Liver resection for hepatocellular carcinoma in 313 Western patients: Tumor biology and underlying liver rather than tumor size drive prognosis

Background & Aims

Treatment decisions for hepatocellular carcinoma are mostly guided by tumor size. The aim of this study was to analyze resection outcomes according to tumor size and characterize prognostic factors.

Methods

Patients resected at a Western center between 1989 and 2010 were grouped by largest tumor size: <50 mm, 50–100 mm, and >100 mm. The primary end points were overall- and recurrence-free survival. Univariate associations with primary endpoints were entered into a Cox proportional hazard regression model.

Results

Three hundred thirteen patients underwent resection: 111 (36%) had tumors <50 mm, 113 (36%) had tumors between 50 and 100 mm, and 89 (28%) had tumors >100 mm. Five-year overall and disease-free survival rates for the three groups were 67%, 46%, and 34%, and 32%, 27%, and 27%, respectively. Thirty-five patients, mostly from <50 mm group, underwent transplantation which was associated with a 91% 5 year survival rate. Tumor size was not an independent predictor of overall or recurrence-free survival on multivariate analyses. Independent predictors of decreased overall survival were: intraoperative transfusion (HR = 2.60), cirrhosis (HR = 2.42), poorly differentiated tumor (HR = 2.04), satellite lesions (HR = 1.69), alpha-fetoprotein >200 (HR = 1.53), and microvascular invasion (HR = 1.48). The use of salvage transplantation was an independent predictor of improved survival (HR = 0.21). Recurrence-free survival was predicted by intraoperative transfusion (HR = 2.15), poorly differentiated tumor (HR = 1.87), microvascular invasion (HR = 1.71) and cirrhosis (HR = 1.69).

Conclusion

By studying a large group of patients across a distribution of tumor sizes and background liver diseases, it is demonstrated that size alone is a limited prognostic factor. Tumor biology and condition of the underlying liver are better prognosticators and should be given closer attention. Although hampered by recurrence rates, resection is safe and offers good overall survival. In addition, it may allow for better selection for salvage transplantation after consideration of histopathological risk factors.

Introduction

Surgical resection and liver transplantation remain the gold standard therapies for hepatocellular carcinoma (HCC). Liver transplantation is considered the best curative treatment by treating both the tumor and the underlying liver disease and it is the only surgical option in patients with decompensated cirrhosis [1]. However, it suffers major limitations: most allocation systems limit transplantation to early HCC and, more importantly, it is significantly hampered by severe donor organ shortage. By contrast, liver resection is readily available and not limited by tumor size, its only limitations are determined by functional hepatic reserve and portal hypertension. This recognizes that surgical resection has become increasingly safe, and that new techniques such as laparoscopy have demonstrated reduced morbidity in selected cirrhotic patients [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13].

The objective of this study was to analyze the prognostic factors of survival after resection for HCC in a large Western series of patients with various causes of liver disease at a tertiary referral center offering all modalities of treatment. Since outcomes for HCC are generally believed to be related to tumor size, patients were stratified according to tumor diameter.