Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we're highlighting colorectal metastasis in liver transplantation. Joining me is Dr. Robert Cannon. He's the surgical Director of the Liver Transplant Program at UAB Medicine.

Dr. Cannon, thank you so much for joining us. So, we were talking a little off the air, and you and I had talked similarly about colorectal metastases recently, and we had talked about liver transplantation as well. Now, we're putting these things together. So, tell us a little bit about how this has evolved and what we're seeing now.

Robert Cannon, MD: Yeah, I mean, I think just a few years ago when we were talking about whether patients could be transplanted for this disease, the answer in most places around the country was no, just with the outcomes and recurrence being very high. But since that time, we've had some really great data coming out of clinical trials, particularly from Norway and over in Europe, showing that with proper patient selection, liver transplant really can be life-saving and life-prolonging for our patient population without any other good treatment options. It's really starting to take off worldwide and we're really happy and proud to be a part of it.

Melanie Cole, MS: That's really exciting. It's an exciting time in your field now. So, let's speak about patient selection for patients with colorectal cancer and liver metastases. Tell us a little bit about the criteria that determine eligibility for liver transplantation.

Robert Cannon, MD: Yeah, the main thing is going to be the fact that if the metastasis are limited only to the liver, then that's something that essentially is going to be replaced and taken care of by the liver transplant. So, the main selection criteria is the metastasis have to be liver only. So, someone who's already got pulmonary metastas or peritoneal carcinomatosis or anywhere outside the liver, unfortunately, liver transplant's still not going to be able to provide a benefit in that setting. So, there's criteria number one.

And then, number two really is just based off disease biology. And that comes from a prolonged period observing the patient. The selection criteria most trials and most centers are now using is patients need to be observed on chemotherapy for at least a year from the time of their diagnosis. And patients who have stable disease or a response to chemotherapy, those are the ones that we really think can do well post-transplant.

There's a few other sort of random selection criteria that have to do with molecular profiles of the tumor. So, for example, tumors that have a BRAF mutation, those do not do well after transplant. So, we typically don't offer transplant there. On the flip side, patients who have microsatellite unstable tumors, they actually do exceptionally well with immunotherapy. So, that's a case where transplant's actually just not needed because we have better options available or less invasive options.

Aside from that, the primary tumor needs to be resected. That's not a normal thing you would do in a patient on chemotherapy for unresectable liver metastasis, but that's part of the pathway. Once we've accepted someone for transplant and then they meet all the other criteria, we would have them referred to a colorectal surgeon to have the primary tumor removed in preparation for transplant.

Melanie Cole, MS: That's so interesting. So, let's speak a little bit about the treatment protocols. I'd like you to expand a bit when someone is on the transplant list now and you've determined their eligibility, speak about managing the colorectal cancer while they are on that waitlist and that transplant list and the criteria and things that they are doing to manage their disease.

Robert Cannon, MD: Yeah. So at that point, essentially, we want the patients to continue to get the same standard of care they've gotten without liver transplant being considered. So, we don't make any alterations to the chemotherapy. We work closely with the patient's treating oncologist. But the chemotherapy regimens don't change whether or not a patient's going to be on a transplant list.

 There might be some tighter followup. We'll do scans every three months to make sure we don't have any progression and that we don't have any development of extrahepatic disease. We may do a PET scan more frequently to make sure we're right about that if there's any areas of uncertainty. But other than that, when I talk to the treating oncologist, essentially, our advice is use whatever regimen you would be using in this patient if we weren't talking about transplant, because that's the best thing for them at this time. And most protocols allow for up to third-line chemotherapy in the event of a progression. And if the patient can be stabilized with alternate regimens, then transplant still becomes a possibility.

One of the particular questions that people will have is bevacizumab or Avastin's a common component of colon cancer chemotherapy. And in general, that's not an agent that we like to do elective operations on because of wound healing complications and the like. But unfortunately, you can't predict when a donor graft will become available. So, we've made a decision as a center that if an oncologist believes the patient would benefit from Avastin, we like the patient to stay on it. And we'll still do a transplant even in a patient on Avastin. And that's been sort of a point of some concern and controversy in different areas of management in this. But right now, for a deceased donor transplant, they would stay on their Avastin if that's what their oncologist thinks is best. Once we get living donor going for this, then we'd be able to schedule it and we might be able to have some time to adjust their chemotherapy ahead of time.

Melanie Cole, MS: So then, speak about outcomes a little bit, Dr. Cannon. What are you seeing if these patients are now eligible for liver transplantation because it's more localized and has stayed in the liver? What are you seeing for outcomes for these patients for their colorectal cancer?

Robert Cannon, MD: So in some of the best trial data, we have patients who make it through the selection criteria and get a transplant. Their five-year survival is 60 to 70%. So, very similar to patients transplanted for more standard malignancies like hepatocellular cancer or non-malignant indications. So, survival is really excellent in these patients. And the best way to Look at the survival and outcomes for any new treatment is to compare it to the other standard of care.

So right now, standard of care treatment, chemotherapy for patients with unresectable colon metastasis, five-year survival is only 10%. So, there is a tremendous patient survival benefit. Half or more patients will actually have a recurrence after transplant, but that first recurrence tends to be small, slow growing, and in the lungs, and is often amenable to resection. So even after the first recurrence, patients have an excellent survival benefit.

Melanie Cole, MS: And since you know that, that's probably something that you're keeping a close eye on yes?

Robert Cannon, MD: That's correct. So, we're having tight surveillance afterwards. We're doing scans every three months to catch any recurrences after transplant early. And again, all the data show us that these recurrences can be resected with excellent survival afterwards.

Melanie Cole, MS: Speak about the surgical procedure itself, Dr. Cannon. Anything exciting or new?

Robert Cannon, MD: So right now, the standard liver transplant procedure itself doesn't change at all if we have a whole graft for the patient. Couple exciting things that have been done elsewhere and that are coming down the pipeline, for living donor transplant, and actually more recently this has been described in deceased donor transplant as well, is there's a technique known as RAPID. And that allows us to use a very small partial graft, such as the left lateral segment. For a living donor, that's much safer because it's much less liver volume to remove. For a deceased donor, it allows the bulk of the liver to still go to another recipient who needs a whole liver while providing a small graft to a colon recipient. So, that's the graft that wouldn't initially be large enough if we were to remove the whole diseased liver from the patient upfront.

This RAPID technique allows us to remove half of the diseased liver, and then place a small left lateral segment liver graft. And then, over the next two weeks, that small graft will grow up to become large enough to sustain the patient, and then we can go back and remove their remaining liver. So, that is a really innovative and exciting technique that we hope to be launching here at UAB with the pending launch of our living donor liver transplant program. So, more to come there.

Melanie Cole, MS: Wow, this is really, really exciting. Dr. Cannon, what about multidisciplinary collaboration and interdisciplinary as these are now very complex patients and while they're waiting for liver transplantation? Speak about the importance of that.

Robert Cannon, MD: It's crucial. So, all cancer care, multidisciplinary expertise is just really paramount to achieving the best possible outcome. So within our liver tumor clinic, I think we've talked about this in the past, we have a multidisciplinary component where a medical oncologist or radiation oncologist, our interventional radiologist all join us. There's also a multidisciplinary colon cancer clinic that's similarly staffed by surgeons and by radiation and medical oncology. And this really provides multidisciplinary expertise. And that's one of the things that we're starting to discuss in all these meetings, is who's going to be an appropriate patient for transplant and make sure we get them on that pathway.

And this dovetails nicely and there's also a hepatic artery infusion pump program run through our Division of Surgical Oncology and Medical Oncology. And so, we share patients back and forth and we all put our expertise as a group. We really have just deep multidisciplinary expertise within the O'Neal Cancer Center and within the Transplant Institute here, and it's a real joy to work together with our colleagues.

Melanie Cole, MS: Emerging trends, Dr. Cannon, or research that could potentially improve the outcomes in this patient population. Is there anything you're looking forward to in the future?

Robert Cannon, MD: Yeah. What we're looking forward to again, is just trying to figure out these patient selection criteria are quite tight right now. We expect we should be able to open these up. Anecdotally, from the centers who really pioneered this, what they tell us is that almost all patients are really going to have a benefit from this. And then, the real limitation to overcome is scarcity. So, I think seeing living donor become more common in this disease process is going to allow us to treat even more patients.

Melanie Cole, MS: So, there aren't that many centers doing this now. Is this growing in popularity now?

Robert Cannon, MD: It is. We're seeing more and more centers start to take this up. So, we've launched our protocol within the last year. We actually just transplanted our first patient recently under this protocol. And we expect it to become a faster growing thing and seeing more and more centers offer this and seeing centers already doing it like ourselves start to expand it.

Melanie Cole, MS: What would you like to say as a final thought, Dr. Cannon? You're always such a great guest. To other providers that are listening and saying, "Wow, that's new and pretty cool," what would you like the key takeaways to be?

Robert Cannon, MD: I think the thing to take away now is that this is a disease that where there is some hope through transplant, previously dogmas and the established literature told us that metastatic disease was a contraindication for transplant and that is no longer the case. So if you have a patient with liver-only unresectable colorectal metastases, please consider referring them for transplant evaluation.

Melanie Cole, MS: Thank you so much, Dr. Cannon, for all of your expertise on this topic. And for more information, you can always visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.