Synergy of nodal factors in predicting recurrence after treatment of N1b papillary thyroid carcinoma

Abstract Background Nodal factors are important predictors of prognosis for papillary thyroid carcinoma (PTC), but their synergistic effect is not well understood. We aimed to explore their synergy in predicting recurrence of clinical N1b (cN1b) PTC. Methods Patients who underwent surgery for cN1b PTC from 2013 to 2017 were enrolled. The association between nodal factors and recurrence was assessed using Cox proportional hazards regression models. Interaction and stratified analyses were conducted according to significant nodal factors. Results Of 1067 cN1b PTC patients included, all nodal factors (bilateral metastasis, largest dimension > 3 cm, micro and gross extranodal extension (mENE, gENE), number of metastatic lymph nodes [MLN], lymph node yield [LNY], and ratio LNR]) were significantly associated with all site and nodal recurrence in the univariate analysis (all P < .05). Multivariate analyses revealed largest dimension > 3 cm, gENE and LNR > 0.21 were associated with elevated both all site (hazard ratio [HR] [95% CI], 2.58 [1.67-4.00], 1.87 [1.26-3.01], 1.68 [1.11-2.42], all P < .01) and nodal recurrences (HR [95% CI], 2.63 [1.67-4.13], 1.90 [1.15-3.12], 1.76 [1.17-2.66], all P < .01). LNR and gENE had interactive effect (all site recurrence: P for interaction = .009; nodal recurrence: P for interaction = .02). LNR was significantly associated with recurrence in patients without gENE (HR [95% CI], all site recurrence: 2.41 [1.50-3.87]; nodal recurrence: 2.51 [1.52-4.14], all P < .001), while when gENE appeared, LNR was no longer associated with recurrence (HR [95% CI], all site recurrence: 0.81 [0.43-1.54], P = .53; nodal recurrence: 0.85 [0.43-1.67], P = .64). Conclusion Nodal factors have synergistic effect in predicting recurrence in cN1b PTC patients. Increasing lymph nodes harvest may only decrease recurrence in patients without gENE, while not in gENE patients.