Hepatocellular Carcinoma: Therapeutic Guidelines and Medical Treatment

Abstract

Western and Eastern perspectives on therapeutic guidelines for hepatocellular carcinoma (HCC) have many commonalities but may also differ in certain aspects, as described in this article. In view of the limited therapeutic options for advanced HCC, evidence-based therapies are few, and thus there is a dependence on consensus-based guidelines. This article focuses on the Italian Association for the Study of the Liver guidelines and the Japanese approaches to therapy, while drawing attention to certain controversies from other academic bodies where applicable and appropriate.

Keywords: Hepatocellular carcinoma; Practice guideline; Treatment; Treatment algorithm.

Fig. 1

Treatment algorithm for patients undergoing TACE, according to the recommendation of AISF. The flowchart is valid for any session of TACE. For conventional TACE (cTACE), MRI is preferable since lipiodol uptake causes beam hardening artifacts on CT that mask residual tumor tissue. The response to treatment is assessed by the modified Response Evaluation Criteria in Solid Tumor (mRECIST). Reproduced with permission from Bolondi N, et al. [4]

Fig. 2

JSH Evidence-based Treatment Algorithm. Modified with permission from Kokudo N, et al. [40]

Fig. 3

JSH-LCSGJ Consensus-based Treatment Algorithm for HCC as revised in 2014. Reproduced with permission from Kudo M, et al. [14]^aTreatment should be performed as if extrahepatic spread is negative, when extrahepatic spread is not regarded as a prognostic factor. ^bSorafenib is the first choice of treatment in this setting as a standard of care. ^cIntensive follow-up observation is recommended for hypovascular nodules by the Japanese Evidence-Based Clinical Practice Guidelines. However, local ablation therapy is frequently performed in the following cases: (1) when the nodule is diagnosed pathologically as early HCC, (2) when the nodules show decreased uptake on hepatocyte phase Gd-EOB-MRI, (3) when the nodules show decreased portal flow by CTAP or (4) decreased uptake is shown on the Kupffer phase of Sonazoid-enhanced US, since these nodules are known to frequently progress to typical hypervascular HCC. ^dEven for HCC nodules exceeding 3cm in diameter, combination therapy of TACE and ablation is frequently performed when resection is not indicated. ^eTranscatheter arterial chemoembolization (TACE) is the first choice of treatment in this setting. Hepatic arterial infusion chemotherapy (HAIC) using an implanted port is also recommended for TACE-refractory patients. The regimen for this treatment is usually low-dose FP (5FU+CDDP) or intraarterial 5FU infusion combined with systemic interferon therapy. Sorafenib is also a treatment of choice for TACE-refractory patients with Child-Pugh A liver function. ^fResection is sometimes performed even when more than 4 nodules are present. Furthermore, ablation is sometimes performed in combination with TACE. ^gMilan criteria: Tumor size <3cm and tumor number <3; or solitary tumor <5cm. Even when liver function is good (Child-Pugh A/B), transplantation is sometimes considered for frequently recurring HCC patients. ^hSorafenib and HAIC are recommended for HCC patients with Vp1,2 (minor portal vein invasion) or Vp3 (portal invasion at the 1st portal branch). Sorafenib is not recommended for HCC patients with Vp4 (portal invasion at the main portal branch), whereas HAIC is recommended for such patients with tumor thrombus in the main portal branch. ⁱResection and TACE is frequently performed when portal invasion is minimal, such as Vp1 (portal invasion at the 3rd or more peripheral portal branch) or Vp2 (portal invasion at the 2nd portal branch). ^jLocal ablation therapy or subsegmental TACE is performed even for Child-Pugh C patients when transplantation is not indicated and there is no hepatic encephalopathy, no uncontrollable ascites, and a low bilirubin level (<3.0mg/dl). Although it is a well-accepted treatment in the routine clinical setting, there is no evidence of a survival benefit in Child-Pugh C patients. A prospective study is necessary to clarify this issue. Even in Child-Pugh A/B patients, transplantation is sometimes performed for relatively young patients with frequently or early recurring HCC after curative treatments.