OBJECTIVES: To determine the relative 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) outcomes for adjuvant interferon therapy in the treatment of head and neck cutaneous melanoma (HNCM) with parotid gland involvement. METHODS: A retrospective cohort study was conducted at a single tertiary care institution to analyze patients undergoing parotidectomy for cutaneous head and neck melanoma involving the parotid gland from 2000 to 2014. Time-to-event analyses were performed using Kaplan-Meier curves with log-rank p-values and Cox proportional hazards models. RESULTS: The sample consisted of 82 patients who underwent surgical resection of stage III HNCM with parotid involvement. The mean follow-up was 67.8 months (SD 65) after diagnosis. Twenty-one patients received adjuvant interferon therapy, 12 patients received adjuvant radiation therapy, and 49 patients received no adjuvant therapy. Crude 5-year OS rates were 95.0% for interferon therapy, 33.3% for adjuvant RT, and 40.4% for no adjuvant therapy. Crude 5-year RFS rates were 75.2%, 19.5%, and 40.8% respectively. In the fully adjusted model, adjuvant interferon therapy was associated with improved 5-year OS compared to adjuvant RT (HR 0.10, 95% CI 0.011-0.837
p = 0.034). There was no significant association between adjuvant interferon therapy and 5-year RFS in the fully adjusted model. CONCLUSION: Adjuvant interferon therapy for surgically resected stage III cutaneous melanoma with parotid gland involvement may be associated with improved survival outcomes. These findings support the growing evidence for the use of immunotherapy in melanoma, and potentially a unique role for when melanoma involves the lymphatic-rich parotid gland. LEVEL OF EVIDENCE: 3 Laryngoscope, 135:1098-1104, 2025.