Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

Abstract

In the study by Wu et al, patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization (TACE) as a conversion therapy in order to render their tumors suitable for resection. A nomogram was devised and shown to be effective in predicting the survival of these patients. Generalization of the results, however, is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE. Immunotherapy can be considered to be an option for conversion therapy. However, markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking. The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

Key Words: Conversion therapy, Immunotherapy, Liver resection, Survival, Transarterial chemoembolization, Unresectable hepatocellular carcinoma

Core Tip: In addition to transarterial chemoembolization (TACE), immunotherapy should also be among the options for conversion therapy for rendering unresectable hepatocellular carcinoma suitable for resection. For patients unsuitable for TACE, immunotherapy can be an alternative.

TO THE EDITOR

We read with interest the article “Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy” by Wu et al[1]. Some points in the article are noteworthy, and the authors are to be complimented for their insightful reporting.

The authors reported the results of a nomogram for predicting the survival of patients with unresectable hepatocellular carcinoma (HCC) who had received transarterial chemoembolization (TACE) as a conversion therapy before liver resection. The results were promising as they would help predict survival after liver resection following a successful conversion therapy. However, a few points are to be noted. The selected group for analysis consisted of patients who had undergone liver resection. As previously reported in the literature, only 9.5% to 28.8% of patients receiving TACE were able to undergo conversion therapy[2,3]. Therefore, it remains questionable whether the survival data of this group of patients can also represent the survival of patients with the same disease who intend to receive conversion therapy but are unable to do so.

The Up-to-seven criteria have been proposed as a predictor for tumor response to TACE as a conversion therapy[4]. TACE is considered effective in patients with a low tumor burden, but it is considered ineffective in those with a high tumor burden. Therefore, for patients with a high tumor burden, alternative conversion therapies may be considered instead of TACE.

Recently, several treatments for unresectable HCC have shown promising results, including those in the HIMALAYA[5] and Imbrave150 trials[6]. Immunotherapy-such as that featuring anti-programmed death ligand 1 antibody (atezolizumab) or that featuring anti-vascular endothelial growth factor antibody (bevacizumab)-is in emerging use. It should be considered to be a treatment option in conversion therapy, particularly as an alternative for patients who are not suitable for TACE[7,8].

Lastly, the selection of patients is worth mentioning. Unfortunately, markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking. The question of whether effective conversion therapy can truly enhance overall survival remains unanswered, particularly when considering the efficacy of emerging types of agents in treating selected patients. In this study, conversion therapy allowed for resection of HCC and consequently achieved better survival outcomes compared to conventional palliative treatment for initially unresectable HCC. Data from studies like this are crucial for refining guidelines and guiding further research to identify parameters for predicting survival.