Identification of Patients with Early-Stage Hepatocellular Carcinoma Benefiting from Neoadjuvant Chemotherapy-A SEER-Based Study

J Gastrointest Cancer. 2025 Jun 29;56(1):144. doi: 10.1007/s12029-025-01264-2.

Abstract

Background: The effectiveness of neoadjuvant chemotherapy (NAC) for individuals with early-stage hepatocellular carcinoma (HCC) is still a subject of controversy and uncertainty. This study sought to create a risk categorization model using a nomogram to pinpoint patients with early-stage HCC that might derive benefits from NAC.

Methods: This retrospective cohort study was based on data from the SEER Research Plus database (April 2021 release), covering the years 2006 to 2018. The definition of NAC was chemotherapy performed prior to surgery, while that of no NAC (No-NAC) was surgery without chemotherapy before the operation. We implemented stepwise Cox regression to discover prognostic factors and utilized these factors to develop a nomogram for forecasting the 3-, 5-, and 10-year cancer-specific survival (CSS) for patients with early-stage HCC. We utilized receiver operating characteristic curves, calibration curves, and decision curve analysis to evaluate the prognostic capacity of the nomogram. Finally, prognostic stratification was performed based on the optimal boundary value of the nomogram score, and we utilized the Kaplan-Meier method to analyze the survival rate.

Results: A sum of 11,721 HCC patients was incorporated in the analysis. After adjustment through propensity score matching, the baseline characteristics of the NAC and No-NAC groups were not statistically different. A total of 4030 patients, with the clinical data of their marital status, tumor number, fibrosis, alpha fetoprotein, grade, age, T stage, tumor size, race, and surgical approach (i.e., 11 variables) were employed in the building of the nomogram. The constructed nomogram exhibited good discriminatory ability and accuracy in predicting CSS in patients with early-stage HCC. Based on the nomogram, individuals can be classified into three distinct risk categories. In the group identified as high-risk, the CSS of the patients was significantly enhanced by NAC.

Conclusions: This study developed and validated a nomogram for predicting 3-, 5-, and 10-year CSS in early-stage HCC patients, incorporating demographic and clinical factors. Risk stratification identified high-risk patients who benefited significantly from NAC. These findings support personalized treatment decisions, though external validation is needed.

Keywords: Cancer-specific survival; Early-stage hepatocellular carcinoma; Neoadjuvant chemotherapy; Nomogram; Risk stratification.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Chemotherapy, Adjuvant / methods
  • Female
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Neoplasm Staging
  • Nomograms
  • Prognosis
  • Retrospective Studies
  • Risk Assessment / methods
  • SEER Program / statistics & numerical data
  • Survival Rate