Poor tumor differentiation is an independent adverse prognostic variable in patients with locally advanced oral cavity cancer––Comparison with pathological risk factors according to the NCCN guidelines

Li Yu Lee, Chien Yu Lin, Nai Ming Cheng, Chi Ying Tsai, Chuen Hsueh, Kang Hsing Fan, Hung Ming Wang, Chia Hsun Hsieh, Shu Hang Ng, Chih Hua Yeh, Chih Hung Lin, Chung Kan Tsao, Tuan Jen Fang, Shiang Fu Huang, Li Ang Lee, Chung Jan Kang, Ku Hao Fang, Yu Chien Wang, Wan Ni Lin, Li Jen HsinTzu Chen Yen, Chun Ta Liao*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

18 Scopus citations

Abstract

Methods: We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results: Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three-level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5-year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p < 0.001), distant metastases (DM, 6%/18%/40%, p < 0.001), disease-free survival (DFS, 78%/63%/46%, p < 0.001), disease-specific survival (DSS, 85%/71%/49%, p < 0.001), and overall survival (OS, 68%/55%/39%, p < 0.001). Multivariable analysis identified the following variables as independent prognosticators for 5-year outcomes: ENE (LC/NC/DM/DFS/DSS/OS), poorly differentiated tumors (NC/DM/DFS/DSS/OS), positive margins (LC/DFS), lymphatic invasion (DFS/DSS/OS), perineural invasion (DM), and age ≥65 years (OS). Conclusions: In addition to ENE, poor tumor differentiation was identified as the second most relevant adverse RF for patients with pT3–4 OCSCC. We suggest that the NCCN guidelines should include poor tumor differentiation as an adverse RF to refine and tailor clinical management.

Original languageEnglish
Pages (from-to)6627-6641
Number of pages15
JournalCancer Medicine
Volume10
Issue number19
DOIs
StatePublished - 10 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Keywords

  • histopathological risk factors
  • oral cavity
  • prognosis
  • squamous cell carcinoma
  • tumor differentiation

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