Journal of Liver Cancer

Review Article

Intermediate-stage hepatocellular carcinoma: refining substaging or shifting paradigm?: Bernardo Stefanini, Luca Ielasi, Dante Pio Pallotta, Sofia Penazza, Mariarosaria Marseglia, Fabio Piscaglia; J Liver Cancer. 2024;24(1):23-32. Published online March 12, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.21

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This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.

Citations

Citations to this article as recorded by

Usefulness of preoperative peripheral blood GPC3‐positive circulating tumor cells in subclassification of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma: a retrospective cohort study
Yosuke Namba, Tsuyoshi Kobayashi, Yoshito Hirata, Takeshi Tadokoro, Sotaro Fukuhara, Ko Oshita, Naruhiko Honmyo, Ryosuke Nakano, Hiroshi Sakai, Seiichi Shimizu, Shintaro Kuroda, Hiroyuki Tahara, Masahiro Ohira, Kentaro Ide, Yuka Tanaka, Hideki Ohdan
Hepatology Research.2025; 55(8): 1172. CrossRef
Potential anticancer therapeutic targets of resveratrol and its role in the therapy of hepatocellular carcinoma
Wasnaa H. Mohammed, Ghassan M. Sulaiman, Hamdoon A. Mohammed
Food Bioscience.2025; 69: 106935. CrossRef
Role of immune checkpoint inhibitor combinations in resectable and unresectable, embolization-eligible hepatocellular carcinoma
Brandon M. Meyers, Howard J. Lim, Mayur Brahmania, Dave M. Liu, Vincent C. Tam, Deanna McLeod, Ravi Ramjeesingh, Jennifer J. Knox, Arndt Vogel
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
The Neoangiogenic Transcriptomic Signature Impacts Hepatocellular Carcinoma Prognosis and Can Be Triggered by Transarterial Chemoembolization Treatment
Rosina Maria Critelli, Federico Casari, Alberto Borghi, Grazia Serino, Cristian Caporali, Paolo Magistri, Annarita Pecchi, Endrit Shahini, Fabiola Milosa, Lorenza Di Marco, Alessandra Pivetti, Simone Lasagni, Filippo Schepis, Nicola De Maria, Francesco Di
Cancers.2024; 16(20): 3549. CrossRef

Original Article

Subclassification of Hepatocellular Carcinoma with Barcelona Clinic Liver Cancer Intermediate Stage: Hye Won Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Snag Hoon Ahn, Kwang-Hyub Han, Beom Kyung Kim; J Liver Cancer. 2016;16(1):17-22. Published online March 31, 2016; DOI: https://doi.org/10.17998/jlc.16.1.17

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Abstract PDF: Background/Aims
Hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer (BCLC) intermediate stage includes a highly heterogeneous population. Here, we aimed to subclassify hepatocellular carcinoma with BCLC intermediate stage for better prognostification.
Methods
Between 2003 and 2008, 325 patients who were newly diagnosed as HCC with BCLC intermediate stage were considered eligible. Tumor factor and liver function were used for sub-classification. Overall survival (OS) was analyzed using Kaplan-Meier method with a comparison by log-rank test.
Results
A total of 325 patients with intermediate stage HCC were analyzed. Patients with tumor size ≥7 cm, tumor number ≥4 and Child-Pugh class B had the worse OS compared to those with tumor size <7 cm, tumor number <4 and Child-pugh class A, respectively (all P<0.05). These three variables affected the OS independently from multivariate Cox regression analysis (all P<0.05). So, using these three variables, patients were finally sub-classified as those with fulfilling none of three factors (B-a), one of three factors (B-b), two of three factors (B-c) and all of three factors (B-d) with the median OS of 39.2, 20.6, 12.0 and 8.3 months with statistical significances (all P<0.05 between B-a and B-b, between B-b and B-c, and between B-c and B-d), respectively.
Conclusions
Sub-classification of HCC with BCLC intermediate stage may be useful in not only prognostification but also guidance of treatment strategies. (J Liver Cancer 2016;16:17-22)

Review Articles

The Issues for Improving Prognosis in Intermediate Stage of Hepatocellular Carcinoma: Yang Jae Yoo, Ji Hoon Kim; J Liver Cancer. 2014;14(2):80-88. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.80

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Abstract PDF: Hepatocellular carcinoma (HCC) is one of major malignant tumor with heterogeneity and poor prognosis. In contrast to other solid malignant tumors, the prognosis of HCC is affected by not only progression of tumor itself but also residual liver function. Therefore, diverse staging systems are developed in HCC and there was no universal consensus for best staging system. However, Barcelona Clinic Liver Cancer (BCLC) system, which was endorsed by Western expert guidelines, is most commonly used staging system. BCLC system defined intermediate stage as single tumor more than 5cm, 2-3 tumor more than 3cm or ≥ 4 tumor at any size with Child-Pugh A or B and performance status 0-1 and allocated transarterial chemoembolization (TACE) as primary treatment for this stage. Intermediate stage include heterogeneous patients population and inevitably showed diverse prognosis. Among HCC patients, about 20% belonged to intermediate stage and intermediate stage means relatively little progressed stage, fair liver function and performance status. Therefore, improvement of survival of intermediate HCC patients may be a cornerstone leading improvement of survival of overall HCC patients. Hence, the strategy for optimal classification and treatment modality for intermediate HCC patients at pre and post treatment to improve prognosis in this patients will be discussed in this review. (J Liver Cancer 2014;14:80-88)

Primary hepatic carcinoma with mixed features: Young Nyun Park; Journal of the Korean Liver Cancer Study Group. 2007;7(1):13-15. Published online June 30, 2007

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