Study reveals liver- and tumour-specific indicators against repeat TACE in HCC patients

Repeat transarterial chemoembolization (TACE) is not recommended for patients with hepatocellular carcinoma (HCC) who have persistent liver function deterioration after initial TACE, particularly if they have suboptimal baseline liver function or excessive tumour burden, according to researchers from the Chinese University of Hong Kong (CUHK).

Repeat TACE is indicated for residual or recurrent intrahepatic tumours after initial TACE. “Liver condition is crucial to clinical outcomes of repeat TACE,” the researchers explained. “Identifying objective and specific indicators predictive of suboptimal survival outcomes following repeat TACE would be clinically valuable because these could guide decisions on whether to pursue repeat TACE or switch to systemic therapy.” [Hong Kong Med J 2025;31:32-40]

The researchers therefore explored liver- and tumour-specific indicators predictive of suboptimal overall survival (OS) after repeat TACE in 300 treatment-naïve patients with intermediate-stage unresectable HCC (median age, 65 years; men, n=255) who presented between January 2005 and December 2019 and underwent TACE treatment.

The patients were divided into two groups: those with persistent albumin-bilirubin (ALBI) grade deterioration (PABD group), defined as modified ALBI (mALBI) grade deterioration that did not resolve within 90 days after initial TACE (n=81), and a non-PABD group that included those with no ALBI grade deterioration (NABD; n=65) and those with temporary ALBI grade deterioration (TABD; n=154) that resolved within 90 days after initial TACE. OS of these two groups of patients, according to subgroups stratified by baseline mALBI grade and tumour burden by the up-to-7 and up-to-11 criteria, was compared with OS of patients who received sorafenib or supportive care (SC) during the same period.

OS was significantly longer in the non-PABD and PABD groups (23.13 and 8.03 months, respectively) than the sorafenib and SC groups (5.11 and 2.57 months, respectively) (p<0.05). Among patients with TABD or NABD, OS was similar (23.83 and 22.40 months, respectively), indicating that TABD did not adversely affect treatment outcomes and repeat TACE remains feasible for those with TABD.

In all post-TACE non-PABD and PABD subgroups regardless of baseline liver condition, repeat TACE provided a survival benefit over sorafenib or SC. However, the survival benefit of repeat TACE was not significant in two subgroups of patients who developed PABD after initial TACE, namely, those with baseline mALBI grade 1 or 2a and tumour burden exceeding the up-to-11 criteria, and those with baseline mALBI grade 2b regardless of tumour burden.

“Based on these findings, repeat TACE is not recommended for patients with PABD and a baseline liver condition of mALBI grade 2b, regardless of tumour burden, because survival outcomes in this subgroup are unlikely to be superior to those achieved with sorafenib or SC,” the researchers advised.

“For the same reason, repeat TACE is not recommended for patients with PABD, a baseline liver condition of mALBI grade 1 or 2a, and tumour burden beyond the up-to-11 criteria. Systemic therapy is preferred for this subgroup, considering that its effectiveness is likely maximized in patients with better liver function [ie, ALBI grade 1 or mALBI grade 2a, as stated in an (Asian-Pacific) expert consensus],” they continued. [Liver Cancer 2020;9:245-260]

A limitation of the study was the use of sorafenib as control. With newer systemic therapies such as lenvatinib or atezolizumab-bevacizumab demonstrating OS benefits vs sorafenib, the latter is no longer a first-line systemic therapy for HCC. [Lancet 2018;391:1163-1173; J Hepatol 2022;76:862-873] As such, the researchers acknowledged that using sorafenib as control may lead to overestimation of the value of repeat TACE. “However, a sufficiently large database with long-term clinical outcomes for newer systemic therapies was not accessible for the local population,” they explained, adding that the validity of the liver- and tumour-specific indicators identified as criteria for contraindicating repeat TACE was not compromised.