Imaging-based prediction of hepatocellular carcinoma recurrence after microwave ablation as bridge therapy: A glimpse into the future

Abstract

Liver transplantation (LT) remains the treatment of choice for early-stage hepatocellular carcinoma (HCC) and offers the best long-term oncological outcomes. However, the increasing waiting list for LT has led to a significant dropout rate as patients experience tumor progression beyond the Milan criteria. Currently, locoregional therapies, such as microwave ablation (MWA), have emerged as promising bridge treatments for patients awaiting LT. These therapies have shown promising results in preventing tumor progression, thus reducing the dropout rate of LT candidates. Despite the efficacy of MWA in treating HCC, tumoral recurrence after ablation remains a major challenge and significantly impacts the prognosis of HCC patients. Therefore, accurately diagnosing tumoral recurrence post-ablation is crucial. Recent studies have developed novel imaging features based on magnetic resonance imaging of HCC, which could provide essential information for predicting early tumoral recurrence after MWA. These advancements could address this unresolved challenge, improving the clinical outcomes of patients on the LT waiting list. This article explored the current landscape of MWA as a bridge therapy for HCC within the Milan criteria, highlighting the emerging role of novel imaging-based features aimed at improving the prediction of tumor recurrence after MWA.

Key Words: Liver transplantation; Hepatocellular carcinoma; Ablation techniques; Multiparametric magnetic resonance imaging; Interventional oncology; Liver disease; Microwaves

Core Tip: Microwave ablation (MWA) is a locoregional treatment used as bridge therapy to prevent tumor progression in patients with hepatocellular carcinoma (HCC) within the Milan criteria for liver transplantation. Growing evidence suggests that MWA provides technical advantages over other ablative techniques and offers lower complication rates compared to surgical resection. Accurate and timely detection of recurrence remains an unresolved challenge due to high rates of HCC tumor recurrence after ablative therapies. Recent advances in imaging-based assessments have shown promising results that could help predict tumor recurrence after MWA, thereby improving the management and prognosis of patients with HCC awaiting liver transplantation.

INTRODUCTION

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third-leading cause of cancer-related death worldwide[1,2]. Managing HCC presents a crucial challenge due to the wide variety of therapeutic options, which depend on the patient’s intrinsic liver function, tumor burden, and treatment intention[3]. Among potentially curative therapies, liver transplantation (LT) is considered the treatment of choice for early-stage HCC occurring in the setting of clinically significant portal hypertension and/or decompensated cirrhosis[4]. In this sense, LT not only provides the best long-term oncological results but also replaces the premalignant cirrhotic parenchyma that could potentially lead to future HCC development[5]. However, the limited supply of liver donors results in long wait times for LT, causing some patients to be removed from the transplant list due to tumor progression beyond the Milan criteria while waiting for LT[6].

The growing use of locoregional therapies (LRT) as a bridge to LT has helped maintain patients within transplant criteria by inducing tumor death and preventing HCC progression that would otherwise lead to waitlist dropout if the patient cannot be downstaged[7,8]. Microwave ablation (MWA) has emerged as a promising LRT for HCC, demonstrating utility both as a bridge therapy for patients awaiting LT[9-11] and as a potentially curative treatment for certain subsets of early-stage HCC[12]. Overall survival rates comparable to those of liver surgery are achieved, with significantly lower rates of complications[13,14]. Currently, the 5-year overall survival of patients with HCC after ablation has been reported as 41.3%-72.0%[15,16]. However, despite continuous progress in the development of ablative therapies for HCC, tumoral recurrence occurs in up to 39.3%-81.7% of patients by 5 years, which notably worsens patient prognosis[9,15,16]. Therefore, improving the ability to predict HCC recurrence after MWA remains a critical challenge.

In this context, recent research on imaging features for patients with HCC undergoing MWA as a bridging therapy to LT has developed novel assessment methods, which may aid in predicting the risk of recurrence after MWA, thereby optimizing treatments and resources for patients undergoing bridge therapy to LT[8,17]. This article explored the current landscape of MWA as a bridge therapy for HCC, highlighting the promising role of novel imaging-based features in predicting tumor recurrence after MWA.

CURRENT LANDSCAPE ON MWA AS BRIDGE THERAPY FOR HCC: WHERE ARE WE NOW?

MWA has emerged as a safe and effective LRT for treating early-stage HCC, achieving excellent results in local disease control[7-11]. Compelling studies have compared the utility of MWA with different LRT for HCC, demonstrating its crucial role not only as an effective bridge treatment for patients awaiting LT[10,18] but also as a potentially curative therapy[12]. A large retrospective study comprising 321 patients with subcapsular HCC within the Milan criteria, who received either MWA or surgical resection, showed that MWA presents comparable long-term therapeutic outcomes to surgical resection with significantly shorter postoperative hospital stays, lower complication rates, and fewer blood transfusions compared to surgical resection[13].

Notably, these findings are consistent with a large meta-analysis showing that MWA had fewer overall complications than surgical resection for HCC[14]. In addition to the advantages of MWA over other thermal ablative techniques such as radiofrequency ablation (RFA)[9,18,19], studies comparing the oncological outcomes of these therapies have shown controversial results[20,21]. Although patients with HCC treated with MWA or RFA ablation both show high efficacy and durable response, those treated with MWA have lower rates of local tumor progression after treatment[22,23], especially among the group of HCC with a diameter smaller than 5 cm[24].

A recent study including 195 patients with subcapsular HCC who met Milan criteria and underwent locoregional treatment with MWA or RFA revealed that the cumulative rates of tumor recurrence beyond Milan criteria and overall survival at 5 years were both lower in the MWA group than in the RFA group (73.4% vs 61.4%, respectively)[25]. These findings support MWA as an effective and safe bridge LRT for HCC within the Milan criteria, demonstrating high rates of local disease control with a lower rate of complications.

CAN WE IMPROVE THE IMAGING-BASED PREDICTION OF HCC RECURRENCE? EXPLORING NEW HORIZONS

As mentioned above, tumoral recurrence after ablation significantly hinders survival and is considered one of the main causes of worsened prognosis for patients with HCC within the Milan criteria[15,16]. Consequently, interesting studies have aimed to shed light on this unresolved challenge by developing new methods for predicting tumor recurrence based on imaging findings, which could facilitate the accurate and timely detection of tumor recurrence after MWA.

A recent study investigated a novel method to assess the tumoral response after MWA by analyzing the tumor ghost on magnetic resonance imaging, which was defined as a hypointense signal area on non-enhanced T1-weighted images, surrounded by hyperintense ablated hepatic parenchyma. Interestingly, the authors demonstrated that an ablative margin with at least a 5 mm distance between the tumor ghost and the ablated area was an independent risk factor for both tumor progression and recurrence in several subgroups of HCC[26].

Zhang et al[27] demonstrated that tumor ill-defined margins, lack of capsule enhancement, apparent diffusion coefficient (ADC), exponential ADC (eADC), and changes in ADC and eADC after MWA were crucial imaging parameters for predicting HCC recurrence after MWA. They developed a nomogram based on an image response regression coefficient, which aimed to predict the probability of early recurrence of HCC after MWA.

More recently, a pioneering study by Chen et al[28] developed a novel deep learning radiomics model based on magnetic resonance imaging, which could aid physicians in predicting the individualized risk of HCC local recurrence after ablative therapy, thereby improving the prognosis and management of each patient undergoing MWA. Taken together, these findings lay the foundation for continuing to increase efforts in developing new methods for early prediction of tumor recurrence in patients with HCC who are candidates for LT.

CONCLUSION

Currently, tumoral recurrence after ablation significantly hinders survival for patients with HCC, which has prompted efforts to develop novel imaging-based prediction methods. Recent studies highlight several promising approaches, including novel analysis of tumor ghosts on magnetic resonance imaging, critical imaging parameters such as ADC and eADC, and a deep learning radiomics model. These advancements offer valuable tools for predicting HCC recurrence and improving patient prognosis after ablative therapy. Future research should focus on further refining these imaging techniques and integrating them into clinical practice to enhance patient selection and to optimize multidisciplinary treatment planning.

ACKNOWLEDGEMENTS

Lindner C would like to express profound gratitude to Juan P Maureira for his continuous support and unwavering assistance during the development of this manuscript. His insightful feedback was crucial in the successful completion of this study.