Between 50% to 70% of patients with hepatocellular carcinoma (HCC) are diagnosed at a stage when radical treatment (percutaneous ablation, partial hepatectomy, liver transplantation) are no longer an option (1). Limitations due to size, number and location of tumours, as well as quantity and quality of liver remnant, prohibit partial hepatectomy. Percutaneous radiofrequency ablation can produce good long-term survival in patients with a solitary or a few small HCC nodules (2). Liver transplantation removes not only the tumour, but replaces the underlying cirrhotic liver with a normal liver. It is not surprising that liver transplantation offers the best overall and tumour-free survival in selected patients (1,2).
The Milan criteria [one HCC nodule ≤5 cm, or ≤3 nodules ≤3 cm, and with no macrovascular invasion (MVI)] remain the benchmark for selection of HCC patients for liver transplantation, despite a number of proposed extensions to the Milan criteria to capture patients with an increase number or size of HCC nodules who may achieve similar post-transplant survival outcomes (3). A recent meta-analysis showed that patients with chronic hepatitis and cirrhosis and HCC within the Milan criteria achieved post-transplant survival rates similar to those with non-HCC indications (4).
Improvements in locoregional and systemic treatments have been reported to downstage an advanced staged HCC into an earlier stage, thus making an unresectable HCC to become resectable, and an untransplantable HCC beyond the Milan criteria to become transplantable (within the Milan criteria). The main reasons why after downstaging HCC patients become resectable or transplantable are: shrinkage of tumours, disappearance of secondary tumours, disappearance of tumour venous thrombi and/or hypertrophy of non-tumorous liver. It is important to differentiate between tumour downstaging and neoadjuvant therapy. For tumour downstaging, the tumour is unresectable or untransplantable to start off with, and the downstaging treatment makes the tumour resectable and transplantable. For neoadjuvant therapy, the HCC is resectable or transplantable and the therapy aims to improve long-term survival outcomes after surgical treatment. Similarly, it is important to differentiate between tumour downstaging to liver transplantation and bridging therapy in liver transplantation. Bridging therapy in liver transplantation aims to control progression of the tumour while the patient is put on a waiting list for liver transplantation so that the waiting time for liver transplantation can be prolonged while the long-term survival of liver transplantation will not be affected.
Yttrium-90 microspheres were first reported by Lau et al. to be able to downstage unresectable HCC to become resectable in the year 2004 (5). Subsequently a lot of reports came out, not only supporting that yttrium-90 microspheres can downstage unresectable HCC to become resectable, but also untransplantable HCC to become transplantable (1,2,4,6,7). In actual fact, when HCC is downstaged, the chance of salvage liver transplantation is higher than salvage liver resection as liver transplantation does not depend on the preoperative liver functional status of the patient and the position of the tumour to determine operability. Even when the liver function is decompensating, as long as the HCC has been downstaged to be within the Milan criteria, liver transplantation can still be carried out. The long term survival of these patients after HCC downstaging to be within the Milan criteria has been reported to be similar to those who had initial tumours within the Milan criteria who underwent liver transplantation (1-4,6,7).
Patients with HCC with portal vein tumour thrombosis (PVTT) are in BCLC-stage C. The BCLC recommendation is sorafenib and the median survival of these patients is 11 months (2,6,7). Yttrium-90 microspheres have been recommended in guidelines and in expert consensus statements to be used in HCC with PVTT as numerous reports have shown their effectiveness in these patients (2,7,8). The article written by Levi Sandri et al. entitled “hepatocellular carcinoma with macrovascular invasion treated with yttrium-90 radioembolization prior to transplantation” which is published in this issue of the Journal (9) is interesting. The authors treated four patients with HCC with PVTT with Yttrium-90 microspheres. In 3 patients, the PVTT staging was Vp1 (third order branch of main portal vein) and in 1 patient it was Vp3 (first order branch of main portal vein). The PVTT staging which they used was based on the staging system of the Liver Cancer Study Group of Japan (10). After treatment with yttrium-90 microspheres, complete thrombus regression was observed in these four patients, enough for these patients to be included in the waiting list for liver transplantation as they were all within the Milan criteria. After liver transplantation a disease-free survival of 39.1 months (range, 1–76 months) was obtained. This article is interesting because although occasional patients with HCC with PVTT had been reported to be downstaged with yttrium-90 microspheres from untransplantable to become transplantable, this report is on a series of four patients who were so treated with good results in long-term overall and disease-free survival.
Conflicts of Interest: The author has no conflicts of interest to declare.
- Iñarrairaegui M, Pardo F, Bilbao JI, et al. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. Eur J Surg Oncol 2012;38:594-601. [Crossref] [PubMed]
- Park HC, Yu JI, Cheng JC, et al. Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials. Liver Cancer 2016;5:162-74. [Crossref] [PubMed]
- Ettorre GM, Levi Sandri GB, Santoro R, et al. Bridging and downstaging to transplantation in hepatocellular carcinoma. Future Oncol 2014;10:61-3. [Crossref] [PubMed]
- Clavien PA, Lesurtel M, Bossuyt PM, et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012;13:e11-22. [Crossref] [PubMed]
- Lau WY, Ho SK, Yu SC, et al. Salvage surgery following downstaging of unresectable hepatocellular carcinoma. Ann Surg 2004;240:299-305. [Crossref] [PubMed]
- Lau WY, Lai EC, Leung TW. Current role of selective internal irradiation with yttrium-90 microspheres in the management of hepatocellular carcinoma: a systematic review. Int J Radiat Oncol Biol Phys 2011;81:460-7. [Crossref] [PubMed]
- Lau WY, Teoh YL, Win KM, et al. Current role of selective internal radiation with yttrium-90 in liver tumors. Future Oncol 2016;12:1193-204. [Crossref] [PubMed]
- Cheng S, Chen M, Cai J, et al. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus: 2016 edition. Oncotarget. 2017;8:8867-76. [PubMed]
- Levi Sandri GB, Ettorre GM, Colasanti M, et al. Hepatocellular carcinoma with macrovascular invasion treated with yttrium-90 radioembolization prior to transplantation. HepatoBiliary Surg Nutr 2017;6:44-8.
- Kokudo T, Hasegawa K, Matsuyama Y, et al. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol 2016;65:938-43. [Crossref] [PubMed]