Yonsei Med J.  2017 Jul;58(4):737-742. 10.3349/ymj.2017.58.4.737.

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma

• Suh SW
• Choi YS

• KMID: 2419078
• DOI: http://doi.org/10.3349/ymj.2017.58.4.737

Abstract

PURPOSE
Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma (HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR).
MATERIALS AND METHODS
First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosed resectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determine their influence on survival.
RESULTS
Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031-25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031-25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027-0.497; p=0.004).
CONCLUSION
AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.

Keyword

Predictors; micrometastases; Barcelona Clinic Liver Cancer classification B hepatocellular carcinoma; surgical resection; transarterial chemoembolization

MeSH Terms

Adult
Carcinoma, Hepatocellular/*classification/*pathology
Demography
Disease-Free Survival
Female
Humans
Liver Neoplasms/*classification/*pathology
Male
Middle Aged
Neoplasm Micrometastasis/*diagnosis/pathology
Neoplasm Recurrence, Local/pathology
Neoplasm Staging
Probability
Prognosis
Proportional Hazards Models
Prothrombin/metabolism
Risk Factors
Vitamin K/metabolism
alpha-Fetoproteins/metabolism
alpha-Fetoproteins
Vitamin K
Prothrombin

Figure

• 

  Fig. 1 Recurrence-free survival and overall survival in surgical resection patients. The cumulative probability of tumor recurrence. The frequency of recurrence was significantly different according to the levels of AFP and PIVKA-II, especially during the first year (1-year recurrence-free survival: AFP <110 and PIVKA-II <800, 78.6%; AFP ≥110 or PIVKA-II ≥800, 20.8%). The curves continued to diverge during 2 years of follow-up, but then continued parallel (p=0.009). AFP, α-fetoprotein; PIVKA-II, prothrombin induced by vitamin K absence-II.

• 

  Fig. 2 The cumulative probability of overall survival in all patients. A significant difference was found in overall survival according to the type of procedure and combined levels of AFP and PIVKA-II (p=0.001). The curve of Group 1 significantly diverged from that of the other groups (HR=0.116; 95% CI, 0.027–0.497; p=0.004). SR, surgical resection; TACE, transarterial chemoembolization; AFP, α-fetoprotein; PIVKA-II, prothrombin induced by vitamin K absence-II; HR, hazard ratio; CI, confidence interval.

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