The Role of Lymphadenectomy in the Surgical Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Background: Lymphadenectomy in the operative management of hepatocellular carcinoma (HCC) remains controversial, with no recommendation for routine practice. Our study aimed to assess the effects of lymphadenectomy in addition to hepatic resection (HR) compared to HR alone for adults with HCC. Methods: This systematic review was conducted according to PRISMA guidelines until March 2023, searching and selecting the relevant literature comparing lymph node dissection or sampling, combined with HR, and with no lymph node removal. Critical appraisal of the included studies was performed using the ROBINS-I tool. Fixed- or random-effect meta-analysis models were carried out, and inter-studies were assessed for heterogeneity. Results: Fourteen studies were selected during the screening process. Data from eight studies containing 32,041 HCC patients were included in the quantitative synthesis. In total, 12,694 patients underwent lymph node dissection (LND), either selectively for preoperatively diagnosed or intraoperatively suspected lymph node metastasis (LNM) or unselectively (i.e., regardless of suspected LNM). According to LN status, 1-, 3- and 5-year mortality rates were higher in the LNM group with respect to both clinically negative LN (OR 3.25, 95% CI 2.52-4.21; p < 0.001; OR 3.79, 95% CI 2.74-5.24; p < 0.001; OR 3.92, 95% CI 2.61-5.88; p < 0.001) and proven LN0 (OR 1.75, 95% CI 1.0-3.04; p = 0.05; OR 2.88, 95% CI 1.79-4.63; p < 0.001; OR 2.54, 95% CI 1.33-4.84; p < 0.001). Moreover, the summary estimates of two controlled trials showed no significant difference in overall survival between LND groups and those without LND for negative LN patients. Conclusions: Lymph node dissection does not appear to improve overall survival, according to the available literature; thus, this does not support its routine adoption as part of standard liver resection for HCC. A case-by-case decision remains advisable.

Keywords: hepatic resection; hepatocellular carcinoma; lymph node dissection; lymph node metastasis.

Figure 1

PRISMA 2020 flow diagram. Selection of studies in review of the role of lymphadenectomy in HCC patients.

Figure 2

Traffic light (up) and domain summary (down) plots of risk of bias assessment for OS outcomes from the included studies in the meta-analysis [18,19,20,22,24,28,29].

Figure 3

Forest plot comparing (a) 1 y, (b) 3 y and (c) 5 year mortality in LND, LNM vs. no-LND groups [18,22,24,28].

Figure 4

Forest plot comparing (a) 1 y, (b) 3 y and (c) 5 year mortality in LN0 vs. LNM groups [19,28,29].

Figure 5

Forest plot comparing overall survival in LND vs. no-LND groups [20,25].