Abstract: Objective:To investigate the overall survival prediction of the Bolondi substaging model for patients in intermediatestage of Barcelona clinic liver cancer (BCLC) after hepatectomy.
MethodsThe retrospective cohort study was adopted. The clinical data of 343 patients with intermediatestage hepatocellular carcinoma (HCC) who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University between February 2008 and January 2010 were collected. All the patients received the detailed medical history collection, physical examination, laboratory and imaging examinations after admission, and then hepatectomy was performed according to the results of above examinations. Research methods: (1) patients were allocated into the B1, B2 and B3/4 groups based on the Bolondi′s substaging model, and the prognostic analyses among groups were conducted. (2) The related factors affecting the prognosis of patients in the B1 and B2 groups were analyzed. (3) The patients in the B1 and B2 groups were allocated into the 4 groups ［patients of B1 group with negative microvascular invasion (MVI) were divided in the M1 group, patients of B1 group with positive MVI in the M2 group, patients of B2 group with negative MVI in the M3 group and patients of B2 group with positive MVI in the M4 group］ according to the situations of MVI, and stratified analysis was conducted. Observation indicators: basic clinical and pathological features and survival of patients in the B1, B2 and B3/4 groups were observed. Risk factors analysis affecting the prognosis of patients and stratified analysis of MVI in the B1 and B2 groups were conducted. All the patients were followed up by outpatient examination and telephone interview up to February 2014, and the abdominal ultrasound, liver function and serum alphafetoprotein (AFP) tests was performed once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively. The continuous variables and categorical variables were respectively represented as M(Qn) and percentage. The comparisons of continuous variables and categorical variables among groups were analyzed by ANOVA or KruskalWallis test and chisquare test or Fisher exact probability, respectively, and oneway ordinal categorical variables were analyzed by the KruskalWallis test. The survival curve was drawn using the KaplanMeier method. The univariate analysis and multivariate analysis were done using the Logrank test and COX regression model.
Results: (1) The basic clinical pathological features: of 343 patients with HCC, 143, 183 and 17 patients (12 in the B3 substaging and 5 in the B4 substaging) were respectively allocated into the B1, B2 and B3/4 groups. There were statistically significant differences in the age, peritoneal effusion, total bilirubin (TBil), albumin (Alb), alanine transaminase (ALT), prothrombin time (PT), platelet (PLT), alphafetoprotein (AFP), extent of liver resection, surgical margin ivasion, tumor diameter, number of tumor, EdmondsonSteiner grade, Upto7 score, Upto7 standard and Childpugh score among the 3 groups (F=3.377, NA, 11.245, 32.616, 6.884, 11.564, 33.100, 12.902, NA, NA, 239.089, 10.357, χ²=8.906, F=251.508, χ²=343.000, 106.790, P<0.05). (2) Survival of patients: all the patients were followed up for 2.8-70.8 months with a median time of 38.7 months. The 1, 3, 5year survival rates and median survival time in the B1, B2 and B3/4 groups were 85.8%, 72.8%, 52.9% and 63.2%, 47.5%, 16.8% and 45.5%, 30.4%, 8.4% and 55.1 months, 35.1 months, 12.2 months, respectively, showing a statistically significant difference (χ²=22.800, P<0.05). (3) Risk factors analysis: the results of univariate analysis showed that the peritoneal effusion, Alb, Hb, AFP, esophagogastric varices, surgical margin invasion, tumor diameter, MVI and EdmondsonSteiner grade were related risk factors affecting the prognosis of patients with HCC after hepatectomy ［HR=2.04, 2.46, 2.50, 1.78, 1.55, 3.54, 1.71, 1.76, 1.69, 95% confidence interval (CI): 1.13-3.69, 1.20-5.02, 1.51-4.15, 1.29-2.45, 1.06-2.25, 1.65-7.61, 1.23-2.38, 1.23-2.51, 1.08-2.64, P<0.05］. The results of multivariate analysis showed that the Alb<35 g/L, Alb<low limit of normal, tumor invading to surgical margin, tumor diameter > 5 cm and positive MVI were independent risk factors affecting the overall survival of patients with HCC after hepatectomy (HR=2.82, 2.16, 2.93, 1.48, 1.53, 95%CI: 1.37-5.80, 1.27-3.69, 1.33-6.44, 1.05-2.09, 1.06-2.22, P<0.05). (4) There were 61, 82, 57 and 126 patients in the M1, M2, M3 and M4 groups, and M2 and M3 groups were merged into the M2/3 group because of being similar survival situations of patients. The 1, 3, 5year survival rates and median survival time in the M1, M2/3, and M4 groups were 90.0%, 83.2%, 67.7% and 68.8%, 59.9%, 41.6% and 52.7%, 42.1%, 23.6% and 69.0 months, 49.2 months, 24.9 months, respectively, with a statistically significant difference among the 3 groups(χ²=20.200, P<0.05).
Conclusions: The Bolondi substaging model produces an optimal survival prediction for patients in intermediate stage of BCLC after hepatectomy. The patients in the B1 and B2 substaging have better longterm survival outcomes after hepatectomy.