Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Hi, I'm Dr. Roni Nitecki Wilke, and I'm an assistant professor at the department of Gynecologic Oncology and Reproductive Medicine at MD Anderson Cancer Center. Today I am joined by my colleague, Dr. Amir Jazaeri, who's a professor of Gynecologic Oncology and Reproductive Medicine at MD Anderson Cancer Center. And this is the Cancerwise Podcast. Hi, Dr. Jazaeri.  

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Hi, Roni. It's great to be here with you. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Thank you for joining me. We are going to discuss personalizing ovarian cancer treatment and what that means, all the way from individualizing care for women with ovarian cancer, who are getting treatment to what it means to individualized treatment for patients who are at risk of getting ovarian cancer. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine That sounds great. There's been a lot that's been happening in this area. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Let's talk about personalizing ovarian cancer treatment first. So, the first thing I'd like to ask you is what is minimal residual disease? What has interested you in this concept and how have you applied it to ovarian cancer care? 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Yeah. Thank you for that question. So, when I think back that the, we're using the same treatments in ovarian cancer now then, that, that haven't changed since I was a medical student, that, that's troubling. And so, as you know, the problem with ovarian cancer isn't the initial treatments. The surgery and the chemotherapy works pretty well. But the problem is that many women who appear to be in remission, in fact, have residual disease that until now have been difficult to detect. And that's where we sort of refer to as minimal residual disease or MRD. And as you know, a few years ago we started to offer these women a minimally invasive outpatient procedure called second-look laparoscopy. And what we found was really amazing, that at the time of surgery, we can detect residual cancer in 25 to 65% of women who otherwise would have a normal CT scan and a normal CA-125 tumor marker. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine So, you mean that women can have a completely normal scan and have a normal tumor marker, and still have disease that can be seen at the time of surgery? 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Unfortunately, the answer is yes for a large proportion of women. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine I'm sure that some of our listeners would also be surprised to hear this. And do you think that this may be the reason why ovarian cancer can, and for most women, does recur? 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Absolutely. And of course, when we use terms like recurrence or the cancer is back, I think that makes sense on some level. But the truth is that the cancer never leaves the body. So, it's this residual disease that over time stays, grows, and eventually shows itself in the form of clinically detectable disease. Only then patients are restarted on chemotherapy and after they become resistant to those treatments do we think about investigational treatments or clinical trials. And I think one of the ways we are trying to push the field forward is to say if women have minimal residual disease, and if we know that that's associated with a worse outcome, why not offer patients these investigational treatments at this point, rather than wait until the cancer becomes bigger and more difficult to treat? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine So, it sounds like minimal residual disease could be an opportunity for patients, or at least the knowledge that the minimal residual disease exists, could be an opportunity to initiate treatment earlier than patients would get otherwise. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine You know, I find it always interesting to have this discussion with patients. When you tell women that even though you're giving them good news with a CT scan that's normal and a CA-125 that's normal, that there may be still residual disease, most of the patients that I talk to are interested in knowing. You know, I think in the past we have kind of turned a blind eye to this, or at least I would always hope that my patients are in that 10 or 15% of patients that might be cured. But the reality is that, of course, most patients are not. And to offer them something better than just hope that may not be based on reality. I think that's something that patients really relate to and quite frankly, demand. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yeah, I would agree with that entirely. So, what happens when you take a patient to the operating room and you discover MRD, or minimal residual disease? What do you offer the patient at that point? 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine That's a great question. First of all, it may sound counterintuitive, but sometimes during the surgery, many times during the surgery, we're not even sure if there is minimal residual disease present or not. During the second-look laparoscopy, we often try to biopsy areas that look different. For example, there may be scar tissue from the initial surgery, but even if not, we try to cover areas with biopsies that are favorite hiding places for ovarian cancer. Because we can only biopsy so many areas, we also put in sterile saline into the abdominal cavity, and we aspirate the saline. That saline touches all the surfaces and collect cells that may exfoliate or fall off of surfaces into the fluid. That fluid is then collected along with all the biopsies, and everything is sent to the pathology lab. It often isn't until we get the final pathology report that even I know if there has been minimal residual disease or not. And of course, then we share this information with the patients and together we come up with the next best step. For some patients that have minimal residual disease, we have clinical trials that might be the right treatment option. This is the use of immunotherapy to intervene at a time where we think residual cancer cells that might be present might be relatively chemo-resistant, since they've lasted through six or seven cycles of chemotherapy. For other patients who are negative or otherwise might have PARP inhibitors as an option, we still don't have any evidence that PARP inhibitors don't work if you have minimal residual disease. So, for many of those patients, the treatment options that currently are existing are the best we have. But even then, we are trying to really identify what might be the Achilles heel of this MRD so that we can come up with more effective treatments for patients. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine That's really exciting that patients have these opportunities at MD Anderson to take part in a clinical trial so early in their disease course. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Of course, you're no stranger to individualization of treatment, and I've heard about the wonderful work that you're doing in trying to prevent ovarian cancer. I think our audience would love to know that we are actually succeeding in ovarian cancer prevention. So, why don't you tell us about how incidence of ovarian cancer is changing over time? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yeah, absolutely. That is a great question, Dr. Jazaeri. Thank you for the invitation to speak about this. I really think that one of the most important things about ovarian cancer prevention is to talk about who really prevention matters for, and I would argue that it probably matters for everyone, for every person that has ovaries and fallopian tubes. But I think it matters particularly for patients who we know have a genetic predisposition to develop ovarian cancer. In fact, what we now call ovarian cancer, we really think starts in the fallopian tube. And that knowledge over the past few decades has really opened doors for alternative treatment strategies. Now you may ask, why do we need alternative treatment strategies? So, for any patient with a BRCA1 or a BRCA2 mutation, there is a recommendation to undergo a risk-reducing surgery. During the surgery, the surgeon would remove both the fallopian tubes and the ovaries in women who are quite young. So, for patients who are BRCA1 carrier, the recommended age to have the surgery is between age 35 and 40, and for BRCA2 carriers it is between 40 and 45. So, for most of these patients, they will still be premenopausal, meaning their ovaries are still working, making estrogen and progesterone that impacts their entire bodies. And while this strategy that is the recommendation and is the standard of care, has been shown to decrease both the risk of ovarian cancer and the risk of death in these patients, it comes at a cost. And I think going through menopause early is a big cost, both in terms of, sort of, short-term symptoms, but also there are some more long-term impacts that patients can see. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Yeah. Why don't you share with our audience what some of the long-term health results of early menopause or surgical menopause are? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yeah. So, certainly, you know, when we talk about the long-term impacts, we think of things like bone loss, which I think is very important for patients who are expected to live for a longer time. We're preventing cancer and then we put them at risk for osteopenia and osteoporosis. We've also shown in studies that removing ovaries too early is tied to an increased risk of cardiovascular death. Now, that risk may be small, but it's certainly been seen in modeling studies in the literature. There's also some data, I would say, not quite as clear cut that shows an increased risk, potentially with some cognitive disorders like Alzheimer's. So, you know, the story is not 100% clear. But we know that removing ovaries very early does have long lasting impacts. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine So what are we doing at MD Anderson to try to address this issue of we want to prevent cancer, but we don't want patients to go through early menopause? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine So going back to this idea that we think that the majority of these cancers probably start in the fallopian tube opens up an opportunity to offer an alternative strategy. But essentially the idea is, if we think that the origin of these cancers is in the fallopian tubes, what if we removed fallopian tubes first and allowed patients to have more time with their ovaries? So, we would be removing the agent that we think is responsible for cancer development but preserve the ovaries and prevent women from going into early menopause. And the study that we currently have open is the TUBA-WISP II trial. And what it allows is for women to keep their ovaries for an extra five years beyond what the guidelines recommend. So, for a woman with a BRCA1 mutation, she could have her fallopian tubes removed by the age of 40, but then she can hold on to her ovaries until age 45. For a woman with BRCA2, she could hold on to her ovaries until age 50. And this allows a lot of women to get what we hope is ovarian cancer prevention, but not at the expense of going into menopause so early in their lives. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine You know, some of our audience may have heard the term opportunistic salpingectomy. What is that? And, and how do you think that might impact rates of ovarian cancer? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yeah. Thank you for that question. That's an excellent question. I would like to differentiate the strategy that we're talking about in TUBA-WISP II from opportunistic salpingectomy. So, opportunistic salpingectomy means that when a woman is getting surgery for any indication, whether it's a C-section or a hysterectomy or a procedure that has nothing to do with a Gyn organ, there is an opportunity to remove the fallopian tubes. If a woman is getting, for example, a hernia repair and the surgeon is able to see the fallopian tubes, removing them at that time would be an opportunistic salpingectomy. This is a strategy that has been employed in increasing rates since 2010, and it's very popular in women that are getting gynecologic surgery. But we hope that that also expands to women who are getting any surgery, because once the fallopian tubes are no longer needed for spontaneous pregnancy, they really have no function. And in areas where there is more and more of this opportunistic salpingectomy, we are starting to see hints of a decrease in the incidence of ovarian cancer. So, my gut feeling is that this strategy works on a population level. There needs to be years more of data for us to know for sure. The reason I want to make a distinction between this strategy, which I think is a really important one for our audience to know, and the strategy that we're employing in TUBA-WISP II is that for women at a population level, risk of ovarian cancer, opportunistic salpingectomy is an incredible opportunity. For women who have a predisposing mutation, their risk of ovarian cancer is so high, and we already have a strategy that we know works. We have to be able to compare this alternative strategy of removing fallopian tubes first to the standard of care, to make sure that it is as efficacious, meaning that it works as well, before we can recommend it to everyone. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine I think another question that comes up, you touched upon mutations in BRCA1 and BRCA2 genes. Are there genetic mutations that would put women at elevated risk for breast or ovarian cancer? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yes, there certainly are. And thank you for mentioning that. Mutations in RAD51C and D, BRIP1, PALB2, they're, just to name a few, there are others, but that whole group that I just mentioned, they are also eligible to participate in the TUBA-WISP II trial. Those mutations, I think there's less known about them than with BRCA1 and BRCA2, but it is an important group to consider and thank you for mentioning that. They are also eligible for this trial. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine And can you mention the huge role that our genetic counselors play in in genetic testing and helping patients understand their results? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Our genetic counselors play an enormous role, and they are an incredible resource to a lot of patients at this institution. In our department, every patient that is diagnosed with a new ovarian cancer is referred to our genetic counselor for testing. And also, anybody that has seen anywhere in the hospital that has a family history that indicates that their family may have an increased risk of having one of these hereditary genetic cancer syndromes are referred to our genetic counselors as well. They spend time with our patients talking to them about their family history, figuring out exactly what their risk is before testing, recommending testing if it's appropriate, and then going through the results with our patients after they have completed testing to make sure that the patients understand exactly what they are and are not at risk for, and what are the things that they can do to either screen for cancer or prevent cancer? 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine I think another area of research for risk reduction is in the area of cascade testing, and I believe Dr. Rauh Hain has interest. Can you briefly tell our audience about some of that? 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Cascade genetic testing is incredibly important. Basically, in lieu of population level genetic testing, which is not something that we're doing right now. It's not something that is recommended. It's not something that we have the sort of public health infrastructure for. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine And by that you mean testing everybody. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Everybody. The best way to figure out if you have one of these mutations is to look at your family. And if there is a person in your family that has one of these mutations, any first degree relative has a 50% chance of carrying that same mutation. And so, cascade genetic testing, what it does is it focuses on that family unit to increase testing amongst a population of people that have a higher risk of having a positive genetic test. And the importance of that is, the more people that we find that have these mutations, the more cancers we can prevent. And that is, that is why I'm so passionate about this work, because once cancer develops, we do everything that we can. But wouldn't it be amazing if we could prevent it from ever happening? So, patients do not have to go through all of the difficult treatment and surgery that we ask of them to do when they're diagnosed with an advanced malignancy. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine Yeah. Well, that sounds like a lot of good news so that patients don't ever have to deal with ovarian cancer. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yes. I'm hoping we'll know more and more with the years to come and develop more and more strategies to figure out who's at risk and how to best care for them. Dr. Jazaeri, I wanted to ask you, for our younger patients that are diagnosed with early-stage disease, do we have any options for fertility sparing if that is something that they desire? 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine That is a great question. You know, with the recognition that many young patients deal with cancer and that that cancer treatment can impact their fertility, ASCO, which is the American Society for Clinical Oncology, has put out guidelines several years ago that recommends evaluation of young and reproductive age men and women for possibility of infertility before initiation of cancer therapy. I think we're very lucky at MD Anderson to have colleagues in our Oncofertility department who see actually patients not just with gynecologic cancers, but across the entire institution to counsel them on ways to retain their fertility while undergoing effective cancer treatment. And of course, these are Dr. Terri Woodard and Dr. Laurie McKenzie in our Oncofertility department. You know, I think many of our audience may not know, but cancers such as cervical cancer, ovarian cancer, certain types of uterine cancer may be successfully treated without loss of fertility or with preservation of opportunities for future assisted reproductive technologies. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine Yeah, the, they're an incredible, incredible service to our patients. And I'm so happy that we're able to collaborate with them so closely. Well, thank you so much for joining me for this enlightening conversation. I had a great time. 

Amir Jazaeri, M.D., Professor, Gynecologic Oncology and Reproductive Medicine This has been very fun. 

Roni Nitecki Wilke, M.D., Assistant Professor, Gynecologic Oncology and Reproductive Medicine And thank you for tuning in today. If you enjoyed this episode, be sure to follow or subscribe on Apple Podcasts, Spotify, YouTube, or wherever you get your podcasts. And don't forget to comment or review. For more information or to request an appointment at MD Anderson, call 1-877-632-6789 or visit MDAnderson.org. Thanks for listening to the Cancerwise Podcast from MD Anderson Cancer Center.