Prognosis and staging system analysis of hepatocellular carcinoma patients with negative serum alpha-fetoprotein

Objective To investigate the effect of negative expression of serum alpha-fetoprotein ( AFP) ( < 20 ng/L) on the prognosisand staging of patients with hepatocellular carcinoma ( HCC) , the risk factors for postoperative survival rate of AFP-negative patients, andthe best scoring system for clinical outcome evaluation. Methods A retrospective analysis was performed for the clinical data of 188 patientswith HCC who underwent surgical resection in Xiangyang First People's Hospital Affiliated to Hubei Medical College from January 2012 toDecember 2017, among whom 127 had positive AFP ( AFP-positive group) and 61 had negative AFP ( AFP-negative group) . The twogroups were compared in terms of tumor-related factors, surgery-related factors, and other clinical data. The t-test was used for compari-son of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally dis-tributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier survival curve was used to calculate overall survival rate and relapse-free survival rate, and the log-rank test was used for compari-son of survival between two groups. The Cox proportional hazards model was used for univariate and multivariate analyses to identify the riskfactors for survival rate in the AFP-negative group and to evaluate the value of TNM system, Barcelona Clinic Liver Cancer ( BCLC) sys-tem, Cancer of the Liver Italian Program ( CLIP) score, Chinese staging ( CS) system, Japan Integrated Staging ( JIS) score, and Okudastaging system in judging postoperative survival of the AFP-negative group. Results Of all 188 HCC patients, 61 ( 32. 45%) had negative AFP. Moreover, compared with the AFP-positive patients, the AFP-negative patients tended to have a more complete capsule ( χ2=7. 234, P = 0. 007) , a better pathological stage ( χ2= 6. 698, P = 0. 01) , a higher survival rate ( χ2= 9. 580, P = 0. 002) , and a lower recurrence rate ( χ2= 8. 407, P = 0. 004) . Child-Pugh class B HCC ( hazard ratio [HR]= 1. 711, 95% confidence interval [CI]: 1. 073 ～39. 921, P = 0. 001) , a high level of bilirubin ( HR = 1. 044, 95% CI: 1. 006-1. 083, P = 0. 021) , and absence of tumor capsule ( HR =7. 025, 95% CI: 1. 319-37. 401, P = 0. 022) were independent risk factors for a reduced overall survival rate in the AFP-negative group.Tumor diameter > 3 cm ( HR = 4. 172, 95% CI: 1. 271-13. 691, P = 0. 019) , absence of tumor capsule ( HR = 8. 901, 95% CI: 2. 352-33. 693, P = 0. 001) , and vascular invasion ( HR = 0. 043, 95% CI: 0. 003-0. 584, P = 0. 018) were risk factors for an increased recurrence rate of tumor in the AFP-negative group. The univariate analysis showed that among these six staging systems, the TNM and BCLC staging systems were significantly associated with overall survival rate and relapse-free survival rate ( P < 0. 05) and the CS system was only significantly associated with overall survival rate ( P < 0. 05) ; the multivariate analysis showed that only the BCLC stating system was significantly associated with overall survival rate ( HR = 0. 124, 95% CI: 0. 038-0. 401, P < 0. 01) and that the TNM staging system ( HR =0. 339, 95% CI: 0. 158-0. 952, P = 0. 039) and the BCLC staging system ( HR = 0. 177, 95% CI: 0. 058-0. 539, P = 0. 002) were significantly associated with relapse-free survival rate. Conclusion AFP-negative patients often have good liver reserve function and biological behavior and high survival rate and relapse-free survival rate. Among the above six staging systems, only the BCLC staging system is significantly associated with both overall survival rate and relapse-free survival rate after surgery, and therefore, it is the best system for evaluating postoperative survival and prognosis in AFP-negative patients.