ONCAlert | Upfront Therapy for mRCC

Case 1: Considerations for Neoadjuvant Therapy

Targeted Oncology
Published Online:1:05 PM, Thu May 23, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Robert L. Coleman, MD: So this is a great segue into the next question, which is, what is the treatment approach, right? What we are talking about here is the surgical approach, and obviously the alternative approach would be to go with chemotherapy first. Susana, maybe you can give us a little bit of an idea of what that literature is telling us about now?

Susana M. Campos, MD, MPH: Sure. By definition, we have a stage IV ovarian cancer at this point. We’ve had many different studies, in terms of neoadjuvant therapy versus adjuvant therapy: The EORTC, the CHORUS study, the JCOG, and, of course the SCORPION trial; and soon, hopefully, to be the true test will be the TRUST data coming up.

The ones that we concentrate on the most are the EORTC and the CHORUS data. And just recently published in the Lancet in 2018 was a pooled analysis of both the EORTC and the CHORUS trials. It was 1200 patients, so it was a sizable group of individuals. They looked at the data and the data showed that the end result didn’t change very much. Neoadjuvant therapy was really similar to that of primary debulking surgery in the group as a whole.

But you know, they made some very important comments: Patients had 3 centimeters and less than 5 centimeters of extrapelvic disease, versus stage III with greater than 5 centimeters extrapelvic disease. And they made some distinctions as to which patients really would do better with primary debulking surgery. It’s 1,200 patients, but only 19% really had stage IV disease. But even in that stage IV, granted it’s 19% of individuals, if you looked at median survival, the median survival was better with neoadjuvant therapy in stage IV in that particular review — about 3 months — and so was progression-free survival. So one could be mindful that this is a stage IV ovarian cancer.

Robert L. Coleman, MD: So Dave, what’s your experience with the impact of neoadjuvant therapy on surgery?

David O’Malley, MD: It’s pretty clear that you’re going to have less bowel surgery, less colostomies, less ICU [intensive care unit] admissions, less blood transfusions. So when we’re really looking at those patients, it clearly is going to be a less morbid surgery. I always talk to my fellows and say, “But it’s always tougher than you think it’s going to be. You have a bunch of fibrosis, you end up digging off the omentum for forever and trying not to do a transverse colectomy.”

I think it’s a really important aspect. Now, one thing you just brought up is, again, one of the most underquoted statistics is that in less than 5 centimeter disease, particularly if it’s isolated, those patients did significantly better with primary debulking.

Susana M. Campos, MD, MPH: Absolutely, yes.

David O’Malley, MD: So identifying those patients who we shouldn’t be operating on, and on the same side, identifying those patients who we should absolutely be operating on.

Robert L. Coleman, MD: That’s right. One of the prerequisites of the 2 neoadjuvant trials was they had to have some convincing evidence if the path wasn’t non-GYN [gynecologic] — that it was GYN — that double-negative there. What kind of things can we use to help convince us that this biopsy we took of the omentum is actually ovarian cancer?

Gregory Riedlinger, MD, PhD: But actually, in the follow-up with that, not that long ago we would do cytology via the ascites and we thought that was good enough.

Robert L. Coleman, MD: Right, yes.

Gregory Riedlinger, MD, PhD: Do we need core biopsies on these, or FNAs [fine needle aspirations], or what?

Robert L. Coleman, MD: I think we’ll definitely get to that. During one of the other cases, I want to bring that question up. Thanks for bringing it up. But if we have a specimen, let’s say we biopsy the omentum, how can you convince us that it’s of Mullerian origin?

Gregory Riedlinger, MD, PhD: There are certain markers, and we kind of touched on the PAX8, which seems to be … it’s positive in thyroid, and in some kidney, but it tends to be mainly positive in Mullerian. Especially with the so-called high-grade serous, it’s one of the diseases that’s defined by a specific molecular alteration where all of the high-grade serous have p53. With the immunohistochemistry, if we feel confident that it’s going one way or the other, that all of the cells have high expression of p53, or it’s the complete null, that certainly goes with ....

Robert L. Coleman, MD: What about for mucinous? We see this in mucinous cancer as well — the same kind of disease distribution, but the markers are all different, aren’t they?

Gregory Riedlinger, MD, PhD: Yes. I guess I’m not as familiar with how that would be different.

Robert L. Coleman, MD: Usually, from what I understand, the CK .…

Shannon N. Westin, MD: The CK7 [cytokeratin 7], CK20.

Gregory Riedlinger, MD, PhD: Can be helpful.

David O’Malley, MD: Helpful.

Robert L. Coleman, MD: And you know, the other thing in the trials, just to be fair, is that the way we did it is we also kind of broke down the CA 125 [cancer antigen 125], CEA [carcinoembryonic antigen] and they had a ratio of 25 to 1. And so, that was another piece. We do our best. Sometimes we’re wrong. Even in the study that we did, we found that about 10%, 11% of the time, when we did the scope and got tissue biopsy from the ovary, we were actually wrong. It was actually a non-GYN primary.

David O’Malley, MD: But I think if you use that criteria, you can be fairly confident that you’re treating a Mullerian or GYN primary.

Robert L. Coleman, MD: Yes. And I would guess that this disease type is probably the better one to at least, potentially, see a response to therapy.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Robert L. Coleman, MD: So this is a great segue into the next question, which is, what is the treatment approach, right? What we are talking about here is the surgical approach, and obviously the alternative approach would be to go with chemotherapy first. Susana, maybe you can give us a little bit of an idea of what that literature is telling us about now?

Susana M. Campos, MD, MPH: Sure. By definition, we have a stage IV ovarian cancer at this point. We’ve had many different studies, in terms of neoadjuvant therapy versus adjuvant therapy: The EORTC, the CHORUS study, the JCOG, and, of course the SCORPION trial; and soon, hopefully, to be the true test will be the TRUST data coming up.

The ones that we concentrate on the most are the EORTC and the CHORUS data. And just recently published in the Lancet in 2018 was a pooled analysis of both the EORTC and the CHORUS trials. It was 1200 patients, so it was a sizable group of individuals. They looked at the data and the data showed that the end result didn’t change very much. Neoadjuvant therapy was really similar to that of primary debulking surgery in the group as a whole.

But you know, they made some very important comments: Patients had 3 centimeters and less than 5 centimeters of extrapelvic disease, versus stage III with greater than 5 centimeters extrapelvic disease. And they made some distinctions as to which patients really would do better with primary debulking surgery. It’s 1,200 patients, but only 19% really had stage IV disease. But even in that stage IV, granted it’s 19% of individuals, if you looked at median survival, the median survival was better with neoadjuvant therapy in stage IV in that particular review — about 3 months — and so was progression-free survival. So one could be mindful that this is a stage IV ovarian cancer.

Robert L. Coleman, MD: So Dave, what’s your experience with the impact of neoadjuvant therapy on surgery?

David O’Malley, MD: It’s pretty clear that you’re going to have less bowel surgery, less colostomies, less ICU [intensive care unit] admissions, less blood transfusions. So when we’re really looking at those patients, it clearly is going to be a less morbid surgery. I always talk to my fellows and say, “But it’s always tougher than you think it’s going to be. You have a bunch of fibrosis, you end up digging off the omentum for forever and trying not to do a transverse colectomy.”

I think it’s a really important aspect. Now, one thing you just brought up is, again, one of the most underquoted statistics is that in less than 5 centimeter disease, particularly if it’s isolated, those patients did significantly better with primary debulking.

Susana M. Campos, MD, MPH: Absolutely, yes.

David O’Malley, MD: So identifying those patients who we shouldn’t be operating on, and on the same side, identifying those patients who we should absolutely be operating on.

Robert L. Coleman, MD: That’s right. One of the prerequisites of the 2 neoadjuvant trials was they had to have some convincing evidence if the path wasn’t non-GYN [gynecologic] — that it was GYN — that double-negative there. What kind of things can we use to help convince us that this biopsy we took of the omentum is actually ovarian cancer?

Gregory Riedlinger, MD, PhD: But actually, in the follow-up with that, not that long ago we would do cytology via the ascites and we thought that was good enough.

Robert L. Coleman, MD: Right, yes.

Gregory Riedlinger, MD, PhD: Do we need core biopsies on these, or FNAs [fine needle aspirations], or what?

Robert L. Coleman, MD: I think we’ll definitely get to that. During one of the other cases, I want to bring that question up. Thanks for bringing it up. But if we have a specimen, let’s say we biopsy the omentum, how can you convince us that it’s of Mullerian origin?

Gregory Riedlinger, MD, PhD: There are certain markers, and we kind of touched on the PAX8, which seems to be … it’s positive in thyroid, and in some kidney, but it tends to be mainly positive in Mullerian. Especially with the so-called high-grade serous, it’s one of the diseases that’s defined by a specific molecular alteration where all of the high-grade serous have p53. With the immunohistochemistry, if we feel confident that it’s going one way or the other, that all of the cells have high expression of p53, or it’s the complete null, that certainly goes with ....

Robert L. Coleman, MD: What about for mucinous? We see this in mucinous cancer as well — the same kind of disease distribution, but the markers are all different, aren’t they?

Gregory Riedlinger, MD, PhD: Yes. I guess I’m not as familiar with how that would be different.

Robert L. Coleman, MD: Usually, from what I understand, the CK .…

Shannon N. Westin, MD: The CK7 [cytokeratin 7], CK20.

Gregory Riedlinger, MD, PhD: Can be helpful.

David O’Malley, MD: Helpful.

Robert L. Coleman, MD: And you know, the other thing in the trials, just to be fair, is that the way we did it is we also kind of broke down the CA 125 [cancer antigen 125], CEA [carcinoembryonic antigen] and they had a ratio of 25 to 1. And so, that was another piece. We do our best. Sometimes we’re wrong. Even in the study that we did, we found that about 10%, 11% of the time, when we did the scope and got tissue biopsy from the ovary, we were actually wrong. It was actually a non-GYN primary.

David O’Malley, MD: But I think if you use that criteria, you can be fairly confident that you’re treating a Mullerian or GYN primary.

Robert L. Coleman, MD: Yes. And I would guess that this disease type is probably the better one to at least, potentially, see a response to therapy.

Transcript edited for clarity.
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