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Page 8 of 17 Li et al. Hepatoma Res. 2025;11:25 https://dx.doi.org/10.20517/2394-5079.2025.63

Recent advances in imaging technologies have led to the development of novel modalities that improve the
precision of ablation and the assessment of therapeutic outcomes. For instance, CEUS based on colony-
stimulating factor 1 receptor (CSF-1R)-targeted nanobubbles has shown promise in accurately delineating
[47]
ablation margins and detecting residual HCC lesions . Another novel approach is indocyanine green
(ICG)-guided optical imaging (OI), which allows for real-time visualization of tumor boundaries and
[48]
differentiation between viable and necrotic tumor tissue . Collectively, these technological advancements
offer clinicians high-resolution, real-time insights that can significantly improve the safety and efficacy of
ablation therapy. However, the clinical utility and translational potential of these methods remain to be
rigorously validated in large-scale, multicenter studies.

In summary, the continuous advancement of imaging technologies has significantly enhanced the precision
and dynamic monitoring capacity of ablation therapy for HCC, providing robust support for intraoperative
decision-making and postoperative management. Notably, some advanced imaging modalities have already
been standardized in clinical practice at select centers - for example, intraoperative CEUS combined with
CT/MRI fusion imaging and real-time efficacy evaluation using PET/CT - demonstrating promising clinical
feasibility and adaptability [12,49,50] . However, reliance on imaging alone remains insufficient to completely
prevent tumor recurrence. Given the complex biological characteristics of residual lesions and the adaptive
mechanisms within the tumor microenvironment, the integration of postoperative adjuvant therapies has
become increasingly essential. Based on these considerations, the following sections will focus on recent
advances in combining ablation with other local treatments, chemotherapy, targeted therapy, and
immunotherapy, aiming to provide both theoretical rationale and practical guidance for developing a
multidimensional, integrated treatment paradigm.

Postoperative adjuvant therapy
With the advancement of imaging technologies, the ability to detect residual lesions during and after
ablation has been significantly improved, providing critical guidance for precise ablation procedures and
individualized patient management. Imaging surveillance has become an essential reference for formulating
postoperative treatment strategies, particularly in patients with a high risk of recurrence or suspected
insufficient ablation. Imaging-based monitoring and postoperative adjuvant therapies should be regarded as
an integrated interventional approach to collectively enhance overall treatment efficacy. Although ablation
achieves a relatively high rate of local tumor control, recurrence remains frequent - especially in patients
with minimal residual disease or highly aggressive tumors. Therefore, there is an urgent need to explore
more effective adjuvant strategies to delay recurrence and improve long-term survival outcomes.

For local therapies, several studies have investigated combining ablation with transarterial
chemoembolization (TACE), showing promise for tumor control, though large-scale randomized controlled
trials (RCTs) are still needed . According to current studies, TACE is potentially beneficial for reducing
[51]
early recurrence in patients who have high-risk features, such as microvascular invasion (MVI), a tumor
diameter ≥ 5 cm, multiple tumors, or suspected residual lesions [52-54] . Combining ablation with radiotherapy
[55]
has demonstrated efficacy in preclinical models . However, due to the limited tolerance of the liver to
external beam radiotherapy, in patients with sufficient liver reserve who are suitable for arterial-based
therapies, pairing ablation with transarterial radioembolization (TARE) may offer a more viable option .
[56]
In a multicenter, prospective trial, early-stage HCC patients with 2-5 cm lesions received holmium-166
microspheres ( Ho-MS) infusions 5-10 days post-RFA. Among 12 patients followed for one year, no local
166
recurrence was observed .
[57]