Updating on a previous meta-analysis, new data which pooled survival estimates of patients undergoing transarterial radioembolization (TARE) has shown the treatment to be a valid option for unresectable intrahepatic cholangiocarcinoma (ICCA), particularly if the patient is naïve to previous treatments. These results were recently published in the journal Cardiovascular and Interventional Radiology (CVIR).
Lead researchers Maria Adriana Cocozza and Elton Dajti (both IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy) note that this update was based on a prior 2017 meta-analysis from the same study group which included nine studies, and revealed encouraging results for ICCA patients undergoing TARE. This preliminary evaluation identified one, two and three-year survival rates to be 55.7%, 33.1% and 20.2%, respectively.
The authors note that, although the results were promising, studies have since emerged which have bolstered these findings—notably, Julien Edeline (Centre Eugène Marquis, Rennes, France) et al’s 2020 trial on the combined benefit of TARE plus chemotherapy in unresectable ICCA. Despite these compelling data, Cocozza and Braccischi observe that the role of locoregional therapies in the guidelines remains “unclear” and recommendations for their use are weak, as emphasised by the 2023 European Association for the Study of the Liver (EASL) update.
To provide a “benchmark” for survival rates following treatment with TARE for patients with ICCA, the authors identified 27 studies which included 1,365 patients. The mean patient age in this cohort was 64 years and 49% of patients were male. Concerning tumour characteristics, 48% of tumours were bilobar and 54% of tumours were multifocal. Extrahepatic disease—mainly consisting of lymph node metastases—presented in 36% of patients. Importantly, the rate of patients who were naïve to previous treatment was 25%, while 49% received concomitant chemotherapy.
The main result was that at one-, two- and three-year intervals, survival estimates were identified as 53%, 27% and 17%, respectively, with a mean survival of 15.8 months following TARE, and 24 months after diagnosis. As heterogeneity was high between the included studies, the authors conducted a meta-regression analyses of study and patient characteristics.
The authors identified that previous treatment naiveté was the “sole pre-treatment determinant of survival”, stating that the predicted one-, two- and three-year survival rates were 70%, 45%, and 36% in treatment-naïve patients, and 44%, 18%, and 7% in patients who had received previous treatments. The mean survival for treatment-naïve ICCA patients was 19.7 months and 12.2 months for non-naïve patients.
Further, in a secondary evaluation, the authors observed tumour response through computed tomography (CT) and magnetic resonance imaging (MRI) according to RECIST 1.1 and modified RECIST (mRECIST) in 20 and four studies respectively.
The proportion of patients who achieved objective response according to RECIST 1.1 criteria was 19.6% and were associated with improved one-year survival at meta-regression analysis. In responders, the precited one-, two- and three-year survival rates were 83%, 51%, and 37% respectively, and mean survival was 23.8 months. In non-responders, these rates fell to 43%, 18%, and 8% and the precited mean survival was 11.6 months.
According to mRECIST criteria, the summary proportion of patients that achieved objective tumour response was 67%, and this was associated with a one-year increase in survival. The precited one-, two- and three-year survival rates in responders was observed as 81%, 63%, and 57%, with a mean survival of 20.1 months. Survival rates for non-responders was identified as 16%, 0%, and 0%, with a mean survival of 4.8 months.
The authors also calculated the rate of successful downstaging to surgery which was 0% in many studies, but this figure ranged between 3% and 54% in other series. However, they state that at meta-regression analysis, the increasing proportion of patients who were successfully downstaged to surgery positively correlated with increased survival, with a predicted mean survival of 34.8 months.
The authors comment that TARE shows promise as a “transformative” treatment for ICCA, potentially downstaging tumours to enable resection and increase survival. However, the success of downstaging varies significantly in their analysis, due to the high heterogeneity among the baseline clinical and tumoral features in the included studies.
“This [heterogeneity] likely mirrors the inherent diversity within the group of patients subjected to various previous treatments, encompassing surgical interventions, locoregional therapies, and the number of failed chemotherapy lines, among other factors,” the authors write. Ultimately, this diversity poses a challenge when interpreting the long-term outcomes of TARE across studies, limiting the likelihood of their uptake in the current guidelines. To this, the authors state that further research must refine patient categorisation to address these limitations, but they maintain that their present analysis provides “new possibilities” for managing inoperable ICCA.
