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Amanda Wilde (Host): Next, explore what your body may be telling you about gynecologic health with gynecologic oncologist, Dr. Gulden Menderes and Dr. Levent Mutlu. This is Putting Your Health First, the podcast from Health First. I'm Amanda Wilde.

Doctors, thank you so much for joining me on the podcast today. I know you are focused on the surgical side of things, the minimally invasive techniques you specialize in, and you also specialize in the management of systemic treatments. And Dr. Mutlu, I'm going to start with you. Bloating, pelvic pain, fatigue are quite common for women. So, women often dismiss those symptoms as diet or stress or hormones. How do doctors help us sort through these rather vague symptoms?

Dr. Levent Mutlu: Amanda, as you said, it is very difficult to go through these symptoms, and oftentimes there's a delay in the diagnosis. And women see many, many doctors before they see gynecologic oncologist. I think the key here is if you are having enough of these symptoms to have a high suspicion, go see your gynecologist very early on because you'll need an exam, you'll need a thorough history-taking, and we need to go through your family history. And as indicated, we may need to obtain more images to understand what is causing these symptoms.

Host: And are there screening tools available for ovarian and uterine cancers like we have for cervical cancer?

Dr. Levent Mutlu: For cervical cancer, we do have a very effective screening tool. It is pap smear and it is recommended for everybody after age 21 right now, up to age 65. And for special groups such as immunosuppression or any HIV-infected patients, then this screening is more often. And this screening effectively reduces the risk of invasive cancer.

Unfortunately, at this point, we do not have a very effective screening tool for ovarian or uterine cancers. Luckily, most of the time, uterine cancers will come up with symptoms such as postmenopausal bleeding. After the menopausal, you should not have any bleeding. If you're having bleeding, go see your gynecologist. And this leads to an earlier diagnosis. However, this is not a screening tool. Unfortunately, we do not have effective screening either for ovarian or uterine cancer.

Host: Are there then preventive steps women can take to reduce their risk of gynecologic cancers?

Dr. Levent Mutlu: Absolutely. Especially in the case of cervical cancer, we do have very effective vaccines available right now. United States FDA and CDC approved HPV vaccines, and they're usually administered in United States for all children around age 11 to 12. And the recommended age group is between nine to 26 years old. However, after age 26, you can still discuss the HPV vaccine with your provider, and certain individuals might benefit from this.

Host: What red flags might a woman notice that should be a sign to call her doctor sooner rather than later.?

Dr. Levent Mutlu: I think, in gynecologic care, most of the symptoms in any gynecology cancer could be very silent, especially in case of ovarian cancer. So, I would say, in any case, if you are experiencing something that is abnormal for your body, any unexplained pain, any abnormal bleeding, any unexplained fatigue, definitely call your doctor. See your gynecologist as early as you can. Most of the time, if these cancers are diagnosed at an early stage, they're treatable and even curable. However, I think there's a lot of delay in getting to see the doctor, and it impacts the survival and the outcomes in patients.

Host: So, as you said earlier, you're really emphasizing that point about getting to your doctor sooner rather than later. And then, when is it time for a provider who isn't a gynecologic expert to escalate a case to a gynecologic oncologist like yourself?

Dr. Levent Mutlu: Any complex case should be deferred to gynecologic oncologist, such as any ovarian masses that are large, complex looking, there's a high suspicion for cancer. Any confirmed cancer case should be managed by a gynecologic oncologist. There is a lot of data right now that indicates that gynecologic oncologists, when they operate on these patients, the survival is better compared to other type of surgeons, because we are trained in the specialty very specifically, and patients have better outcomes and we are also assisting with complex gynecologic cases as well, such as big, large uterus. If the gynecologist is not feeling comfortable taking care of these women, we are happy to assist them as well.

Host: Well, Dr. Menderes, I'd love to bring you in here to talk about surgery. You do the minimally invasive and robotic-assisted surgery. What role does this surgery play in treating gynecologic cancers? Is it the go-to? Is it the gold standard? Where does it fit into the treatment plan?

Dr Gulden Menderes: The role of minimally invasive surgery in managing gynecologic cancers, Amanda, has evolved significantly since early 2000s. I was an OB-GYN resident in early 2000s, and I remember operating on every patient with GYN cancer with a 30 centimeter up and down incision. Patients had to go through a ton to tolerate the surgery and to recover from the surgery, which would take them at least a month and a half to two months to be able to get back to their lives.

So since early 2000s, A lot has changed for the better in caring for our patients surgically, it initially started with conventional laparoscopy. For our cancers, I'll divide it as uterine, ovarian, and cervical cancers. Since those are the major type of cancers we manage surgically. These surgeries that used to be done with laparotomy and big up and down incisions, in early 2000s, we started employing conventional laparoscopy for uterine cancer. The earliest randomized control trial we had was in 2009. And the gynecologic oncology surgeons started trying to understand if it was feasible and safe to use laparoscopy to replace open surgeries in uterine cancer staging, which is our most common cancer, which comes up to 70,000 cases every year in United States.

And with this first study, the surgeons, although they were very early on in their learning curve of laparoscopy, they were able to show that minimally invasive techniques were non-inferior to open surgery in terms of the ability to obtain the lymph nodes that we need to stage these patients and without impairing their oncologic outcomes, meaning the patients' likelihood of having a recurrence or overall survival was not impaired by changing the surgical technique to minimally invasive surgery.

Later on, we were able to employ sentinel lymph node, sampling for uterine cancer patients using conventional laparoscopy and robotics, where the quality of life of our patients went up significantly, where these patients who were operated in late 1990s, early 2000s would be cured from their uterine cancer, but they would walk around with very swollen legs due to the number of lymph nodes that we used to remove without having this surgical technology.

Now, not only that we are able to stage every uterine cancer, minimally invasive surgery routes such as conventional laparoscopy or robotics. We are also able to improve their quality of life by getting them back to their lives in a day, instead of keeping them in the hospital for two weeks. And if there is a need for any adjuvant treatment, these patients who recover so much faster compared to open surgeries are able to initiate their systemic treatment in as short as two weeks. And this translates into improved oncology outcomes overall.

For metastatic uterine cancer patients, select GYN oncologists are able to debulk metastatic cancer with robotic technology, which is a very significant improvement in the quality of surgical care we are providing to these patients. We are able to manage select recurrences for patients with uterine cancer robotically as well. As far as ovarian cancer, it is a bit more complex because, as Dr. Mutlu stated, this used to be called a silent killer among gynecological oncologists, where patients would not show up to see a gynecologist or a GYN oncologist until the tumor would spread from ovary all the way up to their diaphragm, covering their intestines, filling their lungs up with fluid. So, the Italian group popularized laparoscopy for ovarian cancer staging. Dr. Fagotti is an outstanding surgeon from Italy who in 2006 came up with this idea based on our confidence that we were building on uterine cancer patient surgical management, and she popularized conventional laparoscopy for staging metastatic ovarian cancer.

Then, in 2010, around that time, we had four randomized control trials that came from Europe and US, that looked over 600 patients in each study, where we were able to understand at that time that we can give ovarian cancer patients chemotherapy first as opposed to upfront surgery that we used to do traditionally. And those upfront surgeries are no joke for any human being. We used to test the limits of human body by putting them through those extensive surgeries without trying to shrink the cancer with chemotherapy first.

Once we established upfront chemotherapy for metastatic ovarian cancer as opposed to upfront surgery, then as a community of GYN oncology, we started questioning then can we use robotics to debulk these patients internally instead of putting them through an up and down incision upfront. And we do have a significant amount of data accumulated in the last five to ten years, including patients with over 8,000 patients from national cancer database looking at almost every institution across the nation where we were able to prove the feasibility and safety of interval debulking surgery with a laparoscopic, but mainly robotic approach given the complexity of these cases. And those patients, again, we're able to start their chemotherapy so much shorter after their surgery that this has been translating to their improved oncology outcome and overall survival.

There are still a group of patients among ovarian cancer patients that we use robotic technology for management of their recurrences. This is not for everyone. The patient has to have good performance status. We shouldn't have a widespread metastatic disease to be able to handle these cases with robotic surgery. And it is also very dependent on the competence and the skillset of the surgeon. But it is an option for those surgeons who feel comfortable. And I'm grateful to have a very surgically skilled partner, Dr. Mutlu. And we are able to provide robotic surgery for managing uterine cancer staging, uterine cancer recurrences, debulking metastatic uterine and ovarian cancer robotic, which is only done select academic institutions here in the U.S., and we have been able to provide this service to our community here in Brevard.

As far as cervical cancer, until 2018, when a big randomized control trial was published, cervical cancer patients were benefiting tremendously from robotic surgery for staging and managing early cervical cancers. After that trial, which has been criticized significantly, the standard of care for cervical cancer patients changed from being minimally invasive surgery back to open. There are some ongoing trials that is going to change that trend and we are going to keep up with the technology and minimize morbidity that the robotics enable the surgeon to provide and the patient to benefit from, but across any type of uterine, ovarian, and cervical cancer patient early stage.

Host: That is a perfect outline of how evolving techniques have improved patient outcomes. Dr. Menderes, beyond surgery, are there other treatment advances women should know about?

Dr Gulden Menderes: There has been significant advances in the last decade in terms of how we manage our GYN oncology patients. So, the biggest advance, I would say is our ability by partnering with technology companies to get tumor mutational profiling. So, we are able to send a specimen to this lab. And essentially, they're able to give us a 10-plus-page report of every single mutation they detect on the patient's particular tumor, where we can exploit that data on patient's behalf and use targeted treatments, immunotherapy, new agents such as antibody drug conjugates that are human-engineered, brilliant anti-cancer drugs. And we are able to see results that we haven't seen since 1980s in managing these patients in terms of response rate, in terms of duration of response, and the number of patients that we are able to cure even in advanced metastatic stages.

The other big progress that I am proud on behalf of our GYN oncology societies, how we are able to provide some of our patients with maintenance strategies. So as far as ovarian cancer, everyone with stage III, IV ovarian cancer would say, "Oh, I probably have less than five years to live." And now, we have been seeing results that we have never experienced before with maintenance strategies such as PARP inhibitors for metastatic ovarian cancer patients that delay the recurrence and improve their longevity. There are immunotherapy agents we use for cervical cancer and uterine cancer patients with significant prolongation in the duration of response to these treatments.

The other advance that we have seen in the last five years or so, which is quite exciting for both of us, is being able to pick up recurrences so much earlier on by utilizing a blood sample of a patient to see if there is any tumor cell DNA floating in the blood to kind of say, "All right, we are expecting a recurrence and we are going to detect it so much earlier," instead of waiting another couple months for anything to show up on a CAT scan or a PET CT. And the clinical trials have always been very instrumental in GYN oncology, but I think we are able to come up with these way more sophisticated agents like antibody drug conjugates, which are so specific just for the cancer cells without hurting the patient's healthy cells and overall not impairing their performance status.

So, tons of new advancements have been happening in the last five to ten years in the field of GYN oncology, and we are going to be able to objectively see these advances translating into oncology outcome of the patients in the next decade.

Host: So, it will be exciting to look forward to further progress in targeted treatments. Because as you've alluded, the earlier you pick up issues like recurrence or cancer itself, there are greater chances of treating those issues successfully. Dr. Mutlu, are there family history factors like BRCA genes that should trigger genetic testing or closer monitoring?

Dr. Levent Mutlu: Absolutely. As Dr. Menderes said, with the advances we made of understanding the role of genetics in gynecologic cancers, we have recovered certain genes that could get increased risk of developing ovarian cancer. And one such gene is BRCA gene, BRCA1, BRCA2, and these women are at very high risk of developing ovarian cancer. So, we need to have high suspicion index for these individuals to be tested to diagnose the BRCA mutation, such as if you have multiple family members that is affected with breast or ovarian cancer, pancreatic cancer, male breast cancer, go talk to your doctor to be tested, to understand if you have this gene or not. And if women is diagnosed with BRCA gene, then we do close surveillance of these individuals before age 35. And risk-reducing surgery is recommended for this women between age 35 to 40 or 40 to 45, depending on what kind of mutation they have.

Host: And Dr. Menderes, speaking of risk factors, are women in the stages of menopause or perimenopause, having those hormonal shifts more at risk for gynecologic cancers?

Dr Gulden Menderes: For certain cancers, yeah, there is a increased risk. As far as cervical cancer, the risk is linked to HPV very strongly, and HPV exposure usually happens early on with the onset of sexual intercourse. So, those patients are not particularly affected by the hormonal fluctuations that the women experiences around age 50, which is the average age of menopause.

For uterine cancer, I can say that, yeah, the menopause and the ovaries shutting down and essentially cessation ovulation is going to lead to a decrease in the progesterone levels of the patients. And the body fat, which is the second source of estrogen in women's body, continues to traditionally kind of go higher as we age. So then, these women around the age of menopause have an unequal, unopposed level of estrogen, meaning their body would continue to produce estrogen through their increasing body fat, but with their ovaries failing and not producing progesterone, that excessive estrogen would increase their uterine cancer risk significantly.

So, menopause and after menopause is when we start seeing uterine cancer patients for the most part. Although the increasing obesity across the nation and globally is, unfortunately, leading to these early age uterine cancer incidences and diagnosis. But as far as uterine cancer, we do see an increase in that cessation of ovulation, and not producing progesterone anymore puts them at risk with continued production of estrogen in the body.

As far as ovarian cancer, the hormonal fluctuations do not affect the incidence of ovarian cancer. It's by statistic diagnosed in 60s and 70s, but the ovarian cancer is very rarely hormonally linked. So, the most common cancer in GYN is uterine cancer, which is about 70,000 cases diagnosed every year. And unfortunately, 13,000 women dying of this disease, there is an increased risk with these hormonal fluctuations.

Host: Well, we've talked about some amazing and advanced and progressive ways to medically address these cancers. Dr. Mutlu, when someone is diagnosed with gynecologic cancer, what kinds of support groups or resources are available to help them through the emotional side of this journey?

Dr. Levent Mutlu: Amanda, I think this is a very important part of the cancer care. There's medical. We do all these amazing surgeries and there's advances on medical treatment. However, as a patient, emotional burden is very, very big. And I often see my patients, they like to talk to other people, share their experiences, and we have support groups available for all of our patients, and they can share their experience with other cancer survivors, and it's a big part of cancer care. And some of our patients go through financial toxicity. All these medications could be expensive, sometimes not covered, and there could be financial resources available. I think when you are approaching cancer care, most gynecologic oncologist now understand this is not just surgical or medical management, but treatment as a person as a whole.

Host: Focusing on the whole person. Dr. Mutlu, what is one message you want women to walk away with about knowing their bodies and trusting their instincts?

Dr. Levent Mutlu: I always say that patient knows her body best. And if something doesn't feel right, if you're having an unexplained symptom and you are not feeling yourself, do not postpone seeing a doctor. Please come to see us. Please come to see your gynecologist or your primary care. And the patient is always the best judge about themselves.

Host: Do you agree, Dr. Menderes?

Dr Gulden Menderes: I couldn't agree more with what Dr. Mutlu stated. This is a big journey. It's very emotionally and physically tolling, but more so emotional on our patients. And I am grateful for our wonderful care group, which is located in Brevard, supporting our patients through treatments, through their recurrences, through their challenges. Most of these members are previous patients who are in remission and cancer free, who are essentially cheerleading this group and bringing speakers such as myself and Dr. Mutlu, educating the patients multiple times a year. Just kind of being sisters to each other saying, "You are not alone in this." So, we are very lucky to have care support group. And we do care tremendously about the whole human, emotionally and physically when it comes to caring for our patients.

And along those lines, I'm very excited to announce with Dr. Mutlu's partnership that we are going to be starting a Quality of Life Clinic at Gateway in January 2026, where we will solely focus on improving quality of life by managing their menopausal symptoms, intimacy issues, you know, decreased libido. So, we don't want to just leave it at. We are removing the uterus, we are giving radiation and chemotherapy and we don't know what to do with the aftermath. So, it's an all around care. This is a very sensitive time in the life of our patients. So, we just want to walk this road with them from beginning to end.

Host: I appreciate that emphasis on comprehensive care and support. If a woman is concerned, what is her first step? I'll let you both take time to answer that. Dr. Menderes, perhaps you'll go first.

Dr Gulden Menderes: The patients know themselves the best, and I want each and every single woman experiencing a change in their health to trust their instinct and to advocate for themselves, to raise their voice. "This is not normal. I don't know what this is." You don't need to know. Sometimes we don't know as physicians, but just come and see a provider where we can get you in the right trajectory for seeking management, understanding what's wrong, figuring it out early on instead of saying, "Oh, this is nothing. Maybe I just ate something wrong and that's why I'm bloated. Maybe I'm gluten-free," you know?

You know, just kind of trust your instinct and call a provider that you trust. Preferably, in this case, a gynecologist would be a great start. And if patients want to come and see us directly after they are worried about an abnormal bleeding, a new pelvic pain, we don't turn anyone down. We take everyone's concern seriously. We would talk to our patients. We would do an exam. We would get appropriate imaging. We would figure out early on with their partnership and collaboration with us early on so that we don't wait until things get out of hand. So, trust your instinct. Go see a gynecologist or come see us.

Host: Well, Dr. Mutlu, you have already said that earlier in the interview. Is there anything more to add to that? It's so easy to dismiss something that seems simple, that possibly it'll go away. I mean, that's usually our first go-to.

Dr. Levent Mutlu: Absolutely. I agree with what Dr. Menderes said. I think trusting your body and instincts are the best. And please go ahead and seek care. Do not delay it. Especially in gynecologic cancer's., Early diagnosis and treatment is key. And we can truly make a huge difference if you diagnose the problem early on. I think, you know, seeking care early on is the key step here.

Host: So, trust in yourself, which is always good advice to listen to yourself. Dr. Menderes, Dr. Mutlu, thank you so much for your time today and for giving us even more hope than ever for patients facing these gynecological cancers.

Dr Gulden Menderes: Thank you, Amanda. We are privileged to be here. And we love serving this community. We appreciate it.

Dr. Levent Mutlu: Thank you, Amanda.

Host: If you have a concern and would like to schedule an appointment with a gynecologist or primary care provider, visit hf.org/findadoc. And if you enjoyed this episode, be sure to tell a friend share on social media and check out our entire podcast library. We look forward to you joining us again. This is Putting Your Health First, the podcast from Health First.