Objectives: The management of patients with cervical metastasis in head and neck cancer of unknown primary (HNCUP) remains controversial. This current multicenter retrospective study investigated the treatment outcomes of patients with HNCUP. Methods: The study included patients who were treated curatively at 12 institutions in Japan from January 2006 to December 2015. Results: Eighty patients with HNCUP were included. The median follow-up period was 34 months. The three-year overall survival (OS), disease-specific survival (DSS), regional relapse-free survival (RRFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) rates were 72.5%, 80.3%, 74.0%, 89.7%, and 86.9%, respectively. Nodal status was a significant factor for OS, DSS, RRFS, and DMFS; and extracapsular extension (ECE) was significant for OS and DSS. There was a distinct difference between the survival rates of patients with N1–2a and N2b–3 disease. RT was a significant positive factor for LPFS (3-year LPFS, RT 93.0% vs. no RT 83.0%, p =.043). Conclusions: For N2a as well as N1 disease without ECE, a single treatment modality, including ND or RT alone is acceptable. When ND alone is performed, thorough monitoring should be continued during follow-up to identify the emergence of the primary lesion.
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