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Page 2 of 6 Zhong et al. Hepatoma Res 2019;5:18 I http://dx.doi.org/10.20517/2394-5079.2019.01

In recent two decades, nine systems have been proposed for staging HCC from Western to Eastern,
[4]
[5]
including Cancer of the Liver Italian Program (CLIP) , French Score , Barcelona Clinic Liver Cancer
[6]
[7]
[8]
(BCLC) staging , the Model to Estimate Survival for HCC patients , China liver cancer (2017 Edition) , Chinese
[9]
[10]
University Prognostic Index , Hong Kong Liver Cancer (HKLC) system , Japan Integrated Staging
[11]
[6]
Score , and Italian Liver Cancer (ITA.LI.CA) system [8,12] . Among these stage systems, only the BCLC ,
[10]
[8]
HKLC , and China liver cancer (2017 Edition) staging systems propose stage-appropriate treatment
[13]
modalities. Even so, BCLC stage system is the only one endorsed by each version of the EASL and
[14]
AASLD .
However, each stage system has its own limitations. They leave large treatment gaps. For example, not
each individual with HCC fall completely into his/her prespecified treatment modalities, and even those
within the same HKLC or BCLC stage system may differ completely because of their different liver disease
background. Many studies compared performance of different stage systems. Studies based on Western
population found the BCLC system can predict overall survival and/or disease-free survival more accurately
for Western patients with HCC than Eastern ones. However, studies based on Estern population found
HKLC or China liver cancer (2017 Edition) staging system is better than Western ones [15,16] . Therefore,
selection of stage system should be based on population characteristics.
Intermediate stage disease of BCLC system includes HCC involving asymptomatic multinodular tumors
with a maximum diameter > 3 cm or > 3 tumors without vascular invasion or extrahepatic spread. Earlier
version of the BCLC system classified large solitary HCC beyong 5 cm with an expansive growth as
intermediate disease. Namely, intermediate disease definition includes a wide range of patients according to
liver function and tumour burden, which triggered a major controversy to further stratify intermediate stage
HCC according to tumor burden and liver function [17-19] . Nowadays, guideline from European Association
[13]
for the Study of the Liver and several reviews written by BCLC proponents seems trying to recalibrate
their position stating that if technically feasible patients with large solitary HCC beyond 5 cm should be
classified as BCLC stage A. Anyhow for patients with solitary HCC, hepatectomy is first-line treatment with
good long-term OS.

Western official guidelines only recommend palliative treatments for intermediate disease, but not
hepatectomy. Their recommendations did not completely reflect newest evidence by continuing to
recommend transarterial chemoembolization, particularly in comparison with hepatectomy. The efficacy
of transarterial chemoembolization is far from clear. Our systematic review involving large sample size
with large solitary or multinodular HCC found median 1-, 3-, and 5-year OS after hepatectomy were
[20]
81%, 56%, and 42% . For 4,945 patients with multinodular HCC, the corresponding OS were 75%, 48%,
[21]
and 30% . A recent large meta-analysis found significant OS benefits for hepatectomy over transarterial
chemoembolization in BCLC stage B patients (hazard ratio, 0.59; 95% confidence interval, 0.51-0.67; P <
[22]
0.001) . Nowadays, substantial evidence supported that hepatectomy would provide better OS than other
palliative therapies, implying the possibility that some Western HCC guidelines are restricting many
populations with intermediate stage HCC to palliative treatment. But actually, these populations could
obtain more benefit from more aggressive hepatectomy.

[2]
In China, about half of HCC patients are diagnosed as HCC in an advanced stage . Many studies compared
the safety and efficacy of hepatectomy to transarterial chemoembolization [3,23,24] . Patients receiving either
treatment modality showed similar safety. However, hepatectomy provided significantly longer median
survival than transarterial chemoembolization, even after using propensity score analysis. Two recent
large retrospective studies from Japan also found hepatectomy was associated with better OS for patients
with portal vein tumor thrombus (PVTT) or hepatic vein thrombus [25,26] . The first study compared OS of
2,093 HCC patients with PVTT who underwent hepatectomy and 4,381 patients who received palliative