Clearance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection or Liver Transplantation

SIMPLE SUMMARY: Liver transplantation and surgical resection are potentially curative options in patients with liver cirrhosis and hepatocellular carcinoma. However, tumor recurrence is frequent, and it is associated with a poor prognosis. The selection of candidates is paramount to maximize survival while decreasing tumor recurrence rates, particularly regarding liver transplantation in a context of worldwide organ shortage. Circulating tumor cells are an attractive method of liquid biopsy that could represent a novel strategy to delineate the optimal therapeutic approach in hepatocellular carcinoma. This observational, prospective study aims to assess the role of circulating tumor cells in patients undergoing surgical resection or liver transplantation, as well as their potential association with other widely known surrogate markers of poor prognosis. ABSTRACT: Background: In patients with hepatocellular carcinoma (HCC), a complete clearance of circulating tumor cells (CTCs) early after liver transplantation (LT) or surgical resection (LR) could prevent tumor recurrence. Methods: prospective pilot study including patients with HCC who underwent LR or LT from September 2017 to May 2020. Enumeration of CTCs was performed in peripheral blood samples (7 mL) using the Isoflux(®) system (Fluxion Biosciences) immediately before surgery, at post-operative day 5 and at day 30. A clinically relevant number of CTCs was defined as >30 CTCs/sample. Results: 41 HCC patients were included (mean age 58.7 ± 6.3; 82.9% male). LR was performed in 10 patients (24.4%) and 31 patients (75.6%) underwent LT. The main etiology of liver disease was chronic hepatitis C (31.7%). Patients undergoing LR and LT were similar in terms of preoperative CTC count (p = 0.99), but clearance of CTCs within the first month was more pronounced in the LT group. Clusters of CTCs at baseline were associated with incomplete clearance of CTCs at day 30 (54.2% vs. 11.8%, p = 0.005), which in turn impacted negatively on survival (p = 0.038). Conclusion: Incomplete clearance of CTCs after surgery could be a surrogate marker of HCC aggressiveness.