When Does Invasion Mean the War is Lost

The significance of macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) is ill defined. Although the Barcelona Clinic Liver Cancer Classification System classifies disease associated with MVI as stage C and recommends that patients with MVI be offered palliative therapy with the oral multikinase inhibitor sorafenib, several centers have reported successful liver resection with good outcomes in patients with MVI. The paper by Roayaie et al. provides an excellent opportunity to revisit the significance of MVI in HCC. We congratulate the authors for their thorough evaluation of their results, critical discussion of their data, and comprehensive summary and analysis of the available relevant literature. The authors performed a retrospective analysis of 165 patients with Child’s class A cirrhosis and MVI treated with primary hepatic resection during the period from 1992 to 2010. Median survival time after surgery was 13.1 months, and the 5-year survival rate was 14 %. These outcomes compare favorably to the 8-month median survival of patients with MVI who received sorafenib during the important SHARP trial (108 patients, 36 % of the patients in the sorafenib group). In their multivariate analysis, Roayaie et al. determined that alfa-fetoprotein level greater than 30 ng/mL, tumor size greater than 7 cm, and more extensive vascular invasion were independent predictors of worse overall survival. Furthermore, hepatic vein or inferior vena cava invasion was associated with significantly worse overall survival following resection (median 4.7 months) than was portal venous invasion (median 9.2 months). Possible reasons for the poor outcomes of patients with hepatic vein or inferior vena cava invasion undergoing resection might be ready access of the tumor to the systemic venous circulation or the high morbidity of the surgery itself. A question that could have been addressed in the paper in more detail is whether there are shades of gray when it comes to portal venous invasion by HCC. We think the answer is ‘‘yes.’’ Ikai et al. published a paper in 2003 that showed that there are survival differences according to the order of portal branch involved, a parameter that allows accurate prognostication (Fig. 1). The Liver Cancer Study Group of Japan has adopted and incorporated this concept. Therefore, MVI of the portal vein is helpful for determining outcome, as shown by Roayaie et al., but might be defined more precisely as a discrete variable (tumor thrombus in first-, second-, or third-order branch) than as a qualitative variable (presence or absence of MVI). An issue raised by the authors is the 60 % rate of detection of MVI on preoperative imaging. Although the long time interval covered by the study (1992–2010) saw advances in operative techniques (the reported mortality rate of 28 % for patients with hepatic vein or inferior vena cava involvement might be lower today) and the 2005 approval of sorafenib by the Food and Drug Administration, the preoperative detection sensitivity and specificity of Vp1-4 MVI might still only be around 70 and 80 % respectively. Preoperative detection of major vascular invasion (Vp3) is important to determine the need for preoperative transarterial chemoembolization (TACE). Roayaie et al. were surprised by the results of the study by Minagawa et al., in which 18 patients undergoing TACE plus liver resection were compared to 27 patients who did not undergo hepatectomy. This study was conducted at a center with specialized expertise in a cohort of patients This is an editorial to the article available at doi:10.1245/s10434013-3074-7.