Adjuvant Chemoradiotherapy for Oral Cavity SCC With Minor and Major Extranodal Extension

Importance Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. ENE is stratified into minor (≤2 mm) or major (>2 mm) extent. The role of adjuvant chemoradiotherapy, particularly for the minor ENE subgroup, is unclear. Objective To determine the impact of adjuvant chemoradiotherapy on oncological outcomes depending on the extent of ENE. Design, Setting, and Participants This retrospective, multicenter cohort study was conducted across 4 high-volume head and neck surgery centers in Australia, the US, and Canada. The study included patients with surgically resected OSCC with pathologic positive nodal disease treated between 2005 and 2018. Statistical analysis took place between 2022 and 2025; final follow-up was in 2022. Exposures Extent of ENE was restaged on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended per standard guidelines. Outcomes Univariable and multivariable analysis were used to assess the effect of chemotherapy for the entire group and for propensity score–matched cohorts on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) stratified by minor vs major ENE. Results A total of 755 patients (mean [SD] age, 61.7 [12.9] years; 36% female) were included in the study: 126 (17%) with minor ENE and 243 (32%) with major ENE. A total of 50 (39.7%) patients with minor ENE and 116 (47.8%) with major ENE received adjuvant chemotherapy. On multivariable analysis, chemotherapy was not associated with improved LRC (hazard ratio [HR], 1.07 [95% CI, 0.49-2.32]), DFS (HR, 0.96 [95% CI, 0.56-1.66]), or OS (HR, 0.97 [95% CI, 0.55-1.73]) in patients with minor ENE. However, in patients with major ENE, chemotherapy improved DFS (HR, 0.58 [95% CI, 0.41-0.81]) and OS (HR, 0.61 [95% CI, 0.38-0.98]). In propensity score–matched cohorts, chemotherapy did not improve LRC (71% vs 75%; difference, 4% [95% CI, −18% to 26%]), DFS (56% vs 56%; difference, 0% [95% CI, −25% to 25%]), or OS (57% vs 57%; difference, 0% [95% CI, −25% to 25%]) for patients with minor ENE, but improved DFS (33% vs 11%; difference, 22% [95% CI, 5%-38%]) and OS (41% vs 15%; difference, 26% [95% CI, 8%-44%]) but not LRC (61% vs 62%; difference, 1% [95% CI, −17% to 21%]) in patients with major ENE. Conclusions This multicenter cohort study found that in patients with OSCC, adjuvant chemotherapy is beneficial in patients with major ENE, but may not be beneficial in patients with minor ENE.