Minimally invasive hepatectomy vs. thermoablation for single small (≤3 cm) hepatocellular carcinoma: A weighted real-life national comparison

Abstract

Background & aims: For patients with single small (≤3 cm) hepatocellular carcinoma ablation is the first-line treatment, although a high rate of recurrence has been reported. The aim was to compare videolaparoscopic liver resection (laparoscopic resection group) vs. percutaneous thermoablation (ablation group) in terms of overall survival, recurrence-free survival and early recurrence in a real-life national scenario.

Methods: The study is a retrospective collection with subsequent survival analysis. Data were collected from two Italian HCC registries, ITA.LI.CA and HE.RC.O.LE.S. An inverse probability of treatment weighting analysis was performed to balance baseline differences between groups. The Kaplan-Meier method and double-robust Cox multivariable regression were run to estimate the survival and the risk of mortality and recurrence.

Results: Between 2008 and 2022, 1,465 patients were enrolled. The laparoscopic resection group and ablation group consisted of 496 and 969 patients, respectively. At baseline, the ablation group had more advanced liver disease, with higher rates of cirrhosis (90.7% vs. 77.3%, p <0.001) and Child-Pugh B status (18.4% vs. 8.8%, p <0.001). After a median follow-up of 59 months and after weighting median overall survival was 60 months (95% CI 52-66) for the ablation group and 93 months (95% CI 75-110) for the laparoscopic resection group (hazard ratio [HR] 0.607, 95% CI 0.533-0.691, p <0.001). Median recurrence-free survival was 26 months (95% CI 23-29) for the ablation group and 39 months (95% CI 30-55) for the laparoscopic resection group (HR 0.736, 95% CI 0.659-0.822, p = 0.0013). Laparoscopy was associated with a reduced risk of early recurrence (HR 0.747, 95% CI 0.655-0.853, p = 0.011).

Conclusions: This study provides real-world evidence that for patients with single ≤3 cm HCC, videolaparoscopic liver resection offers superior long-term oncological outcomes compared with thermoablation. These findings support the preference for surgical treatment in this patient population.

Impact and implications: Percutaneous thermoablation is considered an appropriate alternative to liver resection for small (≤3 cm) single hepatocellular carcinoma because of not-inferior overall survival, although several authors reported increased recurrence risk. Whether videolaparoscopic liver resection could guarantee comparable survival but superior oncologic control of the disease is a matter of debate. This study comparing videolaparoscopy vs. thermoablation in a large national cohort of 1,465 patients observed that the former guaranteed significant prolonged OS (93 months [95% CI 75-110] vs. 60 months [95% CI 52-66] for the ablation group) and recurrence-free survival (26 months [95% CI 23-29] for ablation patients and 39 months [95% CI 30-55] for laparoscopic resection patients) even after weighting all the preoperative and oncologic differences among the groups. Our results clearly address the need to rethink the role of thermoablation for single small HCC as a second-line treatment when laparoscopic liver resection is not feasible.

Keywords: HE.RC.O.LE.S; ITA.LI.CA; Mini-invasive liver surgery; Small HCC; Thermoablation; Treatment hierarchy.

Graphical abstract

Fig. 1

Survival curves between patients treated by videolaparoscopic liver resection (laparoscopic resection group) or by thermoablation. Overall survival (A) before IPTW and (C) after IPTW. Recurrence-free survival (B) before IPTW and (D) after IPTW. Comparison among groups was made using the log-rank test before weighting and by double-robust univariate Cox regression after the weighting.

Fig. 2

‘Love’ plot depicting the effect of the treatment weighting (IPTW) in terms of mean difference. The continuous black line represents the best possible weighting among variables, and the area among the two dashed lines represent an optimal balance obtained after IPTW. The red dots are the mean differences between groups for that variable before the weighting, and the blue dots are the mean difference after the weighting. ‘Ns’ before a continuous variable means that splines were applied to model that variable, and the relative total number of degrees of freedom (df) was indicated, with the reported results of each one of them. ECOG-PS, Eastern Cooperative Oncology Group - Performance Status; IPTW, inverse probability of treatment weighting.

Fig. 3

Exploratory analysis: Forest plot reporting the effect of the treatment (after weighting) among different subgroups. The red dashed line represents the non-inferiority point adopted in this study. (A) The effect of the treatment on overall survival (OS). (B) The effect of the treatment on recurrence-free-survival. Comparison among groups was made by double-robust univariate Cox regression after the weighting.

Fig. 4

Survival curve reporting the early-recurrence free survival between the two treatment groups. Comparison among groups was made using univariate double-robust Cox regression.