Role of surgical resection for multiple hepatocellular carcinomas

Abstract

Aim: To clarify the role of surgical resection for multiple hepatocellular carcinomas (HCCs) compared to transarterial chemoembolization (TACE) and liver transplantation (LT).

Methods: Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008, 160 patients who met the following criteria were retrospectively enrolled: (1) two or three radiologically diagnosed HCCs; (2) no radiologic vascular invasion; (3) Child-Pugh class A; (4) main tumor smaller than 5 cm in diameter; and (5) platelet count greater than 50 000/mm(3). Long-term outcomes were compared among the following three treatment modalities: surgical resection or combined radiofrequency ablation (RFA) (n = 36), TACE (n = 107), and LT (n = 17). The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test. To identify the patients who gained a survival benefit from surgical resection, we also investigated prognostic factors for survival following surgical resection. Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model.

Results: The overall survival (OS) rate was significantly higher in the surgical resection group than in the TACE group (48.1% vs 28.9% at 5 years, P < 0.005). LT had the best OS rate, which was better than that of the surgical resection group, although the difference was not statistically significant (80.2% vs 48.1% at 5 years, P = 0.447). The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group (88.2% vs 11.2% at 5 years, P < 0.001). Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6% (20/36) in the resection group and 93.5% (100/107) in the TACE group. There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients, multi-site resection was performed in 5 patients, and combined resection with RFA was performed in 8 patients. In the TACE group, only 34 patients (31.8%) were recorded as having complete remission after primary TACE. Seventy-two patients (67.3%) were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection, the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis (80.8% vs 25.5% 5-year OS rate, P = 0.006; 22.2% vs 0% 5-year disease-free survival rate, P = 0.048). Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE (25.5% vs 24.7% 5-year OS rate, P = 0.225). Twenty-nine of the 36 patients who underwent surgical resection experienced recurrence. Of the patients with cirrhosis, 80% (16/20) were within the Milan criteria at the time of recurrence after resection.

Conclusion: Among patients with two or three HCCs, no radiologic vascular invasion, and tumor diameters ≤ 5 cm, surgical resection is recommended only in those without cirrhosis.

Keywords: Chemoembolization; Cirrhosis; Hepatectomy; Hepatocellular carcinoma; Liver transplantation.

Figure 1

The overall and disease-free survival curves according to treatment modality and presence of liver cirrhosis in surgical resection patients. A: The 1-, 3- and 5-year overall survival (OS) rates were 94.1%, 80.2% and 80.2%, respectively, in the liver transplantation (LT) group; 91.7%, 83.3% and 48.1%, respectively, in the resection group; and 88.7%, 55.6% and 28.9%, respectively, in the transarterial chemoembolization (TACE) group. The OS rate was significantly higher in the surgical resection group than in the TACE group (P < 0.005). LT showed the best OS rate (better than the surgical resection group, but not statistically significant, P = 0.447); B: The 1-, 3- and 5-year disease-free survival rates were 88.2%, 88.2% and 88.2% in the LT group and 60%, 30.3% and 11.2% in the resection group, respectively. The disease-free survival rates were also significantly higher in the transplantation group than in the surgical resection group (P < 0.001); C: The 1-, 3- and 5-year OS rates were 100%, 100% and 80.8% in patients without cirrhosis (-) and 87.5%, 75% and 25.5% in patients with cirrhosis (+), respectively (P = 0.006); D: The 1-, 3- and 5-year disease-free survival rates were 75.0%, 50.0% and 22.2% in patients without cirrhosis (-) and 52.3%, 18.7% and 0% in patients with cirrhosis (+), respectively (P = 0.048).

Figure 2

Overall survival curves of surgical resection and transarterial chemoembolization in patients with liver cirrhosis. Among patients with cirrhosis, the overall survival (OS) rates were not different between the surgical resection group and the transarterial chemoembolization (TACE) group (25.5% vs 24.7% 5-year OS rate, P = 0.225).