Resection margin width as a risk factor for hepatocellular carcinoma recurrence

Background: Surgery is the main treatment modality for hepatocellular carcinoma (HCC). However, not all patients die from cancer. Some deaths result from progression of the underlying liver disease and hepatic insufficiency. Factors that increase the risk of cancer recurrence after surgery are now actively being sought. According to published data, risk factors include tumor size and number, the degree of tumor cell differentiation, viral etiology of HCC, vascular invasion (hepatic veins and portal vein), and high alpha-fetoprotein (AFP) levels. However, the question of how resection margin width affects recurrence remains open. In our study, we showed that margin width does indeed influence recurrence.

Aim: To evaluate how resection margin status affects tumor recurrence and survival after surgical treatment for HCC.

Methods: We conducted a study with prospective outcome assessment. The analysis included 55 patients with morphologically verified HCC who underwent liver resection of various volumes (anatomical, atypical, hemihepatectomy) at the P.A. Hertzen Moscow Oncology Research Institute between 2010 and 2024. Follow-up was performed every 3 months, with documentation of recurrence episodes and deaths. The study groups (margin <1 cm vs. ≥1 cm) were comparable in terms of age, sex, BCLC stage, and liver function (p > 0.05). Overall survival (OS) was defined as the time from surgery to death; recurrence-free survival (RFS) was defined as the time from surgery to first confirmed progression. Analysis was performed using Kaplan–Meier methods and Spearman correlation in IBM SPSS Statistics 25.

Results: Mean overall survival was 24 months, and mean recurrencefree survival was 12 months; cumulative 1, 3, and 5year OS rates were 62.0%, 33.0%, and 18.0%, respectively. Spearman correlation coefficient between resection margin width and OS was ρ = 0.25 (p = 0.31), and between margin width and RFS was ρ = 0.26 (p = 0.29). Patients with a resection margin >1 cm showed a trend toward improved OS and RFS; however, no statistically significant differences between the subgroups were identified.

Conclusion: Resection margin width was not a significant factor for OS or RFS on multivariate Cox analysis (HR = 0.74 and 0.72, respectively). Important predictors of OS were BCLC stage B/C (HR = 2.14; 95% CI: 1.14–4.02; p = 0.017) and microvascular invasion (HR = 1.87; 95% CI: 1.02–3.44; p = 0.044). In patients with a margin ≥1 cm, OS improved (median 29 vs. 19 months) and the recurrence rate decreased (75.0% vs. 92.6%), confirming the oncologic benefit of achieving a wide resection margin, especially in the presence of microvascular invasion (MVI).