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

SIMPLE SUMMARY: Melanoma of the skin is the most lethal form of skin cancer. Almost 40% of the patients who die of metastatic melanoma did not have metastases at first diagnosis. More knowledge about patient and tumour characteristics as well as patterns of disease progression is needed. We described the characteristics and disease patterns of early-stage melanomas that progress into metastatic disease. We observed that more than half of the patients with metastases were initially diagnosed with early-stage disease. Additionally, we found that melanomas in some specific body sites were likely to metastasize to certain organs. Our finding that a substantial proportion of patients with metastases were initially diagnosed with early-stage disease highlights the need to investigate who these high-risk patients are. ABSTRACT: 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.