Usefulness of preoperative peripheral blood GPC3-positive circulating tumor cells in subclassification of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma: a retrospective cohort study.

Aim: The treatment strategy for hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage B, representing the intermediate stage, remains unclear. This study aimed to evaluate the utility of glypican-3 (GPC3)-positive circulating tumor cells (CTCs) in subclassifying BCLC stage B.

Methods: The present retrospective cohort study included patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and March 2022. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS).

Results: A total of 338 patients were included in the analysis. GPC3-positive CTCs were significantly associated with a positive rate of microscopic portal vein invasion. In BCLC stages 0/A, there was no significant difference in survival rates between patients with GPC3-positive CTC counts. However, in BCLC stage B, both OS and RFS were significantly lower in the high number of GPC3-positive CTC group (p = 0.02 and p = 0.03, respectively). Further analysis using a four-group classification based on BCLC stage and GPC3-positive CTC count revealed that both OS and RFS were significantly lower in BCLC stage B with the high number of GPC3-positive CTC group (p < 0.01). Multivariate analysis identified Child-Pugh B status and beyond up-to-7 criteria as independent risk factors for poor OS (p = 0.01 and p = 0.04, respectively). For RFS, beyond up-to-7 criteria and a high number of GPC3-positive CTCs were identified as independent predictive factors (p = 0.04). Based on BCLC stage B, combining GPC3-positive CTCs with the up-to-7 criteria significantly stratified OS and RFS.

Conclusions: Glypican-3-positive CTCs are effective for subclassifying BCLC stage B HCC. When combined with the up-to-7 criteria, they may help with the development of new treatment strategies.