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Background <p>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.</p> Methods <p>This retrospective study analyzed 559 patients with locally advanced OSCC who received NICT followed by radical surgery across two centers (training cohort, <i>n</i> = 226; external validation cohort, <i>n</i> = 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.</p> Results <p>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; <i>P</i> = 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.</p> Conclusions <p>The proposed ypN staging system, grounded in viable metastatic lymph node burden and macro-ENE, offers improved prognostic discrimination for post-NICT OSCC.</p>

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

  • 期刊论文

  • 发表日期：

    2026年6月27日

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  • Yao Wu,
  • Xu Zhang,
  • Wei Du,
  • Junhui Yuan,
  • Wenlu Li,
  • Qigen Fang

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

The proposed ypN staging system, grounded in viable metastatic lymph node burden and macro-ENE, offers improved prognostic discrimination for post-NICT OSCC.