Development and Validation of a Novel Pathologic Nodal Staging System for Oral Squamous Cell Carcinoma After Neoadjuvant Immunochemotherapy.

Abstract

Neoadjuvant immunochemotherapy (NICT) has transformed the treatment of locally advanced oral squamous cell carcinoma (OSCC), yet the prognostic reliability of the eighth-edition American Joint Committee on Cancer (AJCC) pathologic nodal staging in this context remains unclear. This study sought to develop a ypN staging system for post-NICT OSCC. This retrospective study analyzed 559 patients with locally advanced OSCC who received NICT followed by radical surgery across two centers (training cohort, n = 226; external validation cohort, n = 333). A proposed ypN staging system integrating viable node burden and macro- extranodal extension (ENE) status was developed and externally validated. Model performance was compared with the eighth-edition AJCC staging using Harrell's C-index, the Akaike Information Criterion, and decision curve analysis. Three prognostic groups emerged (0, 1-2, and ≥3 viable metastatic lymph nodes). Multivariate analysis showed that micro-ENE did not add significant risk (hazard ratio, 1.12; P = 0.79), whereas macro-ENE independently predicted recurrence. The proposed staging framework, which categorizes patients into ypN0 (0 viable nodes), ypN1 (1 to 2 viable nodes without macroscopic ENE), ypN2 (≥3 viable nodes without macroscopic ENE), and ypN3 (≥1 viable nodes with macroscopic ENE), produced a clearly distinct prognostic gradient, with 3-year disease-free survival rates of 84.1, 61.2, 31.8, and 9.1%, respectively. This system outperformed the eighth-edition AJCC staging in both cohorts, demonstrating higher C-indices (0.78 vs 0.70; 0.76 vs 0.69), lower AICs, and superior net clinical benefit. The proposed ypN staging system, grounded in viable metastatic lymph node burden and macro-ENE, offers improved prognostic discrimination for post-NICT OSCC.