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.

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. [ABSTRACT FROM AUTHOR]