Network meta-analysis of the prognosis of curative treatment strategies for recurrent hepatocellular carcinoma after hepatectomy

Abstract

Background: Recurrent hepatocellular carcinoma (rHCC) is a common outcome after curative treatment. Retreatment for rHCC is recommended, but no guidelines exist.

Aim: To compare curative treatments such as repeated hepatectomy (RH), radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and liver transplantation (LT) for patients with rHCC after primary hepatectomy by conducting a network meta-analysis (NMA).

Methods: From 2011 to 2021, 30 articles involving patients with rHCC after primary liver resection were retrieved for this NMA. The Q test was used to assess heterogeneity among studies, and Egger's test was used to assess publication bias. The efficacy of rHCC treatment was assessed using disease-free survival (DFS) and overall survival (OS).

Results: From 30 articles, a total of 17, 11, 8, and 12 arms of RH, RFA, TACE, and LT subgroups were collected for analysis. Forest plot analysis revealed that the LT subgroup had a better cumulative DFS and 1-year OS than the RH subgroup, with an odds ratio (OR) of 0.96 (95%CI: 0.31-2.96). However, the RH subgroup had a better 3-year and 5-year OS compared to the LT, RFA, and TACE subgroups. Hierarchic step diagram of different subgroups measured by the Wald test yielded the same results as the forest plot analysis. LT had a better 1-year OS (OR: 1.04, 95%CI: 0.34-03.20), and LT was inferior to RH in 3-year OS (OR: 10.61, 95%CI: 0.21-1.73) and 5-year OS (OR: 0.95, 95%CI: 0.39-2.34). According to the predictive P score evaluation, the LT subgroup had a better DFS, and RH had the best OS. However, meta-regression analysis revealed that LT had a better DFS (P < 0.001) as well as 3-year OS (P = 0.881) and 5-year OS (P = 0.188). The differences in superiority between DFS and OS were due to the different testing methods used.

Conclusion: According to this NMA, RH and LT had better DFS and OS for rHCC than RFA and TACE. However, treatment strategies should be determined by the recurrent tumor characteristics, the patient's general health status, and the care program at each institution.

Keywords: Curative treatment; Hepatocellular carcinoma; Network meta-analysis; Outcome; Recurrence; Survival rate.

Figure 1

Network graph of study number. Numbers appeared on the line of paired studies, and numbers with parenthesis at the angles of connected line were the cumulative number of subgroup of treatment methods in all studies. A: One-year and three-year overall survival (OS); B: Five-year OS. LT: Liver transplantation; RFA: Radiofrequency ablation; RH: Repeat hepatectomy; TACE: Transarterial chemoembolization.

Figure 2

Pooled mean survival rates of disease-free and overall survival of the patients treated by repeated hepatectomy, radiofrequency ablation, transarterial chemoembolization, or liver transplantation in recurrent hepatocellular carcinoma from all studies. A and B: The results of transarterial chemoembolization (TACE) disclosed the inferiority to other treatment options in disease-free survival (DFS) (A) or overall survival (B). The data of DFS were recorded and pooled together from recurrent-free survival in one arm of repeated hepatectomy and radiofrequency ablation and two arms of liver transplantation (LT), progression-free survival in one arm of TACE, and tumor-free rate in one arm of LT. DFS: Disease-free survival; LT: Liver transplantation; OS: Overall survival; RH: Repeated hepatectomy; RFA: Radiofrequency ablation; TACE: Transarterial chemoembolization.

Figure 3

Forest plot analysis demonstrated the odds ratio (95%CI) of 1-year, 3-year, and 5-year disease-free survival in the liver transplantation subgroup compared with repeated hepatectomy, radiofrequency ablation, and transarterial chemoembolization and 1-year, 3-year, and 5-year overall survivalin the repeated hepatectomy subgroup compared with liver transplantation, radiofrequency ablation, and transarterial chemoembolization with the random effects model. A: One-year disease-free survival (DFS); B: Three-year DFS; C: Five-year DFS; D: One-year overall survival (OS); E: Three-year OS; F: Five-year OS. RFA: Radiofrequency ablation; RH: Repeated hepatectomy; LT: Liver transplantation; OR: Odds ratio; TACE: Transarterial chemoembolization.

Figure 4

Hierarchic step diagram of cumulative comparative efficacy of treatment methods based on the effect size displayed with the odds ratio and corresponding 95% confidence interval of the 1-year, 3-year, and 5-year overall survival. All results were presented as the ratio of the x-axis over the y-axis with the Wald test. The better option had an underline and bold letter. LT: Liver transplantation; OS: Overall survival; RFA: Radiofrequency ablation; RH: Repeated hepatectomy; TACE: Transarterial chemoembolization.

Figure 5

Publication bias measured by the comparison of the specific effect for 1-year, 3-year, and 5-year overall survival. P > 0.05 were obtained among all studies after Egger’s regression test. A: One-year overall survival (OS); B: Three-year OS; C: Five-year OS. LT: Liver transplantation; RFA: Radiofrequency ablation; RH: Repeated hepatectomy; TACE: Transarterial chemoembolization.