Treatment Options for Early-Stage Biliary Tract Cancers

Transcript:

Milind Javle, MD: Flavio, you raise important issues. I also wonder about the role of surgery in some of these patients who have MSI [microsatellite instability]–high, but we should move on. As I expected, this panel has a lot to say because you know so much, but we’re running a little behind. I’m going to go to the next topic, which is the principles of management. I’m going to discuss this a little because this is an early stage. I’m going to get your opinion, Anjana and Flavio, because these are the kinds of patients you might end up seeing. For early stage biliary tract cancer, what are some of those surgical considerations? If you see a large mass, Flavio, would you automatically say this is resectable or unresectable, or is there a rule for multimodality therapy today?

Flavio G. Rocha, MD, FACS, FSSO: You’re hitting on what we struggle with in our clinic all the time. The standard of care for localized disease is still surgery, and that’s what all of us want as the goal to get patients to try to get the best long-term outcome. We must focus on a couple of different biological parameters, though. Typically, it’s rare that we’ll see a small peripheral liver lesion that’s clearly resectable, perhaps even minimally invasive. More often than not, we’re seeing a large tumor or a tumor with, let’s say, satellite lesions. The multifocality of intrahepatic cholangiocarcinoma can sometimes be challenging because we don’t know if this is truly a T2 disease or intrahepatic metastases or M1 disease. This is something where we’re trying to refine our management strategy.

The other piece that makes it complicated is the lymph nodes. Often we’ll see patients that perhaps have some liver disease and may have some enlarged lymph nodes perhaps due to their cirrhosis, but are they also perhaps involved with cancer? We know that lymph node–positive disease is obviously going to do a little worse, and maybe those patients should get some up-front therapy, whether that’s systemic therapy or locoregional therapy. Hilar cholangiocarcinomas are probably the more difficult ones because typically, as Ruth suggested, they present with locally advanced diseases that render them either irresectable. Then we have to think about other strategies. As we’ve refined the systemic therapy and the targeted therapy, my hope is to get these in the preoperative setting, particularly for that patient population. I’m curious to hear what Anjana has to say.

Anjana Pillai, MD: Thank you. I agree. I talked to Milind quite a bit through our oncologist and other specialists throughout the United States, when we see some of these patients, [regarding] the approach because it’s so varied. In our practice and maybe it leans to because we do offer transplants, we get maybe some more locally advanced disease. As you said, we always try to see if we can resect these patients. Unless it’s PSC [primary sclerosing cholangitis] or hilar cholangiocarcinoma, transplant is clearly a pure outcome. We try to see if there’s resectability that can be achieved. For patients who have these nodes that you’re mentioning or more infiltrative-type tumor, we do an up-front which is our protocol of chemotherapy. Then we do radioembolization with Y90 [yttrium-90] or TARE [transarterial radioembolization] because in our practice—this may be a Chicago-based thing—in certain centers, [depending on] where you train, you see that nice contralateral hypertrophy that you’d see with portal vein embolization but with the additional tumor adverse effect that TARE offers. That gives us some idea of the biology of these tumors because you have to wait about 3 months to see that ultimate hypertrophy. That’s usually our practice and there are data. UCLA published their data a year or so ago in the Journal of Liver Transplantation. They had very varied tumor types. It was all lumped together in various locoregional therapies. The idea is that multimodal therapy has better, longer outcomes. There’s a role for it in the right patient. I guess that’s what you’re asking: who is the right patient? You do it for everyone. Are there specific criteria? We don’t have enough to know, other than center experiences and talking among ourselves.

Milind Javle, MD: Thank you, Anjana and Flavio. There’s a lot to unpack there. You discussed surgically resectable disease, preoperative chemotherapy, and preoperative TARE in an attempt to hypertrophy the contralateral lobe. Clearly, there’s a role for multimodality therapy in the management of even surgically resectable diseases. Anjana, you touched on an interesting point. When you have a locally advanced disease that is perhaps not resectable, there’s a struggle in terms of the best approach. Do you use radioembolization? Do you use radiation therapy? Do you use hepatic arterial infusion therapy? Chemoembolization in some cases? How do you decide on the choice of liver-directed therapy, or is it mostly center dependent? How do you make that decision? Let’s start with you Anjana and then go to Flavio.

Anjana Pillai, MD: That’s a great question. I often stress that you have to do what your center is really good at. That’s how you get optimal outcomes because we don’t have a true standard of care of which locoregional therapy is ideal. We have data on TACE [transarterial chemoembolization], we have data on TARE, we have data on SBRT [stereotactic body radiation therapy]. I’ve been in conferences where there are debates based on where you practice what’s better. You can always show your data and say, “We do this really well. Everyone should get this.” Or “We do this really well. Everyone should get this.” I don’t necessarily agree with that 1 size for everybody. You have to do what’s best at your center that will give the best outcome.

We don’t personally do a lot of HAI [hepatic artery infusion] because it makes transplant a little difficult, and our surgeons don’t love it. We also see the downstream effects of the biliary issues with it. This could be biased because we see these advanced patients in the sense of liberty compensation after they’ve had HAI for a while, so we don’t do that often. But we’ve used other modalities that you’re describing, including TACE and SBRT, but we tend to move toward TARE. I really think it’s center and expertise dependent.

Flavio G. Rocha, MD, FACS, FSSO: This is where the key is the multidisciplinary discussion. Have all the stakeholders at the table. We also offer the whole gambit from locoregional therapies to transplants. We have a very active hepatic artery infusion program. We have an institutional trial, and we’re participating in other trials because there’s a reasonable rationale for this. Sometimes we have these discussions because we don’t want to burn bridges. For example, if patients have previous TARE, they aren’t candidates for HAI. However, the reverse is possible. A transplant is still possible after HAI. I sometimes hear my transplant colleagues saying that it might be more difficult, but it’s not mutually exclusive. What’s interesting is that the data on HAI have evolved to say that patients with lymph node–positive disease may benefit from HAI prior to surgery. That’s evolving. We haven’t considered the role of adjuvant HAI after resection because the majority of recurrences for intrahepatic cholangiocarcinoma are going to be in the liver. It takes a village to discuss and make all the options available to patients with an eye on treatment sequencing and making sure bridges aren’t burned.

Anjana Pillai, MD: That’s a great way to explain it as far as bridges not being burned. I agree. I’m not saying I don’t like HAI. I’m saying our center experience. You are absolutely right: we do transplants after HAI. I’m not a surgeon. I can tell you only that our surgeons don’t love that field.

Transcript edited for clarity.