Recurrence after surgery for hepatocellular carcinoma: “The seed and the soil” - a multicentre retrospective cohort study

BACKGROUND Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality. Liver resection provides a curative option, though recurrence following resection remains a major clinical challenge, as adjuvant therapies evolve, and preservation of liver function becomes increasingly important. AIM To evaluate factors associated with HCC recurrence in a real-world setting. METHODS We retrospectively reviewed records of patients with HCC who underwent primary liver resection at three tertiary referral hospitals between January 2008 and May 2022. Baseline patient and tumour characteristics were assessed. Risk factors for recurrence were analysed using multivariate Cox regression. RESULTS In this cohort, 235 patients underwent surgical resection for HCC. Median survival was 80.9 months. HCC recurred in 94 (40%) patients with median time to recurrence 18.8 months (interquartile range: 8.6-35). An albumin-bilirubin (ALBI) grade of ≥ 2 [adjusted hazard ratio (aHR): 2.02 (1.27-3.21), P = 0.003], the presence of cirrhosis [aHR: 2.03 (1.27-3.25), P = 0.003], and Barcelona Clinic Liver Cancer (BCLC) stage B/C [aHR: 2.23 (1.23-4.03) P = 0.008] were independently associated with increased risk of recurrence. When combining these risk factors, the adjusted HR for recurrence was 2.73 (1.57-4.75), 4.32 (2.29-8.12) and 7.52 (2.47-22.93) in those with 1, 2, or 3 factors compared to those with 0 (P < 0.001). CONCLUSION HCC recurrence following primary liver resection was independently associated with cirrhosis, ALBI grade ≥ 2 and BCLC stage B/C. The seed (the liver cancer as reflected by BCLC stage), and the soil (the liver function and presence or absence of cirrhosis) are relevant considerations for recurrence prediction.