Abstract

The current 7th TNM staging stratifies N1b papillary thyroid cancer (PTC) patients without distant metastasis into either stage I or stage IV merely by an age threshold (45 years). To date, no studies have adequately quantified the mortality risk of PTC patients with N1b disease. We hypothesized that incorporating lymph node (LN) factors into the staging system would better predict cancer‐specific mortality (CSM). A total of 745 nonmetastatic PTC patients with N1b disease were enrolled. We identified factors related to LNs and cut‐points using Cox regression and time‐dependent ROC analysis. New prognostic groupings were derived based on minimal hazard differences for CSM among the groups stratified by LN risk and age, and prediction of CSM was assessed. Lateral lymph node ratio (LNR) and largest LN size were significant prognostic LN factors at cut‐points of 0.3 and 3 cm. Without LN risk (lateral LNR >0.3 or largest LN size >3 cm), stage IV patients had prognosis [adjusted HR 1.10 (98% CI 0.19–6.20); P = 0.906] similar to stage I patients with LN risk. Patients were restratified into three prognostic groups: Group 1, <45 years without LN risk; Group 2, <45 years with LN risk or ≥45 years without LN risk; and Group 3, ≥45 with LN risk. This system had a lower log‐rank P‐value (<0.001 vs. 0.002) and higher C‐statistics (0.80 vs. 0.71) than the 7th TNM. New prognostic grouping using lateral LNR and largest LN size predicts CSM accurately and distinguishes N1b patients with different prognosis.

Highlights

  • Thyroid cancer is one of the most common cancers, and its detection rate continues to rise worldwide with excellent prognosis [1,2,3]

  • In the 7th AJCC/UICC staging system, all N1b patients 45 years or older are classified as stage IV regardless of other factors [4, 5], and risk of N1b is exaggerated

  • Wang et al suggested that lymph node (LN) burden >17% in the lateral neck is predictive of recurrence, but none of the evaluated LN characteristics predicted cancer-­ specific mortality (CSM) [11]

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Summary

Introduction

Thyroid cancer is one of the most common cancers, and its detection rate continues to rise worldwide with excellent prognosis [1,2,3]. Unlike the other cancer AJCC/UICC staging system, the N stage of thyroid cancer is divided only by the location of metastatic lymph node (LN): N1a, central node metastasis, or N1b, lateral node metastasis. In the 7th AJCC/UICC staging system, all N1b patients 45 years or older are classified as stage IV regardless of other factors [4, 5], and risk of N1b is exaggerated. Considerable efforts have been made to find variable LN factors to subdivide papillary thyroid cancer (PTC) patients with lateral neck metastasis. Most studies have focused on tumor recurrence instead of CSM, and optimal cut-­ points of continuous prognostic values have not been appropriately evaluated in PTC N1b patients

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