Dr. Ebony Hoskins and Dr. Andreas Obermair discuss the surgical management of gynecologic cancers, including the role of minimally invasive surgery, approaches in fertility preservation, and the nuances of surgical debulking.

TRANSCRIPT

Dr. Ebony Hoskins: Hello and welcome to the ASCO Daily News Podcast, I'm Dr. Ebony Hoskins. I'm a gynecologic oncologist at MedStar Washington Hospital Center in Washington, DC, and your guest host of the ASCO Daily News Podcast. Today we'll be discussing the surgical management of gynecologic cancer, including the role of minimally invasive surgery (MIS), approaches in fertility preservation, and the nuances of surgical debulking, timing, and its impact on outcomes.

I am delighted to welcome Dr. Andreas Obermair for today's discussion. Dr. Obermair is an internationally renowned gynecologic oncologist, a professor of gynecologic oncology at the University of Queensland, and the head of the Queensland Center for Gynecologic Cancer Research. Our full disclosures are available in the transcript of this episode.

Dr. Obermair, it's great speaking with you today.

Dr. Andreas Obermair: Thank you so much for inviting me to this podcast.

Dr. Ebony Hoskins: I am very excited.  I looked at your paper and I thought, gosh, is everything surgical? This is everything that I deal with daily in terms of cancer in counseling patients. What prompted this review regarding GYN cancer management?

Dr. Andreas Obermair: Yes, our article was published in the ASCO Educational Book; it is volume 44 in 2024. And this article covers some key aspects of targeted precision surgical management principles in endometrial cancer, cervical cancer, and ovarian cancer.

While surgery is considered the cornerstone of gynecologic cancer treatment, sometimes research doesn't necessarily reflect that. And so I think ASCO asked us to; so it was not just me, there was a team of colleagues from different parts of the United States and Australia to reflect on surgical aspects of gynecologic cancer care and I feel super passionate about that because I do believe that surgery has a lot to offer. Surgical interventions need to be defined and overall, I see the research that I'm doing as part of my daily job to go towards precision surgery. And I think that is, well, that is something that I'm increasingly passionate for.

Dr. Ebony Hoskins: Well, I think we should get into it. One thing that comes to mind is the innovation of minimally invasive surgery in endometrial cancer. I always reflect on when I started my fellowship, I guess it's been about 15 years ago, all of our endometrial cancer patients had a midline vertical incision, increased risk of abscess, infections and a long hospital stay. Do you mind commenting on how you see management of endometrial cancer today?

Dr. Andreas Obermair: Thank you very much for giving the historical perspective because the generation of gynecologic oncologists today, they may not even know what we dealt with, what problems we had to solve. So like you, when I was a fellow in gynecologic oncology, we did midline or lower crosswise incisions, the length of stay was, five days, seven days, but we had patients in hospital because of complications for 28 days. We took them back to the operating theaters because those are patients with a BMI of 40 plus, 45, 50 and so forth. So we really needed to solve problems. And then I was exposed to a mentor who taught minimal invasive surgery. And in Australia he was one of the first ones who embarked on that. And I can remember, I was mesmerized by this operation, like not only how logical this procedure was, but also we did rounds afterwards. And I saw these women after surgery and I saw them sitting upright, lipstick on, having had a full meal at the end of the day.

And I thought, wow, this is the most rewarding experience that I have to round these patients after surgery. And so I was thinking, how could I help to establish this operation as standard? Like a standard that other people would accept this is better. And so I thought we needed to do a trial on this. And then it took a long time.

It took a long time to get the support for the [LACE - Laparoscopic Approach to Cancer of the Endometrium] trial. And in this context, I just also wanted to remind us all that there were concerns about minimal invasive surgery in endometrial cancer at the time. So for example, one of the concerns was when I submitted my grant funding applications, people said, “Well, even if we fund you, wouldn't be able to do this trial because there are actually no surgeons who actually do minimally invasive surgery.” And at the time, for example, in Australia, there were maybe five people, a handful of people who were able to do this operation, right? This was about 20 years ago. The other concern people had was they were saying, could minimally invasive surgery for endometrial cancer, could that cause port side metastasis because there were case reports.

So there were a lot of things that we didn't know anyway. We did this trial and I'm super happy we did this trial. We started in 2005, and it took five years to enroll. At the same time, GOG LAP2 was ramping up and the LACE trial and GOG LAP2 then got published and provided the foundations for minimally invasive surgery in endometrial cancer. I'm super happy that we have randomized data about that because now when we go back and now when people have concerns about this, should we do minimally invasive surgery in P53 mutant tumors, I'm saying, well, we actually have data on that. We could go back, we could actually do more research on that if we wanted to, but our treatment recommendations are standing on solid feet.

Dr. Ebony Hoskins: Well, my patients are thankful. I see patients all the time and they have high risk and morbidly obese, lots of medical issues and actually I send them home most the same day. And I think, you know, I’m very appreciative of that research, because we obviously practice evidence-based and it’s certainly a game changer.

Let’s go along the lines of MIS and cervical cancer. And this is going back to the LACC [Laparoscopic Approach to Cervical Cancer] trial.  I remember, again, one of these early adopters of use of robotic surgery and laparoscopic surgery for radical hysterectomy and thought it was so cool. You know, we can see all the anatomy well and then have the data to show that we actually had a decreased survival. And I even see that most recent updated data just showing it still continued. Can you talk a little bit about why you think there is a difference? I know there's ongoing trials, but still interested in kind of why do you think there's a survival difference?

Dr. Andreas Obermair:  So Ebony, I hope you don't mind me going back a step. So the LACC study was developed from the LACE trial. So we thought we wanted to reproduce the LACE data/LAP2 data. We wanted to reproduce that in cervix cancer.

And people were saying, why do you do that? Like, why would that be different in any way? We recognize that minimally invasive radical hysterectomy is not a standard. We're not going to enroll patients in a randomized trial where we open and do a laparotomy on half the patients. So I think the lesson that really needs to be learned here is that any surgical intervention that we do, we should put on good evidence footing because otherwise we're really running the risk of jeopardizing patients' outcomes. So, that was number one and LACC started two years after LACE started. So LACC started in 2007, and I just wanted to acknowledge the LACC principal investigator, Dr. Pedro Ramirez, who at the time worked at MD Anderson. And we incidentally realized that we had a common interest.

The findings came totally unexpected and came as an utter shock to both of us. We did not expect this. We expected to see very similar disease-free and overall survival data as we saw in the endometrial cancer cohort. Now LACC was not designed to check why there was a difference in disease-free survival. So this is very important to understand. We did not expect it. Like, so there was no point checking why that is the case. My personal idea, and I think it is fair enough if we share personal ideas, and this is not even a hypothesis I want to say, this is just a personal idea is that in endometrial cancer, we're dealing with a tumor where most of the time the cancer is surrounded by a myometrial shell. And most of the time the cancer would not get into outside contact with the peritoneal cavity. Whereas in cervix cancer, this is very different because in cervix cancer, we need to manipulate the cervix and the tumor is right at the outside there. So I personally don't use a uterine manipulator. I believe in the United States, uterine manipulators are used all the time. My experience is not in this area, so I can't comment on that. But I would think that the manipulation of the cervix and the contact of the cervix to the free peritoneal cavity could be one of the reasons. But again, this is simply a personal opinion.

Dr. Ebony Hoskins: Well, I appreciate it.

Dr. Andreas Obermair: Ebony at the end of the day, right, medicine is empirical science, and empirical science means that we just make observations, we make observations, we measure them, and we pass them on. And we made an observation. And, and while we're saying that, and yes, you're absolutely right, the final [LACC] reports were published in JCO recently. And I'm very grateful to the JCO editorial team that they accepted the paper, and they communicated the results because this is obviously very important. At the same time, I would like to say that there are now three or four RCTs that challenge the LACC data. These RCTs are ongoing, and a lot of people will be looking forward to having these results available.

Dr. Ebony Hoskins: Very good. In early-stage cervical cancer, the SHAPE trial looked at simple versus radical hysterectomy in low-risk cervical cancer patients. And as well all know, simple hysterectomy was not inferior to radical hysterectomy with respect to the pelvic recurrence rate and any complications related to surgery such as urinary incontinence and retention. My question for you is have you changed your practice in early-stage cervical cancer, say a patient with stage 1B1 adenocarcinoma with a positive margin on conization, would you still offer this patient a radical hysterectomy or would you consider a simple hysterectomy?

Dr. Andreas Obermair:  I think this is a very important topic, right? Because I think the challenge of SHAPE is to understand the inclusion criteria. That's the main challenge. And most people simplify it to 2 cm, which is one of the inclusion criteria but there are two others and that includes the depth of invasion. Dr. Marie Plante has been very clear. Marie Plante is the first author of the SHAPE trial that's been published in the New England Journal of Medicine only recently and Marie has been very clear upfront that we need to consider all three inclusion criteria and only then the inclusion criteria of SHAPE apply.

So at the end of the day, I think what the SHAPE trial is telling us that small tumors that would strictly fulfill the criteria of a 1B or 1B1 cancer of the cervix can be considered for a standard type 1 or PIVA type 1 or whatever classification we're trying to use will be eligible. And that makes a lot of sense.

I personally not only look at the size, I also look at the location of the tumor. I would be very keen that I avoid going through tumor tissue because for example, if you have a tumor that is, you know, located very much in one corner of the cervix and then you do a standard hysterectomy and then you have a positive tumor margin that would be obviously, most people would agree it would be an unwanted outcome. So I'd be very keen checking the location, the size of the tumor, the depths of invasion and maybe then if the tumor for example is on one side of the cervix you can do a standard approach on the contralateral side but maybe do a little bit more of a margin, a parametrial margin on the other side. Or if a tumor is maybe on the posterior cervical lip, then you don't need to worry so much about the anterior cervical margin, maybe take the rectum down and maybe try to get a little bit of a vaginal margin and the margin on the uterus saccals. Just really to make sure that you do have margins because typically if we get it right, survival outcomes of clinical stage 1 early cervix cancer 1B1 1B 2 are actually really good.

It is a very important thing that we get the treatment right. In my practice, I use a software to record my treatment outcomes and my margins. And I would encourage all colleagues to be cognizant and to be responsible and accountable to introduce accountable clinical practice, to check on the margins and check on the number on the percentage of patients who require postoperative radiation treatment or chemo radiation.

Dr. Ebony Hoskins: Very good. I have so many questions for you. I don't know the statistics in Australia, but here, there's increased rising of endometrial cancer and certainly we're seeing it in younger women.

And fertility always comes up in terms of kind of what to do. And I look at the guidelines and, see if I can help some of the women if they have early-stage endometrial cancer. Your thoughts on what your practice is on use of someone who may meet criteria, if you will. The criteria I use is grade 1 endometrioid adenocarcinoma.

No myometria invasion. I try to get MRI'd and make sure that there's no disease outside the endometrium. And then if they make criteria, I typically would do an IUD. Can you tell me what your practice is and where you've had success?

Dr. Andreas Obermair: So, we initiated the feMMe clinical trial that was published in 2021 and it was presented in a Plenary at one of the SGO meetings. I think it was in 2021, and we've shown complete pathological response rates after levonorgestrel intrauterine device treatment.

And so in brief, we enrolled patients with endometrial hyperplasia with atypia, but also patients with grade 1 endometrial adenocarcinoma. Patients with endometrial hyperplasia with atypia had, in our series, had an 85 % chance of developing a complete pathological response. And that was defined as the complete absence of any atypia or cancer.

So endometrial hyperplasia with atypia responded in about 85%. In endometrial cancer, it was about half, it was about 45, 50%. In my clinical practice, like as you, I see patients, you know, five days a week. So I'm looking after many patients who are now five years down from conservative treatment of endometrial cancer.

There are a lot of young women who want to get pregnant, and we had babies, and we celebrate the babies obviously because as gynecologist obstetricians it couldn't get better than that, right, if our cancer patients have babies afterwards. But we're also treating women who are really unfit for surgery and who are frail and where a laparoscopic hysterectomy would be unsafe. So this phase is concluded, and I think that was very successful. At least we're looking to validate our data. So we're having collaborations, we're having collaborations in the United States and outside the United States to validate these data.

And the next phase is obviously to identify predictive factors, to identify predictors of response. Because as you can imagine, there is no point treating patients with a levonorgestrel intrauterine joint device where we know in advance that she's not going to respond. So this is a very, very fascinating story and we got our first set of data already, but now we just really need to validate this data. And then once the validation is done, my unit is keen to do a prospective validation trial. And that also needs to involve international collaborators.

Dr. Ebony Hoskins: Very good. Moving on to ovarian cancer, we see patients with ovarian cancer with, say, at least stage 3C or higher who started neoadjuvant chemotherapy. Now, some of these patients are hearing different things from their medical oncologist versus their gynecologic oncologist regarding the number of cycles of neoadjuvant chemotherapy after getting diagnosed with ovarian cancer. I know that this can be confusing for our patients coming from a medical oncologist versus a gynecologic oncologist. What do you say to a patient who is asking about the ideal number of chemotherapy cycles prior to surgery?

Dr. Andreas Obermair: So this is obviously a very, very important topic to talk about. We won't be able to provide a simple off the shelf answer for that, but I think data are emerging.  The ASCO guidelines should also be worthwhile considering because there are actually new ASCO Guidelines [on neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer] that just came out a few weeks ago and they would suggest that we should be aiming for R0 in surgery. If we can maybe take that as the pivot point and then go back and say, okay, so what do need to do to get the patient to zero?  I'm not an ovarian cancer researcher; I'm obviously a practicing gynecologic oncologist. I think about things a lot and things like that. In my practice, I would want a patient to develop a response after neoadjuvant chemotherapy. So, if a patient doesn't have a response after two or three cycles, then I don't see the point for me to offer her an operation. In my circle with the medical oncologists that I work with, I have a very, very good understanding. So, they send the patient to me, I take them to the theater. I take a good chunk of tissue from the peritoneum. We have a histopathologic diagnosis, we have a genomic diagnosis, they go home the same day. So obviously there is no hospital stay involved with that. They can start the chemotherapy after a few days. There is no hold up because the chances of surgical complication in a setting like this is very, very low.

So I use laparoscopy to determine whether the patient responds or not. And for many of my patients, it seems to work. It's obviously a bit of an effort and it takes operating time. But I think I'm increasing my chances to make the right decision. So, coming back to your question about whether we should give three or six cycles, I think the current recommendations are three cycles pending the patient’s response to neoadjuvant chemotherapy because my aim is to get a patient to R0 or at least minimal residual disease. Surgery is really, in this case, I think surgery is the adjunct to systemic treatment.

Dr. Ebony Hoskins: Definitely. I think you make a great point, and I think the guideline just came out, like you mentioned, regarding neoadjuvant. And I think the biggest thing that we need to come across is the involvement of a gynecologic oncologist in patients with ovarian cancer. And we know that that survival increases with that involvement. And I think the involvement is the surgery, right? So, maybe we've gotten away from the primary tumor debulking and now using more neoadjuvant, but surgery is still needed. And so, I definitely want to have a take home that GYN oncology is involved in the care of these patients upfront.

Dr. Andreas Obermair: I totally support that. This is a very important statement. So when I'm saying surgery is the adjunct to medical treatment, I don't mean that surgery is not important. Surgery is very important. And the timing is important. And that means that the surgeons and the med oncs need to be pulling on the same string. The med oncs just want to get the cytotoxic into the patients, but that's not the point, right? We want to get the cytotoxic into the patients at the right time because if we are working under this precision surgery, precision treatment mantra, it's not only important what we do, but also doing it at the right time. And ideally, I I would like to give surgery after three cycles of neoadjuvant chemotherapy, if that makes sense. But sometimes for me as a surgeon, I talk to my med onc colleagues and I say, “Look, she doesn't have a good enough response to her treatment and I want her to receive six cycles and then we re-evaluate or change medical treatment,” because that's an alternative that we can swap out drugs and treat upfront with a different drug and then sometimes they do respond.

Dr. Ebony Hoskins:  I have maybe one more topic. In the area I'm in, in the Washington D.C. area, we see lots of endometrial cancer and they're not grade 1, right? They're high-risk endometrial cancer and advanced. So a number of patients with stage 3 disease, some just kind of based off staging and then some who come in with disease based off of the CT scan, sometimes omental caking, ascites. And the real question is we have extrapolated the use of neoadjuvant chemotherapy to endometrial cancer. It's similar, but not the same. So my question is in an advanced endometrial cancer, do you think there's still a role, when I say advanced, I mean, maybe stage 4, a role for surgery?

Dr. Andreas Obermair: Most definitely. But the question is when do you want to give this surgery? Similar to ovarian cancer, in my experience, I want to get to R0. What am I trying to achieve here? So, I reckon we should do a trial on this. And I reckon we have, as you say, the number of patients in this setting is increasing, we could do a trial. I think if we collaborate, we would have enough patients to do a proper trial. Obviously, we would start maybe with a feasibility trial and things like that. But I reckon a trial would be needed in this setting because I find that the incidence that you described, that other people would come across, they’re becoming more and more common. I totally agree with you, and we have very little data on that.

Dr. Ebony Hoskins: Very little and we're doing what we can. Dr. Obermair, thank you for sharing your fantastic insights with us today on the ASCO Daily News Podcast and for all the work you do to advance care for patients with gynecologic cancer.

Dr. Andreas Obermair: Thank you, Dr. Hoskins, for hosting this and it's been an absolute pleasure speaking with you today.

Dr. Ebony Hoskins: Definitely a pleasure and thank you to our listeners for your time today. Again, Dr. Obermair's article is titled, “Controversies in the Surgical Management of Gynecologic Cancer: Balancing the Decision to Operate or Hesitate,” and was published in the 2024 ASCO Educational Book. And you'll find a link to the article in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.

Disclaimer:

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions.

Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

Find out more about today’s speakers:

Dr. Ebony Hoskins

@drebonyhoskins

Dr. Andreas Obermair

@andreasobermair

Follow ASCO on social media:      

@ASCO on Twitter      

ASCO on Bluesky  

ASCO on Facebook      

ASCO on LinkedIn      

Disclosures:  

Dr. Ebony Hoskins: No relationships to disclose.

Dr. Andreas Obermair:

Leadership: SurgicalPerformance Pty Ltd.

Stock and Ownership Interests: SurgicalPerformance Pty Ltd.

Honoraria: Baxter Healthcare

Consulting or Advisory Role: Stryker/Novadaq

Patents, Royalties, and Other Intellectual Property: Shares in SurgicalPerformance Pty Ltd.

Travel, Accommodation, Expenses: Stryker