Thermal Ablation for Hepatocellular Carcinoma: What's New in 2019

Feipeng Zhu; Hyunchul Rhim

Disclosures

Chin Clin Oncol. 2019;8(6):58 

In This Article

Updated Therapeutic Outcomes of Thermal Ablation for HCC

During the past two decades, several randomized controlled studies and meta-analysis studies have proven the clinical benefit and safety of thermal ablation for HCC when compared to surgical resection.[9–18] In fact, three randomized controlled trials of patients with up to 3 HCC tumors (smaller than 5 cm in diameter) compared the outcomes between RFA and resection. One trial demonstrated a survival benefit for resection over RFA, but the other two trials showed no significant difference in recurrence-free and overall survival rates.[16–18] Most meta-analyses also demonstrated that ablation has similar overall survival but inferior local tumor control rates compared to resection. However, two recent meta-analyses showed that resection had better recurrence-free and overall survival compared to RFA.[38,39] According to the interim report of the SURF study from Japan, there was no significant difference in 3-year recurrence-free survival and overall survival between resection and RFA for early-stage HCC.[40]

The two largest cohort studies of RFA reported similar overall survival rates at 5 and 10 years, while there were large differences in local tumor control rates depending on the treatment strategy for insufficient ablative margin[9,10] (Table 1). However, more recently, studies showed significant improvement in overall survival (approaching 80% at 5 years) due to technological advances and post-ablation antiviral therapy.[36,44] A recent cohort investigation of 301 potentially transplantable patients with single HCC ≤3 cm treated by RFA as first line demonstrated that 5-year survival rates after RFA were 79.0% in the HCC ≤2 cm group [vs. 70.9% in the HCC >2 cm group (P=0.01)]. Prognostic factors of post-RFA recurrence outside Milan criteria were larger tumor (>2 cm) and level of serum alpha-fetoprotein.[44,45]

While tumor size and location are well-proven factors regarding the procedure feasibility and tumor control rate, tumor aggressiveness, the addition of a non-hypervascular hepatobiliary phase, hypointense nodule on gadoxetic acid-enhanced MRI was recently found to be an important imaging biomarker related to survival after ablation. For this reason, Lee et al proposed prediction models for microvascular invasion using clinical and imaging variables. For example, in patients with high tumor markers (e.g., AFP, PIVKA II, etc.) and MRI findings suggesting microvascular invasion (e.g., peritumoral enhancement, hepatobiliary peritumoral hypodensity, etc.), the early recurrence rate was higher in the RFA group than resection group.[46] Another study reported that non-hypervascular hepatobiliary phase (HBP) hypointense nodules on liver MRI can be a predictor for recurrence-free survival after RFA and surgery. The 5-year recurrence free survival rates were significantly lower in RFA (51%) than resection (65%) group in patients without those nodules, while the same study showed similar results in the RFA (28%) and resection (34%) groups in patients with those nodules. For this reason, surgery may be the more appropriate treatment modality for even very early stage HCC, if there was not associated with that kind of nodules on pre-treatment MRI.[47]

In terms of the "no touch" technique, Mohkam et al. recently reported a comparative study between no-touch multibipolar RFA (NTM-RFA, n=77) and liver resection (LR, n=62) for single HCC between 2 and 5 cm. In fact, they found no significant difference in local recurrence rates at one and three years between the two groups (RFA 5.5%, 10.0% vs. resection 1.9%, 1.9%). For disease-free recurrence and overall survival at 3 years, there was also no significant difference between the both groups (RFA, 40.8% vs. resection, 56.4%; RFA, 86.7% vs. resection, 91.4%).[48]

In 2019, one interesting study reported contemporary treatment trends and outcomes from the United States National Cancer Database by comparing RFA with surgical resection for HCC. A total of 18,296 patients were evaluated (resection, n=10,085 vs. RFA, n=8,211). RFA was found to be superior to resection in terms of hospital stay duration, unplanned readmission, and 1- and 3-month mortality. For HCC with smaller than 1.5 cm in diameter, RFA and surgical resection yield similar survival rates.[49] However, as Child-Pugh score which represents important predict factor for cirrhosis patients survival was not calculated in this program, more dedicate study is needed in future.

Many clinical studies on MWA for HCC have been published during the last decade.[50] However, most of these studies were retrospective in nature and from single institutions. There were only two RCTs that compare MWA with RFA have been reported.[21,51] The reported therapeutic outcomes of MWA for HCC were promising as follows: technical success rates ranged from 88% to 95%; progression-free survival rates were ≤92 and 5-year survival rates ranged from 43% to 60%.[51] Several retrospective comparative studies also showed that MWA provided better local tumor control than RFA, but failed to prove a survival benefit.[19,22–24] In fact, one meta-analysis that included 16 studies involving 2,062 patients found that either MWA or RFA can be used for effective local therapy for HCC because there was no difference in the outcomes including local tumor progression, overall and disease-free survival as well as adverse events.[20]

In 2017, a phase III RCT in 405 patients with HCCs (<5 cm) were reported to compare the outcomes and safety of MWA with RFA. There was no significant difference in the technique effectiveness and 5 years local tumor progression (MWA, 99.6%, 11.4% vs. RFA, 98.8%, 19.7%) For 5-year disease-free and overall survival rates, there was no significant difference between the both groups (MWA; 36.7%, 67.3% vs. RFA; 24.1%, 72.7%). The major complication rates were 3.4% for MWA and 2.5% for RFA. They concluded that both MWA and RFA are suitable options for early-stage HCC and MWA is more promising due to its higher thermal efficiency.[51]

TACE is currently the standard of care treatment for intermediate-stage HCC in most management guidelines and when combined with ablation, has been proven better than TACE alone in many comparative studies and meta-analyses. One such study by Nouso et al. recently compared overall survival between RFA and TACE group in intermediate-stage HCC. After propensity score matching, the 3 years overall survival rates were higher in RFA group (70%) than in the TACE group (52%).[52]

HBV is identified as one of the most important risk factors in HCC development. Recently, anti-HBV treatment has been reported can prevent HCC recurrence after local therapies. A retrospective cohort study from Taiwan reported that HCC recurrence rates were significantly lower in patients received anti-HBV therapy compared with rates in untreated group after RFA (41.8% vs. 51.4%).[53] Sohn et al. demonstrated that oral antiviral treatment affected the overall survival after RFA for HBV-related HCC. There was significant difference in overall survival at 5 years between the control and treatment group (77.2% vs. 93.5%).[36] Chen et al. also reported the timely treatment with sustained virologic response using PegINF/RBV can decrease tumor recurrence after RFA for HVC related HCC.[54]

As HCC is a complex malignancy with poor hepatic reserve and tendency for recurrence even after curative treatment, a multidisciplinary approach (MDT) is the utmost important to provide the best outcome for the patients with HCC. One recent retrospective study with 6,619 patients with HCC claims that the 5-year survival rate was significantly higher in MDT group compared to that of control group (71.2% vs. 49.4%).[55] Thus, MDT approach may be the promising option to improve the patient's survival which warrants prospective validation.

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