Sinonasal mucosal melanoma in The Netherlands between 2001 and 2021: a clinical and epidemiological overview of 320 cases.

PURPOSE: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. METHODS: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). RESULTS: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only - 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. CONCLUSION: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care.

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study.

BACKGROUND: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. OBJECTIVE: To investigate the cumulative incidence and timing of subsequent cSCCs. METHODS: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. RESULTS: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. LIMITATIONS: Only histopathologically confirmed cSCCs were included. CONCLUSION: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.

Trends in Incidence and Survival of 1496 Patients with Mucosal Melanoma in The Netherlands (1990-2019).

BACKGROUND: Mucosal melanoma (MM) is a rare tumour with a poor prognosis. Over the years, immune and targeted therapy have become available and have improved overall survival (OS) for patients with advanced cutaneous melanoma (CM). This study aimed to assess trends in the incidence and survival of MM in the Netherlands against the background of new effective treatments that became available for advanced melanoma. METHODS: We obtained information on patients diagnosed with MM during 1990-2019 from the Netherlands Cancer Registry. The age-standardized incidence rate and estimated annual percentage change (EAPC) were calculated over the total study period. OS was calculated using the Kaplan-Meier method. Independent predictors for OS were assessed by applying multivariable Cox proportional hazards regression models. RESULTS: In total, 1496 patients were diagnosed with MM during 1990-2019, mostly in the female genital tract (43%) and the head and neck region (34%). The majority presented with local or locally advanced disease (66%). The incidence remained stable over time (EAPC 3.0%, p = 0.4). The 5-year OS was 24% (95%CI: 21.6-26.0%) with a median OS of 1.7 years (95%CI: 1.6-1.8). Age ≥ 70 years at diagnosis, higher stage at diagnosis, and respiratory tract location were independent predictors for worse OS. Diagnosis in the period 2014-2019, MM located in the female genital tract, and treatment with immune or targeted therapy were independent predictors for better OS. CONCLUSION: Since the introduction of immune and targeted therapies, OS has improved for patients with MM. However, the prognosis of MM patients is still lower compared to CM, and the median OS of patients treated with immune and targeted therapies remains fairly short. Further studies are needed to improve outcomes for patients with MM.

Development and Validation of an Algorithm to Identify Patients with Advanced Cutaneous Squamous Cell Carcinoma from Pathology Reports.

To facilitate nationwide epidemiological research on advanced cutaneous squamous cell carcinoma (cSCC), that is, locally advanced, recurrent, or metastatic cSCC, we sought to develop and validate a rule-based algorithm that identifies advanced cSCC from pathology reports. The algorithm was based on both hierarchical histopathological codes and free text from pathology reports recorded in the National Pathology Registry. Medical files from the Erasmus Medical Center of 186 patients with stage III/IV/recurrent cSCC and 184 patients with stage I/II cSCC were selected and served as the gold standard to assess the performance of the algorithm. The rule-based algorithm showed a sensitivity of 91.9% (95% confidence interval = 88.0‒95.9), a specificity of 96.7% (95% confidence interval = 94‒2-99.3), and a positive predictive value of 78.5% (95% confidence interval = 74.2‒82.8) for all advanced cSCC combined. The sensitivity was lower per subgroup: locally advanced (52.3‒86.2%), recurrent cSCC (23.3%), and metastatic cSCC (70.0%). The specificity per subgroup was above 97%, and the positive predictive value was above 78%, with the exception of metastatic cSCC, which had a positive predictive value of 62%. This algorithm can be used to identify advanced patients with cSCC from pathology reports and will facilitate large-scale epidemiological studies of advanced cSCC in the Netherlands and internationally after external validation.

Time Trends in Treatment Strategies and Survival of Older versus Younger Patients with Synchronous Metastasised Melanoma-A Population-Based Study in the Netherlands Cancer Registry.

Around 45% of patients with melanoma are older than 65 years. In recent years, immunotherapy has proven very effective for metastasised melanoma. The aim of this study was to investigate the time trends in treatment strategies and survival in older versus younger patients with synchronous metastasised melanoma. We included all patients diagnosed between 2000 and 2019 from the Netherlands cancer registry. We analysed changes in first-line systemic treatment using multivariable logistic regression models, stratified by age (<65, 65−75, and ≥75). Changes in overall survival were studied using multivariable Cox regression analysis. A total of 2967 patients were included. Immunotherapy prescription increased significantly over time for all age groups (<65 years: 11.8% to 64.9%, p < 0.001; 65−75 years: 0% to 68.6%, p < 0.001; >75 years: 0% to 39.5%, p < 0.001). In multivariable analyses, overall survival improved for patients aged <65 and 65−75 (HR 0.96, 95% CI 0.92−1.00 and HR 0.95, 95% CI 0.89−1.00, respectively), but not in patients over 75 (HR 0.98, 95% CI 0.91−1.05). In conclusion, overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group.

Limited impact of COVID-19-related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis.

BACKGROUND: The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages. OBJECTIVES: To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods. METHODS: In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre-COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t-test. pT-stage groups were compared using a χ2 -test. Outcomes were corrected for multiple testing using the false discovery rate. RESULTS: In total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii-v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre-COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre-COVID (i) and COVID-affected periods (ii-v) for cSCCs. CONCLUSIONS: To date, the diagnostic delay caused by COVID-19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow-up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term.

Cumulative incidence and disease-specific survival of metastatic cutaneous squamous cell carcinoma: A nationwide cancer registry study.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) represents the most serious form of keratinocyte cancers because of its metastatic potential. Studies on nationwide incidence and disease-specific survival rates of metastatic cSCC (mcSCC) are lacking. OBJECTIVE: To investigate the cumulative incidence and disease-specific survival of patients with mcSCC in the Dutch population and assess patient-based risk factors. METHODS: We conducted a nationwide cancer registry study including all patients with the first cSCC in 2007 or 2008, using data from the Netherlands Cancer Registry, the nationwide network and registry of histopathology and cytopathology, and Statistics Netherlands. Cumulative incidence and Kaplan-Meier curves were calculated, and time-dependent Cox proportional hazards regression analyses were used. RESULTS: Of the 11,137 patients, metastases developed in 1.9% (n = 217). The median time to metastasis was 1.5 years (interquartile range 0.6-3.8 years). The risk factors were age (adjusted hazard ratio [aHR] 1.03, 95% CI 1.02-1.05), male sex (aHR 1.7, 95% CI 1.3-2.3), and immunosuppression (aHR [organ transplant recipient] 5.0, 95% CI 2.5-10.0; aHR [hematologic malignancy] 2.7, 95% CI 1.6-4.6). The 5-year disease-specific survival for patients with mcSCC was 79.1%. LIMITATIONS: Only histopathologically confirmed mcSCCs were included. CONCLUSION: About 2% of cSCCs metastasize, with higher risk for men, increasing age, and immunocompromised patients. Disease-specific survival for patients with mcSCC is high.

Primary Melanoma Characteristics of Metastatic Disease: A Nationwide Cancer Registry Study.

The characteristics and disease patterns of primary stage I and II cutaneous melanomas that progress to stage III or IV disease were investigated based on data from the Netherlands Cancer Registry (NCR). Data on stage III or IV melanomas at first diagnosis or during follow-up between 2017 and 2019 were retrieved. Patient and primary tumour characteristics were investigated in relation to time to disease progression and the number of organ sites with metastatic disease using regression models. In total, 2763 patients were included, of whom 1613 were diagnosed with stage IV disease. Among the patients with stage IV disease, 60% (n = 963) were initially diagnosed with stage I or II disease. The proportion of patients who received a sentinel lymph node biopsy increased after the introduction of adjuvant therapy in 2019 from 61% to 87%. Among all patients with stage III disease who were eligible for adjuvant systemic therapy (n = 453) after 2019, 37% were not treated with this therapy. Among patients with stage IV disease, lung metastases were most often detected as the first metastatic site and females presented with more metastatic sites than males. Most patient and primary tumour characteristics were not associated with the distant metastatic organ site, except melanoma localisation in the lower extremities and the head or neck. Our observation that most stage IV patients were initially diagnosed with early-stage disease highlights the need for more accurate risk prediction models.

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study.

BACKGROUND: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. METHODS: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. RESULTS: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use. CONCLUSIONS: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. IMPACT: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.

Stage-specific trends in incidence and survival of cutaneous melanoma in the Netherlands (2003-2018): A nationwide population-based study.

OBJECTIVE: To examine stage-specific trends in the incidence and survival of cutaneous melanoma in the Netherlands between 2003 and 2018, as well as the uptake of the sentinel lymph node biopsy (SLNB) and novel drugs during that period. METHODS: Data were obtained from the nationwide population-based Netherlands Cancer Registry for all patients diagnosed with invasive primary cutaneous melanoma (n = 60,267). We presented age-standardized incidence rates, the proportion of patients with an SLNB, the proportion of patients who received a novel drug (for their primary diagnosis) and one- and five-year relative survival rates. RESULTS: Between 2003 and 2018, the incidence rate increased from 10.9 to 23.9 for men and from 15.6 to 27.3 for women. This increase reflected the increasing incidence rate of patients with stage I and III. The proportion of patients with an SLNB increased from 23% to 64%. A reasonable increase was observed in the proportion of patients with a positive outcome (from 2% to 11%). For patients with stage IV, there was a shift from chemotherapy towards novel drugs as from 2013. The five-year relative survival rate increased from 81% to 92% for men and from 88% to 96% for women. This increase reflected the increasing five-year relative survival rate of patients with stage II, III, and IV. CONCLUSION: We observed an increase in incidence for patients with stage I and III and an improvement in survival for patients with stage II, III and IV. These trends can be partly explained by the introduction of the SLNB and the novel drugs.

Skin melanoma deaths within 1 or 3 years from diagnosis in Europe.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

Incidence of Multiple vs First Cutaneous Squamous Cell Carcinoma on a Nationwide Scale and Estimation of Future Incidences of Cutaneous Squamous Cell Carcinoma.

Importance: Until now, most studies on cutaneous squamous cell carcinoma (cSCC) incidence rates concerned only the first cSCC per patient. Given the increase in incidence rates and the frequent occurrence of subsequent cSCCs per patient, population-based data on the incidence rates of both first and multiple cSCCs are needed. Objectives: To calculate annual age-standardized incidence rates for histopathologically confirmed first and multiple cSCCs per patient and to estimate future cSCC incidence rates up to 2027. Design, Setting, and Participants: A nationwide population-based epidemiologic cohort study used cancer registry data on 145 618 patients with a first histopathologically confirmed cSCC diagnosed between January 1, 1989, and December 31, 2017, from the Netherlands Cancer Registry and all patients with multiple cSCCs diagnosed in 2017. Main Outcomes and Measures: Age-standardized incidence rates for cSCC-standardized to the European Standard Population 2013 and United States Standard Population 2000-were calculated per sex, age group, body site, and disease stage. A regression model with positive slope was fitted to estimate cSCC incidence rates up to 2027. Results: A total of 145 618 patients in the Dutch population (84 572 male patients [58.1%]; mean [SD] age, 74.5 [11.5] years) received a diagnosis of a first cSCC between 1989 and 2017. Based on incident data, European Standardized Rates (ESRs) increased substantially, with the highest increase found among female patients from 2002 to 2017, at 8.2% (95% CI, 7.6%-8.8%) per year. The ESRs for first cSCC per patient in 2017 were 107.6 per 100 000 person-years (PY) for male patients, an increase from 40.0 per 100 000 PY in 1989, and 68.7 per 100 000 PY for female patients, an increase from 13.9 per 100 000 PY in 1989, which corresponds with a US Standardized Rate of 71.4 per 100 000 PY in 2017 for men and 46.4 per 100 000 PY in 2017 for women. Considering multiple cSCCs per patient, ESRs increased by 58.4% for men (from 107.6 per 100 000 PY to 170.4 per 100 000 PY) and 34.8% for women (from 68.7 per 100 000 PY to 92.6 per 100 000 PY). Estimation of ESRs for the next decade show a further increase of 23.0% for male patients (ESR up to 132.4 per 100 000 PY [95% prediction interval, 125.8-139.0 per 100 000 PY]) and 29.4% for female patients (ESR up to 88.9 per 100 000 PY [95% prediction interval, 84.3-93.5 per 100 000 PY]). Conclusions and Relevance: This nationwide epidemiologic cohort study suggests that incidence rates of cSCC keep increasing, especially among female patients, and that the occurrence of multiple cSCCs per patient significantly adds to the current and future burden on dermatologic health care. Revision of skin cancer policies are needed to halt this increasing trend.

Assessment of Cutaneous Squamous Cell Carcinoma (cSCC) In situ Incidence and the Risk of Developing Invasive cSCC in Patients With Prior cSCC In situ vs the General Population in the Netherlands, 1989-2017.

Importance: The incidence rates of keratinocyte cancer are increasing globally; however, the incidence rates of cutaneous squamous cell carcinoma (cSCC) in situ and the risk of developing subsequent invasive cSCC remain unknown. Objective: To estimate annual population-based age-standardized incidence rates of histopathologically confirmed cSCC in situ stratified by sex, age, and body site and to assess the risk of developing invasive cSCC among patients with cSCC in situ compared with the general population. Design, Setting, and Participants: This nationwide epidemiological population-based cohort study used cancer registry data to identify all patients with a first incident of histopathologically confirmed cSCC in situ between January 1, 1989, and December 31, 2017. In addition, all patients with cSCC in situ who subsequently had a first incident of invasive cSCC were identified up to June 11, 2019. Data were analyzed between March 18 and November 12, 2019. Main Outcomes and Measures: Age-standardized incidence rates per year for cSCC in situ, standardized to the 2013 edition of the European Standard Population, were calculated by sex, age, and body site. Cumulative risks, standardized incidence ratios, and absolute excess risks were calculated to assess the risk of invasive cSCC in patients with cSCC in situ compared with the general population. Results: In this population-based cohort study of 88 754 patients with a first incident of cSCC in situ between January 1, 1989, and December 31, 2017, 58.8% were women; the median age was 75 years (interquartile range [IQR], 67-82 years) for women and 73 years (IQR, 65-80 years) for men. Increasing incidence rates were observed, with the highest incidence rates in 2017 among women in general (71.7 cases per 100 000 person-years) and among men 80 years and older (540.9 cases per 100 000 person-years). The most common body site among women was the face (15.9 cases per 100 000 person-years) and among men was the scalp and/or neck (12.3 cases per 100 000 person-years). After 5 years of follow-up, among patients with cSCC in situ, the cumulative risk of developing an invasive cSCC at any anatomic location was 11.7% (95% CI, 11.6%-11.9%) in men and 6.9% (95% CI, 6.8%-7.0%) in women (P < .001). The standardized incidence ratio was highest in the first year of follow-up among both men (16.6; 95% CI, 15.7-17.5) and women (15.1; 95% CI, 14.2-16.1). Conclusions and Relevance: This study reports the first nationwide incidence rates of cSCC in situ to date. The increasing incidence rates of cSCC in situ and the high risk of developing invasive cSCC among patients with cSCC in situ may increase the health care burden associated with precursors of keratinocyte cancer and highlight the need to include cutaneous skin cancer precursor lesions when exploring policies to address skin cancer care.

Increase of sentinel lymph node melanoma staging in The Netherlands; still room and need for further improvement.

AIM: To investigate implementation of the seventh American Joint Committee on Cancer melanoma staging with sentinel lymph node biopsy (SLNB) and associations with socioeconomic status (SES). PATIENTS & METHODS: Data from The Netherlands Cancer Registry on patient and tumor characteristics were analyzed for all stage IB-II melanoma cases diagnosed 2010-2016, along with SES data from The Netherlands Institute for Social Research. RESULTS: The proportion of SLNB-staged patients increased from 40% to 65% (p < 0.001). Multivariate analysis showed that being female, elderly, or having head-and-neck disease reduced the likelihood of SLNB staging. CONCLUSION: SLNB staging increased by 25% during the study period but lagged among elderly patients and those with head-and-neck melanoma. In The Netherlands, SES no longer affects SLNB staging performance.

Increasing Costs of Skin Cancer due to Increasing Incidence and Introduction of Pharmaceuticals, 2007-2017.

Skin cancer is the most common type of cancer and its incidence is increasing. The objective of this study was to describe the trends in reimbursed drug and hospital costs of benign and (pre)malignant skin tumours, and to present future projections. Therefore, nationwide hospital and drug reimbursement data (for the period 2007-17) were used. In 2017, malignant skin tumours were the 4th most costly cancer in the Netherlands (after breast, colorectal, and lung cancer). The total costs for skin tumours increased from €278 million for 384,390 patients (in 2007) to €465 million for 578,355 patients (in 2017). Drug costs increased from €0.7 million to €121 million (over the period 2007-17), resulting in a 26% share of overall costs in 2017. Future costs are projected to reach €1.35 billion in 2030. In conclusion, the increasing costs of skin cancer are strongly affected by the increasing incidence and introduction of expensive drugs, and future projections are for an alarming increase.

Melanoma in older patients: declining gap in survival between younger and older patients with melanoma.

Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades.Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 (n = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conductedResults: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89).Conclusion: The gap in melanoma incidence between younger and older people is increasing due to a strong increase in incidence in older adults. Disparities in survival are declining, related to a narrowing gap in Breslow thickness.