Prognostic Factors For Hepatocellular Carcinoma And Comparisons Of Prognostic And Therapeutic Guiding Values Of 8 Staging Systems In A Chinese Cohort

Background:Hepatocellular carcinoma(HCC) is a major health problem worldwide. Clinical staging of cancers is important for guiding therapeutic interventions and assessing prognosis.Although several staging systems have been developed in the last few years,there is still no worldwide consensus on which is the preferred prognostic staging system for HCC,and only the Barcelona Clinic Liver Cancer(BCLC) staging system embodies therapeutic schedule.Furthermore,few studies were based on the Chinese patients,who account for more than a half of the worldwide cases.Therefore, these staging systems still need to be validated in the Chinese HCC patients.Objective:The aims of this study were to identify independent prognostic factors for HCC,to validate 8 staging systems in Chinese HCC patients and to compare both the prognostic and the therapeutic guiding values of these systems for HCC patients in China.Methods:We retrospectively studied 861consecutive HCC patients without prior anticancer therapy who were admitted in Liver Cancer Institute of Zhongshan Hospital between January 2001 and December 2002.Demographic,laboratory,and tumor characteristics and performance status were determined at diagnosis and before therapy.Factors determining survival were analyzed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models.Tumor-Node-Metastasis(TNM),Okuda,BCLC,Cancer of the Liver Italian Program(CLIP),Japan Integrated Staging score(JIS),Chinese University Prognostic Index score(CUPI),GRoupe d'Etude et de Traitement du Carcinoma Heatocellulaire (GRETCH) and Chinese Scoring System evaluated before treatment were applied. Each system was entered in to the Cox regression model to calculate the LR x~2,AIC and Harrell's C values.The area under the ROC curve was calculated to evaluate the accuracy of prediction of death at 1-,3-,5-year for each staging system.Survival curves for the patients treated with different therapies in each stage category according to the discussed eight staging systems were also calculated using the Kaplan-Meier method and compared by log rank test.Results:At the end of follow-up,496 patients(57.61%) were deceased.A total of 114 patients(13.24%) had withdrawn,including 91 patients(10.57%) being followed up with less than 3 years,and 108 patients(12.54%) less than 5 years.Overall median survival was 38±2.84 months,with estimated 1-,3-,and 5- year survival rates as 74.64±1.52%,51.27±1.78%,and 40.08±1.78%,respectively.By multivariate Cox regression analysis,tumor size,tumor numbers,vascular invention,extra-hepatic invention,cirrhotic node size,ascites,alkaline phosphatase(AKP),HBe antigen (HBeAg),were independent prognostic factors for overall survival.By Kaplan-Meier analysis,all the 8 systems showed prognostic abilities.However,only the JIS,Chinese and BCLC systems showed significant difference among survival rates for each subgroup.With the Cox regression model,BCLC showed the best homogeneity(LR x ~2=158.19) and informative explanatory ability(AIC=5049.75),followed by the Chinese staging system.Chinese staging system showed the best discriminatory ability and monotonicity of gradients than the other systems(Area under the ROC curve:1-year:0.7848;3-year:0.7492;5-year:0.7152,Harrell's C=0.6877),followed by the BCLC and JIS staging systems.On the other hand,only the Okuda,BCLC, CLIP and Chinese systems showed the ability to decide which patients may not benefit from resection.There were no significant survival differences between the surgery group and the TACE/TAE group for patients in Okuda stageⅡ,BCLC stage C,CLIP scores more than 3,and Chinese stageⅢA,while resection may benefit for patients with the earlier stages. Conclusion:The BCLC,JIS and Chinese staging systems revealed best prospective ability,and the Okuda,BCLC,CLIP and Chinese systems revealed good therapeutic guiding ability.Only the Chinese and the BCLC staging systems were good at both prospecting prognosis and deciding preferred treatment for patients.However,the BCLC treatment schedule is not validated by this study.