High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer

Background: Due to unique biology and prognosis, precise identification of predictive parameters is critical for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Prior studies showing absence of prognostication from extracapsular spread (ECS) and/or high N-classification in surgically-treated p16+ OPSCC necessitate new, evidence-based prognosticators. Methods: A prospectively assembled cohort of 220, transoral surgery + neck dissection ± adjuvant therapy-treated, p16+ OPSCC patients was analyzed. Disease recurrence and disease-specific survival (DSS) were primary endpoints. Results: Median follow-up was 59 (12-189) months. Distribution of metastatic node numbers was: 0 in 9.5% (n = 21), 1 in 33.6% (n = 74), 2 in 17% (n = 38), 3 in 14.5% (n = 32), 4 in 8.2% (n = 18), and ≥5 in 17% (n = 37). ECS was recorded in 80% (n = 159), and N2c-N3 in 17% (n = 38). Adjuvant radiotherapy and chemoradiotherapy was administered in 44% and 34%. Recurrence developed in 22 patients (10%); 4 local, 5 regional, 2 regional and distant, and 11 distant. The 3- and 5-year DSS estimates were 94.6% and 93%. Multivariable logistic regression identified ≥5 nodes and T3-T4 classification as predictors for recurrence. In multivariable Cox analyses, ≥5 nodes, T3-T4 classification and margins were prognostic for DSS. ECS, N2c-N3 classification and smoking were not prognostic. Conclusions: Metastatic node number, not ECS or high N-classification is an independent nodal predictor of outcomes in surgically-treated p16+ OPSCC patients. Despite high DSS (∼80%), closer surveillance for recurrence is recommended for patients with ≥ 5 metastatic nodes.