Predictors and Clinical Outcomes of Level IV Nodal Metastasis in Oral Cavity Squamous Cell Carcinoma: A Retrospective Cohort Study of 578 Node-Positive Patients

TL;DR

This study identifies factors linked to level IV lymph node metastasis in oral cancer patients and assesses their impact on survival rates.

Contribution

The study provides new insights into predictors and clinical outcomes of level IV nodal metastasis in oral cavity squamous cell carcinoma.

Findings

27.2% of node-positive OCSCC patients had level IV nodal metastasis, with two-year DFS and OS rates of 55% and 72.2%, respectively.

Level IV metastasis was significantly associated with pT4b, pN3b, larger tumor size, and greater depth of invasion.

Primary tongue tumors, larger tumor size, involved margins, and perineural invasion were independent predictors of poorer DFS and OS.

Abstract

Background

Nodal metastasis in oral cavity squamous cell carcinoma (OCSCC) is associated with poorer prognosis. Limited evidence is available on the predictive factors and prognostic significance of level IV nodal metastasis. This study evaluated patient outcomes by analyzing disease-free survival (DFS) and overall survival (OS) in individuals with level IV nodal involvement.

Methods

The cohort for this retrospective study comprised all patients with node-positive OCSCC who underwent surgery between August 2011 and June 2021. The patients’ demographic and treatment details were abstracted from the electronic medical records. DFS and OS were analyzed using a log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis.

Results

Among the cohort of 578 node-positive patients, 27.2% exhibited level IV nodal metastasis. The two-year DFS and OS rates in the level IV nodal metastasis group were 55% and 72.2%, respectively. Patients with level IV involvement had a median age of 53 years (range: 21-85 years), were predominantly male (69.2%), and had a median follow-up of 30.1 months (range: 1-131.9 months). A significantly higher prevalence of level IV nodal metastasis was associated with pathological tumor stage 4b (pT4b) (45.3% vs. 11.7%, p < 0.01), pathological nodal stage 3b (pN3b) (30.6% vs. 29.0%, p = 0.01), larger maximum tumor size (Tmax) (3.36 cm vs. 3.42 cm, p < 0.01), and greater depth of invasion (DoI) (1.44 cm vs. 1.63 cm, p < 0.01).

In univariate analysis, DFS was significantly associated with the primary site, Tmax, DoI, involved margins, lymphovascular invasion (LVI), perineural invasion (PNI), masticator space involvement, extranodal extension (ENE), and level IV nodal metastasis, in addition to pathological tumor stage (pT), pathological nodal status (pN), and overall stage. In multivariate analysis, the primary site, Tmax, involved margins, LVI, and PNI remained independently associated with DFS. For OS, univariate analysis identified the primary site, Tmax, DoI, involved margins, LVI, PNI, bone involvement, and ENE, as well as pT, pN, and overall stage, as significant predictors. Following multivariate adjustment, the primary site, Tmax, involved margins, and PNI emerged as independent predictors of OS.

Conclusion

The two-year DFS and OS rates for 578 patients with node-positive OCSCC were 55% and 72.2%, respectively. Among these patients, 157 (27.2%) exhibited level IV nodal metastasis, with skip metastasis to level IV observed in only 3.2% of cases. Patients with pT4b disease, pN3b disease, larger Tmax, and greater DoI were significantly more likely to have level IV metastasis. In univariate analysis, level IV metastasis was significantly associated with worse DFS. Additionally, primary tongue tumors, larger tumor size, involved surgical margins, and the presence of LVI or PNI were predictive of poorer DFS. For OS, significant predictors included primary tongue origin, larger tumor size, positive margins, and PNI.

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