Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Case discussion: A 69-year-old man with a history of hepatitis C infection presents with a single 6-cm lesion and is diagnosed with HCC
10:23 minutes.
TRANSCRIPTION:
DR LLOVET: When we visit these types of patients, we are trying to figure out 3 concepts. The first one is the tumor stage. That, in this case, was clear: It was a single tumor without dissemination. The second concept that we look for is the status of liver dysfunction, and in this case the patient had normal bilirubin, which is very important — no portal hypertension. And according to the score of liver dysfunction called Child-Pugh, it was a Child-Pugh A class. That is the best class. This indicates that despite that the patient has cirrhosis, he has a well-preserved liver function, and this is critical to define if the patient may be a candidate for resection. And the third concept that we keep in mind when gathering information for the decision-making is the performance status. We use the ECOG performance status. In this case, zero. So we have a patient with a single tumor, well-preserved liver function, no symptoms. According to the guidelines, the American guidelines and the European guidelines that we’re applying, this patient is a candidate at this point for resection, generally a segmental resection that is more oncogenic than what is called wedge resection. The segmental resection is capturing all the segments. The liver has 8 segments, so one of the segments where the tumor is sitting is completely removed. And here, you can see in the slide, in red, the pathology report means R0, means that you are able to remove all the tumor and the margins were free of disease. No satellites, which is a very important factor, particularly in terms of prognosis, because the satellites in the pathological report indicate that the patient has a very high risk of recurrence; whereas here, in this case, there are no satellites. But there was microvascular invasion. That is the other predictor of recurrence. DR LOVE: Could you go back and could you talk a little bit about how you decide between using a segmental resection, as this patient had, versus liver transplant? DR LLOVET: Yes. Well, all these decisions are taken in the setting of a multidisciplinary team — we have surgeons, hepatobiliary surgeons and transplant surgeon. We have radiologists, interventional radiologists. We have pathologists. We have oncologists and we have hepatologists. In this case the decision was easy for 2 reasons. The most important reason is that we consider patients for transplantation in case of tumors less than 5 centimeters: Single, less than 5. In this case the patient was beyond what are called the Milan criteria. That has also, in the US, been adopted by UNOS in order to indicate transplant. In this case, transplant was precluded for this patient according to the conventional criteria that are adopted by all liver units. And therefore, with a single tumor and well-preserved liver function, he was an ideal candidate for resection. DR LOVE: What’s the rationale and the thinking behind the fact that the tumor has to be 5 centimeters or less to go for transplant? DR LLOVET: This comes from a seminal study published in New England in 1996 by Vincenzo Mazzaferro, establishing outstanding outcome, meaning 5-year survival rate of 70% for a tumor like this, in patients with single tumor less than 5 centimeters in diameter or 3 tumors — up to 3 tumors — less than 3 centimeters in diameter. These are the so-called Milan criteria that were established. And recently there was a meta-analysis with thousands of patients, applying these criteria, because these criteria have been adopted both by the European and the American guidelines. And following these criteria, the outcome is very good, certainly. The 5-year survival is around 70%. Ten-year survival at this point is around 50%. That, for a cancer of this caliber, is an outstanding outcome. So by using these criteria for transplantation, you have the best outcome. The problem is when you are exceeding these criteria — for instance, tumors beyond 5 centimeters in diameter. The likelihood of recurrence is very high and the outcome in terms of survival decreases from 70% to below 50%, which, according to what is in guidelines and academic centers, is suboptimal for liver transplantation. The outcome for patients undergoing liver transplantation with tumors beyond 5 centimeters is controversial at this point and certainly has not been adopted by guidelines. There are some instances in which, for instance, applying a different type of transplant that is called the living donor liver transplantation — we are not using the donor from the pool, but you are using a donor provided by the patient among the relatives or friends or so on. Then, in these circumstances in some centers, including Sinai and also including the BCLC in Barcelona, we are applying extended criteria. And we are accepting patients with tumors up to 7 centimeters. But in this case, the general treatment for these patients almost everywhere is resection. DR LOVE: That’s really fascinating, the liver donor concept. How much of the liver do they take out of the donor? DR LLOVET: If you are using the right hepatic lobe — that is what is used generally in the West — you are removing 60% of the volume of the liver, 6-0. And you have to leave at least 35% of the volume of the liver for the donor to survive. It’s fascinating, the fact that during the first month the liver regrows completely. So if you are performing an MRI every week, at 1 month you have recovered completely the volume of the liver as it was before the resection, which is outstanding, the capacity of regeneration of the liver. In terms of function, the liver already works well between 5 and 7 days after the transplant. So after we are removing 60% of the volume, with the other 35%-40% of the volume — of course these patients need to be admitted to the hospital for 5, 6, 7 days. But at one time point they have normal liver function, and then you can discharge the patient. DR LOVE: So when you look at this man — or when you looked at him originally, after surgery, what was his estimated chance of recurrence? And roughly what is the range of recurrence rates that you see after segmental resection? DR LLOVET: The most important predictors of recurrence are spelled out in this slide, microvascular invasion and satellites. This patient has microvascular invasion but does not have satellites. So with microvascular invasion in place it means that the risk of recurrence is around 50% at 5 years, which is very high. If, on top of that, you have satellites, you can reach a risk of 70% at 5 years. So we at this point, of course, engaged the patient in further controls. At the beginning, every 3 months the first year and every 6 months thereafter in order to check if there was any recurrence in place. Unfortunately at this point we don’t have any effective adjuvant therapy for these patients. We have been participating and leading some of the international trials testing new drugs, for instance, sorafenib or other drugs, multikinase inhibitors, to prevent recurrence. But unfortunately these trials have been negative. There are at least 16 randomized controlled trials. So we don’t have any armamentarium at this point to prevent recurrence in this sort of patients. So we watch them, and upon recurrence we decide the next therapy — in 2014, this patient effectively presented with recurrence with a maximum of 4 centimeters in 1 of the 3 nodules. And this type of stage precludes transplant or radiofrequency ablation. So since the patient still had very well-preserved liver function, Child-Pugh A, was asymptomatic, ECOG 0, and it was a liver-only disease without extrahepatic spread, and AFP was high but not indicating extrahepatic dissemination, we considered the patient for chemoembolization. |