Yao JJ, et al. - In this single-arm, phase 2 clinical trial, researchers investigated the efficacy and safety of primary surgery with postoperative radiotherapy for the treatment of prospectively enrolled patients with non-metastatic, histologically proven head and neck mucosal melanoma (HNMM). This study was conducted at Sun Yat-Sen University Cancer Center. Primary surgery was performed on all patients, which was followed by treatment with intensity-modulated radiotherapy with an equivalent dose at 2 Gy per fraction of 65–70 Gy to CTV1 (high-risk regions including tumor bed) and 50–55 Gy to CTV2 (low-risk regions). With 58 years (range 27–83 years) as median age at diagnosis, 18 (54.5%) patients with T3 disease and 15 (45.5%) patients with T4a disease were analyzed; 61% of the cohort were male. The estimated 3-year overall survival rate was 44.4%, local relapse-free survival rate was 91.7%, regional relapse-free survival (RRFS) rate was 78.1% and distant metastasis-free survival rate was 41.7%. Superior RRFS was noted nearly in relation to prophylactic neck radiation. Generally, mild to moderate toxicities were reported. Excellent local control and acceptable toxicity profile were observed for primary surgery with postoperative radiotherapy for HNMM. Nevertheless, limited survival attributed to high rates of distant metastases was also noted.