Dear Editor,
We appreciate Dr. Chen and colleagues for their interest in our study entitled “Non-contrast MRI for Detection of Late Recurrent Hepatocellular Carcinoma After Curative Treatment: Comparison to CT” and for their thoughtful comment [
1]. Our prospective multicenter study showed that, compared with contrast-enhanced CT (CECT), non-contrast MRI (NC-MRI) achieved higher sensitivity and accuracy in identifying recurrent hepatocellular carcinoma (HCC) in patients who had been recurrence-free for over two years following curative therapy [
2]. Given its advantages, including the absence of radiation exposure and avoidance of contrast-related risks, NC-MRI may be a favorable modality for detecting late recurrent HCC compared with CECT, and our findings provide preliminary evidence supporting its use. While these results underscore the clinical potential of NC-MRI for recurrence detection, we agree with the authors that several important considerations remain for real-world application.
As noted by the authors, the risk of recurrence may influence both the diagnostic performance and cost-effectiveness of CECT and NC-MRI for detecting recurrent HCC after curative treatment. It is well established that recurrence risk after radiofrequency ablation (RFA) is higher than after surgical resection, largely due to an increased incidence of local tumor progression (LTP) [
3,
4]. Consequently, surgical resection generally yields superior 5-year recurrence-free survival compared with RFA [
5]. Therefore, the diagnostic performance and cost-effectiveness of NC-MRI and CECT may differ depending on whether the initial treatment was resection or RFA, although both are considered curative modalities. Importantly, the difference in recurrence risk between resection and RFA also changes over time. Because most LTP occurs within two years after treatment, the gap in recurrence risk is greater during the early posttreatment period. According to the authors’ analysis, the difference in recurrence risk between resection and RFA was 12.8% at 1–2 years, 7.9% at 3–5 years, and 0.9% at 6–10 years.1 In our study, we included patients who had remained recurrence-free for more than two years following curative therapy, and median interval between prior treatment and study enrollment was about 48.0 months; thus, the difference in recurrence risk between resection and RFA was likely less pronounced. Furthermore, recurrence risk and patterns may evolve with advances in antiviral therapy, which can also influence both diagnostic performance and cost-effectiveness of imaging modalities for detecting recurrent HCC. For example, antiviral therapy for hepatitis B virus infection has been shown to significantly reduce recurrence risk, particularly late recurrence after curative treatment [
6]. Nonetheless, larger studies that include patients with varying recurrence-free intervals are needed to better assess how recurrence risk affects the diagnostic performance and cost-effectiveness of NC-MRI compared with CECT. Furthermore, additional data on the diagnostic accuracy of NC-MRI in detecting recurrent HCC are essential to establish a robust cost-effectiveness evaluation.
In addition to recurrence risk, the cost and examination time of each imaging modality are important considerations for real-world application. As noted by the authors, the cost of NC-MRI is generally higher than that of CECT, although the exact expenses vary across countries. Examination time is also longer for NC-MRI; in our study, the average scan time was 9.5 minutes, which is considerably shorter than that of full-sequence contrast-enhanced MRI (>30 minutes), but still longer than CECT, which can typically be completed within 5 minutes. Beyond cost and time, image quality represents another critical factor for the clinical use of NC-MRI in HCC detection. To reduce scan time compared with full-sequence contrast-enhanced MRI, NC-MRI protocols generally focus on essential sequences for HCC detection, such as T2-weighted imaging and diffusion-weighted imaging (DWI) [
7]. High-quality acquisition of these key sequences is crucial to maximize the diagnostic performance of NC-MRI. In particular, DWI is essential for detecting recurrent HCC, which frequently shows diffusion restriction, but it is highly susceptible to artifacts. Therefore, optimization and consistent maintenance of DWI quality are indispensable for the successful clinical implementation of NC-MRI in detecting HCC.
As noted by the authors, patient compliance with follow-up is another important factor in surveillance strategies for detecting recurrent HCC after curative treatment. In our study, 80.9% (170/210) of participants completed the study protocol, indicating a compliance rate of over 80% for imaging surveillance. However, in real-world practice, adherence is often suboptimal. A pooled meta-analysis of 118,799 patients by Wolf et al. reported a surveillance adherence rate of only 24% [
8]. The relatively high adherence in our study may reflect both the high accessibility of medical services in South Korea and the structured nature of a clinical trial, where follow-up schedules were closely managed by study coordinators. Consequently, our findings may represent an optimistic scenario compared with routine clinical settings. To enhance the real-world applicability of NC-MRI for detecting recurrent HCC, strategies to improve patient compliance and expand healthcare accessibility remain essential.
Another notable limitation of our study is the inability to assess overall survival according to imaging modality. Because our study was designed as a single-arm, intra-individual head-to-head comparison in which all participants underwent both NC-MRI and CECT, evaluating differences in overall survival between the two modalities was not feasible. This design also prevented assessment of the incidence of interval cancers attributable to each modality, which represents an important metric for determining the effectiveness of imaging-based surveillance strategies [
9]. As the ultimate goal of surveillance imaging is to improve overall survival by enabling early detection of recurrence and timely curative treatment, further large-scale prospective randomized controlled trials are needed.
In conclusion, our study offers preliminary evidence supporting the utilization of NC-MRI for detecting recurrent HCC following curative treatment, with the benefit of avoiding both contrast agents and radiation exposure. Nonetheless, factors such as individual recurrence risk, relative cost and accessibility compared with CECT, patient adherence to surveillance, and the availability of medical resources to ensure high-quality imaging of NC-MRI must be taken into account for real-world application.
FOOTNOTES
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Conflicts of Interest
The author has no conflicts to disclose.
Abbreviations
contrast-enhanced computed tomography
diffusion-weighted imaging
non-contrast magnetic resonance imaging
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