Metrics of pN-staging in oral squamous cell carcinoma: An analysis of 1,905 patients.

BACKGROUND We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. METHODS Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan-Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. RESULTS All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. CONCLUSIONS The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.