Increasing melanoma incidence with unchanged mortality: more sunshine, better treatment, increased diagnostic activity, overdiagnosis or lowered diagnostic threshold?

Increasing melanoma incidence with less increasing mortality is observed in several countries. This discrepancy is not well understood. In this study, our aim was to discuss factors (UV exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions) that may influence melanoma incidence and mortality in Denmark. This was a register study with the number of melanocyte-related lesions and melanoma mortality based on comprehensive national pathology and mortality databases for the period 1999-2019. We investigated melanocyte-related diagnoses and mortality in a population of 5.5 million with national health care system. Age adjusted melanoma mortality and age-adjusted incidence of benign nevi, atypical lesion, or melanoma-in-situ and of invasive melanoma were computed for data analysis. In total 1,434,798 biopsies were taken from 704,682 individuals (65% female). Mean age at biopsy was 39.8 years in men and 37.6 in women. In men and women, the incidence of invasive melanoma increased by 87% during the period 1999-2011. During the subsequent period it increased by 9% in men but remained unchanged in women. The incidence of melanoma in-situ increased by 476% in men and 357% in women during the study period, while the increases for atypical melanocytic lesions were 1928% and 1686%, respectively. Biopsy rates increased by 153% in men and 118% in women from 1999 through 2011 but fell by 20% in men and 22% in women during the subsequent period. Mortality varied slightly from year to year without any significant time trend for men or women.We identified no evidence of increased UV exposure over the latest 30 years in Denmark. Immunotherapy of advanced melanoma was introduced in Denmark in 2010 and came in general use in 2014. Comprehensive national data demonstrate increasing melanoma incidence correlated with increasing biopsy rates, but with no change in mortality. Previously suggested explanations for such a trend are lowered threshold of melanoma diagnosis among pathologists, increased diagnostic activity in the presence of overdiagnosis and improved melanoma treatment. Because the study is observational and because we have more explanatory factors than outcomes, the findings do not warrant conclusions about causal relationships.