Unknown primary of the head and neck: A long-term follow-up

J Craniomaxillofac Surg. 2015 May;43(4):574-9. doi: 10.1016/j.jcms.2015.03.004. Epub 2015 Mar 9.


Background: A diagnosis of squamous cell carcinoma of an unknown primary (CUP) is a major burden for patients. Because the location of the primary tumor is unclear, patients remain fearful of recurrence, which aggravates the uncertain prognosis of the disease. This study evaluates factors associated with long-term recurrence-free and overall survival of patients with CUP of the head and neck. Additionally, patient survival rates are compared with those of patients with head and neck squamous cell carcinoma (HNSCC).

Methods: A total of 293 consecutive patients operated on between January 1999 and December 2009 with at least a 5-year follow-up (survival permitting), were evaluated retrospectively.

Results: Twenty-six patients with a CUP of the head and neck were identified. Patients with CUP had a low overall survival rate, comparable with that of patients with pN + HNSCC, and recurrent disease occurred with a similar likelihood as in patients with pN + HNSCC. The median recurrence-free survival in the CUP group was 28.5 months compared with 48 months in the whole of the HNSCC group. The median overall survival of the CUP group was 56 months versus 65 months for the HNSCC group. Extracapsular spread was the only independent prognostic factor for overall survival for CUP patients.

Conclusion: Patients diagnosed with CUP syndrome have a poorer prognosis for overall survival compared with other HNSCC patients. Postoperative radiotherapy diminished disease recurrence and improved overall survival. Omission of postoperative radiotherapy resulted in a very high recurrence rate (75%) for CUP patients. Based on these results we suggest postoperative radiotherapy including the oral mucosa for all patients, regardless of histopathological results, possible favorable nodal disease, or favorable lymph node ratios.

Keywords: Carcinoma of unknown primary; Recurrence; Survival.

Publication types

  • Comparative Study

MeSH terms

  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / surgery
  • Chemoradiotherapy, Adjuvant
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / secondary*
  • Head and Neck Neoplasms / surgery
  • Humans
  • Longitudinal Studies
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neoplasms, Unknown Primary / surgery*
  • Prognosis
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Survival Rate