Adjuvant therapy options following curative treatment of hepatocellular carcinoma: a systematic review of randomized trials

Eur J Surg Oncol. 2012 Apr;38(4):286-95. doi: 10.1016/j.ejso.2012.01.006. Epub 2012 Jan 24.


Aims: Numerous postoperative therapies for preventing recurrence of hepatocellular carcinoma (HCC) have been reported, but their efficacy remains controversial and knowledge about adverse effects is limited. A systematic review of randomized controlled trials (RCTs) was performed to gain a comprehensive picture of the efficacy and risks of these therapies.

Methods: MEDLINE, EMBASE and the Cochrane Library were systematically searched through July 2011. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated.

Results: A total of 2989 patients from 28 RCTs involving 10 postoperative therapies were included. For interferon therapy, the estimated RR for the 2-year recurrence rate was 0.84 (95% CI 0.73-0.97, P = 0.02) and the overall survival (OS) was 1.15 (95% CI 1.07-1.22, P < 0.001). Postoperative therapy with the vitamin K2 analog did not lead to a significant reduction in the 1-year recurrence rate, with a pooled RR of 0.60 (95% CI 0.28-1.27, P = 0.18). However, it did slightly improve the 1-year OS, with a pooled RR of 1.03 (95% CI 1.00-1.05, P = 0.03). Transarterial chemotherapy with or without embolization, adoptive immunotherapy and heparanase inhibitor PI-88 therapy may delay tumor recurrence. The effects of acyclic retinoid, lipiodol-iodine-131 and tumor vaccine treatment were promising but require further study. All postoperative therapies except interferon administered intramuscularly were well tolerated by the majority of patients.

Conclusions: Use of adjuvant interferon is definitely associated with an increase in OS. Postoperative therapies involving acyclic retinoid, lipidol-iodine-131, or tumor vaccine may improve the OS of patients with HCC after curative treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery
  • Combined Modality Therapy
  • Disease-Free Survival
  • Humans
  • Interferons / administration & dosage
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / surgery
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Interferons