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Ovarian Cancer: Neoadjuvant Chemo Vs Primary Debulking

Panelists: Bradley J. Monk, MD, FACOG, FACS, University of Arizona; Creighton University School of Medicine; Arizona Oncology; Kathleen N. Moore, MD, University of Oklahoma; Elena S. Ratner, MD, Yale University School of Medicine; Brian M. Slomovitz, MD, Sylvester Comprehensive Cancer Center, University of Miami Health System
Published: Tuesday, May 07, 2019



Transcript: 

Bradley J. Monk, MD, FACOG, FACS: So as we talk about surgery in epithelial ovarian cancer, there are really 4 components: One is risk-reducing surgery, which can include what you call, Brian, ISDO, or interval salpingectomy delayed oophorectomy; second, a staging operation, where for tumors that are generally of early stage, you want to see if it’s spreading, and possibly perform lymphadenectomy, peritoneal assessment, washings, and omentectomy; then, third, debulking; and certainly, the fourth would be secondary debulking. Let’s talk about debulking.

About half of our patients are getting interval debulking, meaning they start with neoadjuvant therapy. That began in 2010 with the EORTC 55971, published in the New England Journal of Medicine by Dr [Ignace] Vergote. At SGO 2019 [the Society of Gynocologic Oncology Annual Meeting], there was a third study—the second being CHORUS, and we’ll talk about that in a minute—called the SCORPION trial. Tell us about the SCORPION trial, Katie.

Kathleen N. Moore, MD: So the trials you alluded to, the EORTC [European Organisation for the Research and Treatment of Cancer] study, the subsequent CHORUS study, and the subsequent study out of the Japanese group all kind of randomized all-comers advanced disease to surgery or no surgery. They had different nuances and areas where people could criticize. One of the main criticisms of all the studies, but especially CHORUS and EORTC, among believers in primary cytoreduction is that there wasn’t a lot of effort there. They didn’t have surgeons who really believed they were going for complete cytoreduction—to an R0, as some would say.

The SCORPION trial, I was truthfully very excited about because that was the study that really was going to kind of put the hypothesis to the test. So you took women who had a laparoscopy initially and had a Fagotti score. The Fagotti score is well established, and it kind of scores based on where you see disease. If you have a Fagotti score greater than 8, that usually references patients to neoadjuvant chemotherapy. In this case, this group said, “OK, we’re going to take that group of patients with really bulky disease and we’re going to randomize them to neoadjuvant versus up-front surgery with really aggressive intent to get to no gross residual.”

And they did that. When you look at their surgical effort in time, they really did it. They did radical surgeries. They achieved no gross residual over 60% of the time in the primary cytoreductive group. They did everything that we kind of said was missing from the other studies, yet they showed absolutely no difference in progression or overall survival despite that. And so that’s the fourth study now really telling us that there’s no difference between primary cytoreduction and neoadjuvant.

Bradley J. Monk, MD, FACOG, FACS: Brian, what are the themes here? We have a number of studies comparing primary debulking versus neoadjuvant, interval debulking. What are the themes? What are the take-home messages for our audience?

Brian M. Slomovitz, MD: One of the themes is that when it comes to the surgery, it’s important that you’re getting treated in a high-volume center that does a lot of these cases. You don’t want to give the physician a choice—surgery or no surgery—if someone doesn’t do a lot of these cases. You want to be in someone’s hands who’s really experienced in deciding to do neoadjuvant or to do up-front surgery. One of the keys here, in regard to Katie’s comments, that wasn’t highlighted on: While there was a similar outcome in the 2 groups, there was a much higher rate of postoperative adverse events in those patients who were...

Bradley J. Monk, MD, FACOG, FACS: That’s the second theme. High-volume center and neoadjuvant is always less morbid.

Brian M. Slomovitz, MD: Less morbid. I mean these women are our mothers, our sisters, our neighbors. We want to get them home. We want to help maintain their quality of life. And if we’re going to have the same clinical outcomes, we need to put that at the forefront, as far as quality-of-life outcomes. And if a patient can get home sooner and have the same outcome, why not offer that to our patients?

Bradley J. Monk, MD, FACOG, FACS: And the third theme, also, is that the neoadjuvant patients probably don’t do quite as well as the patients who have primary debulking where the tumor can be resected and the patient can survive it. So Elena, there’s this discussion that maybe you should look in with a laparoscope. Because you really prefer to do a primary debulking, since CT scan [computed tomography] probably is not sufficiently sensitive, how do you feel about looking with a laparoscope and trying to triage patients to primary debulking versus neoadjuvant chemotherapy?

Elena S. Ratner, MD: This is another field where so much is changing. Much of our debulking surgeries that we do now are done laparoscopically or robotically. There’s now some thought, which we, as surgeons, are not accepting well, that ovarian cancer might actually not be a surgical disease after all. After all this time, where we believed that every…

Bradley J. Monk, MD, FACOG, FACS: You believed. I didn’t believe.

Elena S. Ratner, MD: Where we believed that every ditzel matters, now it all might be biology of disease. So yes, I very much am a supporter of looking with a camera and deciding whether somebody can be debulked at the time. But just like Brian, I think quality of life is key. If I can get somebody to a better quality of life easier, if I can do their surgery robotically after neoadjuvant therapy but would need a laparotomy up front, I will choose the former. I will choose giving them some chemotherapy, allowing this laparoscopic minimally invasive surgery where they go home on the same day or the next morning, changing the course of their recovery.

Bradley J. Monk, MD, FACOG, FACS: I think the evolution has been that maybe half the patients get neoadjuvant chemotherapy. That in and of itself has a prognostic significance. In that group of neoadjuvant chemotherapy, there’s still a prognostic group. That would be the surgical complexity score that you see on laparoscopy, certainly age. Older patients do worse. And then, also, the amount of residual disease at the interval debulking. Do you guys do laparoscopy triage?

Kathleen N. Moore, MD: Yes.

Bradley J. Monk, MD, FACOG, FACS: Yeah, I think that’s evolving. What percentage, Brian, do you think, in the country, have neoadjuvant chemotherapy?

Brian M. Slomovitz, MD: I think it’s higher. I think it’s probably higher than we even have the numbers for. I think it’s important. I’m OK with neoadjuvant therapy. I’m a proponent for neoadjuvant therapy. But those patients, prior to initiating their care for their ovarian cancer, should be seen, in conjunction with a medical oncologist, by their gynecologic oncologist. Again, it’s OK to go to chemotherapy first. We can have that discussion with the patient and come up with a plan for surgery after the cycles, right from the start.

Bradley J. Monk, MD, FACOG, FACS: And that’s what ASCO [American Society of Clinical Oncology] guidelines say, right? There’s been an opinion paper by the American Society of Clinical Oncology that says before you start chemotherapy, have the patient evaluated by what you said: a high-volume surgeon.

Kathleen N. Moore, MD: Back to Dr Ratner’s point, there is individualization of a surgical approach, and I don’t necessarily agree with anything Dr Slomovitz just said, but we were talking earlier, there’s a meta-analysis of the neoadjuvant trials that does suggest that patients with lower volume disease, less than 5 cm, actually benefit more from primary cytoreduction. So there may be a group of patients for whom primary cytoreduction actually does impact their progression-free and overall survival. And so, while I want to maintain safety for my patients, and we all do, I want them to live as long as they can, too. In the past, at my institution we operated on everybody. And, in fact, if you did neoadjuvant therapy, we were kind of accused of giving up early. The complications were the price of doing business to help your patient live longer. Now I think we have more of a balance, but the pendulum shouldn’t swing so far.

Bradley J. Monk, MD, FACOG, FACS: In fairness, though, the EORTC CHORUS meta-analysis in Lancet Oncology in 2018 also showed that in stage IV patients, neoadjuvant trended to do better.

Kathleen N. Moore, MD: Absolutely.

Bradley J. Monk, MD, FACOG, FACS: So that’s important.

Kathleen N. Moore, MD: Absolutely.

Transcript Edited for Clarity

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Transcript: 

Bradley J. Monk, MD, FACOG, FACS: So as we talk about surgery in epithelial ovarian cancer, there are really 4 components: One is risk-reducing surgery, which can include what you call, Brian, ISDO, or interval salpingectomy delayed oophorectomy; second, a staging operation, where for tumors that are generally of early stage, you want to see if it’s spreading, and possibly perform lymphadenectomy, peritoneal assessment, washings, and omentectomy; then, third, debulking; and certainly, the fourth would be secondary debulking. Let’s talk about debulking.

About half of our patients are getting interval debulking, meaning they start with neoadjuvant therapy. That began in 2010 with the EORTC 55971, published in the New England Journal of Medicine by Dr [Ignace] Vergote. At SGO 2019 [the Society of Gynocologic Oncology Annual Meeting], there was a third study—the second being CHORUS, and we’ll talk about that in a minute—called the SCORPION trial. Tell us about the SCORPION trial, Katie.

Kathleen N. Moore, MD: So the trials you alluded to, the EORTC [European Organisation for the Research and Treatment of Cancer] study, the subsequent CHORUS study, and the subsequent study out of the Japanese group all kind of randomized all-comers advanced disease to surgery or no surgery. They had different nuances and areas where people could criticize. One of the main criticisms of all the studies, but especially CHORUS and EORTC, among believers in primary cytoreduction is that there wasn’t a lot of effort there. They didn’t have surgeons who really believed they were going for complete cytoreduction—to an R0, as some would say.

The SCORPION trial, I was truthfully very excited about because that was the study that really was going to kind of put the hypothesis to the test. So you took women who had a laparoscopy initially and had a Fagotti score. The Fagotti score is well established, and it kind of scores based on where you see disease. If you have a Fagotti score greater than 8, that usually references patients to neoadjuvant chemotherapy. In this case, this group said, “OK, we’re going to take that group of patients with really bulky disease and we’re going to randomize them to neoadjuvant versus up-front surgery with really aggressive intent to get to no gross residual.”

And they did that. When you look at their surgical effort in time, they really did it. They did radical surgeries. They achieved no gross residual over 60% of the time in the primary cytoreductive group. They did everything that we kind of said was missing from the other studies, yet they showed absolutely no difference in progression or overall survival despite that. And so that’s the fourth study now really telling us that there’s no difference between primary cytoreduction and neoadjuvant.

Bradley J. Monk, MD, FACOG, FACS: Brian, what are the themes here? We have a number of studies comparing primary debulking versus neoadjuvant, interval debulking. What are the themes? What are the take-home messages for our audience?

Brian M. Slomovitz, MD: One of the themes is that when it comes to the surgery, it’s important that you’re getting treated in a high-volume center that does a lot of these cases. You don’t want to give the physician a choice—surgery or no surgery—if someone doesn’t do a lot of these cases. You want to be in someone’s hands who’s really experienced in deciding to do neoadjuvant or to do up-front surgery. One of the keys here, in regard to Katie’s comments, that wasn’t highlighted on: While there was a similar outcome in the 2 groups, there was a much higher rate of postoperative adverse events in those patients who were...

Bradley J. Monk, MD, FACOG, FACS: That’s the second theme. High-volume center and neoadjuvant is always less morbid.

Brian M. Slomovitz, MD: Less morbid. I mean these women are our mothers, our sisters, our neighbors. We want to get them home. We want to help maintain their quality of life. And if we’re going to have the same clinical outcomes, we need to put that at the forefront, as far as quality-of-life outcomes. And if a patient can get home sooner and have the same outcome, why not offer that to our patients?

Bradley J. Monk, MD, FACOG, FACS: And the third theme, also, is that the neoadjuvant patients probably don’t do quite as well as the patients who have primary debulking where the tumor can be resected and the patient can survive it. So Elena, there’s this discussion that maybe you should look in with a laparoscope. Because you really prefer to do a primary debulking, since CT scan [computed tomography] probably is not sufficiently sensitive, how do you feel about looking with a laparoscope and trying to triage patients to primary debulking versus neoadjuvant chemotherapy?

Elena S. Ratner, MD: This is another field where so much is changing. Much of our debulking surgeries that we do now are done laparoscopically or robotically. There’s now some thought, which we, as surgeons, are not accepting well, that ovarian cancer might actually not be a surgical disease after all. After all this time, where we believed that every…

Bradley J. Monk, MD, FACOG, FACS: You believed. I didn’t believe.

Elena S. Ratner, MD: Where we believed that every ditzel matters, now it all might be biology of disease. So yes, I very much am a supporter of looking with a camera and deciding whether somebody can be debulked at the time. But just like Brian, I think quality of life is key. If I can get somebody to a better quality of life easier, if I can do their surgery robotically after neoadjuvant therapy but would need a laparotomy up front, I will choose the former. I will choose giving them some chemotherapy, allowing this laparoscopic minimally invasive surgery where they go home on the same day or the next morning, changing the course of their recovery.

Bradley J. Monk, MD, FACOG, FACS: I think the evolution has been that maybe half the patients get neoadjuvant chemotherapy. That in and of itself has a prognostic significance. In that group of neoadjuvant chemotherapy, there’s still a prognostic group. That would be the surgical complexity score that you see on laparoscopy, certainly age. Older patients do worse. And then, also, the amount of residual disease at the interval debulking. Do you guys do laparoscopy triage?

Kathleen N. Moore, MD: Yes.

Bradley J. Monk, MD, FACOG, FACS: Yeah, I think that’s evolving. What percentage, Brian, do you think, in the country, have neoadjuvant chemotherapy?

Brian M. Slomovitz, MD: I think it’s higher. I think it’s probably higher than we even have the numbers for. I think it’s important. I’m OK with neoadjuvant therapy. I’m a proponent for neoadjuvant therapy. But those patients, prior to initiating their care for their ovarian cancer, should be seen, in conjunction with a medical oncologist, by their gynecologic oncologist. Again, it’s OK to go to chemotherapy first. We can have that discussion with the patient and come up with a plan for surgery after the cycles, right from the start.

Bradley J. Monk, MD, FACOG, FACS: And that’s what ASCO [American Society of Clinical Oncology] guidelines say, right? There’s been an opinion paper by the American Society of Clinical Oncology that says before you start chemotherapy, have the patient evaluated by what you said: a high-volume surgeon.

Kathleen N. Moore, MD: Back to Dr Ratner’s point, there is individualization of a surgical approach, and I don’t necessarily agree with anything Dr Slomovitz just said, but we were talking earlier, there’s a meta-analysis of the neoadjuvant trials that does suggest that patients with lower volume disease, less than 5 cm, actually benefit more from primary cytoreduction. So there may be a group of patients for whom primary cytoreduction actually does impact their progression-free and overall survival. And so, while I want to maintain safety for my patients, and we all do, I want them to live as long as they can, too. In the past, at my institution we operated on everybody. And, in fact, if you did neoadjuvant therapy, we were kind of accused of giving up early. The complications were the price of doing business to help your patient live longer. Now I think we have more of a balance, but the pendulum shouldn’t swing so far.

Bradley J. Monk, MD, FACOG, FACS: In fairness, though, the EORTC CHORUS meta-analysis in Lancet Oncology in 2018 also showed that in stage IV patients, neoadjuvant trended to do better.

Kathleen N. Moore, MD: Absolutely.

Bradley J. Monk, MD, FACOG, FACS: So that’s important.

Kathleen N. Moore, MD: Absolutely.

Transcript Edited for Clarity
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