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Development of a nodal burden-extranodal extension classification for pathological nodal staging in oral cavity
Hemant Nemade1, Abhinav Thaduri1, Jonathan T Gondi1
1Department of Head and Neck Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India.
Background:
The current AJCC 8th edition pathological N staging for oral cavity squamous cell carcinoma (OSCC) incorporates extranodal extension (ENE) but does not fully account for metastatic nodal burden, leading to considerable prognostic heterogeneity within nodal categories. We aimed to develop a pathological nodal classification that integrates metastatic nodal burden and ENE and to compare its prognostic performance with the AJCC 8th edition system.
Methods:
We retrospectively analysed a prospectively maintained cohort of 3,689 consecutive patients who underwent primary surgery for OSCC between 2015 and 2023. Metastatic nodal burden was evaluated as a continuous variable using restricted cubic spline analysis and categorised into four groups (1, 2, 3-4, and ≥ 5 positive nodes). These categories were combined with ENE status and refined using disease-free survival (DFS) hazard ratios to derive a six-category nodal burden-ENE (NB-ENE) classification. Prognostic performance was compared with AJCC pathological N staging using Cox regression, Harrell's C-index, likelihood ratio χ2 statistics, Akaike information criterion (AIC), bootstrap validation, and time-dependent ROC analysis.
Results:
The proposed classification reclassified 52.3% of AJCC N2b patients and all AJCC N3b patients into distinct prognostic groups. Within AJCC N2b disease, recurrence risk differed significantly between NB-ENE2 and NB-ENE1 (HR 1.57, 95% CI 1.16-2.13) and between NB-ENE3 and NB-ENE1 (HR 2.10, 95% CI 1.42-3.09). Compared with AJCC pathological N staging, the NB-ENE classification demonstrated improved model fit (DFS AIC 20921.3 vs 21007.4), higher discrimination (C-index 0.662 vs 0.652), and a greater likelihood ratio χ2 (410.95 vs 323.53).
Conclusions:
A pathological classification integrating metastatic nodal burden and ENE provides superior prognostic stratification compared with AJCC 8th edition nodal staging and offers a practical framework for future refinement of pathological nodal staging in surgically treated OSCC.