# Intermediate hepatocellular carcinoma (BCLC B)

Source: https://onco.cc/cancers/hcc-intermediate/  
OnCo record `hcc-intermediate` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Intermediate hepatocellular carcinoma is several tumours inside a working liver, too many to cut out but with no spread beyond it. The standard treatment for two decades has been chemoembolisation through the hepatic artery, and trials now show that adding immunotherapy and anti-angiogenic drugs to it delays progression.

## Summary

BCLC stage B covers multinodular hepatocellular carcinoma with preserved liver function, no cancer-related symptoms and no macrovascular invasion or extrahepatic spread. The 2022 BCLC update split it into three groups: patients whose tumour burden allows downstaging or extended transplant criteria, those with well-defined nodules suited to transarterial chemoembolisation, and those with diffuse, infiltrative or bilobar disease who do better moving straight to systemic therapy, a change described as treatment stage migration.

Transarterial chemoembolisation delivers chemotherapy-loaded particles or drug-eluting beads into the arteries feeding the tumours and blocks them; two randomised trials in 2002 (Llovet in Barcelona and Lo in Hong Kong) showed it prolongs survival, and it has been the standard since. Radioembolisation with yttrium-90 microspheres is an alternative with fewer post-procedure symptoms, though phase 3 trials against sorafenib in more advanced disease were negative. Repeated embolisation damages the liver, so the ART and other scores guide when to stop and switch.

Two phase 3 trials published in the Lancet in 2025 added systemic therapy to chemoembolisation: EMERALD-1 combined durvalumab and bevacizumab with TACE and extended median progression-free survival from 8.2 to 15.0 months, and LEAP-012 combined lenvatinib and pembrolizumab with TACE and extended it from 10.0 to 14.6 months; overall survival was immature in both at first analysis. EMERALD-3, testing durvalumab and tremelimumab with TACE, reported a benefit in 2026. The atezolizumab-bevacizumab and other advanced-stage regimens are also used directly in patients with high tumour burden, and ongoing trials compare systemic therapy alone with the combinations.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Intermediate-stage HCC; Multinodular HCC; TACE-eligible hepatocellular carcinoma; BCLC B
- Tags: subtype-page
- Group: gastrointestinal
- Burden: Multiple tumours confined to a liver that still functions, without vein invasion or spread; the most heterogeneous BCLC stage, for which the 2022 update expects a median survival above two and a half years with chemoembolisation and now systemic therapy.
- Subtypes: Multinodular HCC in a cirrhotic liver within the up-to-seven criteria (downstaging or extended transplant); Well-defined nodules suitable for TACE; Diffuse or infiltrative bilobar HCC (systemic therapy first); TACE-refractory HCC; BCLC B treated with TACE plus systemic therapy (EMERALD-1, LEAP-012)
- Biomarkers: Tumour number and size (up-to-seven and other burden criteria); Child-Pugh and ALBI liver function before and after each embolisation; Alpha-fetoprotein response; Modified RECIST response on contrast imaging; Absence of macrovascular invasion and extrahepatic spread (defines the stage)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/hcc-intermediate/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/hcc-intermediate/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/hcc-intermediate/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/hcc-intermediate/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/hcc-intermediate/#treating-it [4 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/hcc-intermediate/#evidence [15 trials, 5 key papers, 5 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/hcc-intermediate/#science [7 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/hcc-intermediate/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/hcc-intermediate/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/hcc-intermediate/coming/ [6 medicines, 13 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/hcc-intermediate/data/ [53 connected records]

## Standard of care

- Well-defined nodules, preserved liver function: Transarterial chemoembolisation, conventional or with drug-eluting beads, repeated on demand; radioembolisation as an alternative. ([Transarterial chemoembolisation (TACE)](https://onco.cc/technologies/tace/), [TACE (transarterial chemoembolisation)](https://onco.cc/terms/tace-term/), [Radioembolisation (TARE / SIRT, yttrium-90)](https://onco.cc/technologies/radioembolisation-tare/), [BCLC staging](https://onco.cc/terms/bclc-staging/))
- TACE plus systemic therapy: Durvalumab with bevacizumab (EMERALD-1) or lenvatinib with pembrolizumab (LEAP-012) added to TACE, where approved; durvalumab-tremelimumab with TACE after EMERALD-3. ([EMERALD-1](https://onco.cc/trials/emerald-1/), [LEAP-012](https://onco.cc/trials/leap-012/), [EMERALD-3](https://onco.cc/trials/emerald-3/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/), [TACE + immunotherapy/anti-VEGF](https://onco.cc/pairings/tace-plus-systemic/))
- High burden or diffuse disease: Systemic therapy as for advanced disease (atezolizumab-bevacizumab or durvalumab-tremelimumab) instead of embolisation. ([Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/), [IMbrave150](https://onco.cc/trials/imbrave150/), [HIMALAYA](https://onco.cc/trials/himalaya/))
- Within transplant criteria after downstaging: Chemoembolisation or radioembolisation as a bridge, then liver transplantation. ([Liver transplantation for cancer (Milan criteria and beyond)](https://onco.cc/technologies/liver-transplant-oncology/), [Bridging therapy](https://onco.cc/terms/bridging-therapy/), [Transarterial chemoembolisation (TACE)](https://onco.cc/technologies/tace/))

## State of the art

- Chemoembolisation remains the backbone, but the 2022 BCLC update sends patients with diffuse or high-burden disease straight to systemic therapy.
- EMERALD-1 and LEAP-012 are the first phase 3 trials to improve on TACE alone in twenty years.
- Whether the combinations lengthen life, not just time to progression, is still awaited.

## Open problems

- No overall survival gain yet shown for TACE combinations.
- Which patients should skip embolisation and go straight to systemic therapy.
- Liver damage from repeated embolisation limits later treatment options.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization
- EMERALD-1 (Lancet 2025): https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02551-0/abstract
- LEAP-012 (Lancet 2025): https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02575-3/abstract
- BCLC 2022 update (J Hepatol): https://pubmed.ncbi.nlm.nih.gov/34801630/
- Wikipedia: https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization

## Connected records

- cancers: [Advanced hepatocellular carcinoma (BCLC C)](https://onco.cc/cancers/hcc-advanced/), [Early hepatocellular carcinoma (BCLC 0 and A)](https://onco.cc/cancers/hcc-early/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/)
- key papers: [Arterial embolisation or chemoembolisation versus symptomatic treatment in unresectable hepatocellular carcinoma](https://onco.cc/key-papers/paper-llovet-tace-lancet-2002/), [BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update](https://onco.cc/key-papers/paper-bclc-2022-reig-j-hepatol-2022/), [EMERALD-1: durvalumab with or without bevacizumab added to transarterial chemoembolisation for embolisation-eligible hepatocellular carcinoma](https://onco.cc/key-papers/paper-emerald-1-lancet-2025/), [HIMALAYA: tremelimumab plus durvalumab in unresectable hepatocellular carcinoma](https://onco.cc/key-papers/paper-himalaya-nejm-evidence-2022/), [LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma](https://onco.cc/key-papers/paper-leap-012-lancet-2025/)
- technologies: [Liver transplantation for cancer (Milan criteria and beyond)](https://onco.cc/technologies/liver-transplant-oncology/), [Radioembolisation (TARE / SIRT, yttrium-90)](https://onco.cc/technologies/radioembolisation-tare/), [Transarterial chemoembolisation (TACE)](https://onco.cc/technologies/tace/)
- terms: [BCLC staging](https://onco.cc/terms/bclc-staging/), [Bridging therapy](https://onco.cc/terms/bridging-therapy/), [LI-RADS (Liver Imaging Reporting and Data System)](https://onco.cc/terms/li-rads/), [TACE (transarterial chemoembolisation)](https://onco.cc/terms/tace-term/)
- trials: [A Phase II/III Trial Comparing Transarterial Tirapazamine Embolization (TATE) With cTACE for Intermediate-stage Liver Cancer.](https://onco.cc/trials/nct06844357/), [A Phase IIa, Single-arm, Open-label Clinical Study to Evaluate the Efficacy, Safety and PK of CVM-1118 in Combination With Sintilimab and TACE in Part](https://onco.cc/trials/nct07521852/), [A Study of AK104+Lenvatinib in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepat](https://onco.cc/trials/nct06371157/), [A Study of PTX-9908 Injection for Non-resectable HCC with TACE](https://onco.cc/trials/nct03812874/), [A Study of TACE Combined With Camrelizumab Plus Rivoceranib (Apatinib) in Patients With Incurable Hepatocellular Carcinoma](https://onco.cc/trials/nct05320692/), [EMERALD-1](https://onco.cc/trials/emerald-1/), [EMERALD-3](https://onco.cc/trials/emerald-3/), [Endovascular Brachytherapy Combined With Stent Placement and TACE for HCC With Main Portal Vein Tumor Thrombus](https://onco.cc/trials/nct02971345/), [GKL-006 Injection Plus TACE Versus TACE Alone in Patients With Unresectable Hepatocellular Carcinoma](https://onco.cc/trials/nct07209813/), [HIMALAYA](https://onco.cc/trials/himalaya/), [IMbrave150](https://onco.cc/trials/imbrave150/), [LEAP-012](https://onco.cc/trials/leap-012/), [Liver Resection Versus Transarterial Chemoembolization for the Treatment of Intermediate-stage Hepatocellular Carcinoma](https://onco.cc/trials/nct02755311/), [To Evaluate Safety and Efficacy of FB-1603 in Hepatocellular Carcinoma Patient Receiving Transarterial Chemoembolization](https://onco.cc/trials/nct06478719/), [Transarterial Chemoembolization Compared With Stereotactic Body Radiation Therapy or Stereotactic Ablative Radiation Therapy in Treating Patients With Residual or Recurrent Liver Cancer Undergone Initial Transarterial Chemoembolization](https://onco.cc/trials/nct02762266/)
- pairings: [TACE + immunotherapy/anti-VEGF](https://onco.cc/pairings/tace-plus-systemic/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)

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JSON: https://onco.cc/api/v1/entities/hcc-intermediate.json