Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma

For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). R...

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Published in:	Cancer 2024-02, Vol.130 (3), p.410-420
Main Authors:	de Almeida, John R, Su, Jie Susie, Kolarski, Mirko Manojlovic, Truong, Tra, Weinreb, Ilan, Perez-Ordonez, Bayardo, Smith, Stephen M, Hosni, Ali, Patel, Snehal, Valero, Cristina, Xu, Bin, Ghossein, Ronald, Katabi, Nora, Clark, Jonathan, Low, Tsu-Hui Hubert, Gupta, Ruta, Graboyes, Evan M, Davies, Joel, Richardson, Mary, Pasham, Vishu, Jester, Rachel, Goldstein, David P, Huang, Shao Hui, Xu, Wei, O'Sullivan, Brian
Format:	Article
Language:	eng
Subjects:	Cancer Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - surgery Classification Head and Neck Neoplasms - pathology Humans Lymph nodes Lymph Nodes - pathology Mouth Neoplasms - pathology Neoplasm Staging Oral cancer Oral carcinoma Oral cavity Prognosis Retrospective Studies Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - pathology
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Summary:	For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.
ISSN:	0008-543X 1097-0142