Long-term Effects of Repeat Hepatectomy vs Percutaneous Radiofrequency Ablation Among Patients With Recurrent Hepatocellular Carcinoma: A Randomized Clinical Trial

Abstract

Importance: Repeat hepatectomy and percutaneous radiofrequency ablation (PRFA) are most commonly used to treat early-stage recurrent hepatocellular carcinoma (RHCC) after initial resection, but previous studies comparing the effectiveness of the 2 treatments have reported conflicting results.

Objective: To compare the long-term survival outcomes after repeat hepatectomy with those after PRFA among patients with early-stage RHCC.

Design, setting, and participants: This open-label randomized clinical trial was conducted at the Eastern Hepatobiliary Surgery Hospital and the National Center for Liver Cancer of China. A total of 240 patients with RHCC (with a solitary nodule diameter of ≤5 cm; 3 or fewer nodules, each ≤3 cm in diameter; and no macroscopic vascular invasion or distant metastasis) were randomized 1:1 to receive repeat hepatectomy or PRFA between June 3, 2010, and January 15, 2013. The median (range) follow-up time was 44.3 (4.3-90.6) months (last follow-up, January 15, 2018). Data analysis was conducted from June 15, 2018, to September 28, 2018.

Interventions: Repeat hepatectomy (n = 120) or PRFA (n = 120).

Main outcomes and measures: The primary outcome was overall survival (OS). Secondary outcomes included repeat recurrence-free survival (rRFS), patterns of repeat recurrence, and therapeutic safety.

Results: Among the 240 randomized patients (216 men [90.0%]; median [range] age, 53.0 [24.0-59.0] years), 217 completed the trial. In the intention-to-treat (ITT) population, the 1-year, 3-year, and 5-year OS rates were 92.5% (95% CI, 87.9%-97.3%), 65.8% (95% CI, 57.8%-74.8%), and 43.6% (95% CI, 35.5%-53.5%), respectively, for the repeat hepatectomy group and 87.5% (95% CI, 81.8%-93.6%), 52.5% (95% CI, 44.2%-62.2%), and 38.5% (95% CI, 30.6%-48.4%), respectively, for the PRFA group (P = .17). The corresponding 1-year, 3-year, and 5-year rRFS rates were 85.0% (95% CI, 78.8%-91.6%), 52.4% (95% CI, 44.2%-62.2%), and 36.2% (95% CI, 28.5%-46.0%), respectively, for the repeat hepatectomy group and 74.2% (95% CI, 66.7%-82.4%), 41.7% (95% CI, 33.7%-51.5%), and 30.2% (95% CI, 22.9%-39.8%), respectively, for the PRFA group (P = .09). Percutaneous radiofrequency ablation was associated with a higher incidence of local repeat recurrence (37.8% vs 21.7%, P = .04) and early repeat recurrence than repeat hepatectomy (40.3% vs 23.3%, P = .04). In subgroup analyses, PRFA was associated with worse OS vs repeat hepatectomy among patients with an RHCC nodule diameter greater than 3 cm (hazard ratio, 1.72; 95% CI, 1.05-2.84) or an α fetoprotein level greater than 200 ng/mL (hazard ratio, 1.85; 95% CI, 1.15-2.96). Surgery had a higher complication rate than did ablation (22.4% vs 7.3%, P = .001).

Conclusions and relevance: No statistically significant difference was observed in survival outcomes after repeat hepatectomy vs PRFA for patients with early-stage RHCC. Repeat hepatectomy may be associated with better local disease control and long-term survival in patients with an RHCC diameter greater than 3 cm or an AFP level greater than 200 ng/mL.

Trial registration: ClinicalTrials.gov identifier: NCT00822562.

Figure 1.. CONSORT Diagram

^aReceived adjuvant transarterial chemoembolization at 45 days after repeat hepatectomy. ^bReceived adjuvant transarterial chemoembolization at 38 and 43 days after percutaneous radiofrequency ablation. ^cReceived adjuvant radiotherapy within 32 to 67 days after percutaneous radiofrequency ablation.

Figure 2.. Kaplan-Meier Plots for Overall Survival and Repeat Recurrence–Free Survival After Repeat Hepatectomy vs Percutaneous Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma

HR indicates hazard ratio; ITT, intention-to-treat.

Figure 3.. Subgroup Analyses for Comparing Repeat Hepatectomy vs Percutaneous Radiofrequency Ablation (PRFA) in the Intention-to-Treat (ITT) Populations

AFP indicates α fetoprotein; HR, hazard ratio; OS, overall survival; rRFS, repeat recurrence–free survival; RHCC, recurrent hepatocellular carcinoma; and TTR, time to recurrence. ^aAge, AFP levels, cirrhosis, diameter, and number of RHCC nodules were based on the data obtained at the recurrent stage. Cirrhosis, diameter, and number of RHCC nodules were based on pretreatment imaging studies.