Preoperative TACE with PD-1 inhibitors and TKIs in beyond "up-to-seven" hepatocellular carcinoma: a propensity score matched analysis

Front Immunol. 2025 Nov 26:16:1657371. doi: 10.3389/fimmu.2025.1657371. eCollection 2025.

Abstract

Background: HCC patients beyond the "up-to-seven" criteria face a high risk of recurrence, and optimal perioperative strategies warrant further investigation. This study evaluated the efficacy and safety of neoadjuvant TACE combined with PD-1 inhibitors and TKIs in this population.

Methods: We retrospectively analyzed 126 HCC patients who underwent curative liver resection between January 2021 and June 2024. Of these, 73 patients received preoperative TACE with PD-1 inhibitors and TKIs (PST group), and 53 underwent direct surgery without preoperative therapy (Surgery group). PSM was applied to control for confounding factors, resulting in 39 matched pairs. The primary endpoints were RFS and OS, with secondary endpoints including intraoperative blood loss, surgical time, and complications.

Results: After matching, the PST group demonstrated significantly superior RFS and OS compared to the Surgery group (P < 0.05). The median RFS was 26 months in the PST group versus 13 months in the Surgery group (P = 0.029). There were no significant differences in postoperative complications between the two groups (P = 0.365). The PST group exhibited longer surgical times (P < 0.001) and slightly higher intraoperative blood loss, suggesting increased surgical complexity due to preoperative therapy. Treatment-related adverse events were predominantly grade 1-2, with few grade 3-4 events.

Conclusion: Preoperative TACE with PD-1 inhibitors and TKIs was associated with improved survival without increasing severe complications in beyond "up-to-seven" HCC, suggesting a promising perioperative strategy for high-risk patients.

Keywords: hepatectomy; hepatocellular carcinoma (HCC); neoadjuvant therapy; propensity score matching (PSM); up-to-seven.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic* / adverse effects
  • Chemoembolization, Therapeutic* / methods
  • Female
  • Hepatectomy
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Preoperative Care
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Propensity Score
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors
  • Programmed Cell Death 1 Receptor