Trial Information

A Randomized Controlled Trial of Multimodality Therapy in the Treatment of Palliative Resectable Hepatocellular Carcinoma With Intrahepatic Vessels Invasion

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and the third cause of
cancer-related death. At initial diagnosis, surgical resection is considered a potentially
curative modality for HCC[1, 2], with the five-year survival rates for resectable patients
50-60%, however, only about 15% of patients have resectable disease and post-operative
recurrence is common, remaining the main obstacle to long-term survival. On the one hand,
the reason may be the multicentric genesis of HCC or the preoperatively micrometastasis that
can not be resected during operation. Shi M, et al [3] reported that the appropriate
resection margin was >= 2cm. The Liver Cancer Study Group of Japan (LCSGJ) defined[4]:
absolute curative resection included liver resection with 1 cm of free surgical margin in
patients with solitary tumor <= 2cm; relative curative resection included liver resection
without 1 cm of free surgical margin but with the excised tumor tissue in patients with
solitary tumor <= 2cm or liver resection with 1 cm of free surgical margin in patients with
tumor >= 2cm (in either instance, no tumor thrombus may remain in the portal vein, hepatic
vein, or bile duct in images of the remnant liver); relative non-curative resection, in
which all macroscopic tumor tissue is removed; and absolute non-curative resection, which is
liver resection with part of the macroscopic tumor tissue remaining. Either overall survival
rates (OS) or disease-free survival rates (DFS) of HCC patients are higher in curative
resection than in non-curative resection[4]. According to this definition, when the giant
tumor located in middle liver, tumor with lymph nodes adjacent to abdominal aorta
metastasis, multiple lesions (>= 3) or tumor with intrahepatic vessels invasion, the surgery
will be non-curative. On the other hand, post-operative adjuvant therapy is one of the most
effective treatment strategies in improving the survival rates of HCC patients[5].
Unfortunately, only about 15 randomized controlled trials have been reported on the
post-operative adjuvant therapy until now. Most of them were single center, little sample
clinical trials.

Recently, a series of studies have been reported that transcatheter arterial
chemoembolization (TACE) is effective in HCC[6, 7]. Best results are seen in patients with
small tumors and good liver function and 1 year survival has been shown to be of 30-50%. A
recent meta-analysis showed a significant benefit of chemo-embolization with improvement in
two-year survival[6]. TACE is one of most important therapy strategies on HCC. The 2007'
NCCN clinical practice guidelines in oncology has included the TACE throughout the treatment
guideline of unresectable HCC or resectable HCC (for some reason, hepatectomy was not
carried out) or adjuvant therapy post-operative. But there are still lack of RCT studies.

In the patients with palliative resectable HCC, the presence of intrahepatic vessels
invasion was usually regarded as the symbol of cancer cells hematogenous dissemination,
which is associate with short-term recurrence and worse survival. For this special group
patients, some authors insisted that aggressive therapy strategy-initial palliative
hepatectomy followed by TACE and/or local regional treatments was most effective to prolong
the survival of patients.While other authors,however,believed that too aggressive therapy
was not best choice for these patients because of the suppression of immune system after
palliative hepatectomy may potentially accelerate the growth of residual cancer cells. A
relative conservative strategy-transcatheter hepatic arterial chemoembolization combined
local regional treatments without hepatectomy should be used. The optimal therapy strategies
are still in controversial.Only the multiple-center, great sample clinical RCT studies can
answer this question[8]. The purpose of this study is to compare the effects of different
multimodality therapy strategies (initial hepatectomy followed by transcatheter hepatic
arterial chemoembolization and/or local regional treatments compare with transcatheter
hepatic arterial chemoembolization combined local regional treatments without hepatectomy)in
the treatment of palliative resectable hepatocellular carcinoma with intrahepatic vessels
invasion.