Assessing Prognostic Value of Quantitative Neck Dissection Quality Measures in Patients with Clinically Node-Negative Oral Cavity Squamous Cell Carcinoma

Importance: In clinically localized (T1-2) oral cavity squamous cell carcinoma (OCSCC), regional lymph node metastasis is associated with a poor prognosis. Given the high propensity of subclinical nodal disease in these patients, upfront elective neck dissections (END) for patients with clinically node-negative disease are common and associated with better outcomes. Unfortunately, even with this risk-adverse treatment paradigm, disease recurrence still occurs, and our understanding of the factors that modulate this risk and alter survival have yet to be fully elucidated. Objective: To investigate the prognostic value of lymph node yield (LNY), lymph node ratio (LNR), and weighted LNR (wLNR) in patients with clinically node-negative T1-2 OCSCC. Design, Setting, and Participants: In this cohort study, data were collected retrospectively from 7 tertiary care academic medical centers. Overall, 523 patients with cT1-2N0 OCSCC who underwent elective neck dissections after primary surgical extirpation were identified. Exposures: Lymph node yield was defined as the number of lymph nodes recovered from elective neck dissection. Lymph node ratio was defined as the ratio of positive nodes against total LNY. Weighted LNR incorporated information from both LNY and LNR into a single continuous metric. Main Outcomes and Measures: Locoregional control (LRC) and disease-free survival (DFS) were both evaluated using nonparametric Kaplan-Meier estimators and semiparametric Cox regression. Results: On multivariable analysis, LNY less than or equal to 18 lymph nodes was found to be significantly associated with decreased LRC (aHR, 1.53; 95% CI, 1.04-2.24) and DFS (aHR, 1.46; 95% CI, 1.12-1.92) in patients with pN0 disease, but not those with pN-positive disease. Importantly, patients with pN0 disease with LNY less than or equal to 18 and those with pN1 diseasehad nearly identical 5-year LRC (69.7% vs 71.4%) and DFS (58.2% vs 55.7%). For patients with pN-positive disease, LNR greater than 0.06 was significantly associated with decreased LRC (aHR, 2.66; 95% CI, 1.28-5.55) and DFS (aHR, 1.65; 95% CI, 1.07-2.53). Overall, wLNR was a robust prognostic variable across all patients with cN0 disease, regardless of pathologic nodal status. Risk stratification via wLNR thresholds demonstrated greater optimism-corrected concordance compared with American Joint Committee on Cancer (AJCC) 8th edition nodal staging for both LRC (0.61 vs 0.57) and DFS (0.61 vs 0.58). Conclusions and Relevance: Movement toward more robust metrics that incorporate quantitative measures of neck dissection quality and regional disease burden, such as wLNR, could greatly augment prognostication in cT1-2N0 OCSCC by providing more reliable and accurate risk estimations.