Prognostic impact of extranodal extension in oral cavity cancers: a retrospective analysis and implications for treatment intensification

Extranodal extension (ENE) and positive surgical margins are recognized high-risk factors in head and neck cancers. Despite their prognostic significance, ENE was incorporated into the AJCC 8th edition staging only recently. This study evaluates survival outcomes in patients with oral cavity squamous cell carcinoma (OCSCC) based on ENE status and its association with radiological ENE and other intermediate-risk features, including lymphovascular invasion (LVI), perineural invasion (PNI), T stage, and depth of infiltration (DoI).

We retrospectively analyzed 198 patients with OCSCC treated between 2015 and 2022 with surgery followed by adjuvant radiotherapy (60 Gy in 30 fractions), with or without concurrent chemotherapy. Chemotherapy was administered in cases with ENE or margin positivity. Patients were followed at 3-month intervals with clinical evaluations and imaging as indicated. Kaplan–Meier analysis was used to estimate overall survival (OS) and disease-free survival (DFS). Differences between groups were assessed using the log-rank test, and univariate and multivariate Cox regression analyses identified prognostic factors.

The mean age was 55 ± 12 years, with 86.4% male patients. The buccal mucosa (61.6%) was the most common subsite. After a median follow-up of 36 months, the 3-year OS and DFS rates were 56.0% and 53.1%, respectively. Patients with pathological ENE had significantly worse outcomes: 3-year DFS was 34.7% vs. 68.6% (HR: 0.303; p < 0.001), and OS was 35.3% vs. 74.0% (HR: 0.270; p < 0.001). Radiological node positivity, LVI, and PNI were also independently associated with poorer survival.

ENE significantly worsens OS and DFS in OCSCC patients, even with standard adjuvant chemoradiotherapy. These findings support the need for treatment intensification strategies, such as radiation dose escalation and/or additional systemic therapy, in this high-risk group.