Optimizing the management of patients with BCLC stage-B hepatocellular carcinoma: Modern surgical resection as a feasible alternative to transarterial chemoemolization

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Abstract

Objective

To analyse the impact of liver resection (LR) in patients with Hepatocellular Carcinoma (HCC) within the Barcelona-Clinic-Liver-Cancer (BCLC)-B stage.

Methods

Analysis of patients with BCLC-B HCC treated with LR or transarterial chemoembolization (TACE) between 2007 and 2012 in our hospital. Survival/recurrence analyses were performed by log-rank tests and Cox multivariate models. Further analyses were specifically obtained for the HCC subclassification (B1–2–3–4) proposed recently.

Results

Eighty patients were treated (44-TACE/36-LR). Number of nodules was [1.8(1.1)], being multinodular in 50% of cases. Although resected patients had a higher hospital stay than those who underwent TACE (14 ± 13 vs 7 ± 6; P = 0.004), the rate and severity of complications was lower measured by Dindo–Clavien scale (P < 0.05). Overall survival was 40% with a median follow-up of 29.5 months (0.07–96.9). Five-years survival rates were 62.9%, 28.1% and 15.4%, respectively (P = 0.004) for B1, B2 and B3–4 stages. Cox model showed that only total bilirubin [OR = 2.055(1.23–3.44)] and BCLC subclassification B3–4 [OR = 2.439(1.04–5.7)] and B2 [OR = 2.79(1.35–5.77)] vs B1 were independent predictors of 5-years-survival. In B1 patients, surgical approach led a significant decrease in 5-years recurrence-rate (25% vs 60%; P = 0.018). In the surgical subgroup analysis, better results were observed if well/moderate differentiation combined with no microvascular-invasion (VI) in 5-years-survival (84.6%; P = 0.001) and -recurrence (23.1%; P = 0.041), respectively. These survival and recurrence trends were remarkable in B1 stages.

Conclusions

Management of Intermediate BCLC-B HCC stage should be more complex and include updated criteria regarding B-stage subclassifications, VI and tumour differentiation. Modern surgical resection would offer improved survival benefit with acceptable safety in selected BCLC-B stage patients.

Introduction

Hepatocellular carcinoma (HCC) is the most common liver neoplasm and the fifth most common cancer worldwide. The most widely used staging system is the Barcelona Clinic Liver Cancer (BCLC) classification, which establishes the prognosis and the best treatment strategy for each stage of the disease. Guidelines from the European Association for the Study of Liver Disease (EASL) and the American Association for the Study of Liver Disease (AASLD) consider patients with very early or early stage HCC suitable for curative treatments, whilst patients on intermediate and advanced-stage disease would only be suitable for palliative treatments.1

According to the EASL/AASLD guidelines the indications for hepatic resection are considered in very early stage cancers (single tumours <2 cm or carcinoma in situ, with a perfect performance status and Child-Pugh A) or in single nodular tumours with optimal performance status (PS) with no signs of portal hypertension. For early stage tumours (single tumours >2 cm or ≤3 nodules ≤3 cm with PS 0 and Child-Pugh A or B) transplantation and/or Radiofrequency are recommended. However, many variables related to liver function and tumour characteristics have been identified in order to find the best candidates to hepatic resection into this group of patients.2, 3

BCLC stage B is a heterogeneous category. Hence, patients with Child-Pugh scores A/B and preserved PS with multiple tumours >3 cm, uninodular with theoretical unresectable criteria, and without extrahepatic spread or macrovascular invasion fit into this stage. For this group of patients, BCLC staging system offers transarterial chemoembolization (TACE) as the main option. TACE extends survival of these patients up to 19–20 months, with a range of 36–45 months for the best responders to 11 months for untreated patients.1 These results are insufficient and many studies have been designed proposing subclassification systems for intermediate stage HCC based on patient characteristics to tailor therapeutic interventions.4, 5 Others have focused their interest on alternative therapeutic managements based on the combination of TACE with other treatments.6, 7, 8, 9, 10, 11 Whether surgery is a suitable approach for B-stage HCC remains unclear. Although EASL/AASLD guidelines leave little room for hepatic resection, some reports promote its wider application. However, there is no strong evidence of which group of patients would be best candidates for surgery instead of TACE on this stage.

The main aim of our study is to analyse our modern series of patients with HCC in BCLC-B stage and find out how surgical approach may improve overall survival and recurrence rates in this group of patients. As secondary aims we performed comparisons with standards of care as defined by EASL/AASLD guidelines and analysed factors affecting survival and tumour recurrence; furthermore, specific analyses in the subgroup of surgical patients to detect potential factors of good/worse prognosis were performed, with special emphasis on B-staging subclassifications.

Section snippets

Study population

All patients referred to our tertiary Hospital with the diagnosis of HCC BCLC-B stage between January 2007 and December 2012 were included. Patients with non-cirrhotic HCC were excluded. All patients included in this study were “Pure-B patients” according to the BCLC-Classification or patients with a single tumour (theoretically BCLC-A) but not suitable for surgery because of the previously reported criteria1: Platelets <100,000 mm3, hepatic venous pressure gradient (HVPG) >10 mmHg, increased

Baseline results

A total of 80 patients that met the above inclusion criteria were included, of which 44 patients underwent TACE and 36 surgical resection. Surgical procedures included 8 subsegmentectomies, 6 segmentectomies, 9 bisegmentectomies, 4 multisegmental resections and 9 major hepatectomies. Considering the BCLC-B stage subclassification, 83% of the patients were stages B1 or B2. In the whole surgical dataset, 97% of them were on B1 or B2 (Table 1).

TACE versus surgery. Baseline differences

In both groups, baseline differences were observed.

Discussion

Hepatocellular carcinoma is a complex tumour with a difficult management. The BCLC staging system can be considered as the standard of care for the patients with HCC. However, although this classification is continuously under review, some patients are not well categorized and thus, better management options may be considered. The “intermediate” BCLC-B stage with TACE-only based strategies offers a median survival of 20-months.1 Our manuscript highlights the potential of modern surgical

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