Incremental adverse impact of pathological factors in head and neck cancer with extranodal extension

Purpose Pathological extranodal extension (pENE) is a well-established adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate multiple adverse pathological features and to demonstrate their cumulative impacts on prognosis among patients with pENE-positive HNSCC. Methods A cohort of 281 patients with pENE-positive HNSCC that underwent upfront surgery followed by adjuvant chemoradiotherapy between 2008 and 2016 was retrospectively analyzed with Cox proportional hazards models being employed to identify factors associated with overall survival (OS) and disease-free survival (DFS). Results The 5-year OS and DFS rates in this cohort were 45.7% and 41.5% respectively. Positive surgical margins, poor tumor differentiation and positive metastatic lymph nodes over 3 (>3) were all independently associated with inferior OS and DFS. Patients were stratified into groups based on the number of these adverse pathological “P” factors (0, 1 or 2). When stratified by the number of these “P” factors, the 5-year OS rates were 55% for patients with none, 37.5% for one, and 6.7% for two factors (p < 0.001). A similar trend was observed for 5-year DFS (50.5%, 34.5% and 0.0% respectively; p < 0.001). The 2-factor group was small (n = 15), resulting in substantial statistical uncertainty. Conclusion Among patients with pENE-positive HNSCC, the accumulation of adverse pathological “P” factors was associated with incrementally poorer survival outcomes despite standard adjuvant chemoradiotherapy. These findings suggest that cumulative pathological risk factors might help identify patients at particularly high risk, although validation in larger independent cohorts is warranted.