Incorporation of grade into stage in oral cavity squamous cell carcinoma: A novel staging schema

While numerous cancer staging systems have incorporated grade into stage, the impact of grade on oral cavity carcinoma (OCC) prognosis has been conflicting. We investigated grade as a prognostic determinant in OCC staging.

Multivariable Cox regression models of OCC patients identified via U.S. cancer registry data were constructed to determine associations between grade (G1 = low-grade, G2 = intermediate-grade, G3 = high-grade) and overall survival (OS). Recursive partitioning analysis (RPA) was used to derive staging schema.

Overall, 46,789 OCC cases were identified across 1,222 institutions. On univariate analysis, higher grade was associated with worse 5-yr OS (G1: 73% [95% CI 72-74%], G2: 61% [95 CI 60-61%], G3: 49% [95% CI 48-51%] (p < 0.001). On multivariable analysis adjusting for other prognostic factors, these survival differences persisted. Compared to G1 tumors, both G2 (HR 1.25 [95% CI 1.19-1.30], p < 0.001) and G3 (HR 1.52 [95% CI 1.45-1.61], p < 0.001) tumors were associated with significantly worse OS. Similar results were seen when utilizing propensity score matching. RPA generated subgroups that mirrored AJCC8E, but with G3 cases performing worse for a given stage. A proposed TNM + G staging schema was created with AJCC8E G3 cases upstaged by one category. Overall, 11.5% (4,745/36,623) cases were upstaged. TNM + G performed better than AJCC8E by c-index (0.673 vs. 0.671) and Brier score (0.174 vs. 0.175).

Large-scale analysis supports grade as an influential predictive determinant in OCC outcomes, with hazard on par with conventional staging factors. Incorporation of grade into stage strengthens existing AJCC OCC schema and pragmatically improves its ability to convey prognosis.