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.