Comparative Study Of Prognostic Value Of Different Staging Systems In Patients With Resectable Hepatocellular Carcinoma

ObjectiveStaging systems were key to predict the prognosis of patients with cancer,to stratify the patients according to prognostic variables in the setting of clinical trials,to allow the exchange of information without ambiguity among researchers and finally to guide the therapeutic approach.Since the first prognostic staging system for HCC (hepatocellular carcinoma) was presented in 1971 in Kampala,in excess of ten classifications were developed throughout the world and only three of them including the CLIP,JIS and BCLC staging systems had been validated from then.The current knowledge of the disease,however, prevented the recommendation of a staging system that could be used worldwide,more and more evaluations of the staging systems including the CLIP score,the BCLC staging classification,the CUPI staging classification,the JIS score,the 2001-year China staging system(CS) and the 6^th edition AJCC/UICC TNM staging system(TNM-6^th) were made in the last decade,with the results conflicting.The aim of the study was to compare the CLIP score,the JIS score and the CS as predictors of survival in patients with resectable HCC and assess which of the three classifications performs best for Chinese patients with HCC.MethodsThe Clinicopathologic and follow-up data of 224 patients who underwent hepatic resection for HCC from January 2000 to July 2005 were retrospectively studied.Overall survival rates were calculated according to the life-table method and Kaplan-meier method was used to plot the curves of accumulative survival rates.Univariate analysis of the prognostic significance of various clinicopathologic characteristics was performed using the log-rank test.Multivariate analysis was performed to identify the independent prognostic factors related to postoperative survival using Cox proportional hazards model.The population distribution and the survival curve for each staging system were used to compare the stratification ability and discriminatory ability for the best prognostic group respectively.The likelihood ratio chi-square test and the linear trend chi-square test were used to compare the homogeneity and the monotonicity of the relationship between stage and mortality rate of each staging system.The increase in the -21oglikelihood statistic on removal of any one staging system was in turn used as a means of ranking the individual staging systems according to their importance within the regression model.A two-tailed P value of＜0.05 was considered statistically significant.The statistical package used was SPSS version 16.0 and Stata SE version 8.0.ResultsThe 224 patients in the study comprised 196 males and 28 females. The overall median survival time was 26 months and 1,3,and 5-year survival rates were 69.0±3.1%,37.9±3.4%,22.8±3.4%,respectively. Multivariate analysis with Cox's proportional hazard model indicated that Child-Pugh grade,surgical free margin,AJCC/UICC TNM-5^th stage,AFP (Alpha-fetoprotein) level and tumor differentiation grade were independent prognostic predictors for HCC patients.Based on the China staging system,the percentages of patients categorized asⅠa,Ⅰb,Ⅱa,Ⅱb,Ⅲa were14.3%,17.4%,21.9%, 31.7%and 14.7%respectively,showing excellent stratification ability. However,nearly 81.6%of the patient population was classified as having a CLIP score of 0-2,which showed poor stratification ability and only 3.1%of the patient population was identified in score 0 category of the JIS scoring system.For the follow-up period,the log-rank test results for all factors and the corresponding Kaplan-Meier survival curves confirmed the capacity for each staging system to differentiate between patient survival times across different stages.The individual pairwise comparisons revealed inconsistencies across the different staging systems.In particular,using the log-rank test,the JIS scoring system and the China staging system were the two systems for which significant differences were forthcoming for patient survival for all pairwise comparisons.By contrast,the CLIP scoring system failed to differentiate significantly between score 2 and score 3 patients.The JIS scoring system can identify the best prognostic group who would benefit from curative and aggressive treatments, whereas the CLIP score's discriminatory value was noted in the intermediate-and advanced-phase HCC patients.The China staging system was shown to have the best homogeneity, overall discriminatory capacity and monotonicity of gradient.The change in the -21oglikelihood statistic on removal of any staging system revealed that for this cohort of patients,the appropriate importance ranking for the independent contribution of each factor to the regression model is:CS＞CLIP＞JIS.ConclusionAmong three clinical staging systems,the China staging system has the highest prognostic value,with better stratification and higher discriminatory capacity than the CLIP scoring system and the JIS scoring system for this cohort of patients undergoing hepatectomy.The CLIP scoring system performs better in identifying the worst prognostic patients.