Refining nodal classification in oral cancer: prognostic impact of nodal burden within N2b and implications for AJCC...

Pathological nodal status remains the most important determinant of prognosis in oral squamous cell carcinoma (OSCC). Although the AJCC 8th edition incorporated extranodal extension (ENE) to improve risk stratification, the N2b category-defined as multiple ipsilateral lymph nodes without ENE-remains biologically heterogeneous. We sought to determine whether nodal burden, defined by the absolute number of metastatic lymph nodes, could refine prognostic discrimination within N2b category and improve staging coherence.

We retrospectively analysed prospectively collected data from 1,049 patients with pathological N2b or N3b OSCC who underwent upfront surgery between 2015 and 2023. Disease-free survival (DFS) was the primary endpoint. Receiver operating characteristic (ROC) analysis was used to derive optimal nodal count thresholds for the N2b and N3b categories. These thresholds were incorporated into alternative nodal classification models and evaluated using Kaplan-Meier analysis, multivariable Cox regression, and Akaike Information Criterion (AIC)-based model comparison.

In N2b category, ≥3 metastatic lymph nodes identified as a high-burden subgroup with significantly inferior DFS (median 19 vs 52 months; p<0.001). Nodal burden remained independently associated with DFS on multivariable analysis. A consolidated burden-based classification demonstrated improved model fit compared with AJCC 8th edition staging (AIC 6048.40 vs 6152.7).

Nodal burden significantly influences prognosis within the N2b category (AJCC 8th edition) of oral cavity squamous cell carcinoma. Patients with ≥3 metastatic lymph nodes have markedly inferior disease-free survival than those with fewer involved nodes, underscoring biological heterogeneity not captured by current staging. Incorporating nodal count-based refinement improved prognostic discrimination while maintaining clinical simplicity.