Sex disparities in melanoma stage, recurrence and mortality: A Danish cohort study, 2004 to 2024

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BACKGROUND: Male sex appears to be associated with more advanced melanoma stage and inferior prognosis, but population-based data on sex disparities in stage-specific recurrence and mortality remain limited. OBJECTIVES: The objective of this study was to examine sex disparities in (1) melanoma stage at diagnosis and (2) stage-specific recurrence and long-term melanoma-specific mortality. METHODS: This population-based cohort study included all Danes with melanoma from 2004 to 2022 identified in the Danish Cancer Register. The impact of sex on melanoma stage diagnosis (Breslow thickness, presence of ulceration, presence of lymph node metastases and presence of distant metastases) was investigated using multivariable logistic regression models. Furthermore, we examined melanoma recurrence, melanoma-specific and overall mortality for stage I + II (localized), stage III (locoregional) and stage IV (metastatic) melanoma in a competing risk model, adjusting for stage at diagnosis, comorbidity, age and calendar year. RESULTS: This study included 30,497 individuals diagnosed with melanoma; the median follow-up time was 8 years, and 14,409 (47%) were male. Males had, compared to females, an increased adjusted odds ratio (aOR) of Breslow thickness >4 mm (aOR 1.45, 95% CI: 1.31-1.59), presence of ulceration (aOR 1.28, 1.18-1.39), >1 lymph node metastases (aOR: 1.58, 1.38-1.80) and distant metastases (aOR: 1.69, 1.48-1.94). In stage-adjusted analyses, males with localized melanoma had an increased adjusted hazard ratio (aHR) of melanoma recurrence (aHR: 1.38, 1.27-1.51) and melanoma-specific mortality (aHR: 1.51, 1.34-1.71). In patients with locoregional and metastatic melanoma, males had an inferior prognosis, but it was less pronounced. CONCLUSIONS: This nationwide cohort study found that males were more likely to be diagnosed with more advanced stages of melanoma. Analyses stratified by stage at diagnosis, showed that males had a 20%-50% higher risk of melanoma recurrence, melanoma-specific and overall mortality across localized, locoregional and metastatic melanoma.

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