Defining clinically relevant extranodal extension in patients with oral cavity squamous cell carcinoma

Abstract

Abstract

Background Extranodal extension (ENE) is a known adverse prognostic factor in oral cavity squamous cell carcinoma (OSCC). However, the prognostic relevance of different extents of ENE remains unclear. This study aimed to identify the threshold at which ENE extent becomes clinically significant in predicting overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS).

Methods We conducted a retrospective cohort study of OSCC patients treated with surgical resection and neck dissection at the University Medical Center Utrecht (2012–2020). Histological slides were re-evaluated by two head and neck pathologists to quantify ENE extent. Time-dependent ROC analyses were used to determine optimal cutoffs for ENE extent predicting OS, DSS, and RFS. Survival outcomes were assessed using Kaplan-Meier and multivariable Cox regression analyses.

Results Among 197 patients, ENE was observed in 90 (46%). Optimal ENE cutoffs were 1.2 mm for OS, 1.8 mm for DSS, and 0.7 mm for RFS. A 1.2 mm threshold, aligning with OS prediction and the mean of all outcomes, was used for dichotomization. ENE >1.2 mm was independently associated with worse OS, DSS, and RFS. ENE ≤1.2 mm had no independent prognostic value.

Conclusion In this single-center study, ENE extent of more than 1.2 mm is independently associated with poorer survival in OSCC. This threshold may aid in refining risk stratification beyond the current 2 mm guidelines. However, larger multicenter studies with broader pathologist participation are needed before recommending changes to clinical practice.