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eUpdate – Hepatocellular Carcinoma Treatment Recommendations

eUpdate – Hepatocellular Carcinoma Treatment Recommendations

Published: 19 June 2020. Authors: ESMO Guidelines Committee

Note: Other eUpdates may have been published for these guidelines. All currently valid eUpdates can be accessed from the page displaying the full guidelines on this topic

Clinical Practice Guidelines

This eUpdate refers to Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Vogel A, Cervantes A, Chau I et al. Ann Oncol 2018; 29 (Suppl 4): iv238–iv255.


Table 4. BCLC staging and treatment options according to level of evidence and approval status   

This replaces the Table 4 text update 14 January 2020

BCLC stage

Treatment (standard of care)

Indication constraints based on tumour burden and liver function

Alternative treatment

0 - A

Single tumour any size or up to 3 nodules ≤ 3 cm

Preserved liver function


Resection [III, A]

Adequate size and function of remnant liver


HDR brachytherapy [III, C]


Transplantation [III, A]

Size ≤ 5 cm, number ≤ 3

Thermal ablation [III, A]

Size ≤ 3 cm, not adjacent to vessels or bile duct


Contraindications against resection and thermal ablation. Bridging to transplantation



Preserved liver function



Size 5-10 cm, tumour nodules accessible to supra-selective catheterisation

Transplantation [III, A]

Resection [III, A]

Systemic therapy (after TACE failure/ refractoriness) [I, A]

SIRT (liver-confined, good liver function, no systemic therapy feasible) 


Portal invasion

Extrahepatic spread

Preserved liver function



Sorafenib (first-line) [I, A]

Lenvatinib (first-line) [I, A; MCBS 4] 


Atezolizumab/ Bevacizumaba (first-line) [I, A] 



Child–Pugh A

SIRT (liver-confined, good liver function, no systemic therapy feasible)


Regorafenib (second-line) [I, A; MCBS 4] 



Cabozantinib (second-line) [I, A; MCBS 3] 


Ramucirumab (AFPhigh, second-line) [I, A; MCBS 1] 




Child–Pugh A,

Tolerability to sorafenib (regorafenib)


End-stage liver function





AFPhigh, elevated alpha fetoprotein; BCLC, Barcelona Clinic Liver Cancer; BSC, best supportive care; ECOG, Eastern Cooperative Oncology Group; EMA, European Medicines Agency; HDR, high dose rate; MCBS, European Society for Medical Oncology (ESMO)-Magnitude of Benefit Scale; PS, performance status; SBRT, stereotactic body radiotherapy; SIRT, selective internal radiotherapy; TACE, transarterial chemoembolisation

aNot EMA-approved



Text update

Immunotherapy in the form of combination regimens (atezolizumab and bevacizumab, IMbrave 150) or monotherapy (nivolumab, CheckMate 459) has been evaluated in untreated patients with BCLC B or C hepatoma, while pembrolizumab has been studied in patients who are intolerant to or have progressed under approved tyrosine kinase inhibitors. The first-line phase III CheckMate 459 trial, comparing sorafenib with nivolumab as a first-line treatment option, failed to meet the primary endpoint of overall survival (OS). The second-line phase III KEYNOTE-240 trial of pembrolizumab failed to meet its co-primary endpoints of OS and PFS, compared with placebo plus best supportive care.

In contrast, the combination of atezolizumab with bevacizumab met both primary endpoints of OS and progression-free survival (PFS) compared with sorafenib, as it was associated with hazard ratios of 0.59 and 0.58 respectively. Based on these data, the combination was approved by the Food and Drug Administration (FDA). Assessment by the European Medicines Agency (EMA) is awaited.


Table 6. Summary of Recommendations, Management of advanced disease

Text update

Immunotherapy with the combination of atezolizumab+bevacizumab, nivolumab (first-line) and pembrolizumab (second-line) have been evaluated for patients with irresectable hepatoma. In view of the positive results of the atezolizumab+bevacizumab combination, the regimen can be considered as first-line therapy (FDA-approved, not EMA-approved) [I, A].

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