Abstract / Summary
Neoadjuvant therapy (NAT) is increasingly used in locally advanced oral cavity squamous cell carcinoma (OCSCC), but its impact on disease control and surgical extent remains insufficiently defined. We evaluated survival, failure patterns and surgical extent after NAT versus upfront surgery within a surgery-plus-postoperative-radiotherapy (PORT) framework. We retrospectively analyzed an ambispective observational cohort of OCSCC patients treated with surgery and PORT between May 2023 and May 2026. Outcomes were compared using propensity-score matching (PSM) and inverse probability of treatment weighting (IPTW). Pretreatment planned surgical procedures were compared with actual post-NAT procedures. Among 78 eligible patients, 32 received NAT and 46 underwent upfront surgery; median follow-up was 20.0 months. In the NAT group, objective response, major pathological response, and pathological complete response rates were 65.6%, 21.9%, and 6.3%, respectively. Overall, 2-year disease-free survival (DFS), locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 84.3%, 93.7%, 91.1%, and 93.4%; distant metastasis was the predominant mode of failure. After PSM, NAT was associated with improved 2-year DFS (100.0% vs. 81.4%; p = 0.029) and reduced flap reconstruction (60.0% vs. 92.0%; p = 0.008). IPTW showed a consistent DFS trend (94.1% vs. 80.6%; p = 0.073). Within the NAT group, surgical extent was reduced in 87.5%, planned flap reconstruction was avoided in 34.4%, and planned glossectomy extent was reduced in 89.5% of oral tongue tumors. In locally advanced OCSCC treated with surgery and PORT, NAT was associated with favorable DFS and reduced surgical extent and reconstructive requirements without compromise in locoregional control. Prospective validation with functional and quality-of-life endpoints is warranted.