{"entity":{"id":"hcc-intermediate","kind":"cancer","name":"Intermediate hepatocellular carcinoma (BCLC B)","aka":["Intermediate-stage HCC","Multinodular HCC","TACE-eligible hepatocellular carcinoma","BCLC B"],"tldr":"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.\n\nTransarterial 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.\n\nTwo 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization","links":[{"label":"EMERALD-1 (Lancet 2025)","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02551-0/abstract"},{"label":"LEAP-012 (Lancet 2025)","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02575-3/abstract"},{"label":"BCLC 2022 update (J Hepatol)","url":"https://pubmed.ncbi.nlm.nih.gov/34801630/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization"}],"tags":["subtype-page"],"related":["hcc-advanced","hcc-early"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-himalaya-nejm-evidence-2022","paper-llovet-tace-lancet-2002","paper-emerald-1-lancet-2025","paper-leap-012-lancet-2025"],"journals":[],"dependsOn":[],"notes":[],"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)"],"standardOfCare":[{"setting":"Well-defined nodules, preserved liver function","approach":"Transarterial chemoembolisation, conventional or with drug-eluting beads, repeated on demand; radioembolisation as an alternative.","refs":["tace","tace-term","radioembolisation-tare","bclc-staging"]},{"setting":"TACE plus systemic therapy","approach":"Durvalumab with bevacizumab (EMERALD-1) or lenvatinib with pembrolizumab (LEAP-012) added to TACE, where approved; durvalumab-tremelimumab with TACE after EMERALD-3.","refs":["emerald-1","leap-012","emerald-3","durvalumab","bevacizumab","lenvatinib","pembrolizumab","tremelimumab","tace-plus-systemic"]},{"setting":"High burden or diffuse disease","approach":"Systemic therapy as for advanced disease (atezolizumab-bevacizumab or durvalumab-tremelimumab) instead of embolisation.","refs":["atezolizumab","bevacizumab","durvalumab","tremelimumab","imbrave150","himalaya"]},{"setting":"Within transplant criteria after downstaging","approach":"Chemoembolisation or radioembolisation as a bridge, then liver transplantation.","refs":["liver-transplant-oncology","bridging-therapy","tace"]}],"stateOfArt":["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."],"history":[{"year":2002,"title":"Llovet and Lo randomised trials: chemoembolisation prolongs survival","refs":["tace"]},{"year":2010,"title":"Drug-eluting bead TACE (PRECISION V) matches conventional TACE with less toxicity","refs":["tace"]},{"year":2022,"title":"BCLC update subdivides intermediate stage and introduces treatment stage migration","refs":["bclc-staging"]},{"year":2025,"title":"EMERALD-1 and LEAP-012: systemic therapy plus TACE delays progression","refs":["emerald-1","leap-012"]},{"year":2026,"title":"EMERALD-3: durvalumab-tremelimumab plus TACE reported positive","refs":["emerald-3"]}],"pipeline":["emerald-3","tace-plus-systemic","radioembolisation-tare","durvalumab","lenvatinib"],"openProblems":["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."],"parent":"hcc"},"route":"/cancers/hcc-intermediate/","neighbours":{"cancer":[{"id":"hcc-advanced","kind":"cancer","name":"Advanced hepatocellular carcinoma (BCLC C)","route":"/cancers/hcc-advanced/"},{"id":"hcc-early","kind":"cancer","name":"Early hepatocellular carcinoma (BCLC 0 and A)","route":"/cancers/hcc-early/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"}],"paper":[{"id":"paper-llovet-tace-lancet-2002","kind":"paper","name":"Arterial embolisation or chemoembolisation versus symptomatic treatment in unresectable hepatocellular carcinoma","route":"/key-papers/paper-llovet-tace-lancet-2002/"},{"id":"paper-bclc-2022-reig-j-hepatol-2022","kind":"paper","name":"BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update","route":"/key-papers/paper-bclc-2022-reig-j-hepatol-2022/"},{"id":"paper-emerald-1-lancet-2025","kind":"paper","name":"EMERALD-1: durvalumab with or without bevacizumab added to transarterial chemoembolisation for embolisation-eligible hepatocellular carcinoma","route":"/key-papers/paper-emerald-1-lancet-2025/"},{"id":"paper-himalaya-nejm-evidence-2022","kind":"paper","name":"HIMALAYA: tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","route":"/key-papers/paper-himalaya-nejm-evidence-2022/"},{"id":"paper-leap-012-lancet-2025","kind":"paper","name":"LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma","route":"/key-papers/paper-leap-012-lancet-2025/"}],"technology":[{"id":"liver-transplant-oncology","kind":"technology","name":"Liver transplantation for cancer (Milan criteria and beyond)","route":"/technologies/liver-transplant-oncology/"},{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","route":"/technologies/radioembolisation-tare/"},{"id":"tace","kind":"technology","name":"Transarterial chemoembolisation (TACE)","route":"/technologies/tace/"}],"term":[{"id":"bclc-staging","kind":"term","name":"BCLC staging","route":"/terms/bclc-staging/"},{"id":"bridging-therapy","kind":"term","name":"Bridging therapy","route":"/terms/bridging-therapy/"},{"id":"li-rads","kind":"term","name":"LI-RADS (Liver Imaging Reporting and Data System)","route":"/terms/li-rads/"},{"id":"tace-term","kind":"term","name":"TACE (transarterial chemoembolisation)","route":"/terms/tace-term/"}],"trial":[{"id":"nct06844357","kind":"trial","name":"A Phase II/III Trial Comparing Transarterial Tirapazamine Embolization (TATE) With cTACE for Intermediate-stage Liver Cancer.","route":"/trials/nct06844357/"},{"id":"nct07521852","kind":"trial","name":"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","route":"/trials/nct07521852/"},{"id":"nct06371157","kind":"trial","name":"A Study of AK104+Lenvatinib in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepat","route":"/trials/nct06371157/"},{"id":"nct03812874","kind":"trial","name":"A Study of PTX-9908 Injection for Non-resectable HCC with TACE","route":"/trials/nct03812874/"},{"id":"nct05320692","kind":"trial","name":"A Study of TACE Combined With Camrelizumab Plus Rivoceranib (Apatinib) in Patients With Incurable Hepatocellular Carcinoma","route":"/trials/nct05320692/"},{"id":"emerald-1","kind":"trial","name":"EMERALD-1","route":"/trials/emerald-1/"},{"id":"emerald-3","kind":"trial","name":"EMERALD-3","route":"/trials/emerald-3/"},{"id":"nct02971345","kind":"trial","name":"Endovascular Brachytherapy Combined With Stent Placement and TACE for HCC With Main Portal Vein Tumor Thrombus","route":"/trials/nct02971345/"},{"id":"nct07209813","kind":"trial","name":"GKL-006 Injection Plus TACE Versus TACE Alone in Patients With Unresectable Hepatocellular Carcinoma","route":"/trials/nct07209813/"},{"id":"himalaya","kind":"trial","name":"HIMALAYA","route":"/trials/himalaya/"},{"id":"imbrave150","kind":"trial","name":"IMbrave150","route":"/trials/imbrave150/"},{"id":"leap-012","kind":"trial","name":"LEAP-012","route":"/trials/leap-012/"},{"id":"nct02755311","kind":"trial","name":"Liver Resection Versus Transarterial Chemoembolization for the Treatment of Intermediate-stage Hepatocellular Carcinoma","route":"/trials/nct02755311/"},{"id":"nct06478719","kind":"trial","name":"To Evaluate Safety and Efficacy of FB-1603 in Hepatocellular Carcinoma Patient Receiving Transarterial Chemoembolization","route":"/trials/nct06478719/"},{"id":"nct02762266","kind":"trial","name":"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","route":"/trials/nct02762266/"}],"pairing":[{"id":"tace-plus-systemic","kind":"pairing","name":"TACE + immunotherapy/anti-VEGF","route":"/pairings/tace-plus-systemic/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}]}}