Surgery with complete resection improves survival in radiooncologically treated patients with cervical lymph node metastases from cancer of unknown primary

Purpose: To assess long-term toxicity, outcome and prognostic factors after multimodal treatment of cervical Lymph node metastases from cancer of unknown primary (CUP). Patients and Methods: In a retrospective study, the treatment results of 84 patients with CUP (median age 63 years, N1 n = 0, N2 n = 44, N3 n = 39, Nx n = 1), treated between 1971 and 2002 with radiotherapy (n = 84, median dose 60 Gy), platinum-based chemotherapy (n = 23) and surgery (n = 69, tonsillectomy [n = 40], neck dissection [n = 52], suprahyoid dissection [n = 18], Lymph node excision [n = 14]), were analyzed. Results: After a mean follow-up time of 25 months (ranging from 0.1 to 260 months), the 3- and 5-year overall (disease-free) survival rates were 30% (39%) and 27% (34%), respectively. 75% of individuals achieved remission, whereas 23% showed no change or progression after treatment. The 3-, 15- and 10-year local control rates were 58%, 58% and 46%, respectively. 40% of patients suffered grade 3/4 Late toxicity: severe skin contracture/induration (n = 2) and severe xerostomia (n = 32). Tonsillectomy (p = 0.003) and neck dissection (p = 0.037) performed before radiotherapy significantly improved outcome. Other prognostic factors were age (p = 0.0235), extracapsular spread (n 63; p = 0.0045), incomplete resection (n = 24; p = 0.0026), nodal disease (p = 0.0034), and distant metastases (n = 17; p = 0.0002). After multivariate analysis only extracapsular spread (p 0.004) and tonsillectomy (p = 0.01) showed impact on survival. Conclusion: Irradiation of cervical lymph node metastases from CUP is an effective treatment option with acceptable late toxicity. Complete tonsillectomy and neck dissection significantly improved survival in N2/N3 disease. Extracapsular spread was the best predictor for survival and Local control. Prospective studies defining a standard treatment are needed.