The origin of regional failure in oral cavity squamous cell carcinoma with pathologically negative neck metastases.

Importance Squamous cell carcinoma of the oral cavity (OSCC) is a common malignant tumor worldwide. Objective To determine if regional failure in patients with OSCC and pathologically negative neck nodes (pN–) is due to an incomplete sampling procedure during surgery. Design, Setting, and Participants We retrospectively reviewed the medical records of 2258 patients from 11 cancer centers worldwide who underwent neck dissection for OSCC (1990-2011) and who were pN−. Of those, 345 had clinical evidence of nodal metastases (cN+) on radiologic workup. The neck specimens were available for reanalysis in 193 patients. Survival rates were calculated using the Kaplan-Meier graphs and analyzed by multivariable analysis. Main Outcomes and Measures Five-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Results Resectioning and analysis of the neck dissection specimens in the cN+/pN− subgroup revealed false-negative results in 29 (15%) of 193 patients. The negative predictive value of the initial pathologic examination was 85%. The 5-year OS and DSS in the cN−/pN− group were 77.6% and 87.2%, respectively. The 5-year OS and DSS of the cN+/pN− group were 62.6% and 78.5%, respectively ( P P  = .03) and poor DSS (HR, 1.46; 95% CI, 1.1-4.1; P  = .04). A cN+ classification was associated with lower DFS (66.3% vs 76.2%; P  = .05) and lower regional recurrence–free survival (68.6% vs 78.8%; P  = .02) but not with local ( P  = .20) or distant recurrence ( P  = .80). Conclusions and Relevance Pathologic staging underestimates the incidence of nodal metastases in cN+ disease. After correction for pathologically missed nodal metastases, radiologic evidence of neck nodes is an independent predictor of outcome, suggesting that traditional sampling during surgery might miss metastases, and this fact might explain the origin of treatment failure in these patients.