Risk Stratification by Extent of Extranodal Extension and Peri-Neural Invasion in Post-Operative Oral Cavity Squamous Cell Carcinoma Undergoing Adjuvant Radio Therapy (EXTENT Study).

BACKGROUND: The AJCC 8th edition recommends subclassifying extranodal extension (ENE) and perineural invasion (PNI) in oral cavity squamous cell carcinoma (OCSCC), though their prognostic relevance remains uncertain. METHODS: Post-operative OCSCC patients (2019-2024) receiving adjuvant radiotherapy or chemoradiotherapy with documented ENE and/or PNI were retrospectively analyzed. ENE (microscopic [miENE] vs. macroscopic [maENE]) and PNI (intratumoral [IPNI] vs. extratumoral [EPNI]) were correlated with disease-free survival (DFS), overall survival (OS), and failure patterns using multivariate Cox models. RESULTS: Among 410 patients (median follow-up: 33 months), 3-year DFS and OS were 45.6% and 53.2%. ENE subtyping did not impact DFS or OS. EPNI independently predicted inferior DFS (43.3% vs. 49.5%, p = 0.019) and OS (50.2% vs. 57.9%, p = 0.02). Combined EPNI, ENE, and lymph-node ratio > 0.05 identified a very high-risk subgroup. CONCLUSION: ENE subclassification lacked prognostic significance. EPNI predicted worse outcomes and, with ENE or high lymph node ratio, defines an aggressive phenotype warranting treatment intensification.