High-volume cervical lymph node metastasis in papillary thyroid carcinoma: development and external validation of an interpretable prediction model.

Background: The transportability of models for postoperative high-volume cervical nodal disease in papillary thyroid carcinoma (PTC) and the incremental predictive value of molecular variables remain uncertain. Methods: We developed models in the public Deyang cohort (521 patients; 90 events) and performed geographic external validation in the independent Liaocheng cohort (193 patients; 73 events). The outcome was >5 pathologically confirmed metastatic cervical lymph nodes. Five algorithms were compared using repeated stratified nested cross-validation with a prespecified 10-variable postoperative feature set. Ridge logistic regression (C = 0.1) was selected and applied without refitting. Paired comparisons of 8-variable clinicopathological and 10-variable clinicopathological-molecular models assessed the incremental value of high-risk co-mutation status and mutation count in both cohorts. Results: Internal validation yielded an area under the receiver operating characteristic curve (AUROC) of 0.795 (95% CI, 0.745-0.842), average precision (AP) of 0.497 (0.406-0.598), and Brier score of 0.115 (0.098-0.134). External AUROC was 0.752 (0.678-0.821), AP 0.601 (0.498-0.728), and Brier score 0.217 (0.180-0.254). Observed and mean predicted risks were 37.8% and 23.9%, respectively; the observed-to-expected ratio was 1.582 (1.319-1.860) and the weak-calibration slope was 0.831 (0.542-1.191). At the prespecified threshold of 0.158, sensitivity was 0.795 and specificity 0.600. Net benefit was 0.254 for the model and 0.261 for classifying all patients as high risk (difference, -0.008; 95% CI, -0.051 to 0.033). External paired differences after adding molecular variables were +0.002 for AUROC (-0.005 to 0.010), -0.002 for AP (-0.016 to 0.010), -0.001 for Brier score (-0.002 to 0.000), and +0.009 for net benefit (-0.003 to 0.026). Conclusion: The model retained moderate discrimination across centers but underestimated absolute risk and did not demonstrate a net benefit advantage over classifying all patients as high risk at the prespecified threshold. High-risk co-mutation status and mutation count showed no clear incremental predictive value. Further validation with standardized lymph-node assessment and patient outcomes is required before clinical application.