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Surgical Controversies in Advanced Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, Arizona Oncology Practice of US Oncology; Oliver Dorigo, MD, PhD, Stanford University Medical Center; Thomas Herzog, MD, University of Cincinnati Cancer Institute; Kathleen Moore, MD, Stephenson Cancer Center; Leslie M. Randall, MD, MAS, University of California, Irvine
Published: Tuesday, Aug 14, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s transition to newly diagnosed advanced ovarian cancer. Unfortunately, that’s the setting in which we, as oncologists and gynecologic oncologists, spend most of our time. I think it’s no secret that most patients with ovarian cancer are diagnosed in the stage 3 and stage 4 setting, and that their risk for recurrence is high. But, it is our largest opportunity for cure. And so, I want to spend a significant amount of time discussing appropriate frontline treatment. Surgery has a role. There has been this controversy that surgery should be done in the beginning, at primary debulking. Or it should be done after 3 cycles, in the neoadjuvant setting. Tom, at the 2018 ASCO Annual Meeting, there was another study that looked at neoadjuvant chemotherapy and interval debulking. Can you summarize those results for us?

Thomas Herzog, MD: The Japanese group did a study looking at upfront primary debulking versus the neoadjuvant approach, as you said, in stage 3/4 ovarian cancer patients. What they found was that the median overall survival was 49 months in the primary debulking group and 44.3 months in the neoadjuvant group. The hazard ratio was 1.052. The curves were apart at the median, but the overall assessment showed no difference. It did cross 1. Because of that, they said they couldn’t reject the noninferiority. Noninferiority studies can be difficult, and they often require more patients. This particular trial had only 301 patients, so it was probably underpowered. I think that’s really what was going on there.

Bradley J. Monk, MD, FACS, FACOG: So, it was not a practice-changing trial. Neoadjuvant chemotherapy is here to stay.

Thomas Herzog, MD: The hazard ratio of 1.052, which was below their threshold—they wanted a 1.16—says that while we can’t officially statistically reject noninferiority for neoadjuvant therapy, it is reassuring that the hazard ratio is 1.052. It fits with the other data sets that we have—from the CHORUS and EORTC studies that suggest that there is no difference. But there are still those who strongly believe in primary cytoreduction in this country.

Bradley J. Monk, MD, FACS, FACOG: I think that we would agree that the best opportunity is surgery in the beginning, and that the goal is complete resection. But, there are some patients in which that’s probably not the right path forward. You mentioned the EORTC and CHORUS papers. Katie, who is the right patient for neoadjuvant chemotherapy and interval debulking? In other words, who would you not do primary debulking on?

Kathleen Moore, MD: That’s the million-dollar question.

Bradley J. Monk, MD, FACS, FACOG: That’s why I asked you.

Kathleen Moore, MD: Before I answer that, I want to point out that in this study, just like the other 2, the primary cytoreduction rate of getting to no gross residual was incredibly low—it was 10%. That’s the other thing we have to keep in mind.

Bradley J. Monk, MD, FACS, FACOG: In primary debulking?

Kathleen Moore, MD: In primary debulking. And only 30% with interval debulking. So, once again, we have this population that really doesn’t get to the surgical endpoint that we’re trying to get to. I think it speaks to the fact that there’s probably patient selection. These are good surgeons, in all of these countries. They didn’t mind not operating. There’s a gestalt that we have when you look at a patient. There are the obvious things—someone who is too sick for surgery. And then there are 2 criteria. One is the likelihood of getting to no gross residual and how you assess that, via laparoscopy with various scoring systems. There are multiple ways to look at that, and what you call not debulkable. So, there’s that group. If you and an expert surgeon cannot get to no gross residual, that’s someone who needs to go to neoadjuvant chemotherapy.

And then the second group is the group of patients for whom you look at and you say that they need 2 bowel resections and a splenectomy to get this out, but her risk of major morbidity is excessive. Again, there are multiple scales for that. Aletti has published a nice one that’s referenced often. If you have a risk score over 3, that’s about an 80% risk for major morbidity.

Bradley J. Monk, MD, FACS, FACOG: But that’s kind of the too-sick cohort. There’s an overlap.

Kathleen Moore, MD: There’s some overlap there.

Bradley J. Monk, MD, FACS, FACOG: I think the most difficult question, in my mind, is who should have neoadjuvant chemotherapy and interval debulking versus primary debulking? The sick patients shouldn’t have primary debulking. They should have neoadjuvant therapy. The patient who you think, “OK, I can’t cut the cancer out,” shouldn’t have it. So, should we do laparoscopy? Or can you just look at the CT scan and a high CA-125 and move on?

Leslie M. Randall, MD, MAS: I think it depends. You can get your medically unfit question in the office.

Bradley J. Monk, MD, FACS, FACOG: That’s easy.

Leslie M. Randall, MD, MAS: The CT can tell you if you have porta hepatis disease, small bowel mesenteric retraction, or significant disease. It can tell you so much. And then you’ll still have this group of patients in whom you just don’t know. To me, laparoscopy is useful in those patients who haven’t met your criteria yet.

Bradley J. Monk, MD, FACS, FACOG: Oliver, do you occasionally do a laparoscopy?

Oliver Dorigo, MD, PhD: Yes, I do.

Bradley J. Monk, MD, FACS, FACOG: How often? You exclude the medically infirm. There’s a group of patients in whom you look at the CT scan—“This isn’t going to work.” How often do you get to that laparoscopic assessment?

Oliver Dorigo, MD, PhD: About half of the patients that I suspect have ovarian cancer will undergo laparoscopy. I also have to say that laparoscopy, at times, does not give you the entire picture. It still, at times, requires a laparotomy, at least a small incision, to evaluate the peritoneal cavity.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s transition to newly diagnosed advanced ovarian cancer. Unfortunately, that’s the setting in which we, as oncologists and gynecologic oncologists, spend most of our time. I think it’s no secret that most patients with ovarian cancer are diagnosed in the stage 3 and stage 4 setting, and that their risk for recurrence is high. But, it is our largest opportunity for cure. And so, I want to spend a significant amount of time discussing appropriate frontline treatment. Surgery has a role. There has been this controversy that surgery should be done in the beginning, at primary debulking. Or it should be done after 3 cycles, in the neoadjuvant setting. Tom, at the 2018 ASCO Annual Meeting, there was another study that looked at neoadjuvant chemotherapy and interval debulking. Can you summarize those results for us?

Thomas Herzog, MD: The Japanese group did a study looking at upfront primary debulking versus the neoadjuvant approach, as you said, in stage 3/4 ovarian cancer patients. What they found was that the median overall survival was 49 months in the primary debulking group and 44.3 months in the neoadjuvant group. The hazard ratio was 1.052. The curves were apart at the median, but the overall assessment showed no difference. It did cross 1. Because of that, they said they couldn’t reject the noninferiority. Noninferiority studies can be difficult, and they often require more patients. This particular trial had only 301 patients, so it was probably underpowered. I think that’s really what was going on there.

Bradley J. Monk, MD, FACS, FACOG: So, it was not a practice-changing trial. Neoadjuvant chemotherapy is here to stay.

Thomas Herzog, MD: The hazard ratio of 1.052, which was below their threshold—they wanted a 1.16—says that while we can’t officially statistically reject noninferiority for neoadjuvant therapy, it is reassuring that the hazard ratio is 1.052. It fits with the other data sets that we have—from the CHORUS and EORTC studies that suggest that there is no difference. But there are still those who strongly believe in primary cytoreduction in this country.

Bradley J. Monk, MD, FACS, FACOG: I think that we would agree that the best opportunity is surgery in the beginning, and that the goal is complete resection. But, there are some patients in which that’s probably not the right path forward. You mentioned the EORTC and CHORUS papers. Katie, who is the right patient for neoadjuvant chemotherapy and interval debulking? In other words, who would you not do primary debulking on?

Kathleen Moore, MD: That’s the million-dollar question.

Bradley J. Monk, MD, FACS, FACOG: That’s why I asked you.

Kathleen Moore, MD: Before I answer that, I want to point out that in this study, just like the other 2, the primary cytoreduction rate of getting to no gross residual was incredibly low—it was 10%. That’s the other thing we have to keep in mind.

Bradley J. Monk, MD, FACS, FACOG: In primary debulking?

Kathleen Moore, MD: In primary debulking. And only 30% with interval debulking. So, once again, we have this population that really doesn’t get to the surgical endpoint that we’re trying to get to. I think it speaks to the fact that there’s probably patient selection. These are good surgeons, in all of these countries. They didn’t mind not operating. There’s a gestalt that we have when you look at a patient. There are the obvious things—someone who is too sick for surgery. And then there are 2 criteria. One is the likelihood of getting to no gross residual and how you assess that, via laparoscopy with various scoring systems. There are multiple ways to look at that, and what you call not debulkable. So, there’s that group. If you and an expert surgeon cannot get to no gross residual, that’s someone who needs to go to neoadjuvant chemotherapy.

And then the second group is the group of patients for whom you look at and you say that they need 2 bowel resections and a splenectomy to get this out, but her risk of major morbidity is excessive. Again, there are multiple scales for that. Aletti has published a nice one that’s referenced often. If you have a risk score over 3, that’s about an 80% risk for major morbidity.

Bradley J. Monk, MD, FACS, FACOG: But that’s kind of the too-sick cohort. There’s an overlap.

Kathleen Moore, MD: There’s some overlap there.

Bradley J. Monk, MD, FACS, FACOG: I think the most difficult question, in my mind, is who should have neoadjuvant chemotherapy and interval debulking versus primary debulking? The sick patients shouldn’t have primary debulking. They should have neoadjuvant therapy. The patient who you think, “OK, I can’t cut the cancer out,” shouldn’t have it. So, should we do laparoscopy? Or can you just look at the CT scan and a high CA-125 and move on?

Leslie M. Randall, MD, MAS: I think it depends. You can get your medically unfit question in the office.

Bradley J. Monk, MD, FACS, FACOG: That’s easy.

Leslie M. Randall, MD, MAS: The CT can tell you if you have porta hepatis disease, small bowel mesenteric retraction, or significant disease. It can tell you so much. And then you’ll still have this group of patients in whom you just don’t know. To me, laparoscopy is useful in those patients who haven’t met your criteria yet.

Bradley J. Monk, MD, FACS, FACOG: Oliver, do you occasionally do a laparoscopy?

Oliver Dorigo, MD, PhD: Yes, I do.

Bradley J. Monk, MD, FACS, FACOG: How often? You exclude the medically infirm. There’s a group of patients in whom you look at the CT scan—“This isn’t going to work.” How often do you get to that laparoscopic assessment?

Oliver Dorigo, MD, PhD: About half of the patients that I suspect have ovarian cancer will undergo laparoscopy. I also have to say that laparoscopy, at times, does not give you the entire picture. It still, at times, requires a laparotomy, at least a small incision, to evaluate the peritoneal cavity.

Transcript Edited for Clarity 
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