Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study

AbstractAIM: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality.METHODS: From January 1999 to December 2010,320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatmentswere followed and managed with supportivetherapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated accordingto Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected for each patient including all clinical, laboratory and imaging variables necessary for the outcome prediction staging systems considered. HCC staging was performed according Barcelona Clinic Liver Cancer(BCLC) and Cancer of the Liver Italian Program scores. Follow-up time was defined as the number of months from the diagnosis of HCC to death. Prognostic baselinevariables were analyzed by multivariate Cox analysis to identify the independent predictors of survival.RESULTS: Seventy-five per cent of patients had hepatitis C. Ascites was present in 169 patients (53%), while hepatic encephalopathy was present in 49 patients (15%). The Child-Pugh score was class A in 105patients (33%), class B in 142 patients (44%), and class C in 73 patients (23%). One hundred patients(31%) had macroscopic vascular invasion and/or extrahepaticspread of the tumor. A single lesion > 10 cmwas observed in 34 patients (11%), while multinodular HCC was present in 189 patients (59%). Thirty ninepatients (12%) were BCLC early (A) stage, 55 (17%) were BCLC intermediate (B) stage, 124 (39%) were BCLC advanced (C) stage, and 102 (32%) were endstage BCLC (D). At the time of this analysis (July 2011),28 (9%) patients were still alive. Six (2%) patients whowere lost during follow-up were censored at the lastvisit. The overall median survival was 6.8 mo, and the1-year survival was 32%. The 1-year survival accordingto BCLC classes was 100%, 79%, 12% and 0%,for BCLC A, B, C and D, respectively. There was a significantdifference in survival between each BCLC class.The median survival of patients of BCLC stages A, B, Cand D was 33, 17.4, 6.9, and 1.8 mo, respectively (P< 0.05 for comparison between stages). The mediansurvival of Child-Pugh A, B and C classes were 9.8 mo (range 6.4-13), 6.1 (range 4.9-7.3), and 3.7 (range1.5-6), respectively (P < 0.05 for comparison betweenstages). By univariate analysis, the variables significantlyassociated to an increased liklihood of mortalitywere Eastern Cooperative Oncology Group performancestatus (PS), presence of ascites, low level of albumin,elevated level of bilirubin, international normalized ratio(INR) and Log-[(α fetoprotein (AFP)]. At multivariateanalysis, mortality was independently predicted by badPS (P < 0.0001), high INR values (P = 0.0001) and elevatedLog-(AFP) levels (P = 0.009).CONCLUSION: This study confirms the heterogeneousbehavior of untreated HCC. BCLC staging remains animportant prognostic guide and may be important indecision-making for palliative treatment.