Advancing Organ Preservation in Rectal Cancer

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepherd, a medical oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics Program and co-directing the Cleveland Clinic Sarcoma Program.

Today I'm very happy to be joined by doctors Emre Gorgun, Vice Chair of the Department of Colorectal Surgery, and Joshua Sommovilla, a colorectal surgeon, assistant professor of surgery, and Director of the Colon Cancer Tumor Board here at Cleveland Clinic. They're here today to discuss organ preservation in rectal cancer treatment and surgery. Welcome, gentlemen.

Emre Gorgun, MD, MBA: Thanks, Dr. Shepherd. Thanks for having us.

Dale Shepard, MD, PhD: Dr. Gorgun, you've been here in the past, and so remind us a little bit about what you do here at the Cleveland Clinic.

Emre Gorgun, MD, MBA: Sure. Thank you, Dale. Thanks again having us. It's always a pleasure to be here and being able to reach out to our patients. Josh and myself, we are part of the cancer section within our department, Department of Colorectal Surgery. Obviously within colorectal surgery, we treat a lot of diseases related to the colon and rectum, which is the lower portion of our intestinal tract. That includes inflammatory bowel disease, motility disorders, Crohn's, colitis, as well as, of course, cancer and polyps. I think the reason that we were kindly invited today is to discuss more about cancer of the colon and rectum, and specifically diseases of rectum in terms of the cancer and how we can help our patients to preserve their organs, meaning the rectum, as well as their intestinal continuity.

Dale Shepard, MD, PhD: Yep, absolutely. Just as, again, a little backdrop, Josh, what do you do here at the Cleveland Clinic? You're a surgeon and what do you do here?

Joshua Sommovilla, MD: Yeah, like Dr. Gorgun mentioned, a lot of colorectal surgeons, we see both patients for cancers and patients for non-cancerous conditions. I see a lot of patients with colorectal cancer, in particular patients with young onset colorectal cancer and patients who have high-risk syndromes that put them at risk for getting colorectal cancer. Those are the few things that within the full breadth of colorectal surgery I see a little bit more of. And like Dr. Gorgon, I also do some advanced endoscopic procedures, where we remove large precancerous polyps or even early cancers with colonoscopy.

Dale Shepard, MD, PhD: Okay. Well, we'll kind of touch on a little bit about that later on. We're talking about rectal cancer, as you mentioned, Emre, we're going to talk about rectal cancers, organ preservation. You kind of alluded to it, but give us an idea what does that mean? What does organ preservation in these surgeries really mean?

Emre Gorgun, MD, MBA: Yeah, absolutely. I think this is a very new technique and emerging approach in the treatment of rectal cancer that we started to apply extensively in the last 5 to 10 years. How we treat rectal cancer has really dramatically changed in the last 10 years, and what we mean by that is we really used to operate on almost all of the rectal cancers and remove the rectum and either reconnecting them, if possible, or in some cases giving our patients a permanent ostomy because we did not have any better approaches to treat them.

However, starting in maybe early 2000s, we started to treat some of the rectal cancer patients with upfront radiation therapy and then operated on them after radiation therapy and then gave them chemotherapy afterwards. But what we find out doing this type of, what we call, sandwich approach, that after chemo radiation, we had even in some patients, complete responses. So what that means is even when we did take their rectums out, we did not find any leftover cancer. So that prompted us to reconsider different approaches and that brought us to give chemotherapy before we operated on these patients, so after the radiation therapy, we also added more chemo for four months and really squeezed everything upfront before the surgery. That helped our patients and us to see more complete responders, meaning after this chemo radiation plus chemotherapy, nowadays, we do see, even up to 40% of the time, that the tumor, the rectal cancer completely disappears. So that's really a huge dramatic change from what we used to see in the past, and of course, by that we mean organ preservation.

Dr. Sommovilla mentioned about the endoscopic sub-mucosal dissection, but sometimes even after chemo radiation, we end up seeing small leftover residual lesions in the intestinal lining or after a while it may be a small regrowth. And even in those circumstances, we push the needle a little bit further and try to remove these small areas with an endoscopic sub-mucosal dissection kind of in a local excision fashion and then sample that tissue. If that specimen does not demonstrate any cancerous structures, then we continue to do the organ preservation. The whole idea and goal to increase our complete response rates even beyond 40%. And if we can reach, one day, 100%, that would be amazing.

Dale Shepard, MD, PhD: That's good. Now, you mentioned that this has been sort of going on for a little while. Josh, when we think about kind of the field, sometimes change takes a while. Are most places or most surgeons academic community, are most people doing more upfront treatment to do organ preservation or is that still kind of at certain centers?

Joshua Sommovilla, MD: I think the trend nationally has certainly moved towards more places doing more of the treatments upfront and giving the radiation treatment and the chemotherapy treatment before surgery. I think organ preservation is lagging behind probably a little bit in that there are a lot of places I think that are doing all the treatments before surgery, which is called neoadjuvant therapy or total neoadjuvant therapy, but still operating on pretty much everybody regardless of what their response is or having a very, very low threshold to operate on anybody who shows any sign of there being residual disease and not looking for every possible opportunity to provide a organ-preserving approach. I think, historically the needle has been moving towards more places attempting organ preservation, but still probably only being done in an aggressive way at academic or tertiary referral centers.

Dale Shepard, MD, PhD: And so, Emre, what do you think drives that way? Obviously if you were to ask patients, you would assume that they would say, "I want to keep my sphincter. I want to keep as much rectum as possible. I don't want to have an ostomy all the rest of my life." What do you think drives that sort of slow change?

Emre Gorgun, MD, MBA: I think you mentioned that, certainly, patient demand and patient awareness is one of the reasons. Certainly that's a strong factor. Second one is, when you first started to do the organ preservation and watch and wait, really, as Josh mentioned, not every center was doing it, but more recently, more and more centers, we see that happening. So I think awareness, like the knowledge being distributed at our conferences and so forth, and now even smaller centers, community centers, they became familiar with this approach and that is being offered, I wouldn't say 100% in the United States, but more commonly for sure.

But interesting point that is, I had several patients coming to see me in my office today. With neoadjuvant-treated patients, they come to see us or they are referred because sometimes they see different responses to this type of treatment. And then some of the physicians are not sure how to manage some little leftovers or some good responses, partial or near complete, but there's still something left behind and what to do then. I think there's some confusion around there, and we are here to help with those types of circumstances.

Joshua Sommovilla, MD: I would just add, there's a lot of nuance to a lot of these decisions that we make and people that we're considering organ preservation on and it requires a lot more than just a really good surgeon. A lot of expertise in our radiation doctors and our radiologists who help us look at the MRIs that are a key part of assessing the response to the neoadjuvant treatments that we give. So I think it requires a center that sees a lot of rectal cancer patients, but also has a lot of expertise in every single field of the different types of physicians who take care of those patients to make the correct decisions about who's a good candidate for this approach and who might not be.

Dale Shepard, MD, PhD: And then I guess in terms of candidate, and we think about who might be a good candidate, maybe if we could think about what would be an ideal patient? Clearly if they have extensive disease, the answer would be no. But what would be an ideal candidate to be at least considering organ preservation?

Emre Gorgun, MD, MBA: This is typically and scientifically offered most commonly to patients that we refer to as locally advanced rectal cancer, so T2s, T3s with nodal involvement. So certainly those are the best candidates. But I think there is some active research going on to possibly even offer earlier rectal cancer patients. I mean, if we can really avoid taking someone's rectum out in an early-stage cancer, even at T2, that would be most beneficial.

Really, in select group of patients, we have some experience with that. We offered some of our patients, for example, morbidly obese or someone T2 early cancer, but it's sitting right at the sphincter muscle that otherwise would require 100% a permanent bag or colostomy or not being able to maintaining their intestinal continuity, we have trialed neoadjuvant treatment in this group of patients. Interestingly enough, our complete response rate in that select group was, for example, 100%. But this is, of course, also developing research and evolving research that we need to get more data to standardize this across the board.

Dale Shepard, MD, PhD: Josh, we've actually had podcast episodes where we talked about endoluminal procedures and some of these sort of different approaches. How does that work into rectal cancers or surgeries related to the sphincter itself? What are we doing that's leading the way in that area?

Joshua Sommovilla, MD: I think since the whole watch and wait organ preservation approach was started, the traditional teaching has been, after the chemotherapy and the radiation treatments have been given that any patient who has any sign of disease that's left over, you would then proceed with removing the rectum with major surgery. And I think what we found over time is that there's some local resection procedures that, for some people, might allow continue to organ preservation.

Some of these local resection procedures involve removing the full thickness of the wall of the area where there's remaining tumor. But then other endoluminal procedures, which we do called ESD, allows you to preserve the deeper layers of the rectal wall, which, if somebody is going to end up needing a bigger surgery, would be less interfering with that. And so we do some of these procedures here where, basically, if there's a small amount of either polyp like tissue remaining or a small irregularity in a scar that's left after chemotherapy and radiation, we can remove that basically with a colonoscopy and preserve the wall of the rectum.

It, number one, gives us a real diagnosis of whether that tissue is truly cancer or not and it allows you to preserve all your options moving forward as far as, if they do still need that radical surgery, it doesn't really interfere with that and it allows you to potentially remove small amounts of precancerous or cancerous tissue that, if they're very superficial, it may be safe to continue watching that and offer further organ preservation.

Dale Shepard, MD, PhD: As we've sort of started doing these procedures with that low volume of residual tumor or not, I guess that's really the question, how often do we find that there's maybe a thought that there's residual tumor left? You go and you do an endoluminal procedure and you find out it really wasn't tumor at all and we've saved people from losing a sphincter.

Emre Gorgun, MD, MBA: We are still collecting our data on that and this is, of course, still early to say, but certainly in our experience so far, and I looked at our data recently, we are up to 80% organ preservation. So we did have some group of patients, about 20% or so, that had in the excision or when we removed, like Dr. Sommovilla indicated in that specimen with after endoluminal procedure with the ESD, some more than high-grade dysplasia invasive cancer. Even if we have negative margins, we prefer to proceed with low anterior resection, or APR, in those circumstances. But I can tell you, in our group, 80% only had either high-grade dysplasia with negative margins, and we continue to monitor those. So I think that 80% is an additional group of patients that will help us to bring that complete responders or organ-preserving rates up in my mind, and that's the goal for the future, of course.

Dale Shepard, MD, PhD: Certainly, we talked about the ability to not have an ostomy and things. When we think about these organ-sparing procedures, what's the impact on things like recovery time, post-operative complications, quality of life, things like that?

Joshua Sommovilla, MD: Yeah, I think anytime that we're able to avoid a major surgery, like a proctectomy, which is removing the rectum, generally that helps with quality of life. I think there are some quality of life implications for the radiation treatment and that can cause some disordered bowel habits like urgency when having to go to the bathroom and things like that.

I think it's important for any of these watch and wait organ preservation approaches to mention that it requires a lot of buy-in from both caregivers and patients for having really close surveillance. We have to, for the first couple of years, examine these patients every three months and get MRIs a couple of times a year. So there's a little risk involved if patients are not able to follow up or are not able to undergo that type of strict surveillance, that there's some risk involved. But overall avoiding major surgery like that, especially for patients who are medically high risk, can really improve their quality of life and allow them to avoid a very risky major operation.

Emre Gorgun, MD, MBA: That's a great point. I mean, it's procedure-related benefits from quality of life perspective, but as well as, if they wouldn't have that local excision or EST or organ preservation, if they would've undergone low anterior resection, that comes with its own package or luggage in the sense of low anterior resection, the rectum is replaced with a new organ, which is colon, and that has its own associated issues and problems as well. And that is directly related with quality of life for our patients, urgency, frequency, feeling of incomplete evacuation, so multiple aspects of that. So surgery has its own quality of life-related issues, obviously in the long term as well.

Dale Shepard, MD, PhD: Right. Somebody might be listening in, they aren't currently really doing this much, what would be the biggest obstacles to starting this kind of procedure?

Emre Gorgun, MD, MBA: I think this is a technically-demanding procedure, especially for the ESD and the endoluminal procedures, and the tendency is to go full thickness, as Dr. Sommovilla said, but then when you do full thickness, he already mentioned, if you need to go low anterior resection, that's going to be difficult, subsequently, as well as, after radiation, the deeper defects have healing issues.

But in terms of physicians, healthcare providers that would be interested in these procedures is finding proper training centers for, for example, ESD. The other thing is, really, in my mind and in our minds, I think even more surgeons should get on the wagon to do these procedures. Obviously we are very familiar with rectal cancer, and this is an area we are watching very carefully, these patients every 3 months with scopes, and I think we would be well suited to approach these patients. So I think being committed to learn these techniques and finding training centers to be able to do these procedures are probably the limitations and challenges for these folks. But we do offer, within our organizations within Cleveland Clinic as well as the American College of Surgeons, [inaudible 00:18:10], and so forth, and also some industry-sponsored training courses nationwide for them to learn these techniques.

Dale Shepard, MD, PhD: Very good. Change gears a little bit. Josh, the rectal cancer program has gotten a national accreditation. Tell us a little bit about that.

Joshua Sommovilla, MD: The NAPRC is a national accreditation organization for rectal cancer where centers have to meet certain criteria to get that accreditation. Rectal cancer management is complicated. It involves a team of different doctors that includes surgeons, medical oncologists, radiation oncologists, pathologists, radiologists, who all need to have their own expertise, and it requires a lot of coordination between the specialties. And so the NAPRC Accreditation Program really provides a lot of strict rules for what you need to do as a group and how you diagnose rectal cancer, discuss rectal cancer patients as a team, and document your discussions and management plans in a specific way.

The requirements are pretty significant and I think there are a lot of places where either because of the volume of rectal cancer that they manage or the amount of work that's involved to maintain all the certifications is just not worth it. But there have been recently a study shown in the Journal of the American College of Surgeons that outcomes are better for patients when they get their care at centers that have the NAPRC accreditation. So we put a lot of effort into maintaining all the criteria that we need to meet those guidelines, and we find it to be helpful for our patients.

Dale Shepard, MD, PhD: Very good. Well, let's close out with a question and I'll ask each of you for your view. What do you think is going to be the next big development that makes organ preservation even more effective?

Emre Gorgun, MD, MBA: Several things. I think future is bright, and I think the surgeons will be operating less and less on rectal cancer in the future. Already, I think we are almost operating 50% less on our rectal cancer patients, which is a good thing. But, of course, we need to find ways to even improve that further, and one of the items are, as I mentioned earlier, for example, earlier stage cancers, how we can really tackle them and prevent them from having permanent ostomies or even organ preservation. So that's number one. I think these endoluminal procedures will also further develop like endorobotics, fully flexible platforms throughout the entire intestinal tract. We can do more challenging procedures in a much more skillful approaches. And then I think the next item is these neoadjuvant treatment modalities will probably be changed, whether it's more targeted treatments, immunotherapies, and changing the regimens, using different chemotherapy agents, and finding the most effective agents for different cancer types, I think, will be in my expectations for the future.

Dale Shepard, MD, PhD: Yeah. Very good. What do you think?

Joshua Sommovilla, MD: Yeah, you didn't leave me a lot to cover there.

Dale Shepard, MD, PhD: Should have started with you first. Right.

Joshua Sommovilla, MD: One area that, as we understand the biology of rectal cancer better, you mentioned the systemic treatments, the immunotherapy and targeted treatments. I think that's one area where in the coming 10 years or so, I think we've already seen this with immunotherapy for certain types of rectal cancer, which is the minority of rectal cancers. But microsatellite unstable rectal cancers are looking to be promising to treat with immunotherapy and potentially be cured without radiation or surgery. I think there may be other things we find out about other types of rectal cancers that maybe there'll be other targeted treatments that might be able to provide similar benefit in the future and allow us to provide more organ preservation in that way.

Dale Shepard, MD, PhD: Excellent. Well, you guys are doing great work to help our patients and appreciate you being with us today.

Emre Gorgun, MD, MBA: Thank you for helping us out to get the word out there, and it's always a pleasure to be here with you, Dale. Thank you for inviting us.

Joshua Sommovilla, MD: Yeah, thank you. It was great being here.

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