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Management of Colorectal Cancer Metastases

Panelists: John Marshall, MD, Georgetown University; Cathy Eng, MD, Vanderbilt University; Tanios Bekaii-Saab, MD, Mayo Clinic; Dustin Deming, MD, University of Wisconsin; Michael Morse, MD, Duke Cancer Institute
Published: Wednesday, Aug 07, 2019



Transcript: 

John Marshall, MD: Mike, you and I have worked over the years on how to deal with patients in whom we resect their metastases. We’ve created this new stage—stage IV, no evidence of disease. We’re resecting livers; we’re doing lungs; we’re doing peritoneal disease. Give me your big-picture overview of where we are in this metastasectomy world.

Michael Morse, MD: Well, this points out the importance of multidisciplinary environments, because obviously, these are often complex surgeries that require decisions about chemotherapy first, going right to surgery, what’s the value of surgery going to be, complex surgical procedures. It would appear that this is, in part, a test of biology. Patients who have had disease that is resectable, or becomes resectable, and a fraction of them can be cured by it, obviously have a different disease than somebody with very widespread involvement. It’s an important point to make.

The second is that it doesn’t seem like there’s anything that’s truly out of balance, in terms of resection. I think liver was one of the first places people went. It’s a common site of metastasis, and of course, lung metastasis, or tumors that are small and peripheral, are very approachable. Even the idea of peritoneal resections, obviously, surgeons are willing to take on. I think the message really has to be that metastatic disease is not an incurable situation to everybody. There should always be a discussion about whether surgery is applicable, whether it’s ever going to be applicable, and how we get people to resectability.

John Marshall, MD: I’ve shifted my thinking from “curative surgery is the only benefit,” to getting people back to zero and getting them back to no evidence of disease, even though I know they still have cancer. Are people nodding heads to that? That’s a shift in how I’m thinking.

Cathy Eng, MD: For appropriate patients, I think we will always have them discussed at multidisciplinary conferences and give them the benefit of the doubt.

John Marshall, MD: Dustin, I’m picking on you one more time. I have no idea what to do with these patients with chemotherapy. I don’t know if I’m having an adjuvant effect. I don’t know if neoadjuvant in a resectable patient is really appropriate. In a tumor board I see how I feel about it that day, and make a decision. How do you apply systemic chemotherapy in a patient with resectable metastatic disease?

Dustin Deming, MD: In the perioperative setting, if they have never received FOLFOX [folinic acid, fluorouracil, oxaliplatin], I will make sure that they receive [folinic acid, fluorouracil, oxaliplatin] either before or after surgery.

John Marshall, MD: So in an adjuvant attempt?

Dustin Deming, MD: Correct. If they have seen [folinic acid, fluorouracil, oxaliplatin] at any time previously, in general, I do not recommend systemic chemotherapy.

John Marshall, MD: Three months? Six months?

Tanios Bekaii-Saab, MD: Zero months.

John Marshall, MD: You don’t do it. Three months or 6 months?

Michael Morse, MD: Like the EPOCH trial, 3 months before and 3 months after.

John Marshall, MD: Yes, so 6 months.

Tanios Bekaii-Saab, MD: Yes. A study that was negative for survival.

Cathy Eng, MD: That was because of cetuximab.

Tanios Bekaii-Saab, MD: No, that’s EPOCH.

Michael Morse, MD: New EPOCH is definitely negative.

Tanios Bekaii-Saab, MD: New EPOCH was definitely negative. Old EPOCH was positive for the PFS [progression-free survival] at 3 years, but it wasn’t positive for OS [overall survival], and ultimately one always has the question: What exactly are we trying to achieve? If the intent is to cure, although I understand that this is more an attempt to remit and then hope to cure, we’re really not adding to the cure with chemotherapy. If it’s a single lesion in the lung or a couple lesions in the peritoneum, and they can be targeted locoregionally, I just do that and watch and wait.

John Marshall, MD: You don’t have to give chemotherapy. The temptation is to give chemotherapy.

Tanios Bekaii-Saab, MD: Of course.

John Marshall, MD: I tend to be a maintenance person in this space and treat them like they have metastatic disease, particularly a very high-risk patient. What about the role for chemotherapy in peritoneal surgery? You’ve got a couple of randomized studies now?

Michael Morse, MD: Well….

John Marshall, MD: It’s not our call. They’re not asking us.

Michael Morse, MD: There are really 2 issues there. One is, whether cytoreductive surgery is beneficial. The consensus seems to be that it is, just like removing metastatic disease elsewhere, although that’s not what these studies actually looked at. They really looked at the addition of heated intraperitoneal extracorporeal chemotherapy. I think the data there would suggest that there isn’t a benefit, although there’s a healthy argument about the choice of chemotherapies and whether they were optimally administered, and optimal choice of chemotherapy. I suspect this will be a lingering issue for those centers that are very active in doing it. They may still see a role for those that aren’t as active; I’m not sure I’d say to get into the high-tech part of it.

John Marshall, MD: Yes, so surgery is not out, but the question of the role for chemotherapy is still there. Is that fair enough?

Michael Morse, MD: Right.

John Marshall, MD: Obviously, this kind of surgery is not to be done by the general surgeon. This is a very specialized team, all the way down to specialized pathologists and radiologists, who work in this area.

Tanios Bekaii-Saab, MD: Can we make it very clear that this is for adenocarcinoma higher-grade tumors, not for the low-grade appendiceal, where the answer is a little bit different.

John Marshall, MD: Yes, to distinguish this. We do have our low-grade colons with peritoneal disease, right?

Tanios Bekaii-Saab, MD: Sure.

John Marshall, MD: It’s often right-sided and that can be a little lower-grade. There are some questions being asked about adjuvant peritoneal surgeries and things like that, so it’s not done.

Transcript Edited for Clarity

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Transcript: 

John Marshall, MD: Mike, you and I have worked over the years on how to deal with patients in whom we resect their metastases. We’ve created this new stage—stage IV, no evidence of disease. We’re resecting livers; we’re doing lungs; we’re doing peritoneal disease. Give me your big-picture overview of where we are in this metastasectomy world.

Michael Morse, MD: Well, this points out the importance of multidisciplinary environments, because obviously, these are often complex surgeries that require decisions about chemotherapy first, going right to surgery, what’s the value of surgery going to be, complex surgical procedures. It would appear that this is, in part, a test of biology. Patients who have had disease that is resectable, or becomes resectable, and a fraction of them can be cured by it, obviously have a different disease than somebody with very widespread involvement. It’s an important point to make.

The second is that it doesn’t seem like there’s anything that’s truly out of balance, in terms of resection. I think liver was one of the first places people went. It’s a common site of metastasis, and of course, lung metastasis, or tumors that are small and peripheral, are very approachable. Even the idea of peritoneal resections, obviously, surgeons are willing to take on. I think the message really has to be that metastatic disease is not an incurable situation to everybody. There should always be a discussion about whether surgery is applicable, whether it’s ever going to be applicable, and how we get people to resectability.

John Marshall, MD: I’ve shifted my thinking from “curative surgery is the only benefit,” to getting people back to zero and getting them back to no evidence of disease, even though I know they still have cancer. Are people nodding heads to that? That’s a shift in how I’m thinking.

Cathy Eng, MD: For appropriate patients, I think we will always have them discussed at multidisciplinary conferences and give them the benefit of the doubt.

John Marshall, MD: Dustin, I’m picking on you one more time. I have no idea what to do with these patients with chemotherapy. I don’t know if I’m having an adjuvant effect. I don’t know if neoadjuvant in a resectable patient is really appropriate. In a tumor board I see how I feel about it that day, and make a decision. How do you apply systemic chemotherapy in a patient with resectable metastatic disease?

Dustin Deming, MD: In the perioperative setting, if they have never received FOLFOX [folinic acid, fluorouracil, oxaliplatin], I will make sure that they receive [folinic acid, fluorouracil, oxaliplatin] either before or after surgery.

John Marshall, MD: So in an adjuvant attempt?

Dustin Deming, MD: Correct. If they have seen [folinic acid, fluorouracil, oxaliplatin] at any time previously, in general, I do not recommend systemic chemotherapy.

John Marshall, MD: Three months? Six months?

Tanios Bekaii-Saab, MD: Zero months.

John Marshall, MD: You don’t do it. Three months or 6 months?

Michael Morse, MD: Like the EPOCH trial, 3 months before and 3 months after.

John Marshall, MD: Yes, so 6 months.

Tanios Bekaii-Saab, MD: Yes. A study that was negative for survival.

Cathy Eng, MD: That was because of cetuximab.

Tanios Bekaii-Saab, MD: No, that’s EPOCH.

Michael Morse, MD: New EPOCH is definitely negative.

Tanios Bekaii-Saab, MD: New EPOCH was definitely negative. Old EPOCH was positive for the PFS [progression-free survival] at 3 years, but it wasn’t positive for OS [overall survival], and ultimately one always has the question: What exactly are we trying to achieve? If the intent is to cure, although I understand that this is more an attempt to remit and then hope to cure, we’re really not adding to the cure with chemotherapy. If it’s a single lesion in the lung or a couple lesions in the peritoneum, and they can be targeted locoregionally, I just do that and watch and wait.

John Marshall, MD: You don’t have to give chemotherapy. The temptation is to give chemotherapy.

Tanios Bekaii-Saab, MD: Of course.

John Marshall, MD: I tend to be a maintenance person in this space and treat them like they have metastatic disease, particularly a very high-risk patient. What about the role for chemotherapy in peritoneal surgery? You’ve got a couple of randomized studies now?

Michael Morse, MD: Well….

John Marshall, MD: It’s not our call. They’re not asking us.

Michael Morse, MD: There are really 2 issues there. One is, whether cytoreductive surgery is beneficial. The consensus seems to be that it is, just like removing metastatic disease elsewhere, although that’s not what these studies actually looked at. They really looked at the addition of heated intraperitoneal extracorporeal chemotherapy. I think the data there would suggest that there isn’t a benefit, although there’s a healthy argument about the choice of chemotherapies and whether they were optimally administered, and optimal choice of chemotherapy. I suspect this will be a lingering issue for those centers that are very active in doing it. They may still see a role for those that aren’t as active; I’m not sure I’d say to get into the high-tech part of it.

John Marshall, MD: Yes, so surgery is not out, but the question of the role for chemotherapy is still there. Is that fair enough?

Michael Morse, MD: Right.

John Marshall, MD: Obviously, this kind of surgery is not to be done by the general surgeon. This is a very specialized team, all the way down to specialized pathologists and radiologists, who work in this area.

Tanios Bekaii-Saab, MD: Can we make it very clear that this is for adenocarcinoma higher-grade tumors, not for the low-grade appendiceal, where the answer is a little bit different.

John Marshall, MD: Yes, to distinguish this. We do have our low-grade colons with peritoneal disease, right?

Tanios Bekaii-Saab, MD: Sure.

John Marshall, MD: It’s often right-sided and that can be a little lower-grade. There are some questions being asked about adjuvant peritoneal surgeries and things like that, so it’s not done.

Transcript Edited for Clarity
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