Superior prognostic performance of modified N staging incorporating N1c in papillary thyroid carcinoma

The current N staging system for papillary thyroid carcinoma (PTC) faces challenges due to prognostic heterogeneity among different lymph node metastasis (LNM). This study aims to evaluate the prognostic significance of various LNM regions and refine the current N staging system (N0, N1a, N1b). We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, including 40,371 PTC patients between 2004 and 2015. Patients were categorized into different groups: N0, N1a, N1b and a new hypothetical and modified N stage, N1c. The effect of different LNM on Cancer-specific survival (CSS) was assessed using hazard ratios (HRs) and absolute survival differences. Cox and Fine-Gray models estimated HRs with 95% confidence intervals (CIs), while logistic regression identified risk factors. The performance of staging systems was compared using C-index, Brier score, and Akaike Information Criterion. We found that patients with LNM in levels I, Vb, and VII showed a similar survival pattern with similarly poor CSS. The introduction of the N1c category revealed a more aggressive clinicopathological characteristics among these patients. Multivariate Cox analysis determined that N1c was associated with the worst CSS (adjusted HR (95%CI) for N1a, N1b, and N1c vs. N0: 2.62 (2.04-3.36), 3.93 (3.04-5.10), and 5.51 (4.02-7.55), respectively). Multivariate logistic analysis identified independent risk factors for N1c LNM including younger age, male, larger size, extrathyroidal extension, and multifocality. The modified N staging system demonstrated superior performance. Therefore, the N staging system for PTC was improved by introducing this hypothetical and modified N1c category for LNM in levels I, Vb, and VII, based on their similar clinical behavior and poor prognosis.