Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2023; 15(1): 1-18
Published online Jan 15, 2023. doi: 10.4251/wjgo.v15.i1.1
Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma
Jing Liang, Yi Bai, Fu-Shuang Ha, Ying Luo, Hui-Ting Deng, Ying-Tang Gao
Jing Liang, Fu-Shuang Ha, Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
Yi Bai, Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
Ying Luo, Hui-Ting Deng, Ying-Tang Gao, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
Ying-Tang Gao, Tianjin Institute of Hepatobiliary Disease, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
Author contributions: Liang J and Bai Y contributed equally to this work; Liang J and Bai Y wrote the paper; Ha FS, Luo Y, and Deng HT collected the literature and data; Gao YT revised the paper; all authors read and approved the final manuscript.
Supported by the Natural Science Foundation of Tianjin Science and Technology Bureau, China, No. 21JCZDJC01050; Tianjin Key Medical Discipline (Specialty) Construction Project, No. TJYXZDXK-034A; and Tianjin Municipal Health Science and Technology Project, No. TJWJ2021ZD003, No. KJ20068, No. KJ20129, and No. TJWJ2022XK029.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Ying-Tang Gao, PhD, Professor, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, No. 83 Jintang Road, Hedong District, Tianjin 300170, China.
Received: September 24, 2022
Peer-review started: September 24, 2022
First decision: November 15, 2022
Revised: December 6, 2022
Accepted: December 27, 2022
Article in press: December 27, 2022
Published online: January 15, 2023

Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.

Keywords: Recurrent hepatocellular carcinoma, Local regional therapy, Systemic therapy, Tumor microenvironment, Recurrence type, Immune checkpoint inhibitors

Core Tip: Hepatocellular carcinoma (HCC) is a highly recurrent malignancy; at present, there is a lack of definite treatment strategies for recurrent HCC. Recurrent HCC has particularities in recurrence mode and tumor microenvironment, so its treatment strategy should be different from that of primary HCC. Systemic therapy based on the immune microenvironment has emerged as a potential alternative treatment option for advanced HCC. Combining local therapy and systemic therapy for recurrent HCC may achieve better effects and is worthy of further exploration.