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Ma et al. Hepatoma Res. 2026;12:43 Page 3 of 22

This narrative review systematically combs through the current evidence on the impact of the number of
TACE on the clinical outcomes of HCC patients, focusing on differences between TACE monotherapy and
TACE combined with targeted therapy plus immunotherapy. Simultaneously, we explored the
methodological evolution of the prediction models.

Literature review methodology
This article is a narrative review. A comprehensive literature search was conducted in PubMed, Web of
Science, and CNKI for articles published up to May 2026. Search terms included combinations of
“hepatocellular carcinoma”, “transarterial chemoembolization”, “TACE refractoriness”, “combination
therapy”, “prognostic model”, and “machine learning”. We prioritized clinical trials, cohort studies, and
high-quality retrospective analyses. Given the narrative nature, formal quality assessment or meta-analysis
was not performed.

THE BASIC PRINCIPLE AND EFFICACY EVALUATION OF TACE
In 2002, two studies [17,18] in Japan found that the median overall survival (mOS) of the TACE group was
significantly longer than that of the best supportive care (BSC) group (20.4 months vs. 15.9 months). The 3-
year survival rate of patients significantly improved (26% vs. 3%). For the first time, high-level evidence
supports that TACE can significantly delay tumor progression, thereby significantly improving the survival
of patients with advanced HCC.

The Barcelona Clinic Liver Cancer (BCLC) 2022 regards TACE as the standard treatment for patients with
[4]
BCLC stage B. The newly proposed BCLC 2026 clearly defines stage B, replacing “multifocality” with “> 3
[10]
nodules, or ≤ 3 nodules but at least one > 3 cm”. Simultaneously, for the treatment of patients with BCLC
stage B, BCLC 2025 proposes that patients will no longer be limited to the initial stage but will be
incorporated into a dynamic decision-making model based on treatment response. Through the decision
node, patients in this stage were divided into three subgroups; patients with a clear tumor boundary, good
portal vein blood flow, and selective access to the tumor feeding artery still recommended TACE as the
standard local treatment. Most Chinese HCC patients have a background of hepatitis B and liver cirrhosis;
therefore, the China Liver Cancer Staging (CNLC) staging system developed in China is more suitable for
Chinese HCC patients. According to the guidelines for the diagnosis and treatment of HCC (2024
Edition) , TACE is suitable for patients with stage CNLC Ib-IIIb, of which stages IIb and IIIa are preferred.
[19]

TACE MONOTHERAPY
Benefit reduction due to the increase in the number of times
Because HCC is prone to recurrence and metastasis, TACE is usually performed multiple times. A body of
research has established that with an increase in the number of TACE sessions, the tumor objective response
rate (ORR) showed a trend of first increasing and then decreasing. In 2021, a retrospective study explored
[6]
the treatment strategy for patients with intermediate-stage HCC after initial failure to respond to
conventional transarterial chemoembolization (cTACE). The study pointed out that the third cTACE was a
key turning point; about 50% of patients who failed to respond to the first two treatments responded at this
time, and the 5-year survival rate of responders (9.1%) was significantly higher than that of non-responders
(3.2%). However, the response rate decreased to less than 10% after the fourth cTACE, and the long-term
survival rate was 0% whether they responded or not, indicating that continuing the fourth cTACE could not
achieve a survival benefit. While the third TACE may represent a potential turning point, the decision to
repeat or stop TACE should be individualized rather than based solely on the number of previous sessions. A
number of key factors, such as tumor response, TACE selectivity, and hepatic reserve, should all be
integrated into clinical decision-making.