Pathological risk factors stratification in pN3b oral cavity squamous cell carcinoma: Focus on the number of positive nodes and extranodal extension

Objective: According to the AJCC 2017 Staging Manual, oral cavity squamous cell carcinoma (OCSCC) with pN2 disease (based on the AJCC 2010 criteria) and extra-nodal extension (ENE) should be classified as pN3b. We performed a detailed outcome analyses in this patient subgroup. Material and methods: We retrospectively reviewed the clinical records of consecutive OCSCC patients who underwent radical surgery between 1996 and 2017. Patients with pN3b disease (n = 365) were divided into a pN+ ≥8/ENE ≥5 subgroup (defined by the presence of pN+ ≥8 nodes or ENE ≥5 nodes, n = 77) and a pN+ ≤7/ENE ≤4 subgroup (defined by the presence of pN+ ≤7 nodes and ENE ≤4 nodes, n = 288). Patients with pN0/pN1/pN2 (n = 1192/179/197) disease were included for comparison purposes. Results: Patients in the pN+ ≥8/ENE ≥5 subgroup had less favorable 5-year outcomes than those in the pN+ ≤7/ENE ≤4/pN2/pN1/pN0 groups (local control, 64%/79%/86%/83%/88%, p < 0.001; neck control, 55%/75%/80%/86%/93%, p < 0.001; distant metastases, 67%/28%/20%/12%/3%, p < 0.001; disease-free survival, 21%/51%/64%/72%/82%, p < 0.001; disease-specific survival, 25%/55%/71%/82%/92%, p < 0.001; overall survival, 19%/40%/54%/64%/82%, p < 0.001; respectively). Among patients with pN3b disease, multivariable analysis identified the pN+ ≥8/ENE ≥5 subgroup, lower neck (level IV/V) metastases, and depth of invasion ≥25 mm as independent adverse prognostic factors for 5-year distant metastases and survival rates. Conclusions: Patients in the pN+ ≥8/ENE ≥5 subgroup have an unfavorable prognosis and their classification as pN3b is advisable. In contrast, patients in the pN+ ≤7/ENE ≤4 subgroup should be classified as pN3a.