Cutaneous angiosarcoma: Long-term outcomes and risk factors of local recurrence, metastasis and disease-specific mortality in a Danish nationwide cohort

BACKGROUND: Cutaneous angiosarcoma is associated with a poor prognosis. Investigation of key prognostic factors is warranted, as methodological constraints and short follow-up periods limit previous studies. OBJECTIVE: To investigate the prognosis and identify risk factors in a comprehensive, nationwide population-based study of patients with cutaneous angiosarcoma. MATERIALS AND METHODS: All patients diagnosed with cutaneous angiosarcoma in Denmark between 2000 and 2023 were included. Absolute 5-year risks were estimated using multivariable cause-specific Cox regression models, treating all-cause mortality as a competing risk. RESULTS: We included 192 patients with cutaneous angiosarcoma with a median follow-up of 8 years. The 5-year risks were 40% for local recurrence, 41% for metastasis, 43% for both disease-specific mortality and overall survival, and 29% for progression-free survival. In the multivariable analysis of 5-year prognostic risk factors, poor tumor differentiation emerged as a strong predictor of local recurrence, metastasis and disease-specific mortality, whereas moderate tumor differentiation was only significant for metastasis and disease-specific mortality. Primary cutaneous angiosarcoma and invasion of the fascia and/or perineural/perivascular invasion were significant predictors of metastasis, while age >73 was associated with local recurrence. CONCLUSION: Cutaneous angiosarcoma should be considered a high-risk tumor and is associated with a poor prognosis across all outcomes. Poor and moderate tumor differentiation, primary cutaneous angiosarcoma, invasion of the fascia and/or perineural/perivascular invasion, and age >73 years were important predictors of adverse outcomes and may be considered potential high-risk features. The absence of these risk factors may therefore constitute a subgroup with a comparatively more favorable prognosis.