melanoma-specific survival. Conclusion: Melanoma development in foot is less related to sun exposure and is associated with pathological features that can account for the worse prognosis and poorer survival.
Chapter
Epidemiologische Methoden sind ein wichtiger Baustein im Forschungsbereich Gesundheitsförderung und Prävention. Viele Studien in diesem Bereich bedienen sich der Vielfalt epidemiologischer Studiendesigns. So können beispielsweise Zusammenhänge zwischen gesundheitsbezogenen Verhaltensweisen und dem Gesundheitszustand ermittelt werden. Epidemiologische Studien eigenen sich auch dazu, Risikogruppen zu identifizieren, die in nachfolgenden Gesundheitsförderungs- und Präventionsmaßnahmen zielgerichtet angesprochen werden können. Zu den epidemiologischen Studiendesigns gehören beobachtende und experimentelle Designs. Beobachtende Designs, denen sich dieses Kapitel widmet, umfassen Kohortenstudien, Fall-Kontroll-Studien und Querschnittsstudien. Daneben gibt es ökologische Studien und Monitoring-Instrumente und es besteht die Möglichkeit, Register- oder Surveillancedaten auszuwerten. In diesem Kapitel werden die wichtigsten Studiendesigns sowie deren Anwendung im Forschungsbereich Gesundheitsförderung und Prävention beschrieben. Dabei werden auch Maßzahlen vorgestellt, die je nach Studiendesign berechnet werden können. Zudem werden Vor- und Nachteile der einzelnen Studiendesigns sowie verschiedene Bias-Arten erläutert, da diese Kenntnisse auch bei der Interpretation von Studienergebnissen hilfreich sind.
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The aim of this study was to investigate recent trends in incidence, mortality and survival in patients diagnosed with malignant melanoma (MM) in relation to stage (Breslow thickness). Cases of primary invasive and in situ MM diagnosed between 1st January 1993 and 31st December 2003 in the former Yorkshire Health Authority were identified from cancer registry data. Over the study period, the incidence of invasive MM increased from 5.4 to 9.7 per 100,000 in male subjects and from 7.5 to 13.1 per 100,000 in female subjects. Most of this increase was seen in thin tumours (< 1.5 mm). Thin tumours were more likely to be diagnosed in the younger age groups and be classified as superficial spreading melanoma. In situ melanoma rates increased only slightly. Over the same time period, mortality rates have been relatively constant in both male and female subjects. Five-year relative survival varied from 91.8% (95% CI 90.4-93.1) for patients with thin tumours to 41.5% (95% CI 36.7-46.3) for those with thick tumours. In multivariable analyses, Breslow thickness was the most important prognostic factor. Age, sex and level of deprivation were also identified as independent prognostic factors. The trends in incidence suggest that the increase is real, rather than an artefact of increased scrutiny, implying that primary prevention in the Yorkshire area of the UK has failed to control trends in incidence. Mortality, in contrast, appears to be levelling off, indicating that secondary prevention has been more effective.
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Worldwide, female melanoma patients have superior survival compared with males, which is usually ascribed to earlier detection among women and/or a more favorable site distribution. We studied gender difference in melanoma survival in a large population-based setting after adjusting for tumor-related variables and offer clues for further research. A total of 10,538 patients diagnosed with melanoma from 1993 to 2004 in The Netherlands were included. Multivariate analyses were carried out to estimate adjusted relative excess risk (RER) of dying for men compared with women, adjusted for the patient and tumor characteristics. Univariate relative survival analyses showed a RER of dying of 2.70 [95% confidence interval (CI) 2.38-3.06] for men compared with women. After adjusting for time period of diagnosis, region, age, Breslow thickness, histologic subtype, body site, nodal and metastatic status, a significant excess mortality risk was still present for males (RER 1.87, 95% CI 1.65-2.10). Among patients with advanced disease and in those < 45 or > or = 60, the adjusted risk estimates were similar. The superior survival of women compared with men persisted after adjusting for multiple confounding variables indicating that factors other than stage at diagnosis and body site reduce mortality risk in female melanoma patients.
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In Europe as a whole, survival from skin malignant melanoma (SMM) has increased constantly since the 1980s. The aim of the SUDCAN collaborative study was to compare the trends in the 5-year net survival from SMM and in related excess mortality rate between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland). The data were extracted from the EUROCARE-5 database (end of follow-up: 01 January 2009). First, the net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain, and Switzerland and from 2000 to 2004 in Belgium and Portugal. The analyses were carried out using a flexible excess rate modeling. Over the 2000-2004 period, the 5-year net survival from SMM ranged from 79 (Portugal) to 90% (Switzerland). In all countries, net survival was higher in women versus men and in young versus old age groups. From 1992 to 2004, the 5-year net survival increased the most in the countries with the lowest survivals in 1992 (+9% in Italy and Spain vs. +2% in Switzerland or +4% in France). The differences between countries decreased between 1992 and 2004. Although survival increased to a lower or higher extent in all countries during the period studied, significant differences in net survival from SMM persisted among the six countries studied. Health policies should mainly enhance early diagnosis by increasing public awareness and with screening campaigns. Furthermore, new immunotherapies, which will be approved soon hopefully, should also be used to improve the outcomes of SMM treatment.
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Background: Research in the United States and Europe has found that women have an advantage over men in surviving a diagnosis of cancer, but the issue has not been systematically studied in Canada. Data and methods: Data are from the Canadian Cancer Registry, with mortality follow-up through record linkage to the Canadian Vital Statistics Death Database. The percentage unit difference in five-year relative survival ratios (RSRs) between women and men and the relative excess risk (RER) of death for women compared with men were used as measures of differences in cancer survival. Results: A significant advantage for women compared with men was observed in 13 of the 18 cancers studied. Point estimates of RER were almost uniformly lower among those diagnosed at younger ages (15 to 54). For all cancers combined, women had a 13% lower excess risk of death-23% lower among women younger than 55. The overall advantage was greatest for thyroid cancer (RER = 0.31), skin melanoma (0.52) and Hodgkin lymphoma (0.65). The advantage for thyroid cancer was somewhat attenuated, though still significant, in earlier time periods. Bladder cancer was the only cancer for which women had a significant disadvantage (RER = 1.23); this excess risk seemed to be restricted to the first 12 to 18 months after diagnosis. Interpretation: The reasons behind sex-specific differences in cancer survival are not well understood. Many explanations are possible, and differences are best explored on a cancer-by-cancer basis. The pronounced advantage for women at younger ages lends indirect support to a hypothesized hormonal influence.
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The four main clinicopathological subsets of melanoma are described and the arguments for their retention in a research setting presented. Further additional subsets are described, including partly regressed primary melanoma, melanoma arising in a congenital naevus and multiple primary tumours. Pathological prognostic indicators are discussed and the pre-eminent significance of tumour thickness and its interaction with ulceration described. The need for accurate personal predictive profiles as distinct from those relevant to populations is discussed, as is the need for a molecular marker of metastatic potential.
Article
Background: The proportion of cases notified by death certificate only (DCO) is a commonly used data quality indicator in studies comparing cancer survival across regions and over time. We aimed to assess dependence of DCO proportions on the age structure of cancer patients. Methods: Using data from a national cancer survival study in Germany, we determined age specific and overall (crude) DCO proportions for 24 common forms of cancer. We then derived overall (crude) DCO proportions expected in case of shifts of the age distribution of the cancer populations by 5 and 10 years, respectively, assuming age specific DCO proportions to remain constant. Results: Median DCO proportions across the 24 cancers were 2.4, 3.7, 5.5, 8.5 and 23.9% in age groups 15-44, 45-54, 55-64, 65-74, and 75+, respectively. A decrease of ages by 5 and 10 years resulted in decreases of cancer specific crude DCO proportions ranging from 0.4 to 4.8 and from 0.7 to 8.6 percent units, respectively. Conversely, an increase of ages by 5 and 10 years led to increases of cancer specific crude DCO proportions ranging from 0.8 to 4.8 and from 1.8 to 9.6 percent units, respectively. These changes were of similar magnitude (but in opposite direction) as changes in crude 5-year relative survival resulting from the same shifts in age distribution. Conclusions: The age structure of cancer patient populations has a substantial impact on DCO proportions. DCO proportions should therefore be age adjusted in comparative studies on cancer survival across regions and over time.
Article
Background: With melanoma incidence rising and mortality stable, some question whether the melanoma epidemic is real. Melanoma thickness and survival trends may provide insights, but previous studies have been limited because of missing data on thickness. Methods: With a validated imputation method for missing thickness data, we characterized melanoma thickness and survival trends among men and women in the Surveillance, Epidemiology, and End Results (SEER)-9 registries between 1989 and 2009. A total of 98,498 cases of invasive melanoma were identified. All statistical tests were two-sided. Results: Incidence per 100 000 person-years increased (13.94, 95% confidence interval [CI] = 13.65 to 14.23, to 21.87, 95% CI = 21.56 to 22.19, P < .001) between 1989 to 1991 and 2007 to 2009, fatal incidence remained stable (2.32, 95% CI = 2.2 to 2.4, to 2.08, 95% CI = 2.0 to 2.2, P = .20) between 1989 to 1991 and 1998 to 2000, and five-year survival increased (88.29%, 95% CI = 87.60% to 88.95%, to 91.68%, 95% CI = 91.22% to 92.12%, P < .001) between 1989 to 1991 and 2001 to 2003. Increase in incidence occurred across all thickness groups. Median thickness decreased (0.73 to 0.58mm). Geometric mean thickness decreased (0.77 to 0.65mm) 4.6% (95% CI = 4.2% to 5.0%) every three years in multivariable analysis. Thickness decreased among T1/T2 tumors (0.01-1.00 and 1.01-2.00mm) and among all age and sex groups, whites, non-Hispanics, and all body sites. However, thickness increased among T3/T4 tumors (2.01-4.00 and > 4.00mm) and nodular melanomas; acral lentiginous melanomas approached statistical significance. Thickness remained unchanged among some racial minorities. Melanoma-specific survival improved (hazard ratio [HR] = 0.89, 95% CI = 0.88 to 0.91) every three years in multivariable analysis. Improvements in survival occurred across all subgroups except nonblack minorities, and nodular and acral lentiginous subtypes. Conclusions: Increasing incidence across all thickness groups coupled with T3/T4 lesions becoming thicker suggests that the melanoma epidemic is real and not simply an artifact of increased detection pressure of earlier-stage T1/T2 lesions. Survival is generally improving independent of thickness, but improvements in survival have not been experienced by certain minorities, and nodular and acral lentiginous subtypes.
Article
Among patients with invasive melanoma, females are known to have higher survival than males globally. However, this survival advantage has not been explored in thin melanomas, the most common form of the disease. In addition, it is unclear if this advantage is true across all age groups. We aimed to compare melanoma survival between males and females by clinical stage and within age groups. Melanomas from 1995 to 2008 were extracted from the Queensland Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) Program, and melanoma-specific deaths were ascertained up to 2011. Flexible parametric survival models compared survival between groups. The Queensland cohort of 28,979 patients experienced 1712 melanoma deaths and the SEER cohort of 57,402 patients included 6929 melanoma deaths. Survival rates were in favour of females across nearly all tumour stages, including thin invasive tumours in both cohorts after adjusting for demographic and clinical factors [odds ratio (OR) death female:male for stage I melanoma = 0.64 in Queensland; and OR = 0.79 in the US, both P < 0.001]. The sex influence on survival interacted with age categories. In particular, the survival advantage was inconsistent in females with stage I melanoma aged under 60. Females with melanoma have a survival advantage over males including in stage I melanomas. However, this advantage is dependent on age at diagnosis, suggesting an underlying biological mechanism influenced by age that exists from the very early stages of the disease.
Article
Background: Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. Methods: In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). Findings: 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73.4% [95% CI 72.9-73.9] vs 81.7% [81.3-82.1]), non-Hodgkin lymphoma (53.8% [53.3-54.4] vs 60.4% [60.0-60.9]), and rectal cancer (52.1% [51.6-52.6] vs 57.6% [57.1-58.1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. Interpretation: The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. Funding: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.
Article
Among melanoma patients, women have a better prognosis than men but the differences might be due to a different presentation of melanoma. The aim of this study was to identify differences in clinical presentation and survival in cutaneous melanoma between men and women in a Spanish population stratified by age. In total, 1,607 consecutive patients with localized cutaneous melanoma and complete clinical and pathological information were evaluated. Average follow-up was 5 years. Patients were stratified by age into three groups: ≤45 years, 46-60 years, and >60 years. Disease-free survival, overall-survival and disease-specific survival were generated using the Kaplan-Meier method. Multivariate survival analyses were evaluated using Cox modelling. Melanoma presented more frequently in the trunk in male patients and in the lower extremities and acral location in female patients. Men presented thicker tumors than women. However, for histological type, mitotic rate and ulceration there were no significant differences between the sexes. In the univariate survival analyses, women showed better disease-free, overall and disease-specific survival in the younger age group, compared with males of the same group. After adjusting for anatomical site, Breslow thickness, mitotic rate and presence of ulceration, there were no differences between males and females in any of the three age groups. The superior survival for women over men did not persist after adjusting for multiple prognostic variables such as anatomical site, Breslow thickness, mitotic rate and ulceration.
Article
Monitoring cancer survival by population-based cancer registries is a prerequisite to evaluate current quality of cancer care. The present study provides 1-, 5- and 10-year relative survival as well as 5-year relative survival conditional on 1-year survival estimates and recent survival trends for Germany using data from 11 population-based cancer registries, covering around one third of the German population. Period analysis was employed to estimate relative survival for 24 common and 11 less common cancer sites for the period 2007-2010. German and United States survival estimates were compared utilizing the Surveillance, Epidemiology and End Results 13 database. Trends in cancer survival in Germany between 2002-2004 and 2008-2010 are described. Five-year relative survival increased in Germany from 2002-2004 to 2008-2010 for most cancer sites. Among the 24 most common cancers, largest improvements were seen for multiple myeloma (+8% units), non-Hodgkin lymphoma (+6.2% units), prostate cancer (+5.2% units) and colorectal cancer (+4.6% units). In 2007-2010, the survival disadvantage in Germany compared to the US was largest for cancers of the mouth/pharynx (-11.0% units), thyroid (-6.8% units), and prostate (-7.5 % units). While survival estimates were much lower for elderly patients in both countries, differences in age patterns were observed for some cancer sites. The reported improvements in cancer survival might reflect advances in quality of cancer care on the population level as well as increased use of screening in Germany. The survival differences across countries and the survival disadvantage in the elderly require further investigation. © 2014 Wiley Periodicals, Inc.
Article
Aim: Estimates of malignant melanoma (MM) incidence and prognosis vary widely. The present study was performed to analyze epidemiologic and prognostic aspects of primary MM mainly in relation to tumor thickness. Methods: We conducted a retrospective study on a cohort of 435 patients with diagnosis of primary MM between 1997 and 2011. Results: In the period 2009--2011, among the MM diagnosed 50.00% were thin, 32.43% in situ and 17.57% thicker while in 1997--1999 MM >1mm accounted for 51.61% of diagnoses. Mean age of patients affected with thin MM was significantly lower than that of patients with MM >1mm, and mean thickness resulted significantly lower in female patients than in males. Mean thickness of MM located on easily self--evaluable body areas was significantly lower than in those not accessible for skin self--examination. The commonest histogenetic type was superficially spreading melanoma. Mitotic rate, ulceration and vertical growth phase all resulted related to MM thickness. Out of 61 patients with thin MM who underwent SLNB, 3 resulted positive (4.92%): neither thickness >0.75 mm, nor ulceration, mitotic rate or Clark level were found to be associated with SLNB positivity. Five--year survival rate was 98.3% for thin MM patients and 76.4% for thick MM patients. Conclusion: Our trend analysis evidences a continuing increase of thinner primary MM throughout the study period, potentially enhancing patient prognosis. Regular skin self--examination could contribute to earlier recognition of MM. Identification of more powerful predictors of thin MM prognosis is necessary.
Article
Prior analyses of survival of patients with primary cutaneous malignant melanoma from Germany were based only on small populations and need to be updated. We give a detailed overview of relative 5-year survival by sex, age group, histology, tumour stage and body site, and of time trends in a population of 33 million (40% of Germany), and compare survival in the federal states. Conventional and model-based period analysis using the Ederer II method was applied to patients with melanoma diagnosed during 1997-2006 in Germany to assess 5-year relative survival (RS) rates and time trends. In total, 37,155 melanoma cases were included. Overall age-adjusted 5-year RS for the time period 2002-2006 was 91·9% for women and 87·0% for men. Survival differences by age group, histology, tumour stage and body site were found. No significant overall trend (2002-2006) was seen either in women or in men. Differences in survival between federal states were small; no clear pattern was seen. Based on the most recent and high-quality data from population-based cancer registries a comprehensive picture on melanoma survival in Germany was given. Survival from cutaneous malignant melanoma was high compared with other cancer sites and did not change during the analysed period 2002-2006. Patterns in melanoma survival by sex, age, tumour stage, histology and body site were in good agreement with previously published findings. No relevant differences between federal states were found.
Article
From July 1, 2003 to June 30, 2004, a population-based skin cancer screening project was conducted in Schleswig-Holstein, Germany. In total, 360,288 individuals aged ≥20 years were screened by means of a whole-body examination. In this report, the authors compare trends in melanoma mortality in Schleswig-Holstein with those in all adjacent regions, none of which had population-based skin cancer screening. Trends in melanoma mortality rates for Schleswig-Holstein and the adjacent regions (Denmark and the German federal states of Mecklenburg-Vorpommern, Hamburg, and Lower Saxony) and in Germany excluding Schleswig-Holstein were compared. Log-linear regression was used to assess mortality trends. In Schleswig-Holstein during the pre skin cancer screening period (1998-1999), the age-standardized melanoma mortality rate (World standard population) was 1.9 per 100,000 for men and 1.4 per 100,000 for women. Melanoma mortality declined by 47% to 1.0 per 100,000 men and by 49% to 0.7 per 100,000 women by 2008/2009. The annual percentage change in the most recent 10-year period (2000-2009) was -7.5% (95% confidence interval, -14.0, -0.5) for men and -7.1% (95% confidence interval, -10.5, -2.9) for women. In each of the 4 adjacent regions and in the rest of Germany, mortality rates were stable, and the decline in Schleswig-Holstein was significantly different from the changes observed in all of the other areas studied. The current data represent strong evidence, but not absolute proof, that the skin cancer screening program produced a reduction in melanoma mortality in Schleswig-Holstein. Cancer 2012. © 2012 American Cancer Society.
Article
The incidence of skin cancer is increasing worldwide. For decades, opportunistic melanoma screening has been carried out to respond to this burden. However, despite potential positive effects such as reduced morbidity and mortality, there is still a lack of evidence for feasibility and effectiveness of organized skin cancer screening. The main aim of the project was to evaluate the feasibility of systematic skin cancer screening. In 2003, the Association of Dermatological Prevention was contracted to implement the population-based SCREEN project (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) in the German state of Schleswig-Holstein. A two-step program addressing malignant melanoma and nonmelanocytic skin cancer was implemented. Citizens (aged ≥ 20 years) with statutory health insurance were eligible for a standardized whole-body examination during the 12-month study period. Cancer registry and mortality data were used to assess first effects. Of 1.88 million eligible citizens, 360,288 participated in SCREEN. The overall population-based participation rate was 19%. A total of 3103 malignant skin tumors were found. On the population level, invasive melanoma incidence increased by 34% during SCREEN. Five years after SCREEN a substantial decrease in melanoma mortality was seen (men: observed 0.79/100,000 and expected 2.00/100,000; women: observed 0.66/100,000 and expected 1.30/100,000). Because of political reasons (resistance as well as lack of support from major German health care stakeholders), it was not possible to conduct a randomized controlled trial. The project showed that large-scale systematic skin cancer screening is feasible and has the potential to reduce skin cancer burden, including mortality. Based on the results of SCREEN, a national statutory skin cancer early detection program was implemented in Germany in 2008.
Article
Studies of cancer survival by population-based cancer registries are a key component in monitoring progress against cancer. Patients notified by death certificates only (DCO) are commonly excluded from such studies. The validity of this "exclude DCO" approach has been questioned and an alternative "correct for DCO" approach has been proposed. We assess the validity of both the "exclude DCO" approach and the "correct for DCO" approach using model calculations. We illustrate implications for population-based cancer survival analyses by analyses of 5-year relative survival of cancer patients in Saarland, Germany. The "exclude DCO" approach provides (too) optimistic survival estimates and the "correct for DCO" approach provides (too) pessimistic survival estimates under plausible assumptions. For example, in case of true survival of 50%, underascertainment of 5% of surviving patients and of 15% of dying patients (yielding a proportion of DCO cases of 7.7%), the two approaches would provide survival rate estimates of 52.8% and 48.8%, respectively. The difference of survival estimates obtained with both approaches increases with incompleteness of registration and the proportion of DCO cases. Trace back of DCO cases shifts survival estimates from the former toward the latter estimate. In case of nonnegligible DCO proportions, cancer survival studies should not be exclusively based on either the "exclude DCO" or the "correct for DCO" approach. A combination of estimates from both approaches may be useful to delineate a plausibility range for true survival. Our results may help to enhance validity and comparability of population-based cancer survival estimates.
Article
Survival studies using data from population-based cancer registries allow assessing effectiveness of cancer care on a population level. However, population-based cancer registries differ in the proportion of cases first notified by death certificate, as well as in the efforts to trace back such death certificate notifications (DCN). We aimed to assess the impact of such trace back on population-based cancer survival estimates. In this study from the population-based Saarland Cancer Registry (Germany) we investigated the survival experience of successfully traced back DCN cases from 1994 to 2003. Five-year relative survival of patients with DCN cancers and the effect of trace back on population-based 5-year relative survival estimates were analysed by age and tumour site. Twelve percent of all cancers were DCN and such cases occurred most often amongst sites with poor prognosis and amongst elderly patients. Approximately half of DCN cases could be successfully traced back. Five-year relative survival of patients with DCN cancers with trace back was 2%. The inclusion of DCN cancers with additional registrations reduced the 5-year relative survival estimate for all cancers combined by 4% points. Reductions were stronger for older patients and highly fatal cancers. Trace back results in increased inclusion of patients with very poor prognosis. Varying extent of trace back across registries may compromise comparability of cancer survival estimates and should be taken into account in comparative cancer survival studies.
Article
Until recently, population-based data of cancer survival in Germany mostly relied on one registry covering ∼1 million people (1.3% of the German population). Here, we provide up-to-date cancer survival estimates for Germany based on data from 11 population-based cancer registries, covering 33 million people and compare them to survival estimates from the United States. Cancer patients diagnosed in 1997-2006 were included. Period analysis was employed to calculate 5-year relative survival for 38 cancers for 2002-2006. German and USA survival rates were compared utilizing the Surveillance, Epidemiology and End Results 13 database. Five-year relative survival >80% was observed for testicular cancer (93.5%), skin melanoma (89.4%), cancers of the prostate (89.1%) and thyroid (87.8%), Hodgkin's lymphoma (84.5%) and cancers of the breast (83.7%) and endometrium (81.0%), which together account for almost 40% of cases. For the majority of cancers, German survival estimates were close to or below those in the United States. Exceptions with higher survival in Germany were cancers of the stomach, pancreas and kidney and Hodgkin's lymphoma. German cancer survival estimates are mostly higher than the 2000-2002 pan-European estimates. Further research is needed to investigate causes responsible for differences between German and USA cancer survival rates.
Article
International comparison of population-based cancer survival is a key component of monitoring progress against cancer. Its validity depends to an unknown degree on completeness of ascertainment of deaths in the cancer registries involved which may vary according to legal and administrative circumstances. The aim of this study was to assess the impact of incomplete registration of deaths through various mechanisms on the validity of long-term absolute and relative survival estimates. For that purpose, we simulated underascertainment of deaths through linkage failure of registry data with death certificates with probabilities between 0.1 and 5%, and underascertainment of deaths by unregistered annual emigration with probabilities between 0.05 and 2%, using data from the Finnish Cancer Registry. The expected impact on estimates of 5-, 10- and 15-year absolute and relative survival was assessed. We demonstrate that even modest levels of under-registration of deaths may lead to severe overestimation of long-term survival estimates, ranging from 0 to 31 percent units in the scenarios assessed. In general, relative survival is much more affected than absolute survival, and potential problems are much larger for relative survival estimates in older compared with younger patients. Potential overestimation strongly increases with length of follow-up, and this increase is particularly pronounced for under-registration of deaths because of unrecorded emigration. Every effort should be made in cancer registry based survival analyses to ascertain deaths with close to 100% completeness. When such completeness cannot be achieved, long-term relative survival estimates and their comparison across populations must be interpreted with much caution.
Article
We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.
Article
We considered, by means of a multivariate approach, trends in survival from cutaneous malignant melanoma in relation to patient and tumor characteristics, using data from the Cancer Registry of the Swiss Canton of Vaud. Between 1980 and 1994, 1,229 cases of incident cutaneous malignant melanoma were registered. There was a decline in the proportion of neoplasms in the head and neck and lower limbs, and a rise in those of the trunk and upper limbs, an increase in superficial spreading melanoma and in tumors of limited thickness, mostly in females. Five-year crude survival was 0.68 for males and 0.82 for females, and relative survival of 0.79 for males and 0.89 for females, corresponding to a multivariate hazard ratio (HR) of 0.63 for females vs. males. Survival was inversely related to age, with 5-year relative survival of 0.92 at age 15-44 years, 0.85 at age 45-64 years, and 0.79 at age > or = 65 years. With reference to histological type, no significant difference was observed in males, but in females nodular melanoma showed reduced survival. Compared with melanoma of the limbs, the HR was 1.46 for melanoma of the trunk, and 1.23 for those in the head and neck, and the difference was greater in females. A strong relation, in both sexes, was observed between survival and tumor thickness, with an HR of 3.96 for tumors > or = 4 mm vs. those < 1.50 mm. After allowance for all other factors considered, most recent calendar period of diagnosis was associated with improved survival in both sexes (HR = 0.72), but mostly in females. Although differences in survival tended to be larger during the first 2 years after diagnosis, the pattern was similar for most prognostic factors considered up to 10 years after diagnosis.
Article
There is now clear evidence that the prevalence of co-morbidity among older cancer patients is high and that older patients (with comorbidity) are often treated less aggressively, which seems to have a negative influence on survival. However, would outcomes really improve if more patients were treated, according to the guidelines that were developed on the basis of results in groups of younger patients without co-morbidity? Would more complications occur in older patients with co-morbidity? If that is the case, is it possible to develop special treatment regimens for older cancer patients with co-morbidity and adapt the guidelines? It remains relevant to study the influence of age and co-morbidity on toxicity from treatment, quality of life and prognosis in unselected groups of patients.
Article
To better understand the factors associated with the well-established gender difference in survival for patients with melanoma. Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood. This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001). Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.
Article
Monitoring of progress in cancer patient survival by cancer registries should be as up-to-date as possible. Period analysis has been shown to provide more up-to-date survival estimates than do traditional methods of survival analysis. However, there is a trade-off between up-to-dateness and the precision of period estimates, in that increasing the up-to-dateness of survival estimates by restricting the analysis to a relatively short, recent time period, such as the most recent calendar year for which cancer registry data are available, goes along with a loss of precision. The authors propose a model-based approach to maximize the up-to-dateness of period estimates at minimal loss of precision. The approach is illustrated for monitoring of 5-year relative survival of patients diagnosed with one of 20 common forms of cancer in Finland between 1953 and 2002 by use of data from the nationwide Finnish Cancer Registry. It is shown that the model-based approach provides survival estimates that are as up-to-date as the most up-to-date conventional period estimates and at the same time much more precise than the latter. The modeling approach may further enhance the use of period analysis for deriving up-to-date cancer survival rates.
Article
The aim was to identify age- related and gender-related differences in the clinical presentation and outcome of patients with primary cutaneous melanoma (CM). A total of 4785 CM patients without clinical evidence of metastasis diagnosed during the period 1976-2001 in southern Germany included in the analysis. Kaplan-Meier analyses were performed to estimate and to compare disease-specific survival (DSS) and survival after first recurrence (SAR). The Cox proportional hazards model was used to evaluate the effect of multiple variables on DSS and SAR. Increasing age and male gender were independently associated with thicker tumors (>2 mm) and histologic ulceration (P< .001). Patients older than 65 years had lower 10-year DSS than younger patients (81.8% vs 88.4%, P< .001) and this difference was more pronounced in women (P< .001) than in men (P= .06). Males had lower 10-year DSS than females (83.5% vs 88.5%, P< .001) but this difference did not reach statistical significance in patients older than 65 years (P= .162). In multivariate analysis adjusted for tumor thickness, ulceration, anatomic site, histologic subtype, DSS, site of first recurrence, time trend, sentinel lymph node status, age, and gender were independent predictors of DSS and SAR (P< .05). Older age and male gender are associated with prognostically unfavorable primary CM. Expansion of current preventive strategies to target these subgroups is warranted. Moreover, age and gender are independent predictors of the outcome of CM patients. Females have a better prognosis than males but this difference disappears after the age of 65. Younger patients have a more favorable prognosis than older patients, a difference more pronounced in women.
Article
The aim of this study was to compare trends in prognostic factors and survival from cutaneous melanoma between 1993 and 2003 in 2 populations with dramatically different underlying incidence rates [Yorkshire, UK, and New South Wales (NSW), Australia] and to look at whether the greater investment in melanoma prevention and early detection in Australia has resulted in any relative differences in survival. Patients diagnosed with invasive melanoma between 1993 and 2003 in Yorkshire (n = 4,170) and NSW (n = 30,520) were identified from cancer registry databases and prognostic information (age, sex, socioeconomic background, tumour site and Breslow thickness) was extracted. Age-standardised incidence rates, 5-year relative survival and relative excess risk of death were calculated. Between 1993-1995 and 2001-2003, the incidence of melanoma increased in both areas. These increases were mainly seen in tumours with thickness <or=1 mm. Five-year relative survival was 86.9% (95% CI 85.2-88.5) in Yorkshire and 88.6% (95% CI 88.1-89.1) in NSW. Compared with that in NSW, survival in Yorkshire was lower for males and for those living in the most deprived areas. Despite the increase in good prognosis of thin tumours, there was no significant change in survival over the time period in either area. After adjustment for differences in prognostic factors, the relative excess risk of death in Yorkshire compared to that in NSW reduced from 1.36 (95% CI 1.20-1.53) to 1.11 (95% CI 0.99-1.23). Differences in tumour thickness appeared to be the most important factor.
Superficial spreading melanoma: an analysis of 97 702 cases using the SEER database.
  • Singh
Skin cancer screening in Germany.
  • Katalinic