De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.