Background: The prognostic value of perineural invasion (PNI) in oral tongue squamous cell carcinoma (OTSCC) is debated. Understanding patterns of failure associated with PNI warrants consideration when recommending adjuvant therapy for this adverse feature in isolation. Additionally, it is unclear if subclassification of PNI improves risk stratification.
Methods: Patients with OTSCC who received primary surgical treatment at Memorial Sloan-Kettering Cancer Center from 2000-2012 were identified. In total, 381 patient’s specimens, stages T1-T4, were reviewed by head and neck pathologists for presence of PNI. In cases with PNI identified, further histopathologic analysis was conducted to sub classify PNI characteristics Overall survival (OS), disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and disease recurrence-free survival (DRFS) estimates were calculated by the Kaplan Meier method as primary endpoints. PNI and characteristics of PNI as predictors of outcome were analyzed by univariate and multivariable Cox proportional hazards regression analysis.
Results: PNI was present in 105 (28.7%) cases. Patients with PNI were more likely to have a higher T-stage tumor, lymph node metastasis (p=0.001) and p=0.001, respectively). A majority of the patients were male (58.3%) and under the age of 60 (55.6%). At a median follow-up of 39.8 months (0.03-150.1 months), the 5-year rates of OS, DSS, LRFS, RRFS, and DRFS for all patients were 71.5%, 81.5%, 79.7%, 83.5% and 92.6%, respectively. On multivariable analysis, when adjusting for tumor size and lymph node status, patients with PNI had a decreased DSS (HR 2.67 CI 1.38-4.79, p=0.003). When adjusting for tumor size, tumor thickness vascular invasion, margin status, lymph node status, and postoperative RT, patients with PNI had a decreased OS (HR 2.74 CI 1.17-4.37, p< 0.001). In contrast, PNI was not predictive of LRFS or RRFS on multivariable analysis. However, when PNI was present, patients were 6.39 (CI: 2.70-15.10, p=0.003) times more likely to have a distant recurrence and 19.40 (CI 6.70-56.14, p<0.001) more likely if foci density (defined as foci of PNI/tumor section) was greater than one on univariate analyses when compared to having no PNI.
Conclusion: Presence of PNI in OTSCC predicts for worse DSS and OS. Distant recurrence is the driving pattern of failure in patients with PNI. Increase foci density is associated with worse DRFS. Recommendation of adjuvant therapy and the development of new strategies should be considered in the context of patterns of failure in patients with PNI as an isolated adverse feature.