Dear Editor,
We would like to thank Dr. Rhee and Dr. Choi for their interest in our study “Non-contrast MRI for Detection of Late Recurrent Hepatocellular Carcinoma After Curative Treatment: Comparison to CT”, and for their thoughtful editorial commentary [
1,
2].
As emphasized in their editorial, current hepatocellular carcinoma (HCC) management guidelines recommend biannual surveillance using ultrasound (US), with or without serum alpha-fetoprotein (AFP), for individuals at risk [
3-
5]. This strategy aims to detect HCC at an early stage when curative treatment options are feasible, thereby improving overall survival. However, US has inherent limitations, including operator dependence, subjectivity, and reduced image quality in patients with obesity or advanced cirrhosis due to the poor sonic window. Notably, a meta-analysis reported a sensitivity of only 47% for detecting early-stage HCC with US, which is suboptimal [
6]. To address these limitations, alternative imaging modalities have been explored for surveillance purposes. Among them, non-contrast MRI (NC-MRI) has demonstrated significantly superior diagnostic performance, lower false-positive referral rates, and improved early-stage HCC detection compared to US [
7,
8], positioning it as a promising tool for HCC surveillance [
9].
In addition to primary surveillance for at-risk individuals without a prior history of HCC, another key population requiring regular imaging surveillance is patients who have undergone curative treatment for HCC. Even after prolonged periods of recurrence-free status, these individuals remain at substantial risk for developing de novo secondary HCC in the remnant liver, underscoring the need for continued surveillance [
10]. Despite this clinical need, the post-treatment surveillance population has been relatively under-investigated, with only a few retrospective studies exploring optimal imaging strategies for detecting recurrent HCC following curative treatment [
11,
12]. In current clinical practice, both contrast-enhanced CT (CECT) and contrast-enhanced dynamic MRI are commonly used for the detection of recurrent HCC and have demonstrated strong diagnostic performance. However, there are notable limitations to CECT, including cumulative ionizing radiation exposure and risks associated with iodinated contrast agents. While contrast-enhanced liver MRI avoids radiation, it also presents challenges such as high cost, extended scan times, and potential concerns related to gadolinium-based contrast agents, including deposition in the basal ganglia. Given these limitations, NC-MRI emerges as a promising alternative to both CECT and contrast-enhanced MRI. NCMRI offers several advantages, including the absence of radiation and contrast agent administration, shorter scan time, and lower cost relative to full-sequence contrast-enhanced MRI. In this context, our study aimed to compare the diagnostic performance of NC-MRI and CECT for the detection of recurrent HCC after curative treatment. We found that NC-MRI demonstrated significantly higher sensitivity and accuracy than CECT in detecting recurrent HCC among patients who had remained recurrence-free for more than two years after curative treatment.
Although our study provides preliminary evidence supporting the use of NC-MRI for detecting HCC recurrence after curative treatment, several important considerations must be addressed for real-world implementation, as appropriately noted in the editorial. A key factor is the individual risk of recurrence, which can influence both the diagnostic performance and cost-effectiveness of imaging modalities. In our study, we enrolled patients who had remained recurrence-free for more than two years after curative treatment, aiming to detect late recurrences likely arising from de novo secondary hepatocarcinogenesis in the remnant liver. As a result, the recurrence risk in this population was relatively low compared to the immediate posttreatment period, and the incidence of aggressive recurrence patterns, such as vascular invasion, disseminated micrometastases, or extrahepatic spread was expected to be minimal. Accordingly, our study did not assess the performance of NC-MRI in identifying these more aggressive forms of recurrence. Due to the absence of contrast administration, NC-MRI may be less effective in detecting vascular invasion compared to CECT or contrast-enhanced MRI. Furthermore, the limited scan coverage of NC-MRI may reduce its ability to identify extrahepatic metastases. To overcome these limitations, future studies should include a broader range of recurrence risk profiles and a larger patient population to more comprehensively evaluate the diagnostic utility of NC-MRI in detecting recurrent HCC. Nonetheless, in patients with a prolonged recurrence-free interval, such as those in our study cohort, the likelihood of aggressive recurrence is lower, and most recurrences are expected to arise from new intrahepatic lesions. Therefore, this group may represent an optimal target population for NC-MRI surveillance.
Given the single-arm, intra-individual, head-to-head comparison design of our study, in which all participants underwent both NC-MRI and CECT, a comparison of overall survival outcomes between the two modalities was not feasible. Since the ultimate goal of surveillance imaging is to improve survival by facilitating early detection of recurrence, future large-scale prospective randomized controlled trials are needed. In addition, cost-effectiveness analyses based on robust diagnostic performance data are essential for informing the broader implementation of NCMRI in post-treatment HCC surveillance.
In conclusion, while our findings support the potential role of NC-MRI in detecting recurrent HCC, particularly in patients at lower risk of aggressive recurrence, it remains necessary to conduct further studies, including randomized controlled trials across varied risk groups, to establish highlevel evidence for its routine clinical use.
FOOTNOTES
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Conflicts of Interest
The author has no conflicts to disclose.
Abbreviations
contrast-enhanced computed tomography
non-contrast magnetic resonance imaging
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