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Page 6 of 22 Ma et al. Hepatoma Res. 2026;12:43

mechanisms constitute the biological basis for TACE resistance.

Therefore, patients with TACE refractoriness should be treated promptly. Previous studies have
[26]
summarized the follow-up treatment of TACE refractoriness, which mainly includes the following categories:
(1) local regional therapy: hepatic arterial infusion chemotherapy (HAIC), drug-eluting beads TACE,
radioembolization, ablation, etc.; (2) molecular targeted therapy: sorafenib, lenvatinib, apatinib, etc.; (3)
immunotherapy and its combination strategy: immune checkpoint inhibitors; (4) TACE combined with
systemic therapy. If the patient has good liver function (Child-Pugh A/B), local treatment combined with
systemic treatment can be considered. If the liver function is poor (Child-Pugh C), systemic treatment will be
given priority. New intrahepatic lesions can be treated with TACE or combination therapies. Patients with
vascular invasion or extrahepatic metastasis should be prioritized for systemic treatment.

The curative effect of TACE depends on the treatment strategy and the number of times it is performed, and
is closely related to the embolization material and the form of chemotherapy drug preparation used. A
research published in 2025 compared the efficacy of an anhydrous cisplatin suspension with lipiodol as a
[27]
carrier with that of a conventional aqueous cisplatin emulsion in TACE. The study showed that the use of
anhydrous cisplatin suspension could significantly improve the complete response rate (CRR) (90% vs. 47%),
prolong the median progression free survival (mPFS) (21.1 months vs. 10.4 months) and mOS (53.3 months
vs. 36.0 months), and there was no significant difference in the incidence of serious adverse events. In
addition to optimizing the dosage form of chemotherapy drugs, the development of new embolic materials
has also brought new possibilities for improving TACE efficacy. For example, thermosensitive hydrogels, as
liquid embolic agents, change phase into a solid at body temperature, which can embolize tumor terminal
vessels more accurately. A study has shown that using thermosensitive hydrogel-loaded epirubicin for
[28]
TACE treatment, the ORR of patients was 80.0%, 63.6%, and 38.9% at 1, 3, and 6 months, respectively; the
disease control rate (DCR) was 92.0%, 86.4%, and 72.3%, respectively; the mOS was 13 months, and the
postoperative pain and other adverse reactions were reduced compared with traditional particle
embolization.

From the initial recommendation of sorafenib as the first choice for subsequent treatment after TACE
refractory based on the evidence of two retrospective studies conducted in Japan [29,30] . Numerous randomized
controlled trials have demonstrated that TACE combined with targeted therapy plus immunotherapy can
significantly improve the prognosis and survival of patients. The treatment of patients with advanced HCC
has entered a new stage. The recently updated BCLC 2026 guidelines propose that once TACE is confirmed
to be refractory, the first and clear recommendation is to switch to systemic therapy .
[10]

Precision TACE
In recent years, the concept of precision TACE has garnered increasing attention. Precision TACE
emphasizes super-selective catheterization of tumor-feeding arteries using a microcatheter, typically guided
by cone-beam Computed Tomography (CT) or C-arm CT, to achieve targeted delivery of embolic materials
and chemotherapeutic agents while minimizing exposure to non-tumorous liver parenchyma .
[11]
Accumulating evidence [31,32] suggests that precision TACE offers several advantages over conventional non-
selective or lobar TACE. First, by limiting ischemic and cytotoxic injury to non-tumorous liver tissue,
precision TACE helps better preserve post-procedural liver function, as reflected by smaller increases in
albumin-bilirubin (ALBI) or Child-Pugh scores. Second, the higher intensity of local tumor necrosis
achieved through super-selective embolization may improve objective response rates and prolong time to
progression. Third, by maximizing the efficacy of each session, precision TACE may reduce the total number
of TACE procedures required to achieve adequate tumor control, thereby lowering the cumulative risk of
treatment-related liver injury and TACE refractoriness. The CCI has incorporated refined TACE techniques