John L. Marshall, MD: Bert, let me come back to you on this a little bit. The way I think about it is sort of high, mid, and low. Marwan mentioned that a little bit. When you see a patient with rectal cancer, knowing the guidelines in the back of your head, can you give us a sense of how you begin the discussion or decision making about approaching the management of that patient?

Bert H. O’Neil, MD: Sure. First and foremost is, do you have the best information you can have radiographically to help make a decision? Does your institution do good-quality pelvic MRIs that you can actually assess?

John L. Marshall, MD: Is EUS being used or is everybody doing MRI?

Wells A. Messersmith, MD, FACP: I haven’t seen it in the United States in several years.

John L. Marshall, MD: It’s been awhile, right? It was the thing for a while. I’m the same way. Sorry.

Bert H. O’Neil, MD: We still see patients who get both. I think it is surgeon dependent for the most part. But whether it’s EUS or MRI, that’s really critical in making your decision. So, what is the nodal involvement? Where is the tumor? We often don’t get accurate assessments of where the tumor is. For a lot of patients who have had a colonoscopy, the report will read tumor 20 cm that you can feel with your fingers. These things are very common, and I think MRI helps clear that up a lot also.

John L. Marshall, MD: Even with all that, interrupting a bit, do you think we’re doing a good job of staging? How accurate do you think we’re overtreating, undertreating, or overstaging?

Gabriela Chiorean, MD: To be honest with you, John, I think that even with MRI, we pick up on so many lymph nodes that we don’t know what they mean. For example, even in the PROSPECT study, a lymph node counted only if it was more than 10 mm. We do know that with the lymph node, it’s not just a matter of size that tells us if it’s involved or not. It’s really the borders, the diffusion-weighted signal. There are so many characteristics in a lymph node that make it looks suspicious or not, and I think the expertise of your radiologist, whom you have to trust that what they’re readying is accurate. And not only that, but I’m not sure that we really truly know how to assess, accurately, MRIs of the rectum.

John L. Marshall, MD: Wells, are you treating high, middle, and low the same?

Wells A. Messersmith, MD, FACP: No. As you get higher into the rectum, we begin to start to think about it a little bit more along the lines of colon cancer, at least feel more comfortable foregoing radiation for high-rectal tumors because the local recurrence rate is quite low. And then as we get lower, we’re more and more insistent about getting the radiation. I’ve also had very difficult conversations with people about colostomies and those low-rectal tumors that sort of bring us into the topic of nonoperative management, which we’ll talk about later. Certainly, for those lower ones, we’re much more commonly doing radiation, but the high ones in younger patients, you might want to have a family, etc, so it’s a lower threshold to forego the radiation.

John L. Marshall, MD: And when we start bringing this up in a multidisciplinary way, we might have this idea, but the surgeon’s got to buy in on this and the radiation oncologist has got to buy in on this. How is that going at your center, for example, in Southern California? Is that accepted, or is there pushback from other members of the team?

Marwan Fakih, MD: No, I think we’re individualizing quite a bit. There’s a lot of involvement of the patients in this decision making, to be honest with you. And we’re seeing more and more patients who are saying, “Hey, I don’t want a colostomy and even the data are not there, and you can make this disappear and watch me carefully. I really want to go that way.” And interestingly, our surgeons do support that, but I think there are a lot of variations in practices across the country right now. And even within one geographic area, you go from one center to another and nobody is following the same algorithm. And it goes back to what Gabby is saying, it’s a disease that has really a lot of gray zones. But the surgeons are onboard, and not everybody gets radiation.

John L. Marshall, MD: Yes. I’ve been surprised at how the surgeons, in some way, have been driving this, putting them out of business. I would have thought they would have been the last group to have said it’s OK not to do surgery, and we’re going to back to that. But the radiation people, those are the ones who, to me, are holding on a little tighter because we’re clearly trying to do them out of business with this sort of pre-chemotherapy approach. Has everybody at least tried once, outside a clinical trial, giving chemotherapy first to a patient? Everybody?

Wells A. Messersmith, MD, FACP: It has been a fairly standard approach based on sort-of institutional considerations.

John L. Marshall, MD: How long? How long have you been doing it standard?

Wells A. Messersmith, MD, FACP: About a year.

John L. Marshall, MD: A year.

Wells A. Messersmith, MD, FACP: Yes.

John L. Marshall, MD: Is that a standard? That’s a new thing still, right?

Wells A. Messersmith, MD, FACP: Yes. It’s in the NCCN guidelines. We found that there’s a couple of advantages. One is the surgeons are, in part, on board because you get a lot more tumor shrinkage, so it makes their job a little easier. And obviously, these are theoretical things that will need to be evaluated in clinical trials. But we’re able to start treatment next week, and when you start chemoradiation or something else, I have to wait and get the insurance approval for capecitabine, blah, blah, blah. It just takes longer. And the other advantage, getting back to our conversations about patients not liking ostomies, is that the ostomy time is about a quarter of what it is with the other approaches, whereas sometimes you have to wait until adjuvant therapy is given to reverse the ostomy. In this case, because surgery is last, you can reverse the ostomy shortly after the operation. In general, we’ve had good results so far. I agree with you, there’s not a phase III trial, and we certainly await further data. We seem to have good experience with it.

John L. Marshall, MD: We’re doing it as an exception, so it is not a standard at our place. We are still sort of chemotherapy/RT or the trial to look at frontline chemotherapy. Is anybody else sort of more like Wells, where it’s more the rule that you’re doing chemotherapy first?

Marwan Fakih, MD: We’ve endorsed it in our center well, and correctors know long-term data from phase III trials. But at least we have data right now that tell you that you can get your chemotherapy in more effectively and to be more compliant. And we know these patients do relapse, and the relapse is more distant relapse, and that’s the cause of death if it’s cancer related in the majority of cases. So, I think I’m comforted by the fact that it’s better tolerated, and there are less admissions because it’s not just the ostomy, it’s an ileostomy. And giving chemotherapy in the setting from the ostomy, especially for your elderly patients when it’s FOLFOX or XELOX, is not always easy.

John L. Marshall, MD: Bert?

Bert H. O’Neil, MD: I guess my only resistance to it is I often use the pathology after resection to sort of risk stratify people and decide what, if any, chemotherapy to give. So, giving the chemotherapy up front, you’re all in already. I think that does run the risk of overtreating some people.

John L. Marshall, MD: Yes, we’re clearly seeing a shift of a lot more preoperative systemic treatment in lots of disease, not just GI cancers. And the advantage is that it is hard to give it afterward too. But you’re right, you then lose that staging, if you will—that feeling going forward.

Transcript Edited for Clarity