Development and Validation of a Novel Model to Predict Regional Lymph Node Metastasis in Patients With Hepatocellular Carcinoma

Xiaoyuan Chen; Yiwei Lu; Xiaoli Shi; Guoyong Han; Jie Zhao; Yun Gao; Xuehao Wang

doi:10.3389/fonc.2022.835957

Development and Validation of a Novel Model to Predict Regional Lymph Node Metastasis in Patients With Hepatocellular Carcinoma

Front Oncol. 2022 Feb 11:12:835957. doi: 10.3389/fonc.2022.835957. eCollection 2022.

Authors

Xiaoyuan Chen^{1

2

3

4}, Yiwei Lu^{2

3

4}, Xiaoli Shi^{1

2

3

4}, Guoyong Han^{2

3

4}, Jie Zhao^{2

3

4

5}, Yun Gao^{2

3

4}, Xuehao Wang^{1

2

3

4}

Affiliations

¹ School of Medicine, Southeast University, Nanjing, China.
² Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
⁴ NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China.
⁵ Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.

Abstract

Background: The evaluation of the nodal status of hepatocellular carcinoma (HCC) is a classic but controversial topic. This study aimed to investigate the incidence of lymph node metastasis (LNM), explore the role of lymph node dissection (LND), and develop and validate a novel model to predict LNM in patients with HCC, not other specified (NOS).

Methods: The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) was calculated using the Joinpoint regression. Survival analyses adopted the competing risk model. The nomogram was constructed based on the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm and validated by calibration curves. The area under the receiver operating characteristic curve (AUROC) was obtained to compare prognostic performance. Decision curve and clinical impact curve analyses were introduced to examine the clinical value of the models.

Results: A total of 8,829 patients were finally enrolled in this study, and 1,346 (15.2%) patients received LND. The LND rate showed no noticeable fluctuation in the last decade, with an APC of 0.5% (P=0.593). LNM was identified in 56 (4.2%) patients and confirmed an independent prognostic factor of HCC patients (P=0.005). There were 2,497 lymph nodes retrieved, and 93 (3.7%) of them were positive. After propensity score matching, LND indicated no direct oncologic benefit and did not worsen competing risks. Moreover, an increased number of lymph nodes retrieved could not improve prognoses. 1,346 patients with LND were further randomly divided into the training and validation sets with the ratio of 1:1. Race, tumor size, clinical T stage, extrahepatic bile duct invasion, and tumor grade were independent risk factors for LNM. The constructed model was well calibrated and showed good discrimination power and net benefits in clinical practice.

Conclusion: LNM is an independent prognostic factor in HCC, but routine LND seems to be unnecessary in HCC patients. The constructed model could predict the presence of LNM in HCC patients with good performance, which is meaningful to patient stratification and individual treatment strategies optimization.

Keywords: hepatocellular carcinoma; lymph node dissection; lymph node metastasis; nomogram; the SEER program.