Staging
Systems for Hepatocellular Carcinoma
Han Zhang, Tian
Yang
Han Zhang, Tian
Yang,
Department of
Hepatic Surgery, Eastern
Hepatobiliary Surgery Hospital, No. 225,
Changhai Road, Shanghai, China
Correspondence
to: Tian Yang, MD, Department of Hepatic Surgery, Eastern Hepatobiliary
Surgery Hospital, No. 225, Changhai Road, Shanghai, China.
Yangtian6666@hotmail.com
Tel:
+086-021-6556608
Fax: +086-021-6556608
Received: May
5, 2013
Revised:
June 28, 2013
Accepted: June 30, 2013
Published
online: September 18,
2013
ABSTRACT
Clinical staging systems for cancer
provide guidelines for patient assessments and treatments. A proper staging is
essential for objective comparison between the outcomes of different
treatments. While the prognosis of most solid tumors is generally dependent on
tumor stage at presentation, prediction of prognosis in hepatocellular
carcinoma (HCC) patients is somewhat more complicated due to various aspects
affecting patient survival including cirrhosis and underlying liver function.
Up to date, at least eight staging systems have been proposed for HCC, but the
optimal staging system for HCC is still under intense debate. Each existing
staging system, characterized by the patient population based on which it was
constructed, may have different predictive power for HCC patient in different
area of the world, roughly the East and the West. The lack of a consensus on
HCC staging systems is mostly in part related to the heterogeneity in treatment
modalities at diagnosis. Therefore, we hereby propose a novel staging system
for HCC, named as the Eastern staging, based on the authors¡¯ previous study
with a large cohort of Chinese patients undergoing surgical resection. Compared
with the six existing staging systems, including CLIP, TNM, JIS, BCLC, CUPI and
Okuda, the Eastern staging appears to have the best predictive ability for
mortality at 1, 3, and 5 years. Thus, we believe the Eastern staging to be a
simple and practical system for prognostic factor evaluation, risk level
determination, and prognosis assessment after surgical resection in patients
with HCC.
© 2013 ACT. All rights reserved.
Key words: Hepatocellular carcinoma, Staging and
Surgical resection
Zhang H, Yang T. Staging Systems for
Hepatocellular Carcinoma. Journal of tumor 2013; 1(4): 20-23
Available from: URL: http://www.ghrnet.org/index.php/jt
INTRODUCTION
Hepatocellular carcinoma is the most common primary malignancy of the
liver and a major cause of mortality. In the last few decades, the management
of HCC has changed significantly due to an improved diagnostic capacity, the
development of evidence-based staging systems, and the availability of
effective treatment. A precise staging before making therapeutic decisions is
helpful to estimate prognosis and satisfactory treatment with greatest survival
advantage. To date, at least 8 staging systems have been proposed from
independent study groups to predict the outcome of patients with HCC[1].
Several staging systems are most widely adopted, such as Tumor-Node-Metastasis
system by American Joint Committee on Cancer, Okuda staging, CLIP (Cancer of
Liver Italian Program) staging, BCLC (Barcelona Clinic Liver Cancer) staging,
CUPI (Chinese University Prognostic Index) staging, and JIS (Japanese Integrated
System) staging[2].
Different
staging systems have different predictive power for HCC patient in different
area of the world. That could be from the difference in tumour biology, the
aetiology of liver cirrhosis and also the difference of treatment modality
strageties. In Eastern countries, studies from China, Korea, and Taiwan
demonstrated that either TNM[3-5] or CLIP[6,7] had better
predictive power than others, while many studies from Japan favored JIS as the
best staging system[7-9]. In contrary, most studies from Western
countries suggested that either BCLC[8-10] or CLIP[11]
had superior discriminatory power.
THE TNM CLASSIFICATION
The TNM staging system is widely used by physicians in several fields.
It has been proposed also as the best classification to assess the outcome of
HCC patients undergoing resection or orthotopic liver transplantation. However,
the TNM staging system only consists of variables regarding tumor morphology
and pathology, while prognosis of HCC patients relies heavily on aspects
related to liver cirrhosis as well. Although the TNM staging system may be
useful to stratify series of patients at different stages, a couple of recent
studies have shown that this classification lacks prognostic value for early
HCC patients treated with resection or transplantation[12,13].
THE CLIP STAGING SYSTEM
The CLIP criteria combine the Child¨CPugh
classification with tumor characteristics including morphology (unino-dular,
multinodular or massive), portal vein thrombosis, and high serum levels of
alpha fetoprotein (AFP, 400 ng/mL). The above factors have been described as
adverse prognostic characteristics in patients with HCC. Inclusion of
tumor-specific prognostic factors has improved the prognostic accuracy of the
CLIP scores. The CLIP scores can adequately separate patients with no adverse
tumor progression factors (CLIP 0), who have the best prognosis, from those
with even one adverse prognostic factor, whose prognosis is significantly
reduced.
THE JIS SCORE
The JIS score consists of the Child¨CPugh classification and the TNM
stage[14], thus taking account of both liver function and tumor
characteristics. The JIS score has been compared with the BCLC and CLIP in a
Japanese study[15] of 1679 patients, and found to be superior in
prognostic determination. However, the JIS score was developed based solely on
Japanese HCC patients, further prospective studies are required among distinct
patients groups, countries, and racial groups.
THE BCLC STAGING SYSTEM
The BCLC staging has emerged during recent years as
the standard classification that is used for trial design and clinical
management of patients with HCC. This classification has been approved by
European Association for the Study of the Liver (EASL) and the American
Association for the Study of Liver Diseases (AASLD) and has subsequently been
corroborated in clinical studies. However, it seems that BCLC is suboptimal to
predict prognosis of HCC patients undergoing surgical resection. Many factors
contribute to interpret this finding. First, BCLC mainly included a small
number of HCC patients undergoing surgery in their original studies, so they
include prognostic variables that theoretically have less predictive power in
the subgroup undergoing surgical resection. Secondly, there is considerable
conflict in surgical indications for HCC in different centers. In the BCLC
staging treatment strategy, surgical resection is only recommended for BCLC A
stage. However, many selected patients with intermediate even advanced HCC
still underwent surgical resection in many centers, especially from Eastern
countries. In 2011, the authors reported a consecutive series of 511 selected
patients from China with advanced HCC (BCLC stage C) who underwent surgical
resection in the authors¡¯ unit from 2001 to 2007[16], which was
obviously distinctive from therapeutic principles by the BCLC constitutors.
Finally, the BCLC system seems to have overemphasized the prognostic effect of
performance status, which leads to relatively poor performance in patient
survival prediction in other settings of patient demographic characteristics.
THE EASTERN STAGING¡ªBETTER PROGNOSIS PREDICTION FOR
SURGICALLY TREATED PATIENTS
Treatment modality is a significant confounding
effect on the prognosis of HCC. The lack of a consensus on HCC staging systems
is mostly in part related to the heterogeneity in treatment modalities at
diagnosis. Therefore, it is necessary to establish specific HCC staging systems
to assess prognosis, directed toward different treatment modalities, so as to own
more powerful discriminatory ability. Therefore, the authors used a large
cohort of surgically treated Chinese patients, and identified independent risk
factors of poor survival by univariate and multivariate analyses. A total of
958 patients with 857 males and 101 females, the median age was 50 years
(range, 10-83 years). The HBsAg positive rate was 91.8%, while the
anti-hepatitis C virus (HCV) positive rate was 2.5%. Although 73.6% of patients
had histologic evidence of cirrhosis in the resected specimens, the majority of
patients presented with well-preserved hepatic function; 88.2% of patients had
biochemical biochemical profiles consistent with Child-Pugh A, and 11.8% with
Child-Pugh B. The tumor was larger than 5 cm in 52.3% in these patients. Macroscopic
vascular invasion was present in 152 patients (15.9%), mainly including portal
vein thrombosis (PVT) in 133 patients. On the basis of this cohort of patients,
a new staging system named the Eastern staging with five stages was proposed
(Table 1).
The Eastern staging was
compared with six existing staging systems (Figure 1). It appears to have the
best predictive ability for mortality at 1, 3, and 5 years. The prognostic
results presented as comparison of 5-year survival of different stages among
five staging systems was shown in table 2. However, it is by no means a
universal staging system for HCC. It focuses predominantly on those patients
subject to scheduled surgical resection. The majority of patients in this
Chinese cohort had chronic HBV infection, which is common situation in many
Eastern countries, thus the results may not be applicable readily to patients
in the United States or other Western countries. In addition, approximately
15-50% of patients in the cohort were in relatively advanced stage by different
staging systems, and this might limit the generalizability of this study. In
brief, from the Eastern staging, it is easy to determine the patient¡¯s risk
level and assess prognosis after surgical resection. So we consider this a
novel staging designed for resectable HCC exclusively, and it will provide
adequate prognostic information to patients, when surgical resection is
adopted, especially in Chinese and other Eastern countries.
CONCLUSION
More than 10 staging systems have been proposed for HCC. The optimal
staging for HCC is still under intense debate. The Eastern staging appears to
be a simple and practical system for prognostic factor evaluation, risk level
determination, and prognosis assessment after surgical resection in patients with
HCC.
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Peer reviewers: Deliang Cao, Ph.D, Associate Professor, Department
of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer
Institute, 913 N. Rutledge Street, Springfield, IL 62794 USA; Hiroshi Nakano, MD, PhD, Associate
Professor, Department of Gastroenterological and General Surgery, 2-16-1 Sugao,
Miyamae-ku, Kawasaki 216-8511, Japan.
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