Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment, and follow-up of patients with hepatocellular carcinoma

Key guideline recommendations

1. Because of the association of HCC with chronic liver disease, universal HBV vaccination at birth (II, A) and early antiviral treatment of HBV and HCV (III, A) are recommended.

   II, A / III, A

2. Antiviral treatment is recommended for all patients with active HBV who develop HCC, particularly those receiving curative and/or systemic treatment.

   II, A

3. HCC surveillance is recommended in all patients with cirrhosis, regardless of its cause, if liver function and comorbidities allow tumour treatment.

   II, A

4. HCC surveillance should consist of abdominal ultrasound (or, where possible, multiphase cross-sectional imaging) every 6 months, with or without AFP measurement.

   II, A

5. In patients with advanced HCC, a histological diagnosis of HCC is recommended before starting systemic treatment.

   III, A

6. Liver resection is recommended for patients with a single tumour larger than 2 cm without evidence of portal hypertension (BCLC 0 to A).

   II, A

7. Microwave ablation (MWA) or radiofrequency ablation (RFA) is recommended in very early stage disease (BCLC 0) and is an alternative to resection in early stage disease (BCLC A).

   II, A

8. Adjuvant systemic treatment with tyrosine kinase inhibitors or immune checkpoint inhibitor-based combinations after resection or ablation is not recommended.

   I, E

9. Liver transplantation (OLT) is recommended for patients within the Milan criteria, when a recurrence rate of less than 10% and 5-year survival of 70% are expected; the UCSF criteria may also be considered in patients beyond the Milan criteria (III, B).

   II, A

10. TACE with drug-eluting beads (DEB-TACE) or conventional lipiodol-based TACE can be recommended for patients with intermediate-stage disease (BCLC B).

    I, B

11. Combining TACE with an immunotherapy regimen plus an anti-angiogenic drug (such as atezolizumab–bevacizumab, durvalumab–bevacizumab or pembrolizumab–lenvatinib) may be considered in intermediate-stage disease, but its long-term benefit has not been proven.

    I, C

12. Combining TACE with lenvatinib may be considered if an immunotherapy plus anti-angiogenic combination is not possible.

    II, C

13. First line in advanced disease: atezolizumab–bevacizumab or durvalumab–tremelimumab is recommended (ESMO-MCBS v2.0: score 5 for both).

    I, A

14. In patients with portal hypertension, assessment of varices before starting atezolizumab–bevacizumab is strongly recommended.

    IV, A

15. Camrelizumab–rivoceranib (not approved by EMA or FDA) or nivolumab–ipilimumab (EMA approved, not FDA) can be recommended.

    I, B

16. Durvalumab (I, A; ESMO-MCBS v2.0: score 4; EMA approved, not FDA) or tislelizumab (I, A; not approved by EMA or FDA) should be considered for patients who are not suitable for combination checkpoint inhibitor therapy.

    I, A

17. Lenvatinib or sorafenib is recommended for patients with a contraindication to immunotherapy.

    I, A

18. In patients with poor liver function and/or ECOG performance status 2 or higher (BCLC D), best supportive care, including stereotactic radiotherapy for pain, is recommended.

    III, A

19. Second line after sorafenib: regorafenib or cabozantinib (both I, A; ESMO-MCBS v2.0: score 3) should be considered; ramucirumab may be considered in patients with AFP ≥400 ng/mL (I, B; ESMO-MCBS: score 1). Sorafenib may be considered after first-line lenvatinib (IV, C).

    I, A

20. Lenvatinib should be considered after first-line immunotherapy (IV, A; not approved by EMA or FDA for second line), and sorafenib may be considered after first-line immunotherapy (IV, B). Sequential use of all approved drugs after immunotherapy combinations or lenvatinib is recommended (III, A).

    IV, A / IV, B

21. Systemic chemotherapy has not improved survival in randomised trials and cannot be recommended.

    II, D

22. Follow-up after radical treatment (surgery or thermal ablation): clinical assessment for liver decompensation and early detection of recurrence with contrast-enhanced multiphase CT or MRI every 3 months for the first 2 years and then every 6 months up to 5 years.

    III, A

Study population

Endpoints

Safety and side effects

Clinical significance and place in guidelines

Limitations