Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis

Highlights

• Liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis should be considered after careful patient selection.

• Patient characteristics, tumor pattern, liver function and surgical approach should be considered as selection criteria.

• Nomograms to predict surgical risks and survival may help in treatment allocation.

Background & Aims

Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival.

Methods

Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed.

Results

A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count <100,000/mm³, 43.5% had preoperative ascites, and 56.9% had portal hypertension. A minor hepatectomy was most commonly performed (84.6%) and 122 (48.2%) were operated on by minimally invasive surgery (MIS). Ninety-day mortality was 4.3% with 6 patients (2.3%) dying from liver failure. One hundred and eight patients (42.7%) experienced complications, of which the most common was ascites (37.5%). Patients undergoing major hepatectomies had higher 90-day mortality (10.3% vs. 3.3%; p = 0.04) and morbidity rates (69.2% vs. 37.9%; p <0.001). Patients undergoing an open hepatectomy had higher morbidity (52.7% vs. 31.9%; p = 0.001) than those undergoing MIS. A prediction model for surgical risk was constructed (https://childb.shinyapps.io/morbidity/). The 5-year overall survival rate was 47%, and 56.9% of patients experienced recurrence. Prediction models for overall survival (https://childb.shinyapps.io/survival/) and disease-free survival (https://childb.shinyapps.io/DFsurvival/) were constructed.

Conclusions

Liver resection should be considered for patients with HCC and CP-B cirrhosis after careful selection according to patient characteristics, tumor pattern and liver function, while aiming to minimize surgical stress. An estimation of the surgical risk and survival advantage may be helpful in treatment allocation, eventually improving postoperative morbidity and achieving safe oncological outcomes.

Lay summary

Liver resection for hepatocellular carcinoma in advanced cirrhosis (Child-Pugh B score) is associated with a high rate of postoperative complications. However, due to the limited therapeutic alternatives in this setting, recent studies have shown promising results after accurate patient selection. In our international multicenter study, we provide 3 clinical models to predict postoperative surgical risks and long-term survival following liver resection, with the aim of improving treatment allocation and eventually clinical outcomes.

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third leading cause of cancer-related deaths worldwide.[1], [2] When feasible, curative options such as liver transplantation (LT) and resection represent the treatment of choice as they offer long-term survival.[3], [4] HCC occurs primarily in patients with underlying liver disease, negatively affecting prognosis and increasing the complexity of treatment;[5], [6] liver cirrhosis, in fact, is an independent prognostic factor for both short and long-term outcomes, and the assessment of liver function remains critical in the management of patients with HCC as selected treatments may induce collateral liver damage, eventually leading to decompensation.⁷ Child-Pugh classification has been proposed as a scoring system to grade liver function and is currently adopted by most of the available guidelines on HCC treatment.[7], [8], [9], [10], [11], [12], [13]

According to the Barcelona Clinic Liver Cancer (BCLC) algorithm which has been advocated by most as the optimal staging system to predict prognosis and guide treatment for HCC, only patients with early-stage tumors may be considered for liver resection as they are associated with long-term survival; furthermore, preserved liver function is required, namely “Child-Pugh A without any ascites, are considered conditions to obtain optimal outcomes after liver resection”.⁹ Conversely, it is generally agreed that in the setting of Child-Pugh C cirrhosis, patients without significant risk factors should be listed for transplantation according to well-defined inclusion criteria.¹⁴ Eventually, no clear recommendations are disclosed for patients with HCC and Child-Pugh B cirrhosis; treatment allocation remains difficult and controversial as these patients have an intermediate, partially compromised situation in between well preserved and terminal liver function.[15], [16] Patients fulfilling the selection criteria are generally referred for LT, but are at risk of being removed from the waiting list because of tumor progression or liver decompensation: indeed, despite transplantation being a “definitive” treatment as it removes both the tumor and the liver disease, this is limited to a group of selected patients and worldwide organ availability is scarce. On the other hand, locoregional and systemic therapies are mainly adopted when patients are excluded from LT; in such conditions, survival outcomes have been reported to be worse compared to curative treatments and the hazards of inducing collateral liver damage are still unclear, with some reports disclosing a high chance of decompensation.[9], [15], [16]

As a result of recent improvements in preoperative patients' assessment, surgical techniques, and postoperative care, more and more patients with intermediate and advanced HCC or with impaired liver function are referred for liver resection, achieving good short and long-term outcomes.[3], [17], [18], [19] The BCLC recommendations have been questioned as they exclude many patients who may benefit from surgery;[20], [21], [22] stratification of results within each BCLC class according to liver function is warranted as suggested by the guidelines themselves.⁹ In this setting, liver resection in Child-Pugh B cirrhosis has been reported as an alternative to LT with acceptable short- and long-term outcomes.[14], [23], [24], [25] Despite this, data is scant and originates primarily from single center case series with a small number of patients, leading to controversy and a lack of shared recommendations.²⁶

The aim of this study was to evaluate the short- and long-term outcomes of patients undergoing liver resection for HCC in the setting of Child-Pugh class B liver cirrhosis, pooling data from international referral centers, and eventually formulating a prediction model for surgical risks and survival.