Journal of Liver Cancer

Review Article

Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future: Sang-Youn Hwang, Hyunwook Choi, Wan Jeon, Ryoung-Go Kim; J Liver Cancer. 2024;24(2):171-177. Published online September 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.30

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Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out ‘inclusion criteria’ and defining ‘successful downstaging.’ Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.

Citations

Citations to this article as recorded by

A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024
Hyunjae Shin, Su Jong Yu
Journal of Liver Cancer.2025; 25(1): 19. CrossRef
The Lancet Commission on addressing the global hepatocellular carcinoma burden: comprehensive strategies from prevention to treatment
Stephen Lam Chan, Hui-Chuan Sun, Yang Xu, Hongmei Zeng, Hashem B El-Serag, Jeong Min Lee, Myron E Schwartz, Richard S Finn, Jinsil Seong, Xin Wei Wang, Valérie Paradis, Ghassan K Abou-Alfa, Lorenza Rimassa, Jia-Horng Kao, Bo-Heng Zhang, Josep M Llovet, Jo
The Lancet.2025; 406(10504): 731. CrossRef
Liver Transplantation for Hepatocellular Carcinoma: A Comprehensive Review
Seok-Hwan Kim
Convergence Hepatology.2025; 1(1): 24. CrossRef
Radioembolization of primary liver tumors for patients with pre-existing ascites: beyond Child-Pugh score
Fayez J. Jabboure, Joshua A. Marlow, Wyatt D. Reed, Naganathan B. Mani, Nassir Rostambeigi
Abdominal Radiology.2025;[Epub] CrossRef

Case Reports

From Down Staging to Curative Treatment: Based on Hepatic Arterial Infusion Chemotherapy in a Hepatocellular Carcinoma Patient: Chung-Hwa Park, Myung Joon Song, Seung Kew Yoon, Jong Young Choi, Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2011;11(1):46-49. Published online February 28, 2011

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Abstract PDF: Hepatic arterial infusion chemotherapy (HAIC) is performed in patients with advanced hepatocellular carcinoma (HCC) in which locoregional therapeutic methods such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) or radiofrequency ablation (RFA) could not be the best choice. Sorafenib, the only approved systemic chemotherapeutic agent for HCC, improves survival rate, but is associated with a low tumor response rate. Thus combining these therapeutic modalities to treat HCC in advanced stage may help downstaging and leading to better treatment results without taking risk for hepatic failure. Here we report a case treated to a complete remission by combining HAIC, PEI and sorafenib.

A Case of Hepatocellular Carcinoma with Bile Duct Invasion Surgically Resected after Transarterial Chemoembolization; Curative Resection after Tumor Downstaging: Nae-Yun Heo, Han Chu Lee, Ju Hyun Shim, Kang Mo Kim, Young Suk Lim, Young-Hwa Chung, Yung Sang Lee, Dong Jin Suh; Journal of the Korean Liver Cancer Study Group. 2011;11(1):69-74. Published online February 28, 2011

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Abstract PDF: A surgical resection is a major curative treatment of hepatocellular carcinoma (HCC) in Korea. However, the respectability of HCC at the time of diagnosis is low (10-30%) because the cancer is often identified as advanced stage. Nevertheless, some of the patients were known to have a curative resection after successful downstaging therapy. We report a HCC with bile duct invasion which was successfully downstaged by the transarterial chemoembolization and treated by surgical resection.

Review Article

Hepatic Resection Following Adjuvant Treatments in Hepatocellular Carcinoma: Sae-Byeol Choi, Kyung Sik Kim; Journal of the Korean Liver Cancer Study Group. 2008;8(1):32-38. Published online June 30, 2008

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Abstract PDF: The optimal treatment of hepatocellular carcinoma has become increasingly complex with myriad of available treatment options. Although recently the liver transplantation has been accepted the best treatment for survival, the shortage of donor limits the extension of this procedures. As the neoadjuvant chemotherapy is being increasingly employed to downsize colorectal metastasis, the clinical trials have been extended to the hepatocellular carcinoma. Therefore we reviewed the use of liver resection following tumor downstaging with chemotherapeutic agents and Radiation therapy to treat unresectable HCC. Key Words: Hepatic resection․Downstaging․Transarterial chemoembolization․Radiation

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