Topic: Advances in Neoadjuvant and Adjuvant Therapy for Operable Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. The majority of new cases present with large tumours and impaired liver function [Altekruse, S.F.; Torre, LA. et al.]. Liver transplantation, hepatic resection, and ablation techniques are the three main pillars of curative-intent surgical management.

Based on the American Association for the Study of Liver (AASLD) and European Association for the Study of the Liver (EASL) guidelines, surgical management is focused mainly on Barcelona Clinic Liver Cancer (BCLC) stage A patients [Gavriilidis, P. et al.]. Additionally, approximately 11% of patients are diagnosed with portal vein thrombus tumours, placing them in BCLC stage B-C. According to the guidelines of EASL and AASLD, systemic therapy with sorafenib is recommended for this subset [Llovet, JM. et al.]. However, specialized hepatic surgery centres in East Asian countries have demonstrated potential benefits of hepatic resection for patients with BCLC B-C stage disease, emphasizing patient stratification for effective treatment [Gavriilidis, P. et al.]. The overall five-year survival rate for patients with very early HCC is between 25% and 50% [Bruix, J. et al.]. Nevertheless, high recurrence rates, ranging from 40% to 70%, significantly impact the long-term survival of operated patients [Tampaki, M. et al.]. Recurrences occur predominantly within two years post-operation, exhibiting different patterns, mechanisms, risk factors, and prognosis for early versus late recurrences [Nevola, R. et al.]. Notably, metastases mainly occur in the remaining liver tissue, due to disseminated malignant cells released by surgical manipulations during surgery and pre-existing undetectable microscopic tumour foci [Nevola, R.; Finkelstein, S.D. et al.]. In contrast, late recurrences are commonly associated with de novo neoplasms [Nevola, R.; Finkelstein, S.D. et al.; Nahon, P. et al.]. Different surgical treatments carry varying recurrence rates: radiofrequency ablation at 70%, hepatic resections at 25-50%, and liver transplantation at the lowest rate of 12-20% [Nahon, P.; Xing, H.; Lee, I.C.; Gory, I. et al.].

In the future, the efforts of all specialists involved in the multimodal treatment of HCC will be focused mainly on two targets; first, on the management of the recurrence rate by maximizing the effectiveness of loco-regional techniques, as well as optimizing patient selection and individualizing treatment schemes to achieve the best pre- and perioperative systemic therapies. Second, the use of optimal neoadjuvant therapies for patients on the waiting list for liver transplantation to keep the drop-out percentage of patients low.

Implications for research:

1. Types of loco-regional neoadjuvant therapy prior to hepatic resection.

2. Neoadjuvant therapy as a bridging therapy for liver transplantation.

3. Role of transarterial chemoembolisation (TACE) followed by portal vein embolisation in preparation for major hepatectomy.

4. Role of adjuvant antiviral therapy after curative treatment for HBV-related HCC.

5. Timing and benefits of antiviral therapy for HCV-related HCC.

6. The use of other adjuvant systemic regimens: a) atezolizumab plus bevacizumab, b) hepatic arterial infusion, c) TACE, d) radiolabelled lipiodol, and e) sorafenib.

7. The role of immunotherapy in the management of HCC: a) challenges in finding the right place in the treatment sequence, b) the role of Yttrium-90 radioembolisation in the management of HCC.

8. Post-treatment surveillance.

10 May 2024