Adjuvant immunotherapy improves recurrence-free and overall survival following surgical resection for intermediate/advanced hepatocellular carcinoma a multicenter propensity matching analysis

Front Immunol. 2024 Jan 8:14:1322233. doi: 10.3389/fimmu.2023.1322233. eCollection 2023.

Abstract

Background & aims: The effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC.

Methods: Using a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS.

Results: Among the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC.

Conclusion: This real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence.

Keywords: BCLC staging; adjuvant therapy; hepatocellular carcinoma; immune checkpoint inhibitors; overall survival; propensity matching analysis; recurrence; recurrent-free survival.

Publication types

  • Observational Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Adjuvants, Pharmaceutic
  • Carcinoma, Hepatocellular* / surgery
  • Humans
  • Immunotherapy
  • Liver Neoplasms* / surgery

Substances

  • Adjuvants, Immunologic
  • Adjuvants, Pharmaceutic

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (No. 81972726 and 82273074 for TY; 82372813 for M-DW, 82241223 and U20A20360 for G-YL), Dawn Project Foundation of Shanghai (No. 21SG36 for TY), Shanghai Health and Hygiene Discipline Leader Project (No. 2022XD001 for TY), Shanghai Outstanding Academic Leader Program (No. 23XD1424900 for TY), the Natural Science Foundation of Shanghai (No. 22ZR1477900 for M-DW) and Shanghai Science and Technology Committee Rising-Star Program (No. 22QA1411600 for M-DW).