Melanie Cole, MS (Host): Welcome to AHN MedTalks, an informative resource for physicians across various specialties, as we delve into the latest medical insights and best practices, ensuring you stay at the forefront of your field. I'm Melanie Cole, and joining me today to highlight ovarian cancer trends, risk factors, symptoms, and when to refer patients to Gynecologic Oncology is Dr. Eirwen Miller. She's an American Board of Obstetrics and Gynecology Certified Gynecologic Oncologist with the Allegheny Health Network.

Dr. Miller, it's a pleasure to have you join us today. Before we get into ovarian cancer, give us a little bit of an overview of your role at AHN, your expertise. Tell us a little bit about yourself and how you came to Allegheny.

Dr. Eirwen Miller: Hi, Melanie. Thanks for having me today. This is an exciting opportunity to talk a little bit about ovarian cancer, and what I do on a day-to-day basis here at AHN. So as part of the Women's Institute here at AHN, I am one of the six GYN-oncologists covering the network. I also am the quality officer for the Women's Institute, the Fellowship Director for the GYN-Oncology Fellowship Program here and the Chief Surgeon at West Penn. I've been with the network now going on seven years. I joined the network right out of fellowship. I did my GYN-Oncology Fellowship at Albert Einstein College of Medicine in the Bronx, New York, and finished that approximately seven years ago.

You know, I think what really excited me and drew me into the field of GYN-Oncology was the opportunity to provide care to women over a sustained period of time. And our patients come to us in moments of vulnerability, certainly with a new cancer diagnosis and really becoming a part of their lives and part of their journey through treatment and survivorship. And ultimately, it requires involvement in end-of-care life as well, and it really is a special relationship with a patient that you develop, providing all of those spectrums of care for a continuum of time, so it's a great field.

Melanie Cole, MS: Well, it's certainly an exciting time in this field, and thank you for sharing that. So, what have you seen in the ovarian cancer trends? Speak about the current state of ovarian cancer in the country.

Dr. Eirwen Miller: Ovarian cancer incidence is relatively stable. If anything, it's declining somewhat across the United States. On average, approximately one in 70 American women will be diagnosed with ovarian cancer in their lifetime, so that's about 1.7% of women in the United States. What's really exciting to us is while the incidence is stable or potentially decreasing somewhat, our prevalence is increasing because women are living a longer period of time with their diagnosis of ovarian cancer. In the last five to seven years, we've really seen some remarkable advances in the chemotherapeutics that we have available to our patients.

Melanie Cole, MS: Speak a little bit about risk. Are there specific patients that are most at risk for ovarian cancer and what role does inherited trait play in developing this type of cancer? Speak a little bit about genetic predisposition and any other risk factors.

Dr. Eirwen Miller: We know that approximately 25% of ovarian cancers come along with a genetic predisposition. We've known for a good while now about BRCA1 and BRCA2 genetic mutations predisposing to ovarian cancer, and those may account for 10-15% of our diagnoses. But we've learned of additional what we call BRCA-like genes such as RAD51C, RAD51D, BRF1. There's a variety of others that also when diagnosed with a germline mutation, patients are at higher than average risk for developing ovarian cancer and others.

Really, the way to identify a patient's predisposition to this is a really solid family history. And I think that patients will come to us with their diagnosis of ovarian cancer. And when you kind of delve into that family history, you're learning that there's a strong family history of breast and some ovarian cancer in the family. So, a family history is a really important part of their healthcare maintenance.

Melanie Cole, MS: One of the most challenging things about this type of cancer obviously is catching and detecting it early. So, I'd like you to speak about any symptoms that might possibly show up and recommended evaluation if someone does suspect something and they go to see you and you order a CT and it shows carcinomatosis. Is there further evaluation? What is helpful to initiate really that diagnostic criteria?

Dr. Eirwen Miller: Ovarian cancer is known somewhat informally amongst the GYN-Oncology community as the silent killer because the symptoms are relatively vague and maybe relatively asymptomatic until presenting with advanced stage symptoms.

In the early stages, when disease is confined to an ovary, it may be entirely asymptomatic or patients may present with very vague symptoms of, you know, symptoms intermittent lower abdominal pain, perhaps change in urination with an increased frequency of urination or some sense of urinary urgency. We can often see similar symptoms with change in bowel movements of some rectal urgency, change in the caliber of stool, any sort of compressive symptoms on those other pelvic organs.

In its more advanced stages, ovarian cancer presents with carcinomatosis and ascites and will cause symptoms of early satiety, perhaps some symptoms of reflux, abdominal distention and bloating. Very often the symptoms of ovarian cancer are attributed to GERD as well as constipation. So, it's a really common story that I hear from patients that they were having IBS or reflux, and they were prescribed an H2 blocker or Prilosec and their symptoms persisted and that prompted a CT scan. And so, I certainly would encourage providers that are seeing these patients with these symptoms to consider CT scans as well as pelvic ultrasounds when these patients have symptoms that are refractory to their normal management.

I think that when we see patients with carcinomatosis, the first decision we have to make in GYN-Oncology is whether to start with neoadjuvant chemotherapy or a primary debulking surgery. But in order to make that decision, we have to confirm first that this is a gynecologic malignancy. Certainly, not all carcinomatosis is ovarian cancer. We can see colon cancer or pancreatic cancer present very similarly. So, it's helpful for us if a patient shows up to our office with an IR-guided biopsy of omental disease. When carcinomatosis is seen on imaging, we have a preference not to biopsy a mass in the pelvis, and typically are requesting from our Interventional Radiology colleagues that it's the omentum or some other site of carcinomatosis that's biopsied. But I think that that information is really helpful in expediting our ability to care for a patient with advanced ovarian cancer.

Melanie Cole, MS: I'd like you to speak about advancements in those diagnostic techniques as well as the development of biomarkers and giving you that improved ability to detect this disease earlier. Is there anything that's really exciting to you?

Dr. Eirwen Miller: I think that early diagnosis has hampered us in ovarian cancer for a long time. In patients that are at general population risk for ovarian cancer, we have not identified any screening studies to date that results in prolonged overall survival with those patients that go on to develop ovarian cancer. So, we've looked at strategies for a variety of serum biomarkers as well as screening pelvic ultrasounds at various intervals and have not found those to be studies that result in improved survival in the way that colonoscopy and mammogram and Pap smears prolong survival in the general population as screening modalities.

In patients that are at high risk for ovarian cancer based on a germline genetic predisposition, there is some data to support using routine ultrasound and CA-125, in addition to pelvic exam on an every 6 to 12-month basis, and that that might improve survival. That data is a little bit unclear, And we will offer those screening modalities. But in general, we have not found a great serum biomarker for ovarian cancer screening.

I think one thing that is very interesting to us in the Oncology field moving forward is looking at circulating tumor DNA, potentially as a screening study. That obviously is yet to be clinically accessible, nor do we understand whether or not that will result in survival benefit or is accurate for early ovarian cancer diagnosis, but certainly a field that we are interested in and looking in moving forward in the field.

Melanie Cole, MS: Before we get into treatment options that are exciting in your field, Dr. Miller, what about fertility preservation before or during treatment? At what point do you recommend preservation be considered? When should a fertility specialist be brought in?

Dr. Eirwen Miller: I would say there are a couple of requirements to consider fertility preservation. The most important of which is the patient's desire for future fertility. With ovarian cancer, the standard of care recommendation is that patients have a complete hysterectomy and bilateral salpingo-oophrectomy as part of their staging operation. Anything less than that is an incomplete staging. So for patients that express a desire for fertility preservation, I think a referral to Reproductive Endocrinology and Infertility is warranted. And often, what we find for those patients is that the next barrier for them might be the financial means for future reproductive technologies. But I think the most important factor for patients is their desire for future fertility. And then beyond that, it's a risk-benefit conversation of how much of a staging surgery can be performed, should we harvest oocytes, and freeze either oocytes or embryos before they have a complete operation.

Melanie Cole, MS: Now, I'd like you to speak, Dr. Miller, about how treatment options have evolved in recent years and how a multidisciplinary approach is really the standard of care now. The introduction of targeted therapies such as PARP inhibitors for BRCA-mutated cancers. I'd like you to speak about some of these advancements that have improved progression-free survival and, in some cases, overall survival.

Dr. Eirwen Miller: Yeah. I think we've had some really exciting advancements in ovarian cancer in the last five to seven years. Targeted therapy will be the direction of treatment in the future of ovarian cancer. I think that leading the way in this is homologous recombination deficiency and utilization of PARP inhibitors, though, you know, PARP inhibitors are FDA approved for all-comers in the upfront setting. Those patients that have BRCA1 and 2 germline mutations do have increased access to PARP inhibitors in a variety of treatment settings that other patients do not.

As we look towards the future in ovarian cancer care, we are really interested in the development of antibody drug conjugates FDA-approved this year was our first antibody drug conjugate for ovarian cancer called mervituximab. That drug is targeted towards the folate receptor on the surface of ovarian cancer cells. We predict approximately 35 percent of ovarian cancers highly express that protein. There are a variety of additional antibody drug conjugates that are currently in clinical trial pipelines, as well as some that have been approved in GYN disease sites other than ovarian cancer. We are finding that these antibody drug conjugate molecules, we can perhaps exchange the target on the surface of that antibody drug conjugate carrying a cytotoxic payload to cancer cells, and then really selecting the drug on the basis of the proteins that the cancer cells express. So, it is relatively standard of care now that patients have somatic tumor testing to understand their homologous recombination status as well as the proteins, the IHC expression on the cancer cell surface as we develop their treatment options, both in the first line and in subsequent lines of treatment.

Melanie Cole, MS: This is such an interesting discussion that we're having here today, Dr. Miller, and really such an interesting challenge is ovarian cancer. I'd like you to wrap it up with when you think it's important that referral be made to gynecologic oncology. Do all ovarian masses need to be referred? What would you like other providers to take away from today's discussion?

Dr. Eirwen Miller: I think that certainly not every ovarian mass needs to be evaluated by a GYN-oncologist. Certainly, we know that the largest majority of pelvic masses are benign. I think in triaging the decision for referral to Gynecology versus Gynecologic-Oncology, we need to have an understanding of what's their a priori risk of malignancy. Are they pre-menopausal? Are they post-menopausal? You know, post-menopausal patients certainly have a higher risk of ovarian cancer than our younger women. And so, our younger women are. I think. Safe to be seen by a gynecologist. Perhaps our postmenopausal women should go straight to GYN-Oncology.

Another factor that we look at in triaging a priori risk is what is the quality of the mass on imaging? A simple cystic lesion without neural nodularity or solid components in the absence of ascites is almost universally benign and appropriate for an OB-GYN. Those masses that are more complex with solid components, the presence of ascites, all of these factors are going to increase their risk of malignancy and should be seen by a GYN-oncologist.

And the last factor I'll add in is that I think our referring providers are pretty savvy with using CA-125 as a tumor marker to triage malignancy risk. And We understand the limitations of a CA-125 and its sensitivity and specificity for ovarian cancer specifically. But those post-menopausal patients that have a pelvic mass with an elevated CA-125 certainly need to be seen by a GYN-oncologist. The utility of a CA-125 in a premenopausal patient is more complex than that. But I think certainly those postmenopausal patients with an elevated CA-125 and a pelvic mass warrant oncology evaluation.

Melanie Cole, MS: Thank you so much, Dr. Miller, for joining us today and sharing your incredible expertise To learn more or to refer a patient, please call 844-MD-REFER, or you can visit ahn.org. Thank you so much for listening to this edition of AHN MedTalks with the Allegheny Health Network. I'm Melanie Cole.