Non-Operative Organ Sparing Approach for 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 Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today I'm happy to be joined by Dr. Emre Gorgun, section head for surgical colorectal oncology here at Cleveland Clinic. Dr. Gorgun is here today to talk to us about non-operative organ sparing approaches for rectal cancer. So welcome and thank you for being with us today.

Emre Gorgun, MD: Thank you, Dale. Thank you for inviting me, and it's my pleasure to be chatting with you today.

Dale Shepard, MD, PhD: Maybe just start out telling us a little bit about what you do here at Cleveland Clinic.

Emre Gorgun, MD: I'm a colorectal surgeon. I treat diseases of the colon and rectum. Of course my passion and my interest here is mainly treating neoplasia and malignancies and cancer. Having said that, certainly we do treat large variety of diseases in terms of also inflammatory bowel disease, Crohn's disease, ulcerative colitis, diverticulitis, and also anorectal diseases like hemorrhoids, fistulas, fissures, prolapse. A large spectrum of diseases. That is part of the problems that you can get in our colon and rectum.

Dale Shepard, MD, PhD: Okay, that's a pretty wide range.. And today we're going to talk about rectal cancer, and rectal cancer and management. And so a lot of the physicians that may be listening in may not do this on a regular basis, so we're going to talk about some of the changes that are taking place in management. So maybe you could briefly tell us kind of what the standard of care has been, and then we'll talk about where things might be going.

Emre Gorgun, MD: Well, this is an actually very timely and important topic because a lot of things are currently changing in the United States and in the world. And the treatment strategies for rectal cancer is very fluid, very liquid. It changes all the time, and it sometimes gets really hard to keep up with. So I think this podcast might, hopefully, help some of our audience to understand and see what's out there, available, and what is the cutting edge approaches are in the treatment of rectal cancer. For a long time, we have been treating rectal cancer with neoadjuvant chemo radiation. We're talking about, of course, locally advanced rectal cancer, stage twos, stage threes.

And with neoadjuvant chemo and radiation, in other words, giving them chemo and radiation before we even operate on them, and then we would wait about eight weeks, two months or so. We would see some responses, some shrinkage in the tumor size and anatomy, followed by, we would operate on them. We would either do permanent colostomies, or take the rectum out and put it back together. Then after, we would wait a little bit more time and give them chemotherapy in the form of adjuvant chemotherapy.

So with this type of approach, we have seen that there is up to 20% of the time, complete responses. So we would do the operation and we would not even find one out of five patients, no cancer. So then we started to think, "Why are we doing this? Why we are operating on this patients? Maybe we can give the chemotherapy before surgery, maybe increase that complete response rate." Not only that, in addition, another benefit was here that if you operate on these patients, sometimes there are delays that you can start the adjuvant chemotherapy, the therapy that they receive after surgery, and the compliance would be lower because they are either not feeling well, or they might have some complications after surgery.

So the thought process was there might be a lot of advantages if you would give the chemotherapy, not necessarily after surgery, but before surgery, thinking that that would not necessarily harm the patient in the form of having their cancer progressed. And believe it or not, with this new approach where we slit the chemotherapy after surgery, before the surgery, this approach has become standard for our center here and also for a few other centers in the United States. And this is also a treatment modality that NCCN also supports and recommends as well.

Having said that, I would say across the board, across the United States, I think most centers do not treat rectal cancer patients using this approach. We believe, and I believe, that there is room for improvement here for all the centers across the United States. And with our experiences so far, I think this new approach is much more advantageous for the care of our patients with rectal cancer.

Dale Shepard, MD, PhD: So by eliminating the surgery, essentially, certainly you don't have that as a moment in time where people are getting that treatment. And it sounds like, of course, everything is compressed in terms of their total therapy. What kind of timeframe are we looking? So newer approach, how many weeks? Old approach, about how many weeks? How much time can we eliminate, in addition to the surgery?

Emre Gorgun, MD: Yeah. The timing is changed and that's something that we are still evaluating and trying to master it, if you will, and find the best timing and intervals in terms of treatment. But we do similar to what we used to do, five and a half weeks chemo radiation. We treat patients with that as we were doing before, so with chemo and radiation therapy. Then after, we rescan them about four weeks, five weeks after this treatment. And the reason for that is to make sure that there is no progression of disease, and very rarely this is the case.

Then we just break that algorithm, the pathway, and we go directly to surgery like we used to do. As long as there's no progression which majority of the time there isn't, about six weeks to eight weeks we start them on chemotherapy. And then that's, as you know, a classical about four months of chemotherapy, multiple cycles. That's the standard adjuvant chemotherapy cycle that a patient needs to get after surgery, so that's about four months.

And you might remember the complete response rate with our new adjuvant chemo radiation upfront was about 20%. So with this type of combination and TNT, or total neoadjuvant therapy, squeezing or bundling all this medical treatments before the surgery, we actually have seen increase in complete response rates up to even 40%. And in some cases even higher. And almost half of our patients, their complete response rates are very high. That means large number of patients, we even end up avoiding the surgery altogether.

So then they are done with the whole treatment modality in, you can think about in a term of six months, they are completely done. Of course, for complete responders I'm talking about. But then we put them on a very strict watch and wait protocol, active surveillance, where we really monitor these patients extremely closely and we watch them like a hawk. Every three months for the three years we give flexible scopes, make sure the endoscopy, there's no signs of recurrence, and also MRI every six months to make sure that there's no signs of any disease recurrence in the deeper tissues.

But with this approach, the emphasis I want to make here is that for some patients that your tumors might be really, really lower, only alternative for surgery would have been APR, or Abdominal Perineal Resection, with permanent colostomies, that I think this is a huge quality of life improvement. And of course avoidance of morbidity, even in some cases, mortality, that these patients really avoid all that and they get to keep their native organs and their rectum. So therefore this approach is commonly referred to as "organ sparing approach", and these patients really, greatly benefit from it.

For the ones that do not show complete response however, then of course we operate on them. That's about also six to eight weeks after completion of the chemotherapy, and then they have the surgery. Obviously we do have cutting edge, minimally invasive approaches for that; robotic approach or transanal from the bottom, TATME for more obese patients. And of course in our hands here at our center, we are specialized also for sphincter preserving. We can still keep their control muscles in place, so they don't have to have a permanent back.

Dale Shepard, MD, PhD: When you think about patients with this upfront therapy, and potentially not surgery, what kind of differences have you noted in either local or distant recurrence?

Emre Gorgun, MD: This is definitely an approach that has been studied widely in the literature. As you might know, this was something that was popularized in Brazil and there's a large data on that. The main question is that the distant diseases, comparable and overall, in long-term survivals are similar. To the best of our ability to tell, the studies so far are completely favorable in terms of keeping these rates with our classical approaches.

Dale Shepard, MD, PhD: So with the apparent advantages of having a pretty large number of people being able to keep their rectum with the upfront treatment, why the controversy? Why haven't more centers adopted this?

Emre Gorgun, MD: I think there are main current controversies. I think lack of knowledge, I would say, and lack of adaptation. Especially this is now the COVID hit, I think we would have probably advertised this a little bit more. I think what you're doing is also very important, the outreach, as much as we can go out and spread out the worth. I think that's very important to do. Really, patients are referred here after receiving chemo radiation like they were before for, for surgery. And then they have chemo radiation completed, and they come in with their physicians telling them, "Hey, you're going to go to the Cleveland Clinic and have surgery." We say, "No, we're not going to operate on you. We're going to just give you chemotherapy." They get surprised. Really, I would say lack of knowledge, and not maybe keeping up with more current treatment approaches out there.

I think attending conferences probably was helping a lot of physicians, and that shows the importance of these meetings, as well, to all of us. One way or another we were updating ourselves, and certainly with COVID last year, this hasn't been perfect. But maybe one other, maybe smaller, possibility is the concern that what if we don't operate on these patients, what happen to these patients? And what if in the long-term, the tumor comes back? That's a big question and concern of the course, but we know that from the data that's a very low incidence, about 20% or so, maybe there's some regrowth in the lumen side, intestine side. And with frequent watch and monitoring, these can be certainly salvaged at that time, and we know that the salvage operations are very successful as well.

Dale Shepard, MD, PhD: Do you find that if there's a hesitancy to move forward with this upfront treatment, is it more on the doctor's side or more on the patient side?

Emre Gorgun, MD: Definitely more on the doctor's side I think, if there is any hesitation. But again, I think that if any limitation, that's mostly a lack of knowledge. But if not, doctor's side I would say, because patients love this. They come here all the time to avoid permanent ostomies, for patients that has had really low cancers. And I think this is a great opportunity and chance for these type of patients. For any patient, but especially low ones, that you totally can avoid surgery. That's not a low chance, like 44%, 50% of the time. You may completely a more surgery. And for the ones that are distal, we do still do good sphincter preserving operations, but nevertheless, their functions are affected.

These are very, very tight connections. You kind of need to shave off the little bit control muscles, and that can be associated with seepage, leakage, some urgency. Of course, over time these improve, but certainly if you could avoid all this, that would be great. Having said that, of course there's another flip side of the coin, where we don't know. And that's something that I'm very excited and passionate about studying, and there's no data on this yet. What about their functional results, with the ones that keep their colons or rectums in place, that they didn't need to go to surgery? Because there's certainly going to be some effects of radiation and chemotherapy as well. And that's something that as the head of the colorectal section, I'm very excited to lead that, to look into that.

Dale Shepard, MD, PhD: You mentioned kind of this frustration sometimes, where people show up and they've had part of their therapy and they want surgery. If you think about patients that may not be showing up or... There are patients that you think this is best for, so is there any patient selection in play? Clearly the stage twos and threes, but are there any other characteristics that you'd say, "Well, it'd be awesome if we get this group here because this really benefits them"? Are there populations that may benefit more than others?

Emre Gorgun, MD: The ones that are locally advanced, stage two or three, that are really low, like I said before. Rectal muscle involvement or control muscle involvement, these are I think the best, to be honest, because... And also, the ones at higher risk. Either they have comorbidities, that they cannot easily tolerate surgery, or they have morbid obesity, surgery would be really hard on these patients. Narrow pelvis, male patients. So these patients, even for small tumors, getting these rectums out, surgically removing, is very, very challenging. If we could avoid surgery altogether, that's a huge gain. So this group of patients, I think, would benefit from this incredibly well. Of course, to expand this to other patients, maybe even early cancers. Because if these more advanced tumors are responding maybe a rate of 40, 50, maybe very early cancers may respond even higher with that.

And yes, they are at a lower risk for local recurrences or distant recurrences, but if we can avoid operating on those patients, I think that would be something to expand upon. Obviously the works are in place for that, the research, we don't know results of this, but I think that's what we're going to be seeing more and more. And one other area is, and these are kind of future directions, I think we classically always said if tumor is invading into the rectum control muscles, then even if there's a response, we always went with APR permanent bag. We still, ultimately, after chemo radiation, we did take their muscles out. But with this, if there's good response, because there's additional adjunct treatment with chemotherapy, maybe I think this can also increase our sphincter preserving rates as well. So that's another area for benefit, approaching this way.

Dale Shepard, MD, PhD: And so you'd mentioned previously that there were still considerations about how exactly to give the chemotherapy and lengths of time, and that's all being sorted out, and then you just mentioned something about maybe being able to do things like the sphincters a little bit easier. Are there other surgical changes taking place to sort of account for the fact that a greater number of patients may have good responses, and you may be dealing with less tumor? So either less extensive surgeries, or what does that look like?

Emre Gorgun, MD: Yeah, thank you for asking that. We recently submitted our video on that. With this TNT, occasionally what we see is there's extremely good response. Radiologically, almost complete response, but endoscopically, we may still see some irregular mucosa, some small scar areas that not completely look epithelized, that we want to make sure what's in there. So for that, we certainly have local excision methods, and I'm privileged to be leading our endoluminal surgery center for the lower GI. And with that, we do endoscopic, some causal dissection, and endoscopically go in and take these areas completely excised in an en bloc fashion.

Or we can certainly do these with techniques called TAMIS, transanal minimally invasive surgery. So still organ preserving approach, organ saving approach, but just taking these areas, locally excising those and making sure that there's no cancer left. Or even if there is, it's confined into the space and we can completely excise that in an en bloc fashion. But majority of the time, we either find adenoma tissue or high-grade dysplasia, which of course makes us feel good, and we stay on that watch and wait protocol and monitoring registry.

Dale Shepard, MD, PhD: Well, you guys are doing great work to improve the lives of our patients with rectal cancers. This is really some interesting work, and look forward to seeing what comes up next. So any additional comments?

Emre Gorgun, MD: This is a very important effort to put this word out there. Organ preservation and organ sparing approach and TNT, total neoadjuvant therapy, should be advertised across the United States more frequently, and I'm looking forward to have more patients take advantage of this approach and get to save their rectums and have better functions down the road.

Dale Shepard, MD, PhD: Excellent. Well, thank you very much for being with us today.

Emre Gorgun, MD: My pleasure. Thank you very much, Dale. Have a great day.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real-time updates from Cleveland Clinic's cancer center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening, please join us again soon.