Risk Factors and a Prediction Model of Lateral Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma Patients With 1-2 Central Lymph Node Metastases

Abstract

Background: Papillary thyroid cancer (PTC) in clinically lymph node-negative (cN0) patients is prone toward lymph node metastasis. As a risk factor for tumor persistence and local recurrence, lateral lymph node metastasis (LLNM) is related to the number of central lymph node metastases (CLNMs).

Methods: We performed LLNM risk stratification based on the number of CLNMs for cN0 PTC patients who underwent thyroidectomy and lymph node dissection between January 2013 and December 2018. A retrospective analysis was applied to the 274 collected patients with 1-2 CLNMs. We examined the clinicopathological characteristics of the patients and constructed a LASSO model.

Results: In the 1-2 CLNM group, tumors >10 mm located in the upper region and nodular goiters were independent risk factors for LLNM. Specifically, tumors >20 mm and located in the upper region contributed to metastasis risk at level II. Hashimoto's thyroiditis reduced this risk (p = 0.045, OR = 0.280). Age ≤ 30 years and calcification (microcalcification within thyroid nodules) correlated with LLNM. The LASSO model divided the population into low- (25.74%) and high-risk (57.25%) groups for LLNM, with an AUC of 0.715.

Conclusions: For patients with 1-2 CLNMs, young age, calcification, nodular goiter, tumor >10 mm, and tumor in the upper region should alert clinicians to considering a higher occult LLNM burden. Close follow-up and therapy adjustment may be warranted for high-risk patients.

Keywords: CLNM; LASSO; LLNM; PTC; cN0.

Figure 1

Overall flowchart of the study design.

Figure 2

Forest plots of risk factors for levels II–IV (A–C) and independent risk factors for LLNM (D). (A) Tumor sizes over 20 mm and located in the upper region contribute to level II LLNM and HT reduces its risk. (B, C) Tumor size over 10 mm, nodular goiter, and the number of CLNMs were risk factors for level III (p = 0.001, OR = 2.742; p = 0.033, OR = 3.262; p = 0.002, OR = 2.535) and level IV (p = 0.003, OR = 2.964; p = 0.031, OR = 3.489; p = 0.036, OR = 1.834). High risk evaluated by the LASSO model is an independent risk factor for all levels. (D) Tumor size over 10 mm, nodular goiter, and upper location were independent risk factors for LLNM. In detail, tumor size over 20 mm and located in the upper region are independent risk factors and HT is an independent protective factor for level II. Nodular goiter is an independent risk factor for level IV.

Figure 3

Multivariate risk model constructed by LASSO regression (A, B) and ROC curves of the LLNM risk scores for cN0 PTC patients with one to two CLNMs (C, D). (A, B) The LASSO model is best constructed with eight factors when Log(λ) equals to -3.5. The eight factors were tumor size 1 (over 10 mm), tumor size 2 (over 20 mm), tumor location, HT, calcification, bilaterality, CLNM number, and nodular goiter. (C) The ROC curve of patients who underwent LLND (levels II, III, and IV) presented AUCs of 0.715 (preoperative assessment group with six factors, blue line), 0.708 (intraoperative frozen group with CLNM number enrolled, green line), and 0.701 (postoperative assessment group, yellow line). (D) The ROC curve of patients who underwent LLND (levels III and IV) presented AUCs of 0.726 (preoperative assessment group with six factors, blue line), 0.733 (intraoperative frozen group, green line), and 0.722 (postoperative assessment group, yellow line).