Skip to main content

Advertisement

Log in

A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Hepatectomy is considered as the potentially curative treatment for hepatocellular carcinoma (HCC) and used in some selected Stage IIIA HCC, which include multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) (UICC TNM staging system, sixth edition). Transcatheter arterial chemoembolization (TACE) was used in retrospective studies to improve the survival outcome of resected HCC. However, its beneficial effect on the survival outcomes of the Stage IIIA patients has not been evaluated. The present study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA HCC result in better long-term survival outcome when compared with hepatectomy alone.

Methods

From January 2001 to March 2004, we conducted a prospective randomized trial in patients with Stage IIIA HCC (NCT00652587), recruiting 115 Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE (HT arm) or to undergo hepatectomy alone (HA arm) in our cancer center. Survival outcomes of the two arms were analyzed.

Results

The demographic data were well matched between the two arms. There were no significant differences in the morbidity and in-hospital mortality between the two arms of patients. The most significant toxicities associated with adjuvant TACE were nausea/vomiting (54.4%) and transient hepatic toxicity (elevation of aminotransferase, 52.6%). Although there was no significant difference in the rate of recurrence between the two arms (50/57 vs. 56/58, P = 0.094), HT arm seemed to have more proportion of single lesion of recurrent HCC (χ 2 = 3.719, P = 0.054) and more proportion of potential curative therapy for recurrence (χ 2 = 4.456, P = 0.035). Until the time of censor, 92 patients had died. The 1-, 3-, and 5-year overall survival rates and median overall survival for HT arm were 80.7, 33.3, 22.8% and 23.0 months, respectively. The corresponding overall survival rates and median overall survival for HA arm were 56.5, 19.4, 17.5% and 14.0 months, respectively. The difference was significant (stratified log-rank test, P = 0.048). The 1-, 3-, and 5-year disease-free survival rates and median disease-free survival for HT arm were 29.7, 9.3, 9.3% and 6.0 months, respectively; correspondingly, for HA arm were 14.0, 3.5, 1.7% and 4.0 months, respectively (stratified log-rank test, P = 0.004).

Conclusions

For Stage IIIA HCC, hepatectomy with adjuvant TACE efficaciously and safely improved survival outcomes when compared with hepatectomy alone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Asahara T, Itamoto T, Katayama K et al (1999) Adjuvant hepatic arterial infusion chemotherapy after radical hepatectomy for hepatocellular carcinoma–results of long-term follow-up. Hepatogastroenterology 46:1042–1048

    CAS  PubMed  Google Scholar 

  • Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236. doi:10.1002/hep.20933

    Article  PubMed  Google Scholar 

  • Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430. doi:10.1016/S0168-8278(01)00130-1

    Article  CAS  PubMed  Google Scholar 

  • Chen XP, Huang ZY (2005) Surgical treatment of hepatocellular carcinoma in China: surgical techniques, indications, and outcomes. Langenbecks Arch Surg 390:259–265. doi:10.1007/s00423-005-0552-9

    Article  PubMed  Google Scholar 

  • Cheng HY, Wang X, Chen D et al (2005) The value and limitation of transcatheter arterial chemoembolization in preventing recurrence of resected hepatocellular carcinoma. World J Gastroenterol 11:3644–3646

    PubMed  Google Scholar 

  • Edwards BK, Brown ML, Wingo PA et al (2005) Annual report to the nation on the status of cancer 1975–2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst 97:1407–1427

    Article  PubMed  Google Scholar 

  • Fan J, Zhou J, Wu ZQ et al (2005) Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol 11:1215–1219

    PubMed  Google Scholar 

  • Fattovich G, Stroffolini T, Zagni I et al (2004) Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127(suppl):35–50. doi:10.1053/j.gastro.2004.09.014

    Article  Google Scholar 

  • Freedman LS (1982) Tables of the number of patients required in clinical trials using the logrank test. Stat Med 1:121–129. doi:10.1002/sim.4780010204

    Article  CAS  PubMed  Google Scholar 

  • Guo RP, Chen MS, Lin XJ et al (2000) Significance of removing portal vein thrombus and TACE in improving outcome of resection for primary liver cancer with portal vein tumor thrombus. Chin J Hepatobiliary Surg 6:374–376

    Google Scholar 

  • Guo RP, Zhong C, Shi M et al (2006) Clinical value of apoptosis and angiogenesis factors in estimating the prognosis of hepatocellular carcinoma. J Cancer Res Clin Oncol 132:547–555. doi:10.1007/s00432-006-0097-5

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa K, Takayama T, Ijichi M, Matsuyama Y et al (2006) Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial. Hepatology 44:891–895. doi:10.1002/hep.21341

    Article  CAS  PubMed  Google Scholar 

  • Ikai I, Arii S, Kojiro M et al (2004) Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer 101:796–802. doi:10.1002/cncr.20426

    Article  PubMed  Google Scholar 

  • Ikeda K, Arase Y, Saitoh S et al (2000) Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer. Hepatology 32:228–232. doi:10.1053/jhep.2000.9409

    Article  CAS  PubMed  Google Scholar 

  • International Union Against Cancer (UICC) (2002) In: Sobin LH, Wittekind C (eds) TNM classification of malignant tumors, 6th edn. Wiley, New York, pp 81–83

  • Izumi R, Shimizu K, Iyobe T et al (1994) Postoperative adjuvant arterial infusion of lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology 20:295–301

    Article  CAS  PubMed  Google Scholar 

  • Ku Y, Iwasaki T, Tominaga M et al (2004) Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma. Ann Surg 239:53–60. doi:10.1097/01.sla.0000103133.03688.3d

    Article  PubMed  Google Scholar 

  • Kubo S, Nishiguchi S, Hirohashi K et al (2001) Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial. Ann Intern Med 134:963–967

    CAS  PubMed  Google Scholar 

  • Kumada K, Ozawa K, Okamoto R et al (1990) Hepatic resection for advanced hepatocellular carcinoma with removal of portal vein tumor thrombi. Surgery 108:821–827

    CAS  PubMed  Google Scholar 

  • Kwok PC, Lam TW, Lam PW et al (2003) Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma. J Gastroenterol Hepatol 18:450–455. doi:10.1046/j.1440-1746.2003.03015.x

    Article  CAS  PubMed  Google Scholar 

  • Lau WY, Leung TW, Ho SK et al (1999) Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet 353:797–801. doi:10.1016/S0140-6736(98)06475-7

    Article  CAS  PubMed  Google Scholar 

  • Lau WY, Lai EC, Leung TW et al (2008) Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival. Ann Surg 247:43–48

    Article  PubMed  Google Scholar 

  • Le Treut YP, Hardwigsen J, Ananian P et al (2006) Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series. J Gastrointest Surg 10:855–862. doi:10.1016/j.gassur.2005.12.011

    Article  PubMed  Google Scholar 

  • Li JQ, Zhang YQ, Zhang WZ et al (1995) Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol 121:364–366. doi:10.1007/BF01225689

    Article  CAS  PubMed  Google Scholar 

  • Li BK, Cui BK, Yuan YF et al (2005) Evaluation of new TNM staging system for hepatocellular carcinoma after hepatectomy. Ai Zheng 24:769–773

    PubMed  Google Scholar 

  • Liver Cancer Study Group of Japan (1990) Primary liver cancer in Japan: clinicopathologic features and results of surgical treatment. Ann Surg 211:277–287

    Google Scholar 

  • Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442. doi:10.1053/jhep.2003.50047

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338. doi:10.1055/s-2007-1007122

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917. doi:10.1016/S0140-6736(03)14964-1

    Article  PubMed  Google Scholar 

  • Lopez PM, Villanueva A, Llovet JM (2006) Systematic review: evidence-based management of hepatocellular carcinoma-an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 23:1535–1547. doi:10.1111/j.1365-2036.2006.02932.x

    Article  CAS  PubMed  Google Scholar 

  • Mondazzi L, Bottelli R, Brambilla G et al (1994) Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: a multivariate analysis of prognostic factors. Hepatology 19:1115–1123

    Article  CAS  PubMed  Google Scholar 

  • Nagasue N, Ono T, Yamanoi A et al (2001) Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis. Br J Surg 88:515–522. doi:10.1046/j.1365-2168.2001.01732.x

    Article  CAS  PubMed  Google Scholar 

  • Ng KK, Vauthey JN, Pawlik TM et al (2005) Is hepatic resection for large or multinodular hepatocellular carcinoma justified? Results from a multi-institutional database. Ann Surg Oncol 12:364–373. doi:10.1245/ASO.2005.06.004

    Article  PubMed  Google Scholar 

  • Ohkubo T, Yamamoto J, Sugawara Y et al (2000) Surgical results for hepatocellular carcinoma with macroscopic portal vein tumor thrombosis. J Am Coll Surg 191:657–660. doi:10.1016/S1072-7515(00)00740-7

    Article  CAS  PubMed  Google Scholar 

  • Ono T, Yamanoi A, Nazmy El Assal O et al (2001) Adjuvant chemotherapy after resection of hepatocellular carcinoma causes deterioration of long-term prognosis in cirrhotic patients: metaanalysis of three randomized controlled trials. Cancer 91:2378–2385. doi:10.1002/1097-0142(20010615)91:12<2378::AID-CNCR1271>3.0.CO;2-2

    Article  CAS  PubMed  Google Scholar 

  • Poon RT, Fan ST, Lo CM et al (1999) Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 229:216–222. doi:10.1097/00000658-199902000-00009

    Article  CAS  PubMed  Google Scholar 

  • Poon RT, Fan ST, Wong J (2000) Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 232:10–24. doi:10.1097/00000658-200007000-00003

    Article  Google Scholar 

  • Ren ZG, Lin ZY, Xia JL et al (2004) Postoperative adjuvant arterial chemoembolization improves survival of hepatocellular carcinoma patients with risk factors for residual tumor: a retrospective controlled study. World J Gastroenterol 10:2791–2794

    PubMed  Google Scholar 

  • Roayaie S, Frischer JS, Emre SH et al (2002) Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg 235:533–539. doi:10.1097/00000658-200204000-00012

    Article  PubMed  Google Scholar 

  • Shi M, Guo RP, Lin XJ et al (2007) Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg 245:36–43. doi:10.1097/01.sla.0000231758.07868.71

    Article  PubMed  Google Scholar 

  • Stefanini GF, Amorati P, Biselli M et al (1995) Efficacy of transarterial targeted treatments on survival of patients with hepatocellular carcinoma: an Italian experience. Cancer 75:2427–2434. doi:10.1002/1097-0142(19950515)75:10<2427::AID-CNCR2820751007>3.0.CO;2-J

    Article  CAS  PubMed  Google Scholar 

  • Tanaka S, Shimada M, Shirabe K et al (2005) A novel intrahepatic arterial chemotherapy after radical resection for advanced hepatocellular carcinoma. Hepatogastroenterology 52:862–865

    PubMed  Google Scholar 

  • Ueno K, Miyazono N, Inoue H et al (2000) Transcatheter arterial chemoembolization therapy using iodized oil for patients with unresectable hepatocellular carcinoma: evaluation of three kinds of regimens and analysis of prognostic factors. Cancer 88:1574–1581. doi:10.1002/(SICI)1097-0142(20000401)88:7<1574::AID-CNCR11>3.0.CO;2-8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by the grant of Science-Techonolgy Project Foundation of Guangdong Province, China, 2006 (No. 2006B36002013).

Conflict of interest statement

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rong-ping Guo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhong, C., Guo, Rp., Li, Jq. et al. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol 135, 1437–1445 (2009). https://doi.org/10.1007/s00432-009-0588-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-009-0588-2

Keywords

Navigation