Impact of margin status on long-term results of liver resection for hepatocellular carcinoma: single-center time-to-recurrence analysis

Abstract

Occult metastasis from the initial tumor and a de novo second primary hepatocellular carcinoma (HCC) were recognized as the main causes for the onset of early and late HCC recurrence, after liver resection (LR). This study aims to compare the time to recurrence after LR for HCC in which a margin ≤ 1 mm or > 1 mm was achieved. A single-center retrospective study involving 256 patients was conducted from June 2005 to June 2019. HCC patients resected with a radical surgical approach were investigated and stratified into groups A (resection margins ≤ 1 mm) and B (> 1 mm), as measured on final pathologic assessment. Kaplan–Meier estimators were used to estimate the probability of recurrence, and the log-rank test was used to compare groups. Uni- and multivariable (stepwise) Cox regression models were used to assess the effect of several HCC pathological characteristics. Twenty patients were excluded for the presence of microscopic tumor invasion at pathologic analysis (R1); 236 patients underwent radical (R0) LR, and were included in the study and divided into group A (n = 61, 26%), and group B (n = 175, 74%). No differences between the two groups were detected regarding: epidemiology, tumor characteristics, type of LR, and follow-up. The estimated probability of recurrence for group A and group B at 12 and 24 months was 27% and 38%, and, 33% and 46%, respectively. Univariate and multivariable Cox regression model estimates showed that tumor grading (HR 2.1, 95% CI 1.2–3.4, p = 0.006), number of nodules (HR 1.2, 95% CI 1.0–1.4, p = 0.015), and extension of the resection (HR 1.8, 95% CI 1.0–1.1, p = 0.047) were independent risk factors for HCC recurrence, with no significant effect of margin status on time to recurrence. A R0 approach that considers a margin of resection > 1 mm does not improve the likelihood of HCC recurrence. Otherwise, our experience confirms that biologic tumor characteristics are the principal factors predictive of local and systemic recurrence.