Cited by 4,319Hepatocellular Carcinoma Treatment and PrognosisColorectal Cancer Treatments and StudiesRenal cell carcinoma treatment

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BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update

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Reig, Maria, Forner, Alejandro, Rimola, Jordi, Ferrer-Fàbrega, Joana, Burrel, Marta, Garcia-Criado, Ángeles, Kelley, Robin K., Galle, Peter R., Mazzaferro, Vincenzo, Salem, Riad, Sangro, Bruno, Singal, Amit G., Vogel, Arndt, Fuster, Josep, Ayuso, Carmen, Bruix, Jordi·2022·Journal of Hepatology

DOI 10.1016/j.jhep.2021.11.018PMC PMC8866082

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Abstract

There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.

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Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma
Shimose, S., Hiraoka, A., Tanaka, M., Iwamoto, H., Tanaka, T., Noguchi, K., Aino, H., Yamaguchi, T., Itano, S., Suga, H., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-21528-2 · Cited by 15
Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC
Chiu, Y., Husain, A., Sze, K. M., Ho, D. W., Suarez, E. M. S., Wang, X., Lee, E., Ma, H., Lee, J. M., Chan, L., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000266 · Cited by 15
Prediction of 3-year recurrence rate of hepatocellular carcinoma after resection based on contrast-enhanced CT: a single-centre study
Lv, C., He, N., Yang, J., Xiao, J., Zhang, Y., Du, J., Zuo, S., Li, H. Y., & Gu, H. (2023) · British Journal of Radiology · doi:10.1259/bjr.20220702 · Cited by 15
Heart rate variability is associated with disease severity and portal hypertension in cirrhosis
Miceli, G., Calvaruso, V., Casuccio, A., Pennisi, G., Licata, M., Pintus, C., Basso, M. G., Velardo, M., Daidone, M., Amodio, E., et al. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000050 · Cited by 17
“superimposed to cirrhosis, never in BCLC D class.[31] Most patients in the cohort had a well-preserved liver function [Child Pugh (CP) class A, n=108; 68.”
Background
Preoperative Immunotherapy in Hepatocellular Carcinoma: Current State of the Art
Laschtowitz, A., Roderburg, C., Tacke, F., & Mohr, R. U. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s347944 · Cited by 17
“For selected patients with early-stage HCC, surgical and ablative treatments are available in a (potentially) curative scenario while liver transplantation (LT) leads to improved long-term survival data in patients with cirrhosis compared to resected patients at the same tumor stage.(6) Nevertheless, both de novo tumo…”
Background
An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians
Cespiati, A., Cinque, F., Meroni, M., Lombardi, R., Dongiovanni, P., & Fracanzani, A. L. (2023) · Biomedicines · doi:10.3390/biomedicines11020586 · Cited by 17
“A single nodule without vascular invasion or metastasis can be surgically resected, while liver transplantation is possible only when the nodule meets the Milan criteria (a single tumor ≤ 5 cm or two to three nodules ≤ 3 cm without vascular invasion or extrahepatic metastasis) [114].”
Background
Short and long-term outcomes after minimally invasive liver resection for single small hepatocellular carcinoma: An analysis of 714 patients from the IGoMILS (Italian group of minimally invasive liver surgery) registry
Giuliante, F., Ratti, F., Panettieri, E., Mazzaferro, V., Guglielmi, A., Ettorre, G. M., Gruttadauria, S., Benedetto, F. D., Cillo, U., Carlis, L. G. D., et al. (2023) · HPB · doi:10.1016/j.hpb.2023.02.007 · Cited by 15
Self-citation
Effectiveness of lenvatinib plus immune checkpoint inhibitors in primary advanced hepatocellular carcinoma beyond oligometastasis
Wang, X., Liu, C., Wen, H., Duan, X., Jiao, Y., Liu, Y., Chen, M., Zhu, K., Mao, X., & Zhou, Q. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1214 · Cited by 13
Hepatic arterial infusion chemotherapy for patients with hepatocellular carcinoma: Applicability in Western countries
He, M., Liu, S., Lai, Z., Du, Z., Li, Q., Xu, L., Kan, A., Shen, J., & Shi, M. (2023) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2023.102362 · Cited by 15
Transarterial Chemoembolization Combined With PD-1 Inhibitors Plus Lenvatinib Showed Improved Efficacy for Treatment of Unresectable Hepatocellular Carcinoma Compared With PD-1 Inhibitors Plus Lenvatinib
Wang, J., Zhao, M., Han, G., Han, X., Shi, J., Mi, L., Li, N., Yin, X., Duan, X., Hou, J., et al. (2023) · Technology in Cancer Research & Treatment · doi:10.1177/15330338231166765 · Cited by 15
“According to the new Barcelona Clinic Liver Cancer (BCLC) staging system, patients in the BCLC-B stage with extensive bilobar liver involvement and BCLC-C stage are recommended to receive systemic therapy.(6) Lenvatinib, a novel multitargeted tyrosine kinase inhibitor (TKI) that targets VEGFR 1-3, fibroblast growth fa…”
Background
Validation of the ALBI-TAE model and comparison of seven scoring systems for predicting survival outcome in patients with intermediate‐stage hepatocellular carcinoma undergoing chemoembolization
Bannangkoon, K., Hongsakul, K., & Tubtawee, T. (2023) · Cancer Imaging · doi:10.1186/s40644-023-00575-6 · Cited by 15
Survival Benefits From Adjuvant Lenvatinib for Patients With Hepatocellular Carcinoma and Microvascular Invasion After Curative Hepatectomy
Dai, M., Liu, S., Lu, W., Liang, L., & Ye, B. (2023) · Clinical Medicine Insights Oncology · doi:10.1177/11795549231180351 · Cited by 15
“Patients were excluded who (1) had recurrent HCC; (2) were less than 18 years old; (3) received neoadjuvant or other adjuvant therapies, including transcatheter arterial chemoembolization (TACE), radiotherapy, and systemic therapy; (4) died or recurrence within 3 months after surgery; and (5) cannot tolerate targeted…”
Background
Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization
Zhong, B., Jiang, J.-Q., Sun, J., Huang, J., Wang, W., Wang, Q., Ding, W.-B., Zhu, X., & Ni, C. (2023) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2023.00099 · Cited by 15
Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma
Asensio, M., Herráez, E., Macı́as, R. I. R., Lozano, E., Muñoz‐Bellvís, L., Sanchez‐Vicente, L., Morente-Carrasco, A., Marı́n, J. J. G., & Briz, Ó. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115681 · Cited by 15
Residual burden of liver disease after HCV clearance in hemophilia: a word of caution in the era of gene therapy
Mura, V. L., Bitto, N., Capelli, C., Caputo, C., Siboni, S. M., Arcudi, S., Ciavarella, A., Gualtierotti, R., Fracanzani, A. L., Sangiovanni, A., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023010723 · Cited by 15
3D fusion is superior to 2D point-to-point contrast-enhanced US to evaluate the ablative margin after RFA for hepatocellular carcinoma
Long, H., Zhou, X., Zhang, X., Ye, J., Huang, T., Cong, L., Xie, X., & Huang, G. (2023) · European Radiology · doi:10.1007/s00330-023-10023-5 · Cited by 15
Significance of malnutrition defined with Global Leadership Initiative on Malnutrition criteria in patients with hepatocellular carcinoma after hepatic resection
Harimoto, N., Tsukagoshi, M., Okuyama, T., Hoshino, K., Hagiwara, K., Kawai, S., Ishii, N., Igarashi, T., Araki, K., & Shirabe, K. (2023) · Hepatology Research · doi:10.1111/hepr.13959 · Cited by 15
Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience
Balzano, E., Bernardi, L., Roesel, R., Vagelli, F., Ghinolfi, D., Tincani, G., Catalano, G., Melandro, F., Petrusic, A., Popeskou, S. G., et al. (2023) · Surgical Endoscopy · doi:10.1007/s00464-023-10358-6 · Cited by 15
“In the case of cirrhotic patients with HCC inside Milan criteria, who represent the majority in the population examined, single-nodule patients were referred to MILS whether patients with two or three HCCs were generally listed for upfront liver transplant if indicated [31].”
A prospective registry study of stereotactic magnetic resonance guided radiotherapy (MRgRT) for primary liver tumors
Bordeau, K., Michalet, M., Dorion, V., Keskes, A., Valdenaire, S., Debuire, P., Cantaloube, M., Cabaillé, M., Draghici, R., Ychou, M., et al. (2023) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2023.109912 · Cited by 15
Meeting at the Crossroad between Obesity and Hepatic Carcinogenesis: Unique Pathophysiological Pathways Raise Expectations for Innovative Therapeutic Approaches
Arvanitakis, K., Papadakos, S. P., Lekakis, V., Koufakis, T., Lempesis, I. G., Papantoniou, E., Kalopitas, G., Georgakopoulou, V., Stergiou, I. Ε., Theocharis, S. E., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914704 · Cited by 16
“…used staging approach for HCC is the Barcelona Clinic of Liver Cancer (BCLC) algo-rithm, which distinguishes patients with HCC into ﬁve clinical stages: very early stage (BCLC 0), early stage (BCLC A), intermediate stage (BCLC B), advanced stage (BCLC C), and terminal stage (BCLC D) [16,121].”
BackgroundMethod
Hepatectomy After Conversion Therapy with Hepatic Arterial Infusion Chemotherapy, Tyrosine Kinase Inhibitors and Anti-PD-1 Antibodies for Initially Unresectable Hepatocellular Carcinoma
Yu, B., Zhang, N., Feng, Y. W., Zhang, Y., Zhang, T., & Wang, L. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s432062 · Cited by 15
“However, most patients are diagnosed at intermediate or advanced stages when they are not candidates for curative resection.(3,4) Despite various therapies for advanced HCC, including interventional therapies, tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies, survival remains poor, with a 5-year survival ra…”
Background
Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study
Hatanaka, T., Kakizaki, S., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2023) · Hepatology Research · doi:10.1111/hepr.13991 · Cited by 15
NR0B1 augments sorafenib resistance in hepatocellular carcinoma through promoting autophagy and inhibiting apoptosis
Tan, X., Wang, Z., Liao, S., Yi, M., Tao, D., Zhang, X., Leng, X., Shi, J., Xie, S., Yang, Y., et al. (2023) · Cancer Science · doi:10.1111/cas.16029 · Cited by 15
“5,6 However, sorafenib resistance is a commonly recognized clinical problem that arises in association with epigenetics, exosomes, apoptosis, autophagy, ferroptosis, glucose metabolism, lactate metabolism, and tumor microenvironment.”
Background
Associations of circulating immunomarkers with the efficacy of immunotherapy for primary hepatic carcinoma
Liu, S., Xu, W., Shu, H., Dai, Y., Du, Y., Liu, Y., Huang, L., & Sun, G. (2023) · Cancer Medicine · doi:10.1002/cam4.6754 · Cited by 14
Radiation Segmentectomy for Hepatocellular Carcinoma
Serhal, M., Dadrass, F., Kim, E., & Lewandowski, R. J. (2024) · Current Oncology · doi:10.3390/curroncol31020045 · Cited by 15
“Treatment of solitary BCLC-A HCC is largely based on the presence or absence of clinically significant portal hypertension (CSPH) due to its association with higher rates of postoperative complications [14,21].”
BackgroundMethodInfluential
Percutaneous microwave ablation versus sclerotherapy for large hepatic hemangioma: a multi-center cohort study
Cai, Q., Qian, T.-G., Zhao, Q., Feng, S.-Y., Yang, Q., Luo, Y., Dai, Y.-Q., Liang, P., Yu, X., Liu, F., et al. (2024) · International Journal of Hyperthermia · doi:10.1080/02656736.2023.2285705 · Cited by 15
“Thermal ablation has gained popularity as a local treatment for liver tumors [14,15].”
Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma
Shewarega, A., Santana, J. G., Nam, D., Berz, A. M., Tefera, J., Kahl, V. H., Mishra, S. K., Coman, D., Duncan, J. S., Roberts, S. J., et al. (2024) · Radiology · doi:10.1148/radiol.232365 · Cited by 15
Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation
SIMONE, P. D., Precisi, A., Lai, Q., Ducci, J., Campani, D., Marchetti, P., Gitto, S., & Crocetti, L. (2024) · Cancers · doi:10.3390/cancers16071243 · Cited by 15
“The definition of EAD was based on the research of Olthoff et al. [16].”
Method
Prognostic significance of postoperative complications for patients with hepatocellular carcinoma relative to alpha-feto protein and tumor burden score
Endo, Y., Tsilimigras, D. I., Munir, M. M., Woldesenbet, S., Yang, J., Guglielmi, A., Ratti, F., Marques, H. P., Cauchy, F., Lam, V. W. T., et al. (2024) · HPB · doi:10.1016/j.hpb.2024.04.013 · Cited by 15
New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma
Liu, H., Wang, C., Wang, R., Cao, H., Cao, Y., Huang, T., Lu, Z., Xiao, H., Hu, M., Wang, H., et al. (2024) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2024.02.06 · Cited by 17
Resin-Based 90Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma
Kokabi, N., Webster, L. A., Dabbous, H., SHAH, A. D., Brandon, D. C., Galt, J. R., Xing, M., Villalobos, A., Davarpanah, A. H., Kappadath, S. C., et al. (2024) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000005198 · Cited by 15
Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab versus Transarterial Chemoembolization Alone in Intermediate‐stage Hepatocellular Carcinoma: A Multicenter Retrospective Study
Zheng, Y., Xiang, Y., Shi, H., Lin, Z., Cheng, S., & Zhu, J. (2024) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s461630 · Cited by 15
“10 More recently, the multiparametric therapeutic hierarchy concept, introduced by Alessandro Vitale et al 22 has emphasized personalized treatment approaches for HCC.”
Background
Prognostic Efficacy of the Albumin-Bilirubin Score and Treatment Outcomes in Hepatocellular Carcinoma: A Large-Scale, Multi-Center Real-World Database Study
Kim, K., Kim, K. M., Ryoo, B., Choi, W.-M., Cha, W. C., Kang, M., Sinn, D. H., Goh, M. J., Kim, D. Y., Lee, M. J., et al. (2024) · Liver Cancer · doi:10.1159/000539724 · Cited by 16
Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue
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Early Changes in Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin Are Useful Predictors of Antitumor Response to Durvalumab Plus Tremelimumab Therapy for Advanced Hepatocellular Carcinoma
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“Based on these positive results, the combination of durvalumab and tremelimumab (Dur/Tre) is now recommended as a first-line systemic therapy for advanced HCC, as is atezolizumab plus bevacizumab (Atz/Bev) [2,3].”
Background
TACE plus lenvatinib and tislelizumab for intermediate-stage hepatocellular carcinoma beyond up-to-11 criteria: a multicenter cohort study
Chen, S., Shuangyan, T., Shi, F., Cai, H., Wu, Z., Wang, L., Ma, P., Zhou, Y.-M., Mai, Q., Wang, F., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1430571 · Cited by 17
New Scenarios in Liver Transplantation for Hepatocellular Carcinoma
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Self-citation
Deep learning radiomics based on contrast enhanced MRI for preoperatively predicting early recurrence in hepatocellular carcinoma after curative resection
Zhao, Y. Y., Wang, S., Wang, Y., Li, J., Liu, J., Liu, Y., Ji, H., Su, W., Zhang, Q., Song, Q., et al. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1446386 · Cited by 18
AI-based tumor-infiltrating lymphocyte scoring system for assessing HCC prognosis in patients undergoing liver resection
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The prognostic role of ACSL4 in postoperative adjuvant TACE-treated HCC: implications for therapeutic response and mechanistic insights
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Molecular and immune landscape of hepatocellular carcinoma for therapeutic development
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Utility of PIVKA-II and AFP in Differentiating Hepatocellular Carcinoma from Non-Malignant High-Risk Patients
Hadi, H. I. A., Shuaib, W. M. A. W., Ali, R. A. R., & Othman, H. (2022) · Medicina · doi:10.3390/medicina58081015 · Cited by 15
TAC score better predicts survival than the BCLC following resection of hepatocellular carcinoma
Lima, H. A., Endo, Y., Moazzam, Z., Alaimo, L., Shaikh, C. F., Munir, M. M., Resende, V., Guglielmi, A., Marques, H. P., Cauchy, F., et al. (2022) · Journal of Surgical Oncology · doi:10.1002/jso.27116 · Cited by 15
Implications of the TACTICS Trial: Establishing the New Concept of Combination/Sequential Systemic Therapy and Transarterial Chemoembolization to Achieve Synergistic Effects
Kudo, M. (2022) · Liver Cancer · doi:10.1159/000527404 · Cited by 15
Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib alone for advanced hepatocellular carcinoma: A systematic review and meta‐analysis
Yin, L. W., Song, X., Guan, Y., Lan, R., Huang, Z., Li, S., & Zhang, L. (2022) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16088 · Cited by 15
Transarterial radioembolization versus chemoembolization for hepatocellular carcinoma: a meta-analysis
Lu, W., Zhang, T., Xia, F.-F., Huang, X., & Gao, F. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2024.1511210 · Cited by 14

Authors: Reig, M., Forner, A., Rimola, J., Ferrer-Fàbrega, J., Burrel, M., Garcia-Criado, Á., Kelley, R. K., Galle, P. R., Mazzaferro, V., Salem, R., Sangro, B., Singal, A. G., Vogel, A., Fuster, J., Ayuso, C., & Bruix, J.
Affiliations: Hospital Clínic de Barcelona (ES)
University of California, San Francisco (US)
University Medical Center of the Johannes Gutenberg University Mainz (DE)
University of Milan (IT)
Northwestern University (US)
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
The University of Texas Southwestern Medical Center (US)
Medizinische Hochschule Hannover (DE)
Corresponding author: Bruix, Jordi
ORCID: Reig, Maria
Forner, Alejandro
Rimola, Jordi
Burrel, Marta
Garcia-Criado, Ángeles
Kelley, Robin K.
Galle, Peter R.
Mazzaferro, Vincenzo
Salem, Riad
Sangro, Bruno
Singal, Amit G.
Vogel, Arndt
Fuster, Josep
Ayuso, Carmen
Bruix, Jordi
Venue: Journal of Hepatology
Publisher: Elsevier BV
Published: 2022-03
Volume: 76
Issue: 3
Pages: 681-693
ISSN: 0168-8278 (ISSN-L)
DOI: 10.1016/j.jhep.2021.11.018
PMC: PMC8866082
OpenAlex: W3213277274
Cited by: 4,319
References: 136
Citations by year: 2026: 684 · 2025: 1071 · 2024: 1166 · 2023: 962 · 2022: 424
FWCI: 83.72
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Hepatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
eScholarship (California Digital Library) (submittedVersion)
Funders: Fundación Científica de la Asociación Española Contra el Cáncer (PI044031)
National Institutes of Health (R01 R01 MD012565, PI18/00768)
Horizon 2020 Framework Programme (952103)
Instituto de Salud Carlos III (AC16/00065, PI18/0358, PI15/00145, PI18/00542, PI19/00742, PI18/00768)
European Association for the Study of the Liver
Horizon 2020
Topics: Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
Keywords: hepatocellular carcinoma, Barcelona Clinic Liver Cancer staging, outcome prediction, treatment guidelines, evidence-based clinical decision-making
MeSH terms: Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Staging, Prognosis, Severity of Illness Index

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BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update

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