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Locally Advanced Rectal Cancer: PROSPECT Trial

Panelists: John L. Marshall, MD, Georgetown University; Bert H. ONeil, MD, Indiana University School of Medicine; Marwan Fakih, MD, City of Hope Comprehensive Care Center; Gabriela Chiorean, MD, University of Washington School of Medicine; Wells A. Messersmith, MD, FACP, University of Colorado Cancer Center
Published: Monday, Aug 27, 2018



Transcript: 

John L. Marshall, MD: Let’s go to 2 other topics and trying to put other people, not oncologists, out of business in the management of rectal cancer. First is the PROSPECT study, which is designed to put radiation oncologists out of business. Everybody either participating or playing in on that were randomized to chemotherapy first, the FOLFOX approach. If response, then go right on to surgery. If no response, chemotherapy/RT [radiation therapy], then to surgery versus the traditional approach. We’re about done, right? We’ve got only about 50 more patients, I think, which is where we are before that study will close and report out. Is it going to take a certain amount of benefit, or is a tie good enough to win? If there’s no difference in PFS and local control, is radiation done, Marwan?

Marwan Fakih, MD: I think so.

John L. Marshall, MD: What if it’s a little risk? It will be interesting to see.

Marwan Fakih, MD: Yes, a tie is a win.

John L. Marshall, MD: It’s a very important study, and I think, really, kudos to the managers and organizers. They really pulled that stop out.

Wells A. Messersmith, MD, FACP: Yes. Again, I think it gets back to this biomarker issue as well. Hopefully, we’ll have some circulating tumor DNA data or some data from the tumors themselves to really help guide us and make a more clear recommendation, personalized.

Bert H. O’Neil, MD: In defense of the radiation oncologists, we need to pay attention to how many patients had to go off study because of lack of response to get radiation. Because if we just wholesale say no more radiation and ignore that, then that’s not covered by this trial.

John L. Marshall, MD: That’s an important coverage point.

Gabriela Chiorean, MD: I think we also have to take into consideration the types of patients who participated in PROSPECT. PROSPECT was, again, a study for not very distil tumors in the middle of the rectum. For the lymph node status, I think they had 10 mm for criteria as node positive. Everything else was considered node negative. You couldn’t be too close to the mesorectal fascia. I think it was, overall, a better prognosis type of patient enrolled in PROSPECT, and I think we have to, again, always be very careful and critical on the details when we see the results.

John L. Marshall, MD: I couldn’t agree more. The group that makes me the most uncomfortable is this transanal local excision group—the T1s, the T2s. I’m seeing more and more people with even higher-stage disease, T3s getting some sort of local resection, neoadjuvant chemotherapy/RT and observation. Anybody else uncomfortable with this? Marwan?

Marwan Fakih, MD: I am very uncomfortable with T3 and even T2. We know the data from years ago that even with T1s, if you follow these patients up to 10 years, you get up to an almost 8% or 10% relapse rate. And I think you can still make a case for the T1s, which are well differentiated in somebody where you want to do a sphincter-saving procedure. Even in those patients, we consider them in our practice for chemoradiation following excision. I think it’s hard to extrapolate to a residual disease from the watchful waiting strategy because the watchful waiting strategy, first of all, has not been validated fully, and it’s for patients with complete response. To me, T2 or T3 resection is experimental. Of course, the patient can reject surgery, and then what else can you do?

John L. Marshall, MD: It’s sort of what Wells was saying earlier. I’ve got patients who say, “I’d rather be dead than have an ostomy.” And so, OK, here’s what we can do. The extension. Marwan was saying you give the chemotherapy, you maybe do chemotherapy/RT, and then they have a complete endoscopic response, right? You can’t see anything. And there’s this decision to just watch and wait that patient. What’s the path CR? What would you quote a patient to their path CR rate of chemotherapy, chemotherapy/RT?

Wells A. Messersmith, MD, FACP: Sort of in the ballpark of 20% to 25%. I think the key there, from my standpoint, is I really go over with the patient that it’s an extreme follow-up schedule. You have to have a very compliant patient who can take a lot of days off work and come in to get all the scopes, the scans, the exams that are necessary to follow those patients. And so, to me, that’s really one of the critical branch points. You’re right. What that means, of course, is 80% of people don’t have that response. And of course, Dr. Google tells you everyone is going to get that response, and so you have to be a little careful about expectations. But following that, try to make sure the patient is going to be able to follow up with that plan, because if they don’t, some of that blame is going to be on you in terms of nonoperative management if the patient is not followed properly. I think it’s always hard as physicians to not feel some of the blame for that if it does come back.

John L. Marshall, MD: Gabby, let me ask a pretty specific question. Let’s say you had a patient with transanal excision with like a T2 lesion, and then they don’t want surgery. Is that a patient you’re recommending radiation to, or is it watchful waiting with a T2? Imaging negative, I’ll give you that.

Gabriela Chiorean, MD: So the patient received neoadjuvant chemotherapy or…?

John L. Marshall, MD: No, just a transanal excision below rectal cancer.

Gabriela Chiorean, MD: I would feel very uncomfortable not offering chemoradiation to that patient. So we would recommend chemoradiotherapy.

John L. Marshall, MD: I see nodding. Everybody there? That’s difficult. Again, no data really to tell us what to do, just odds of lymph node involvement and an attempt to increase local control. But then it’s back to the consequences of the radiation, the pelvic RT. So it’s not a nothing issue. And surgeons are increasingly amazing about how they’re able to do these low hookups and the like. I tend to try to discourage this whenever I can. I kind of am the old fuddy-duddy in this space, but I get it. I have some patients who we’re following now with this. The wild west of rectal cancer. Thanks, that was a great review, everybody.

Transcript Edited for Clarity

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Transcript: 

John L. Marshall, MD: Let’s go to 2 other topics and trying to put other people, not oncologists, out of business in the management of rectal cancer. First is the PROSPECT study, which is designed to put radiation oncologists out of business. Everybody either participating or playing in on that were randomized to chemotherapy first, the FOLFOX approach. If response, then go right on to surgery. If no response, chemotherapy/RT [radiation therapy], then to surgery versus the traditional approach. We’re about done, right? We’ve got only about 50 more patients, I think, which is where we are before that study will close and report out. Is it going to take a certain amount of benefit, or is a tie good enough to win? If there’s no difference in PFS and local control, is radiation done, Marwan?

Marwan Fakih, MD: I think so.

John L. Marshall, MD: What if it’s a little risk? It will be interesting to see.

Marwan Fakih, MD: Yes, a tie is a win.

John L. Marshall, MD: It’s a very important study, and I think, really, kudos to the managers and organizers. They really pulled that stop out.

Wells A. Messersmith, MD, FACP: Yes. Again, I think it gets back to this biomarker issue as well. Hopefully, we’ll have some circulating tumor DNA data or some data from the tumors themselves to really help guide us and make a more clear recommendation, personalized.

Bert H. O’Neil, MD: In defense of the radiation oncologists, we need to pay attention to how many patients had to go off study because of lack of response to get radiation. Because if we just wholesale say no more radiation and ignore that, then that’s not covered by this trial.

John L. Marshall, MD: That’s an important coverage point.

Gabriela Chiorean, MD: I think we also have to take into consideration the types of patients who participated in PROSPECT. PROSPECT was, again, a study for not very distil tumors in the middle of the rectum. For the lymph node status, I think they had 10 mm for criteria as node positive. Everything else was considered node negative. You couldn’t be too close to the mesorectal fascia. I think it was, overall, a better prognosis type of patient enrolled in PROSPECT, and I think we have to, again, always be very careful and critical on the details when we see the results.

John L. Marshall, MD: I couldn’t agree more. The group that makes me the most uncomfortable is this transanal local excision group—the T1s, the T2s. I’m seeing more and more people with even higher-stage disease, T3s getting some sort of local resection, neoadjuvant chemotherapy/RT and observation. Anybody else uncomfortable with this? Marwan?

Marwan Fakih, MD: I am very uncomfortable with T3 and even T2. We know the data from years ago that even with T1s, if you follow these patients up to 10 years, you get up to an almost 8% or 10% relapse rate. And I think you can still make a case for the T1s, which are well differentiated in somebody where you want to do a sphincter-saving procedure. Even in those patients, we consider them in our practice for chemoradiation following excision. I think it’s hard to extrapolate to a residual disease from the watchful waiting strategy because the watchful waiting strategy, first of all, has not been validated fully, and it’s for patients with complete response. To me, T2 or T3 resection is experimental. Of course, the patient can reject surgery, and then what else can you do?

John L. Marshall, MD: It’s sort of what Wells was saying earlier. I’ve got patients who say, “I’d rather be dead than have an ostomy.” And so, OK, here’s what we can do. The extension. Marwan was saying you give the chemotherapy, you maybe do chemotherapy/RT, and then they have a complete endoscopic response, right? You can’t see anything. And there’s this decision to just watch and wait that patient. What’s the path CR? What would you quote a patient to their path CR rate of chemotherapy, chemotherapy/RT?

Wells A. Messersmith, MD, FACP: Sort of in the ballpark of 20% to 25%. I think the key there, from my standpoint, is I really go over with the patient that it’s an extreme follow-up schedule. You have to have a very compliant patient who can take a lot of days off work and come in to get all the scopes, the scans, the exams that are necessary to follow those patients. And so, to me, that’s really one of the critical branch points. You’re right. What that means, of course, is 80% of people don’t have that response. And of course, Dr. Google tells you everyone is going to get that response, and so you have to be a little careful about expectations. But following that, try to make sure the patient is going to be able to follow up with that plan, because if they don’t, some of that blame is going to be on you in terms of nonoperative management if the patient is not followed properly. I think it’s always hard as physicians to not feel some of the blame for that if it does come back.

John L. Marshall, MD: Gabby, let me ask a pretty specific question. Let’s say you had a patient with transanal excision with like a T2 lesion, and then they don’t want surgery. Is that a patient you’re recommending radiation to, or is it watchful waiting with a T2? Imaging negative, I’ll give you that.

Gabriela Chiorean, MD: So the patient received neoadjuvant chemotherapy or…?

John L. Marshall, MD: No, just a transanal excision below rectal cancer.

Gabriela Chiorean, MD: I would feel very uncomfortable not offering chemoradiation to that patient. So we would recommend chemoradiotherapy.

John L. Marshall, MD: I see nodding. Everybody there? That’s difficult. Again, no data really to tell us what to do, just odds of lymph node involvement and an attempt to increase local control. But then it’s back to the consequences of the radiation, the pelvic RT. So it’s not a nothing issue. And surgeons are increasingly amazing about how they’re able to do these low hookups and the like. I tend to try to discourage this whenever I can. I kind of am the old fuddy-duddy in this space, but I get it. I have some patients who we’re following now with this. The wild west of rectal cancer. Thanks, that was a great review, everybody.

Transcript Edited for Clarity
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