Treatment outcomes of primary salivary gland squamous cell carcinoma: A multi-institutional retrospective study in Japan

Objective: Primary salivary gland squamous cell carcinoma (SCC) is extremely rare, accounting for 0.3-10.4 % of all salivary gland malignancies. Due to this rarity, the clinical characteristics of primary salivary gland SCC remain unelucidated. In the present study, we conducted a multi-institutional retrospective analysis-including a large number of cases compared with that of previous studies-to reveal the prognosis, treatment outcomes, and prognostic factors of primary salivary gland SCC. Methods: The clinical course of patients with primary salivary gland SCC between January 2012 and December 2022 was retrospectively investigated. Thirteen university hospitals and cancer centers in Japan participated in this study. The diagnosis of primary salivary gland SCC was based on the following criteria: 1) pathological diagnosis of SCC and exclusion of other histological types and 2) exclusion of metastatic SCCs from other organs. Progression-free and overall survival rates were compared using Kaplan-Meier curves and log-rank tests. Treatment outcomes were assessed using univariate and multivariate analyses with Cox proportional hazards models. Results: In total, 723 patients with salivary gland cancer were admitted to the participating institutions. Among them, 63 patients (8.7 %) were diagnosed with primary salivary gland SCC. The clinical courses of the 58 patients that received definitive treatment and had complete data were analyzed. Primary treatments included surgery in 35 patients (60.3 %), chemoradiotherapy in 16 (27.6 %), radiotherapy in 5 (8.6 %), and chemotherapy in 2 (3.4 %). Complete response and objective response rates to chemoradiotherapy were 62.5 % and 93.8 %, respectively. Five-year progression-free and overall survival rates were 30.1 % and 60.1 %, respectively. Five-year progression-free survival rates for each treatment were 37.7 % (surgery), 33.0 % (chemoradiotherapy), 0 % (radiotherapy), and 0 % (chemotherapy). Overall survival rates were 71.5 % (surgery), 39.5 % (chemoradiotherapy), 53.3 % (radiotherapy), and 0 % (chemotherapy). Multivariate analysis revealed that age >= 70 years, N classification >= 1, and surgery were independent predictors of progression-free (hazard ratios: 3.75, 2.46, and 0.33, respectively) and overall survival (hazard ratios: 3.11, 6.24, and 0.32, respectively). Adjuvant radiotherapy significantly improved progression-free and overall survival in patients with stage IV cancer or positive surgical margins. Log-rank tests revealed no significant difference between patients with or without elective neck dissection in progression-free and overall survival; however, a relatively high percentage of occult lymph node metastasis (50.0 %) was observed. Conclusion: Surgical resection is a favorable first-line treatment option in salivary gland SCC, and definitive chemoradiotherapy would show acceptable complete and objective response rates.