Maximizing Liver Transplant Candidacy in Hepatocellular Carcinoma

[Dr. Sabeen Dhand]
How much variability is there as far as transplant criteria? Is it very strict? Milan and UNOS, what are we talking about? Because sometimes I don't know whether I could send this patient for a transplant or not. Is it variable?

[Dr. John Seal]
It's not variable in the sense that all of deceased donor organ transplantation is governed by UNOS, which is a national organization. They regulate how donors are approached, how organs are shared between centers, and it's based on how high the MELD score is. It was discovered pretty early on in this process that there's lots of people who have cancer who have a real risk of death with cancer, and it's not reflected in how sick their liver is, so with the MELD score. That's where the exception point process came into play.

People who get listed for transplant have an HCC that's within the Milan criteria. Then they can, after a six-month waiting period, get exception points, and they fall into that median MELD score for a region. It gets really complicated, but basically, that's what it means, minus three. A little bit below the average of where that is. As we're suggesting, depending on where that is in the country, that turnover at the top can be so fast that if you're sitting below the average, then you're not ever going to get there. So that's one factor.

The other is you can take slightly larger tumors and you can shrink them and then get the exception points. All that process is going to be dependent upon waiting for those exception points to kick in. That largely dictates how long you wait, with the exception of all that I said there is about deceased donors. The caveat is really living donors, and we can touch on that how that changes your decision.

[Dr. Sabeen Dhand]
Let's touch on that because in the Los Angeles area, there's not many options for living donors, but that seems to be different in your area.

[Dr. John Seal]
That's the strategy that our center is leaning into now. With a living donor, we take if the patient has a potential donor that's healthy and there's a pretty strict criteria, you have to be pretty healthy to put someone through this operation. Donor safety is always number one priority and we're very careful about doing this. If you have a donor, then we remove the right lobe of that liver and then we take that piece and we transplant that.

It's an operation that you have complete control of if you have a living donor because when that's going to happen, you know all the medical care can be optimized, all the treatment can be optimized. We're not doing this today, but really important for cholangiocarcinoma because they get blasted with radiation and if they sit on this for three years, then that's game over. You can't do that. You basically don't have to play by the rules if you have a living donor and you can get people transplanted really quickly.

That way, not everyone has it, not everyone does it, but it's an important option.

[Dr. Sabeen Dhand]
How about around here in San Diego?

[Dr. Gabe Schnickel]
We do living donor as well down in San Diego and I think that's a great option as John mentioned. But we've also leaned into the use of machine perfusion and normal thoracic regional perfusion to access livers that previously were not being used for transplant. With that, we've been able to make more organs available for our patients on our list and transplanted at a much lower MELD. So those patients that have HCC get a nice set of exception points on our list and we're able to actually transplant them pretty quickly.

We really leaned into that and that's really definitely shifted, at least from my perspective, leaning again on those marginal cases, our waiting time after they get their points. So six months after listing, it's less than three months until they get transplanted. That allows us to lean into transplant for marginal cases where if your wait time is three years and I think the literature bears this out, you're certainly at risk of tumor progression and falling off the list despite Sid's best efforts.

We're really reliant on the IOs, the interventionalists, to maintain those patients on the list and to keep them from progressing and falling off the list because their tumor gets outside of the Milan criteria that John mentioned.

[Dr. Sabeen Dhand]
Sid, do you find any trouble with–

[Dr. Sid Padia]
As you said, it's hard because when I see a patient, I make the assumption, whether it's right or wrong, this guy's never getting a transplant. I play to that. If he gets a transplant, great, I didn't lose anything, but I make the assumption that he's never going to get one. What I do is I play for like, okay, what do I need to do in terms of a local regional therapy standpoint, whether it's do nothing, do an ablation, do a TACE, do a Y-90, send them for an SBRT, et cetera, to get you the most number of years possible with the assumption that somehow you're not going to get a transplant, even if you are eligible.

You may not get an organ. You may start drinking again. You may lose your insurance. You may have family issues. You may move out of state, etc. We've had all those patients we thought they were transplant candidates and it didn't happen for them. It becomes tough, not necessarily on day one, but to plan the next treatment for when they get inevitably the next tumor. That's what we try to do now is play that long game. This is where I think concepts like radiation segmentectomy came about.

This is where we're very aggressive on our thermal ablations. This is why chemoembolization has largely fallen out of favor, I think, not only at our place, but I would argue at most transplant centers because chemoembolization works great within the first six months. Then when we look at the recurrence rates at 12, 24, and 36 months, there is a very real recurrence rate. It's fine if you're going to get a transplant in six months, in a way. It's not fine if I'm playing the long game of 36 months or 48 months and finding these recurrences and then I have to come up with a plan B.

[Dr. Sabeen Dhand]
On the other side of the situation, and what comes up in my clinic a lot, is a patient who doesn't want surgery. That's an option and they're like, "oh no, doctor's too much, it's too big of a surgery. I'd want the minimally invasive option." How do you approach those patients, Gabe?

[Dr. Gabe Schnickel]
That's a great question. I think it's really incumbent on the surgeons, and I'd be interested to see John's opinion on this, really to put all the options on the table. I think it's really those options have shifted over time to the point where, when it comes to, okay, you can have a resection that's going to be for me and an open surgery, or you can go to interventional radiology and they're going to give you a TARE or radiation segmentectomy that's going to be really a durable option for them that's really probably not that different than what I'm going to accomplish.

In that patient population that doesn't want a big surgery or, for whatever reason or perhaps their functional status isn't great, it's really a legitimate-- It's hard for me to say that surgery is the right answer for them, whereas it used to be, I feel like pretty clear cut that that was the gold standard.

[Dr. Sid Padia]
At the same time, Sabeen, as an interventional radiologist, if I have a patient who goes, "I don't want surgery." Actually, what more happens, "I don't want chemo." That's 99% of people.

[Dr. John Seal]
Lucky for you. You got the one cancer.

[Dr. Sid Padia]
Exactly. Let's say they say, "There's no way I'm getting cut open," etc. My best-- what I'd like to do is I'd be like, "I'm going to have you meet with our guys. Meet with my hepatobiliary surgeons, let them talk to you about it. If you still don't want it, fine, it's still your choice because they can describe it way better than I can. They can also weigh the risks and benefits way better for a surgical resection or a transplant, a hundred times better than I can." Especially when our surgeons, just like you guys individualize it for each person that we look at based on your specific risk factors, you're a disaster and you don't want surgery.

Or the exact opposite. "They can do that. I'm not very good at that when it comes to surgery." I tell patients, just have a conversation with them. You're not buying into anything. You just have to have a conversation with our surgeons and then you can make the-- at the end of the day, it's still your decision."

[Dr. Sabeen Dhand]
John, you mentioned a robotic approach to surgery. Now, does that increase the amount of patient selection that you have and more patients are–

[Dr. John Seal]
It hasn't really increased the number. Really has to do with that sort of algorithm I described loosely before, which is if you've got-- I do left-sided liver resections robotically. I'm not quite a Gen Z, so all the kids coming out of residency, they need to robot everything, and I have to teach them how to make an incision. That's how that goes. I feel comfortable doing all the left side. Anything that shows up on the left side, I think it's safe to do that robotically. In some people's hands, even trisegmentectomies and big operations are really safe.

Again, I think one of the themes we're picking up on is every part of the country, every set of providers has a little niche of how they've adapted to their local environment and how they're trying to take care of their patients. If you have a jet and infinite amount of money, then I know where to send you. The person's going to do the most aggressive robotic surgery out there. If you want to stay at home, then it's like, oh, this is what I'm comfortable doing. The reality is, I don't know if it's true for you, but we used to do God-awful incisions for surgeries.

I do all liver resections through a little midline.

[Dr. Sid Padia]
With a chevron, yes.

[Dr. John Seal]
We still do. Anyway, that's a sore subject. Our practice is still that for the transplant, but for a liver resection, it's a midline incision and the recovery is really quick and it isn't as morbid as patients often think. The indications for it are shifting and for a patient who has something that we can do robotically, the recovery is really really fast. It's a great tool to have for the right patient.

[Dr. Sid Padia]
Yeah, can I run one question by you guys? There's a couple of trials now and there's medical oncology pushing the limits in terms of bridging or downstaging to OLT with immune checkpoint inhibitors. What are your thoughts on that?

[Dr. Gabe Schnickel]
That's I feel like part of the next frontier, which is really interesting. I think we were one of the earlier centers to report some really negative outcomes in patients transplanted after immunotherapy. You have to really tread lightly. I do think it's an important tool that can be used effectively to downstage folks. It shouldn't be used for maintenance, I think, but downstaging potentially. You have to be very thoughtful about how you transplant them afterwards because you're completely changing their immune system.

That change lasts for longer than you think. The outcomes or the potential for catastrophic outcomes after transplant are significant. Yeah, you just have to be thoughtful about it. I'm interested to hear what John's practice is and what you think about that.

[Dr. John Seal]
Yes, we're very case-by-case. We always like to learn from other people who've tried things. I appreciate those reports.

[Dr. John Seal]
This is such an annoying phrase, but it is true. Biology is king or queen, however, you want to phrase it. What that really is going to do is it's going to shrink it. The pictures look better, but have we really changed the biology of the tumor? For us, that really critical period is that first three months off of it and just to see what the tumor is doing. If we see active tumor biology in a short window off of that immunotherapy, then I don't know that those are great candidates.

Because I do think you need that big buffer to get the immune system, the washout period. We've learned that, too. We are not using it a ton. I think we probably have, three or four cases a year that we're doing it. They don't all make it. There's also the denominator that doesn't always get reported, which is the people don’t get downstaged.

[Dr. John Seal]
No one writes those papers. It's a tool. It's evolving. It's exciting to have something else because we have had nothing. It's just like, cut it out as quick as you can. Burn it, fry it, and cut it out. It's like, oh, let's be a little less caveman about it.