Neoadjuvant Treatment Approaches to Oral Cancer

Background/Objectives: The high prevalence of oral squamous cell carcinoma (OSCC) has driven the development of surgical and oncologic techniques to improve survival. Despite advancements in surgical technique and chemoradiation protocols, survival rates for locally advanced OSCC remain low due to high recurrence and metastasis. This has driven the exploration of neoadjuvant treatment protocols as a potential pathway towards improving organ-preserving resection, de-escalating adjuvant treatment, and improving overall and recurrence-free survival. Methods: This is a narrative review summarizing the current literature and ongoing trials on neoadjuvant treatment for OSCC. PubMed was searched using a snowballing technique to capture all relevant clinical trials. Results: 21 clinical trials were identified. Although neoadjuvant chemotherapy was associated with favorable pathologic outcomes, clinical trials demonstrated variable survival outcomes. In contrast, neoadjuvant immunotherapy for OSCC demonstrated improved pathologic responses and survival outcomes, with a low incidence of grade 3-4 adverse events. Conclusions: Neoadjuvant therapy in OSCC shows promise but does not yet constitute standard of care. Neoadjuvant immunotherapy has encouraging response rates and lower treatment-related toxicities in comparison to neoadjuvant chemotherapy. Although recent clinical trials have presented strong evidence to support the use of neoadjuvant immunotherapy in the treatment of locally advanced OSCC, further randomized trials are required to establish standardized neoadjuvant protocols and biomarkers to assess treatment response.