Restratification of survival prognosis of N1b papillary thyroid cancer by lateral lymph node ratio and largest lymph node size

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.