Considerations in the HCC Transplant Setting

Richard Finn, MD: While a patient is waiting for transplant, they’ll generally be imaged on a regular basis. It’s not uncommon for patients to develop a recurrence while waiting for transplant and then have another local regional treatment.

At this time, there isn’t really any strong role for the use of systemic treatment while waiting for transplant. We know that sorafenib has been proven repeatedly to improve survival for advanced liver cancer, but for a patient in the pretransplant or early liver cancer setting, there has really been no strong role for the use of that drug.

So, now the patient makes it to transplant. At the time of transplant, we get their specimen sent to pathology and often they are seen postoperatively by oncology or hepatology to review their pathology. At this time, we have to make an assessment of what the patient’s risk is for recurrence after transplant. While, pre-transplant, that assessment is made on radiographs, CT, MRI, or imaging, after transplant, that assessment is made on a histologic diagnosis. So, we look at the number of nodules at the time of transplant; we look at whether or not there’s necrosis from the prior procedure; and, very importantly, we look for evidence of lymphovascular invasion. Is there microscopic invasion into blood vessels and the liver, or even macroscopic invasion into larger vessels that might not have been seen on imaging pretransplant?

Those things will help us assess our risk for recurrence. I think we know that, for patients who are within the monthlong criteria both on imaging preoperatively and pathologically, their cure rate posttransplant is very high—80% or higher. These patients can do very well and be cured of their liver cancer.

And then, as we go beyond Milan criteria or add in a differentiated-fact histology or vascular invasion, that drops. So, the question has always been around—can we salvage these patients? Can we do something to help improve their outcomes posttransplant? At this time, the answer is no. There have never been any data to suggest that the use of systemic treatment such as sorafenib—or before sorafenib, chemotherapy—prevents recurrence after transplant.

There are data from phase I studies that we participated in that show sorafenib can be given safely after transplant, though it seems, usually, the maximum dose they tolerate is 200 mg/twice a day versus the full dose used in advanced disease at 400 mg/twice a day. This likely reflects their being on many other medications and their recovering after a very large surgery.

There is an ongoing adjuvant, multinational study being conducted. It is being headed up, by Ron Busuttil here at UCLA, across many large transplant centers in the United States, asking the question for patients who have high risk for recurrence after transplant: does adjuvant sorafenib improve their outcome? That study is ongoing, so we don’t have any data to comment on, but I think that, outside of a clinical study, management after transplant is pretty much observation.

Transcript edited for clarity.

December 2014

• A 64-year old male positive with HCV presents to his PCP with nausea, vomiting, syncope
• ECOG=1
• Child-Pugh B
• T bilirubin 2.1; albumin 3.2; INR 1.1; no ascites, no encephalopathy; platelets 78
• CT scan revealed one 4-cm lesion in the liver
• No extrahepatic disease; no portal vein invasion
• Laboratory results: AFP=400 ng/ml
• Patient is within Milan criteria
• Bridge using TACE until liver transplantation