Retrospective evaluation of the Barcelona Clinic Liver Cancer staging classification and treatment schedule and development of a newprognostic staging system with treatment guidelines for Hong Kongpatients with hepatocellular carcinoma

Abstract

There are a number of existing staging systems for patients with hepatocellular

carcinoma (HCC). Yet, Barcelona Clinic Liver Cancer (BCLC) staging

classification is the only one which suggests treatment guidance. Although

BCLC staging is widely used in Western countries, it may not fit in the management

of HCC patients in Hong Kong as they mostly have different etiologies

and have more aggressive treatment strategy when compared with their counterparts

in Western countries. It is aimed in this thesis to develop a new

prognostic staging system in conjunction with treatment guidelines for HCC

patients in Hong Kong.

Three thousand eight hundred and fifty six adult HCC patients presented

to the Department of Surgery, Queen Mary Hospital between January 1995

and December 2008 were included. The patient data were randomly separated

into a training set and a test set for scheme development and performance

assessment respectively. Four established prognostic factors which have determinative

roles in treatment, namely Eastern Cooperative Oncology Group

performance status, Child-Pugh grade, tumor status, and presence of extrahepatic

vascular invasion/metastasis, were selected in building the scheme.

Cox proportional hazards regression on overall survival was used to derive a

relative coefficient for each category of these four factors. Clinical knowledge

in addition to the relative coefficients was involved in the proposal of the prognostic

stages. Then a classification and regression tree analysis was performed

to elicit a set of simple clinical decision rules given the factors. This tree-structured

classifier was adjusted with clinical judgment and reconciled with

the proposed prognostic staging system for treatment guidelines.

This Hong Kong Combined Liver Cancer (HKCLC) prognostic classification

scheme stratifies patients to stages I to V with distinct overall survival

outcomes. Its performance was compared to BCLC scheme for their discriminatory

ability as staging systems and effectiveness of treatment guidelines. The

former used receiver operating characteristics (ROC) analysis and concordance

index as measures of the ability to distinguish patients with different prognosis

for overall survival. HKCLC staging had significantly larger 1-year, 3-year

and 5-year area under ROC curve values and higher concordance index vis-a-vis

BCLC staging. The latter compared the overall survival of patients who

received different treatments. The overall survival of patients with the same

BCLC stage and the same HKCLC stage but received HKCLC recommended

treatments were compared with those received BCLC recommended treatments

by Kaplan-Meier plots and log-rank test. HKCLC treatment guidelines had

wider indications for more aggressive treatments than the BCLC treatment

schedule, and demonstrated significant survival benefit in our patients.