2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Patient Selection, Resection, and Outcomes
for Hepatocellular Carcinoma
By Claudius Conrad, MD, PhD, and Kenneth K. Tanabe, MD
Overview: Hepatocellular carcinoma (HCC) is an aggressive
malignancy of the liver that most often arises in patients with
cirrhosis and other chronic liver diseases. Worldwide, it is the
sixth most common cancer and the third most common cause
of cancer-related death. Median survival is poor, ranging from
6 to 20 months. Definitive treatment options for HCC are
surgical resection, ablation, or transplantation. The selection
of patients for surgical resection is based on clinical findings,
laboratory data, and imaging. Although a number of staging
systems exist, all have their limitations. A multidisciplinary
approach to patient selection for surgery that includes the
input of an experienced liver surgeon assures optimal outcomes.
Sound understanding of liver segmentation, modern
surgical techniques, and the use of intraoperative ultrasound
have led to a reported perioperative mortality rate below 3%,
THE INCIDENCE of HCC is rising. HCC represents the
fastest growing cause of cancer-related death in men in
the United States, with reported overall survival rates of
20% to 60% for resected patients. 1 In contrast to other
malignancies, the resectability of this tumor is not only
affected by its anatomic location, the extent of disease, and
the overall medical condition of the patient but also by the
degree of underlying chronic cirrhosis of the liver that is
present in more than 80% of patients. The etiology of the
liver cirrhosis is chronic hepatitis B and C in the majority of
cases, although alcoholic liver disease; cryptogenic cirrhosis;
and, increasingly, nonalcoholic steatohepatitis secondary to
the increasing incidence of obesity are clinically relevant as
well. 2 The increased incidence of HCC in the United States
has been primarily attributed to the concomitant increase in
hepatitis C infection. 3 However, one must keep in mind that
15% to 20% of patients with HCC in the United States
develop HCC without any known risk factors. 4 HCC is now
identified earlier with screening of high-risk patients. 2 For
patients with cirrhosis, portal hypertension, and tumors
confined to the liver, orthotopic liver transplantation has
been considered the most effective treatment. However,
there are no prospective randomized controlled trials that
directly compare liver transplantation with liver resection
for HCC. Most studies compare either transplantation or
resection with historical controls and do not analyze according
to “intent to treat,” and a significant selection bias of
these studies cannot be excluded. Transplantation for HCC
is limited by the donor organ shortage, which results in
disease progression and death among patients with HCC
awaiting a donor liver. 5 In addition to the limitations of liver
transplantation, surgical resection for HCC has its challenges
as well. Only 20% to 30% of all patients with HCC in
the United States will be candidates for either resection or
even locoregional therapies, including radiofrequency and
cryoablation or transarterial chemoembolization. This article
will focus on patient selection for surgical resection,
which is mainly determined by extent of disease and liver
function, advances in operative technique, and prognostic
factors that determine outcome.
blood transfusion requirements of less than 10%, and 5-year
survival rates of at least 50%. Advances in laparoscopic
technique and technology have expanded the indications for a
safe and oncologically appropriate minimally invasive resection.
Deciding which treatment option to employ depends on
tumor resectability and the degree of underlying liver disease,
which is present in 80% to 85% of patients with HCC; however,
despite these surgical advances, a high recurrence rate of
70% in patients with cirrhosis and a survival rate of 65% to
80% in well-selected transplant patients are expected. This
article will focus on the evaluation and selection of patients
for surgical intervention, considerations in selecting the appropriate
type of resection, and expected outcomes following
liver resection.
Patient Selection and Assessment of Hepatic Reserve
The existence of a multitude of scoring and staging systems
(e.g., Okuda, Cancer of the Liver Italian Program, and
American Joint Committee on Cancer) suggests that the
ideal one has yet to be identified. Thorough clinical, laboratory,
and imaging assessment and careful preoperative
patient selection by experienced liver surgeons are necessary
for optimal surgical outcomes. Assessment of HCC
resectability and extent of resection requires evaluation of
patient functional status and comorbidities, tumor location,
and underlying liver function. Routine grayscale ultrasound
has value for screening patients with cirrhosis but rarely
has value in surgical planning. Multidetector computed
tomography (CT) with three-dimensional reconstruction and
magnetic resonance imaging (MRI) are superior for surgical
planning, and they provide information on the morphologic
characteristics of the tumor, presence of intrahepatic metastasis
and secondary lesions, extent of chronic liver disease,
and vascular involvement. Special focus should be given to
the number and location of suspicious lesions and any
suspicious regional nodes, as well as any signs of advanced
liver disease (ascites, nodular hepatic contour, enlarged
caudate lobe, splenomegaly, gastrosplenic and umbilical
venous collateral vessels, and fatty hepatic infiltration). 1 In
addition, the anatomic relationship of the tumor to important
vascular structures as well as the presence of a portal or
hepatic vein thrombus are important findings on CT and
MRI. A vascular thrombus that is bulging in appearance and
enhances with contrast is suspicious for tumor thrombus,
whereas nonenhancing thrombus may represent venous clot
rather than tumor. Macrovascular involvement portends a
poor prognosis, unlikely to be improved with surgical resection,
and represents a contraindication to liver transplanta-
From the Massachusetts General Hospital, Department of Surgery, Division of Surgical
Oncology, Harvard Medical School, Boston, MA.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Kenneth K. Tanabe, MD, Massachusetts General Hospital, 55
Fruit St., Yawkey 7.924, Boston, MA 02114; email: ktanabe@partners.org.
© 2012 by American Society of Clinical Oncology.
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