Single-center external validation and reconstruction of multiple predictive models for skip lateral lymph node metastasis in papillary thyroid carcinoma

Objective: The unique metastatic pattern of skip lateral lymph node metastasis (SLLNM) in PTC patients may lead to missed diagnosis of lateral cervical metastatic lymph nodes. Therefore, many different SLLNM prediction models were constructed. In this study, partially eligible models (Hu 2020, Wang 2020, and Zhao 2023 nomograms) were selected for external validation, and then new variables were incorporated for model reconstruction to extend clinical applicability. Methods: 576 PTC patients from our center were selected to evaluate the performance of the three nomograms using the receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA). Three new variables were added to calibrate the model, including assessment of LN status on ultrasound (US-SLLNM), the distance from the tumor to the capsule (Capsular distance), and the number of central lymph node dissections (CLND number). Univariate and multivariate logistic regression analyses were used to screen independent predictors to reconstruct the model, and 1000 Bootstrap internal validations were performed. Results: SLLNM were present in 69/576 patients (12.0%). In external validation, the area under the ROC curves (AUCs) for Hu 2020, Wang 2020, and Zhao 2023 nomograms were 0.695 (95% CI:0.633-0.766), 0.792 (95% CI=0.73-0.845), and 0.769 (95% CI:0.713-0.824), respectively. The calibration curves for the three models were overall poorly fitted; DCA showed some net clinical benefit. Model differentiation and net clinical benefit improved by adding three new variables. Based on multivariate analysis, female, age, and maximum tumor diameter <= 10 mm, located at the upper pole, Capsular distance < 0mm, US-SLLNM, CLND number <= 5 were identified as independent predictors of SLLNM and were used to construct the new model. After 1000 Bootstrap internal validations, the mean AUC of the model was 0.870 (95% CI:0.839-0.901), the calibration curve was close to the ideal curve, and the net clinical benefit was significant. Conclusion: Overall, these nomograms were well differentiated and provided some net clinical benefit, but with varying degrees of underestimation or overestimation of the actual risk and high false-negative rates. New dynamic nomogram was constructed based on the addition of new variables and larger samples, showing better performance.