Rethinking Radiation Therapy for Perineural Invasion in Oral Cancer: Does More Coverage Improve Outcomes?

Introduction: Perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) is linked to aggressive tumour behaviour and poorer survival outcomes. Adjuvant radiotherapy (RT) is recommended for PNI-positive OSCC, but optimal RT target volume remains uncertain.

Methods: This study retrospectively analysed 103 patients with histopathologically confirmed PNI-positive OSCC treated between January 2017 and December 2023. All patients underwent surgery followed by adjuvant RT, with or without concurrent chemotherapy. Recurrence patterns were categorised as in-field, marginal or out-of-field. Survival outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed using the Kaplan-Meier method, and prognostic factors were analysed using univariate and multivariate models.

Results: The median follow-up was 22.2 months. The 2-year OS and DFS were 63% (95% CI: 53%-75%) and 57% (95% CI: 48%-68%), respectively. In-field recurrences constituted 70% of local failures, with no recurrences observed at the skull base despite conservative RT volumes. Extensive PNI, large nerve involvement and extratumoral spread were significantly associated with higher recurrence rates and poorer survival. Multivariate analysis identified advanced tumour stage (T3/T4) and extranodal extension (ENE) as independent predictors of worse OS (HR: 2.67, p = 0.016; HR: 2.08, p = 0.045, respectively), while depth of invasion (DoI) > 10 mm significantly impacted DFS (HR: 0.28, p = 0.04 for DoI ≤ 10 mm).

Conclusion: Our findings suggest that expanding RT volumes to cover entire cranial nerve pathways may not improve outcomes and increase the risk of toxicity. A personalised approach to RT planning, incorporating PNI extent, nerve involvement and other high-risk features, is essential for optimising treatment outcomes in PNI-positive OSCC.