Burden and Chemoprevention of Skin Cancer

The incidence of skin cancer is increasing in the Netherlands since 1989, the first year of the Netherlands Cancer Registry (NCR). In 2010 more than 43,000 patients were newly diagnosed with skin cancer in the Netherlands. During a life time at least 1 in 5 persons living in the Netherlands will develop skin cancer. The most common skin cancer is basal cell carcinoma (BCC), followed by squamous cell carcinoma (SCC) and melanoma. BCC and SCC combined are often referred to as nonmelanoma skin cancer (NMSC). However, technically the group of NMSC also includes other types of skin cancer, such as T cell lymphoma, Merkel cell carcinoma and Kaposi sarcoma. In this thesis we therefore refer to BCC and SCC combined as keratinocytic cancers, because BCC and SCC both arise from the cells located in the epidermis, which is the upper layer of the skin

Long-Term Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Cutaneous Melanoma: Results of a United States Case–Control Study

Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents. This case–control study was designed to assess the associations between cutaneous melanoma (CM) and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins in current users. A total of 400 CM and 600 eligible age- and gender-matched community-based controls were prospectively recruited and interviewed. We assessed participants’ demographic characteristics, CM risk factors, and current and previous use of medications. Multivariable conditional logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between NSAIDs and/or aspirin (ASA), statin exposure, and CM risk. Half of the subjects were men (mean age 60 years). After adjusting for confounders, use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group (adjusted OR=0.57; 95% CI=0.43–0.77). Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use (>5 years adjusted OR=0.51, 95% CI=0.35–0.75). No significant protective effect was observed with statin exposure (OR=0.97, 95% CI=0.73–1.29). Long-term use of NSAIDs, especially ASA, is associated with a significantly decreased risk of CM development. Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclu

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

Trends of cutaneous melanoma in the Netherlands: increasing incidence rates among all Breslow thickness categories and rising mortality rates since 1989

Abstract: Background: It has been debated that the epidemic of melanoma is largely due to overdiagnosis, since increases in incidence were mainly among thin melanomas and mortality rates remained stable. Our objective was to examine this controversy in the Netherlands. Patients and Methods: Information on newly diagnosed melanoma patients was obtained from the Netherlands Cancer Registry (NCR). European Standardised Rates (ESR) and Estimated Annual Percentage Change (EAPC) were calculated for the period 1989-2008.Cohort-based, period-based and multivariate survival analyses were performed. Results: The incidence rate of melanoma increased with 4.1% (95% CI: 3.6-4.5) annually. Incidence rates of both thin melanomas (. 1mm) and thick melanomas (> 4 mm) increased since 1989. Mortality rates increased mainly in older patients (>65 years). Ten-year relative survival of males improved significantly from 70% in 1989-1993 to 77% in 2004-2008 (p < 0.001) and for females the 10-year relative survival increased from 85% to 88% (p < 0.01). Recently diagnosed patients had a better prognosis even after adjusting for all known prognostic factors. Conclusion: Since incidence of melanomas among all Breslow thickness categories increased as well as the mortality rates, the melanoma epidemic in the Netherlands seems to be real and not only due to overdiagnosis

Statin use and its effect on all-cause mortality of melanoma patients:A population-based Dutch cohort study

Preclinical data showed anticancer effects of statins in melanoma, but meta-analyses could not demonstrate a reduced melanoma incidence in statin users. Rather than preventing occurrence, statins might reduce growth and metastatic spread of melanomas and ultimately improve survival. In this population-based study, we investigated the relationship between statin use and survival of melanoma patients. Patients ≥18 years who were diagnosed with cutaneous melanoma (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in PHARMO Database Network between 1 January 1998 and 31 December 2010 were eligible. The hazard ratio (HR) of all-cause mortality was calculated by employing adjusted time-dependent and time-fixed Cox proportional hazard models. Disease-specific survival was estimated by means of 3-year relative survival rates (RSR). A control cohort of randomly selected patients using statins from PHARMO Database Network matched on age and gender was used to compare RSR of statin users to the general population. After melanoma diagnosis, 171 of 709 patients used statins. Use of statins showed a nonsignificantly decreased hazard of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50–1.61). After stratification for gender, male but not female statin users showed a favorable outcome compared to nonusers (HR 0.57, 95% CI 0.32–0.99; HR 1.22, 95% CI 0.62–2.38, respectively). Three-year RSR for male statin users tended to be higher than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved survival of melanoma patients. The trend for better survival of male in contrast to female statin users warrants further research