Dear Editor,
We read with great interest the prospective, multicenter head-to-head comparison study by Kim et al. evaluating non-contrast MRI (NC-MRI) versus contrast-enhanced CT (CECT) for the detection of late recurrent hepatocellular carcinoma (HCC) following curative treatment [
1]. This work addresses a timely and clinically relevant question, especially given the growing attention to surveillance strategies that minimize risk while optimizing diagnostic efficacy. We commend the authors for the rigor of their design and the contribution this study makes to the evolving landscape of HCC management. We would, however, like to offer several constructive comments from a health economic and clinical applicability perspective to help contextualize the implementation of NC-MRI in routine practice. While beyond the scope of Kim et al.’s diagnostic comparison, these issues— including treatment stratification, cost-effectiveness, evolving recurrence patterns, patient adherence, and clinical outcomes—may be valuable for designing surveillance frameworks in future trials.
Although not within the scope of the original study, recur-rence risk remains a key determinant of cost-effective surveillance strategy. Guidelines have shown that surveillance is cost-effective when the annual risk of HCC recurrence exceeds 0.2% in patients without cirrhosis and 0.4% in those with cirrhosis [
2]. Therefore, surveillance following curative treatment of HCC is fundamentally aligned with health economic principles. However, it is crucial to incorporate patients’ initial treatment modality when tailoring follow-up protocols as patients who underwent radiofrequency ablation (RFA) face a higher risk of recurrence. To validate this, data from patients with very early HCC initially treated with either surgical resection (SR) or RFA were systematically analyzed. The analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/PROSPERO/view/369493). After comprehensive selection (
Supplementary Methods), 20 studies with low risk of bias involving 5,692 very early HCC patients treated with SR or RFA were included (
Supplementary Table 1). The results demonstrated markedly different recurrence patterns: For SR, the recurrence rates were 20.5%, 20.2%, and 17.0% at 1–2 years, 3–5 years, and 6–10 years post-treatment, respectively (
Fig. 1A). In contrast, RFA was associated with significantly higher recurrence rates at corresponding time intervals: 33.3%, 28.1%, and 16.1% (
Fig. 1B). Consistently, a metaanalysis demonstrated that SR provided superior 5-year recurrence-free survival compared to thermal ablation [
3]. In terms of recurrence patterns, SR was associated with a significantly lower incidence of local tumor progression (LTP) than thermal ablation, while no significant differences were observed in intrahepatic distant or extrahepatic recurrence rates. One reason for the higher rate of LTP following thermal ablation is its smaller treatment margin, which makes thermal ablation similar to narrow-margin surgery, reducing the chance of clearing micrometastases around the tumor [
4]. Another factor is that incomplete thermal ablation promotes malignant transformation, proliferation, metastasis, and stemness of residual HCC cells [
5,
6], while also creating an immunosuppressive microenvironment characterized by an increase in polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) [
7]. This strongly supports the incorporation of risk-based strategies—tailored the type of initial curative therapy—into surveillance recommendations. Considering these nuanced recurrence dynamics is pivotal to maximizing the clinical benefit and economic value of surveillance programs utilizing NC-MRI. Future research could explore how recurrence rates influence imaging strategies beyond diagnostic accuracy.
While Kim et al. affirmed the superior sensitivity (77.3% vs. 36.4%) and accuracy (96.6% vs. 91.6%) of NC-MRI over CECT in late recurrence detection, the economic implications merit deeper discussion. NC-MRI may incur higher costs [
8], and its longer scan time and limited accessibility may pose challenges in real-world settings, particularly in under-resourced healthcare systems. Therefore, we encourage future analyses incorporating comprehensive cost-utility modeling of NC-MRI vs. CECT in longitudinal follow-up, factoring in budget impact and system-level feasibility.
Additionally, recurrence patterns may change with antiviral therapy. It is noted that 82.8% of participants had hepatitis B virus (HBV)-related HCC. Recent evidence indicates that antiviral therapy significantly reduces the previously prominent late recurrence peak, which typically occurs around 3–4 years post-curative resection or ablation in HBVrelated HCC cases [
9]. Attenuation of late recurrence underscores that surveillance strategies might need to evolve dynamically alongside therapeutic advances. Such findings, although outside the study’s scope, may be relevant for future research direction.
While the study is premised on high follow-up compliance, real-world data show that surveillance adherence is suboptimal—only 24% in a pooled meta-analysis of 118,799 patients [
10]. Improving surveillance utilization is essential for achieving cost-effectiveness and clinical benefit [
11]. The implementation of NC-MRI as a preferred modality must be coupled with systemic efforts to enhance patient engagement and healthcare access. For example, alternating NC-MRI with ultrasound may strike a balance between sensitivity, cost, and patient convenience. A recent Korean prospective study [
12] demonstrated that alternating ultrasound and NC-MRI every six months may enhance compliance and diagnostic performance. Future studies could consider evaluating alternating modality regimens in terms of both diagnostic yield and cost-effectiveness.
Lastly, while not directly related to the study’s primary outcome, an essential yet unanswered question is whether earlier detection through NC-MRI will translate into a survival benefit, as acknowledged in the original article’s limitation. With a median tumor volume doubling time of approximately 4.6 months [
13], there may exist a tolerable time window for diagnostic delay, during which patients remain eligible for repeat radical resection or ablation; however, clinical validation in survival-focused trials remains necessary.
In conclusion, Kim et al. provides important evidence in support of NC-MRI for late HCC recurrence detection. However, broader considerations—including integrating recurrence risk in clinical planning, health economic, evolving recurrence patterns, patient compliance, and survival improvement—should inform future surveillance policy and research design. We believe that integrating these factors will help guide more personalized, effective, and economically sound surveillance strategies for HCC survivors.
FOOTNOTES
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Authors’ contributions
Qi-Feng Chen and Sui-Xing Zhong wrote the manuscript; Ming Zhao revised the manuscript. Qi-Feng Chen, Sui-Xing Zhong and Ming Zhao approved the final manuscript. Mingzhao is the guarantor.
-
Acknowledgements
Supported by the National Natural Science Foundation of China (No. 82402403, 82372061 and 82072022), and the GuangDong Basic and Applied Basic Research Foundation (No. 2025A1515011330).
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Conflicts of Interest
The authors have no conflicts to disclose.
SUPPLEMENTARY MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (
http://www.e-cmh.org).
Figure 1.Recurrence-free survival (RFS) and recurrence rates among very early-stage hepatocellular carcinoma patients after curative treatment with surgical resection (SR) or radiofrequency ablation (RFA). Kaplan–Meier curves showing RFS after SR (A) and RFA (B). At 1, 2, 3, 5, and 10 years, the estimated RFS rates were 90.4%, 79.5%, 71.2%, 59.3%, and 42.3% for SR, and 83.9%, 66.7%, 55.1%, 38.6%, and 22.5% for RFA, respectively. Bar graphs summarizing time-specific recurrence rates. After SR, recurrence rates were 20.5% (1–2 years), 20.2% (3–5 years), and 17.0% (6–10 years); after RFA, recurrence rates were higher at 33.3%, 28.1%, and 16.1% across the same time intervals.
Abbreviations
polymorphonucler myeloid-derived suppressor cells
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Citations
Citations to this article as recorded by
- Hepatocellular carcinoma surveillance: a health economic evaluation
Qi-Feng Chen, Xiong-Ying Jiang, Song Chen, Jiongliang Wang, Ming Zhao
Clinical and Molecular Hepatology.2026; 32(2): 536. CrossRef - Correspondence to letter to the editor on “Non-contrast magnetic resonance imaging for detection of late recurrent hepatocellular carcinoma after curative treatment: a prospective multicenter comparison to contrast-enhanced computed tomography”
Dong Ho Lee
Clinical and Molecular Hepatology.2026; 32(3): e402. CrossRef - Reply to correspondence on “Non-contrast magnetic resonance imaging for detection of late recurrent hepatocellular carcinoma after curative treatment: a prospective multicenter comparison to contrast-enhanced computed tomography”
Qi-Feng Chen, Sui-Xing Zhong, Xiong-Ying Jiang, Ming Zhao
Clinical and Molecular Hepatology.2026; 32(3): e441. CrossRef
