Chapters Transcript Video Advancing the Standard: Gynecologic Cancer Care In gynecologic oncology we're seeing pivotal shifts driven by emerging data. The trust study is reshaping our thinking on primary debulking surgery versus neoadjuvant chemotherapy and advanced ovarian cancer, emphasizing individualized treatment. Meanwhile, the shape trial is redefining surgical. Extent in early stage cervical cancer suggesting that less radical approaches may offer equivalent outcomes and in recurrent platinum resistant ovarian cancer, the Mirrasol study highlights the promise of antibody drug conjugates like Murbituximab offering new hope for targeted therapies. These trials collectively underscore a move towards more precise patient centered care. Thank you for joining us. Welcome to Baptist Health Doctor Doc, a podcast built for innovation and collaboration by physicians for physicians. Hello, I'm Doctor Thomas Morrissey, director of gynecologic oncology at the Eugene M and Christine E. Lynn Cancer Institute, part of Baptist Health at Boca Raton Regional Hospital, and joining me for discussion is Doctor Ryan Conn, fellowship trained gynecologic oncologist at Baptist Health Miami Cancer Institute. Morning, Ryan. Thanks for joining me. Thank you, Doctor Morrissey. It's a pleasure to be here. Very good. So, uh, they've given us the opportunity to discuss, uh, some of the uh advances and, and, and new, uh, topics and, and treatment of gynecologic cancers. Um, again by the introduction, we'll start with the trust study results again, this is a study. Um, that, uh, uh, dealt with, uh, initial treatment of, of ovarian cancer, which, uh, typically, uh, and the standard treatment is to try to do surgery first and remove as much tumor as possible. But in certain situations where patients present with advanced tumor, sometimes if it's unable to be all removed at the time of the first surgery, another strategy is to give chemotherapy first to kind of shrink the tumor to allow surgery to take place later in what we call an interval debulking. And so this study, um. Uh, was, was using a strategy kind of randomize the paces between trying to do surgery first versus giving chemotherapy first, uh, in advanced ovarian cancer patients and see which uh strategy worked better. Yeah, definitely. So this was a groundbreaking study recently presented at the ASCO conference in Chicago in 2025. So everybody was excited to see these results. You know, we've known for about two decades now that doing a cytoreductive surgery and achieving complete gross resection of all the visual disease, uh, tends to put our patients in the best prognostic group. The controversy or the question. It always was, do we start with surgery or do we start with chemotherapy? And that's what the trust study like you mentioned, uh, looked to address. So this was at expert centers from around the world, uh, similar to here at MCI expert centers where they do comprehensive surgery and have, uh, recovery units and are capable of performing these big surgeries. Uh, so we looked at over 650 patients like you said, randomized have to. Uh, primary cytoreductive surgery upfront. The other half to neoadjuvant chemotherapy followed by interval, uh, cytoreductive surgery. So what they found was, uh, as we expected, the patients who did the best were those who, uh, achieved complete gross resection of all visual disease at the time of surgery. Uh, the progression free survival, so the time it took for the disease to come back, was significantly better in the patients who had the primary cytoreductive surgery as compared to new adjuvant. What was interesting was the overall survival was also better in the primary set of reductive surgery group. However, it wasn't statistically significant, and there could be several reasons for that. I, I think the most important things to take away from the trust study is one, the timing of surgery may still make a difference, maybe not as much as we thought before, but. The patients who did the best had primary site reduction up front with complete gross resection. That was seen, uh, that was definitely clear. And I think another takeaway and, and what you can read between the lines is the most important things are, uh, the quality of surgery that the patients receive and the selection of where they have their surgery. So I, I think those were the major take. Was from from the trust studies. So I think, you know, neoadjuvant with interval study reduction is still on the table for patients like you mentioned who uh may be warranted, whether it's uh extent to disease or comorbidities, active DVTs, things like that. um, but primary set of reduction with complete research section when feasible should be offered to our patients as well. Absolutely. Yeah, I think it uh it reinforced kind of what we've been doing for many years, you know, kind of one of the, the dogmas of, of, of treating ovarian cancer patients is to try to, to gain an optimal site of reduction and remove as much tumor as possible, um, ideally for no gross residual disease, uh, that. And then those patients had the best prognosis so this further kind of um reinforces that. But um also, you know, from the other side there are certain patients that aren't candidates for for surgery either due to um concomitant medical issues sometimes, uh, sometimes age sometimes access to care. And that if they do undergo, uh, you know, neoadjuvant chemotherapy and have an optimal attempt at interval surgery, that their overall survival, um, isn't statistically significant. again, it's a little bit less in the study, but Um, that overall, you know, the fact that you couldn't have an initial surgery or weren't able to have an initial surgery doesn't, you know, put you, um, your, your entire disease course at a significant disadvantage compared to patients who are able to have initial surgery. Um, but obviously, you know, again, um, we, we try to, um, um, also reinforce to the community that if a patient with a, with a known or suspected ovarian cancer, peritoneal cancer, uh, or find it's consistent with that, that they need to see a gynecologic oncologist, um, at a center that has the ability to, to, uh, make the maximal attempt at trying to do an initial surgery because that gives your patient the best overall outcome. Absolutely. All right. Um. Again, in terms, so we have, uh, 5 topics to go through today, um, and, and any other things that come up. So we'll move on to the next, uh, study that we mentioned earlier, um, was, uh, resect ability scoring, uh, with, to try to determine which patients are best suited for a primary surgery, um, attempt versus neoadjuvant chemotherapy. And again, you know, the trial we discussed before, the trial was, was randomizing patients in the situation. And then we'll try to figure out, you know, if there are patients that are, if we try to do that, that primary, uh, maximal developing attempt, whether we'll be successful at that or not. And so, uh, what we'd like to do is, is, is make sure that the patients that we take for that maximal attempt we're actually able to achieve that objective because if you do a big operation, but you're only able to remove 80 or 90% of the tumor, you're really not helping them very much based on data that we have when following those patients. And so, um, if there's a way to kind of predict that better, um, uh, before going to the operating room, it may be helpful to uh avoid uh what they call futile, uh, laparotomy surgeries or, or futile attempts at, um, uh, optimal side of reduction and, and may help us, um, kind of, uh, streamline care a little bit. So I know that was uh something that you participate. So yeah, definitely one of the research passions of mine. And yeah, like you said, I wish we had a crystal ball where we could see this patient could definitely get a complete or optimal site of reduction and, and that would make it a lot easier for, for us as surgeons to triage our patients. Unfortunately, CT scans, PET scans are, are very good and, and very accurate, but sometimes they do miss microscopic. disease or disease on the bowel serosa, disease in the peritoneum, as well as certain areas. So what we looked at it while as a fellow at Sloan Kettering, one of the studies we looked at was, uh, modifying and perfecting a resectability score algorithm that used patient clinical characteristics as well as radiologic variables with a synoptic report from a radiologic team. And what we were able to find was we, we did a scoring system with a threshold of high risk of not achieving complete gross resection versus low risk, and we're able to use that to triage our patients. When we found it was highly sensitive and specific for doing so, we had a complete gross resection rate over, over about 80% and a fetal laparotomy rate of less than 5%. So, you know, we're never gonna be perfect in, in determining uh which patient. could go for primary study reduction versus new adjuvant, but we're gonna try to get as close as we can and uh and that's what this study tried to do and it's a real exciting future as, as technology is getting better as artificial intelligence and the ability to mine through large uh data with the use of technology will only make this better and will only get better in the future. And I, I look forward to studying this here as well. Great. Yeah, I mean, in terms of, you know, that study was obviously a lot of um um optimism in the study because, you know, if we can kind of do a laparotomy virtually, but with PET scans and like that to kind of get the same findings, but what's been done, you know, more standardly kind of around the world is to assess patients laparoscopically, um, you know, to make an incision, take a look with the camera and with a couple of investigators are reporting their scoring systems that will predict whether or not you can do. Uh, optimal side of reductions in those cases. So often, um, you know, one of the other um uh methods to go about this is to go for a laparotomy, make an assessment, make a decision whether or not you can complete a gross c reduction, and also, um, take samples, uh, which nowadays can be helpful for tumor analysis, uh, tumor genomic analysis, and, and to help us determine targets for, for treatment as well. Um, in terms of of. How you treat patients with, with this in terms of we always get preoperative scans and such, but is it something that still is part of your armarium is to do a laparoscopy to make the final decision. So yeah, so I, I think it's, it's really resource and facility dependent, uh, depending on where you're, uh, being treated. Uh, laparoscopy with biopsy and, and being able to assess either with a Fagatti score or different scoring systems when looking in is also a standard of care. And yeah, it's, it's definitely something in the armamentarium of a lot of the physicians. What we found throughout the four years of doing the study, there were questions whether very low score was almost, uh, a home run where we know we would definitely get a CGR. But a lot of the times it was in that gray area of, of getting into the 567, mid threshold. So, yeah, a lot of the times we did do a diagnostic laparoscopy to take a look. And like you mentioned, getting a biopsy. Because, uh, that's gonna be key for treating the patient in a timely manner if they do undergo chemotherapy, knowing exactly what type of cancer they have, whether it's from the ovary, the uterus, what type of ovarian cancer, targeted markers as well that we could use now as we're, and we'll talk about more in the upcoming topics, targeted therapies, um, but yeah, absolutely, doing a diagnostic laparoscopy is definitely one of the tools as well, right? So yeah, and in terms of, like I said, that some of the discussions about that study, which was a very well done study, and again, you had um uh some dedicated radiologists who, who take care of mostly gynecologic cancers who are pretty good at looking at things. And so whether or not, you know, every hospital is, is, you know, equipped to make the same predictions. And so, like I said, it's something that, you know, we should be studied and see if we can do it, but I think that, you know, for. For most patients, and you know, at the hospitals that don't have the expertise in terms of this, that I think the standard probably will still be to try to get the patient to a gynecologic oncologist to perform a, a, a laparoscopy or an assessment, or at least have the gynecologic oncologist look at the scans and say, listen, you know, between my exam and the scans, um, I don't think that we're gonna have a be able to do a um a gross initial. A reduction in neoadjuvant chemotherapy is the is the way to go. Yeah, absolutely. Very good. So I'm moving on to from ovary cancer to cervical cancer, um, discuss the um trial that was reported last year in terms of um treating cervical cancer and, and trying to reduce the radicality of surgery. So with cervical cancers of a certain stage and type, usually the standard treatment would be something called a radical hysterectomy, uh, which removes the uterus and the cervix as well as a large portion of the vagina and what's called the parametrium, which is the right and left of the uterus as well as some lymph nodes, and that's. Surgery sometimes can cause some side effects afterwards because it may cause some denervation of the bladder, uh, and kind of has increased risk of short and long term side effects compared to what we call a simple hysterectomy where you just take the uterus and the cervix and the tubes and ovaries out without that extra tissue um around the, around the uterus and around the bladder. Um, in terms of trying to reduce, uh, the, the amount of surgery for patients with smaller tumors, uh, the trial called the SAP trial, uh, which is done to try to, uh, look at early cervical cancers for, you know, tumors that were on the smaller side to see if treating with, uh, again, uh, uh, a, a less extensive hysterectomy called a simple hysterectomy with assessment of the pelvic lymph nodes, uh, would be. Uh, inferior or equivalent to doing a bigger surgery with again with more side effects. And so it was interesting to see the, the results of those trials. Yeah, absolutely. Like you said, I think we're always trying to get better in what we do and do better for our patients. And sometimes that's dialing down the surgery and seeing that they may not need this, this large radical hysterectomy, maybe a simple will do. So yeah, this isn't for all patients. Like you mentioned in the select patients, so 1A2s and 1B1s, so less than 2%. I believe it was a 10 millimeter depth of invasion or less than 50% invasion into the cervical stroma on MRI and uh lower risk histology, so squamous, adenocarcinoma, adenosquamous. So excluding some of the higher risk ones like gastric, neuroendocrine or or clear cell. But yeah, in these, in these. Low risk cervical cancers, they found that performing the simple hysterectomy, and it is important to note that this was done at the discretion of the, uh, or sorry, the discretion of the surgeon was open versus minimally invasive, which is a, a conversation in itself. Um, but yeah, they were randomized half and half, half to simple hysterectomy, half to, to radical hysterectomy of, I believe it was about 700 patients or so. And they found that, yeah, doing this simple hysterectomy when it came to cancer survival, overall survival was non inferior. So it was no worse than doing uh a radical hysterectomy. Uh, what they did find, and like you mentioned and alluded to was, yes, performing a simple hysterectomy did lead to less urinary issues such as urinary retention, bladder injuries. And less long and short term complications as well. So this is another thing that we're seeing over time. This could be a great option for our patients and, and kind of almost uh standard of practice setting where patients who come in now with these low risk cervical cancers may not need this large morbid surgery, they may get away with uh requiring more of a simple hysterectomy as well. Yeah, so again, that's, uh, it's, it is very welcome, um, data for us to try to, to try to actually treat a patient this week using that data, but you know, presenting the, the, the data to the patient to make sure decision making. As you alluded before, kind of, you know, not to get too off topic, and this could be a whole show in itself, but in terms of the use of minimally invasive surgery for Cervical cancer uh has been somewhat controversial based on, you know, uh, a couple of large studies that show that there might be a slight increase in the risk of recurrence in patients who had laparoscopy versus open surgeries. And so for this, at least with very early cancers, again, these tumors are less than 2 centimeters and fairly early in this group. It didn't appear that laparoscopic versus open approach, um. In this study, uh, affected your, your risk of recurrence, um, and also in this study, there were no specific protections, um, um, in terms of, um, treating the cervical tumor, uh, whereas there's, uh, new studies available, including one that's being done in, uh, one of the sites is Baptist Health, the ROC trial, where we're doing radical hysterectomies, laparoscopic versus open in a randomized trial, but as part of that. they're doing things to contain tumor spillage, which involves kind of um making sure that the the the cervical tumor has no access to the peritoneal cavity by by either stapling the upper vagina or using a chlage. Um, in this case, this study, there were no special containment procedures and it didn't appear that laparoscopic versus open had um any difference there. So that was also welcome news from that standpoint. Um, but again, we always talk about kind of the studies to try to advance. Uh, knowledge and advanced care and again uh Baptist Health, the Miami Cancer participating in that study to see whether or not we can safely perform radical hysterectomies laparoscopically, um, without affecting um uh prognosis, and again, that would be a much better option for patients as far as recovery and shorter stay, definitely. And pain management as well, definitely. Yeah, very good. Um, moving on from cervical cancer, we're talking about one of the very welcome um things that has happened in the last couple of years is the is the evolutionary kind of advent of using checkpoint inhibitors in the frontline setting for endometrial cancers. With two large studies in endometrial cancers using pembrolizumab, uh, or also dostarlaab in combination with Taxol and carboplatin, which had been the standard therapy for, for advanced uterine cancer after surgery, um, and showing a very large benefit especially in patients with mismatched repair deficient uh tumors. Um, so those two studies, uh, again, were very, uh, the results of those were very quickly assimilated to our practice, and we've seen a huge difference already. Yeah, absolutely, you know, uh, practice changing studies and, and it's interesting they both came out around the same time or presented SGO several years ago now widely utilized in practice, uh, like you mentioned for decades. We've been using carboplatin and Paclitaxel for uh uterine and advanced and recurrent uterine cancer, so it's a nice welcome and and setting the, the footprint forward for more targeted therapies and, and what does Starlomab and pembrolizumab do is that they're PD one inhibitors like you mentioned, the checkpoint inhibitors where they modulate the patient's own. immune system to try to uh get around the immune evasion that some of these cancers do to try to hide from your own immune system, kind of unlock unlock it and allow the chemo as well as your own immune system to fight the tumors as well. So with Ruby using the Starlomab, uh, they combined the Starlomab with the carbopla Paclitaxel like you mentioned. And followed up with maintenance of the start of life for up to 3 years and found, yeah, like you mentioned, a significant survival benefit and, and it's very stark when you look at these Kaplanmeyer curves, the difference it made, not only in the overall population, all comers, but specifically in the mismatch repair uh deficient tumors as well. So it is important to note that, uh, it, it is available for all patients and very effective in all patients and, and even more so in some of the, the DMMR. Patients as well as seen with pembrolizumab, uh, once again mirroring the uh Ruby study with GY018, uh, where they gave the Pembrolizumab and followed up with up to 2 years of maintenance with the Pembro and once again seeing a stark difference in the survival and, and it is exciting when you're at these conferences and you see such a. A gap between the survival curves where these medications are making a difference for our patients and extending survival, uh, whether it's progression for overall, so very exciting things and I think it's setting the like uh like I mentioned, it's setting kind of the, the blueprint for what the future of, of our immunotherapies and chemotherapies and that these GYN cancers can respond to them. Yeah, absolutely. And again, again, having practiced for a little bit longer, um, in terms of, you know, for many years, we just didn't have very, very good options as far as treating endometrial cancer. Taxol caril being the best of what we had and really no options that had a very high response rate. So. To be able to help these patients and, and again, especially see really dramatic responses in the patients that are mismatched repaired deficient, uh you know with with years long survivals and, and again there may be some that we're we're waiting longer and longer for them to recur or they're just not so even in recurrent disease or seeing responses so it's it's very promising. Uh, and again, kind of opens the door to see, you know, how, how can we integrate this further, um, how long do we need to use them, or the new medicines that are going to be available. So it's, it's an exciting time for, for uh endometrial cancer. Um, in terms of talking about a checkpoint hemorrhism and immune modulation, again, we use these types of medications and treating our other cancers as well. And then again using it in cervical cancer is something that we've done more recently with some benefit being shown from using pembrolizumab with radiation. Uh, with uh primary chemo radiation, so usually we have, uh, a cervical cancer that are too large to do an operation, usually more than 4 centimeters or involving kind of areas outside the cervix. Uh, often the treatment is, is primary chemotherapy with radiation and adding primolizumab to that regimen is shown to, uh, increased, um, efficacy as well. Yeah, absolutely, and like you mentioned, the more tools we have as physic. to help our patients the better and, and what we're seeing too from a lot of these immune checkpoint inhibitors like the Starab and pembrolizumab, very well tolerated. There are side effect profiles and adverse events we do look for such as um like thyroiditis, colitis, other things like that in rare instances, but compared to some of the more conventional chemotherapies, on the majority, patients are better tolerating some of these medications as well. Yeah, very much so. Uh, to move on, uh, keep things moving here. Um, so in terms of, uh, discussing other new medications, um, there are a newer medication called an antibody drug conjugate, uh, where you have, uh, antibody that targets the tumor and it carries a payload of a, a chemotherapy drug and releases that to the cell that it attaches to, which, uh, hopefully, uh, makes less toxicity because the chemotherapy is going exactly where you want it to go. One of those medications called Mervtuximab. Um, and it was studied in a study called the Mirrasol study in, in recurrent platinum resistant ovarian cancer, which is a group that after kind of our initial chemotherapy stops working and the tumor is growing, we haven't had very much success in terms of uh medications or any kind of treatments that will really control disease very well. Um, a few years ago with the, with the advent of bevacizumab, uh, using that with oral cytoxin was kind of one of the first things that showed any. Uh, appreciable response rate in this group of patients and then we've tried a few things since then with using Avastin uh bevacizumab in that group, um, but also now using the antibody drug conjugates like bitutuximab. Yeah, uh, very exciting time for, for ovarian cancer well as well. So like you mentioned, yeah, in the upfront setting, usually most ovarian cancer, especially high grade ovarian cancers do respond very well to platinum-based therapy. A majority will respond. Uh, unfortunately, there is a certain number that do come back and recur over time and become, become more resistant, uh, to chemotherapy drugs over time. And yeah, like you mentioned, there weren't a lot of good options for our patients. So, uh, antibody drug conjugates, I, I think are definitely the future as well. And, and like you mentioned, it's almost like a lock and key where it seeks out the cells that highly express the alpha folate receptor which ovarian cancer cells, uh, majority. The time do, uh, especially with higher uh expression. These were seen to have uh very good results. So what it does is it picks out those cells and leaves out or doesn't, uh, address the other cells such as your normal cells that you don't want the chemotherapy or the, the antibody drug conjugate going to. Uh, so some of the side effect profiles are very different and, and less severe in a lot of cases. There are certain things we look for like eye toxicity, sometimes also, uh, immune events that, that we do, uh, look, but once again, pretty well tolerated with Mervituximab. And, uh, so yeah, this was used for platinum resistant, uh, ovarian cancers that have received one. to 3 previous uh treatment uh modalities in the past. And yeah, this opened a new door in patients that weren't responding to much of, you know, less than 15% response rate. Now we have response rates of greater than 40% or about half the patients are responding to the Mervtuximab. Uh, the select patients with high alpha folate receptor positivity. Uh, so once again, a very exciting time for our patients and I think more coming on the way as well. Um, but I think once again, this is kind of getting to the, the overall theme and what we're talking about in, in going to a gynecologic oncologist and an experience center where they know to test for these things where they could give you these options and, uh, you know, I, I, I think that's so important for the patients to realize. Yeah, no, very much so. And again, you know, in terms of these medications, it, it's, it's helpful, especially new medications to, uh to have a physician who's, uh, uh, who's becoming very experienced kind of very quickly to look for these side effects. They said the Murbitutuximab. Has kind of some unique side effects that, uh, which can be some eye toxicity and things like that that you need to be in a special program of eye drops and have an ophthalmologist look um at, at the, at the eyes every couple of cycles to make sure that um we're doing everything we can to reduce toxicity. So to have kind of some places done that before, uh, is, is, is a good place to be. Um, and then also with the. Rituximab, you talked about kind of the patient group and the Mirrasol study were patients that had a very high level of folate um receptor on their tumors, um, whereas they've done some other studies which show if there's even a lower level folate receptor using the Murbtuximab in combination with bevacizumab, that there's a there's a good response rate in those patients as well. The other thing from, from having patients on, on this medication is, is the patients who tend to respond tend to have a very long response. And so, which again is kind of new for us and, and a very welcome thing for, for treating ovary cancer because usually, With the medications that we had before, we may find a medication that will that will respond and control disease for a little while, then that will become resistant to that medicine, so we switch flavors and use another medication, and then that will give us a response, but it's usually shorter than the previous medications response, whereas we're in with the myrbituximab, we're seeing patients that weren't really responding to other things that we're trying and then had a very good response that was had a long duration. So, um again, it's been a a good um uh advance for us. Um, uh, they're talking about final thoughts now, um, but, uh, just before, I always like to mention this, that the importance of HPV vaccination, um, which is again, is probably the the biggest intervention that we've had, and again, with cervical cancer in the advent of the Pap smear, significantly reducing, you know, the burden of cervical cancer in the United States and now with the HPV vaccination. Significantly reducing the risk of cervical dysplasia, which is the precursor to cancer. We've already seen a significant decrease in the amount of patients that are dealing with these problems and, and again, uh uh vaccine that's, that, that's safe, very effective and, and recommended for, for um um. Everyone between ages of 9 and 26, both males and females and males to to help reduce the risk of, of, of anal cancers and head and neck cancers, uh, but a very important intervention that's that again is one of the, one of the biggest advances that we've had in the last 20 years as well. Yeah, absolutely. Uh, we, you know, study, study after study has shown that the HPV vaccination saves lives across the population. And we are seeing it even, you know, in our own gestalts we're seeing less and less patients come in with some of these more serious cervical cancers, which, um, you know, is a great thing to see. So keeping up with the, um, I would say the public health push for it is so important and for the patients to, to take note. Absolutely, right. All right, so, um, as we look from everything from the trust study to shape and mirror us all, it's clear that we're moving into a new era of gynecologic cancer care. We're learning when to scale back, when to be aggressive, and how to tailor treatments in smarter, more targeted ways. It's not just about survival anymore. It's about quality of life, long term outcomes, and making each decision count. These trials are giving us the evidence to evolve, and that's an exciting place to be for both clinicians and our patients. 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