Study compares surgeries for reducing ovarian cancer risk in women at high risk for the disease

[00:00:00] Host Amber Smith: From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." Gynecologic oncology researchers are testing a surgery that may help women who have a high genetic risk for developing ovarian cancer. Here to tell about this study is Dr. Rinki Agarwal. She's an associate professor of obstetrics and gynecology at Upstate and also the medical director of the Upstate Cancer Center's gynecologic oncology program. Thank you for your time, Dr. Agarwal.

[00:00:29] Rinki Agarwal, MD: Thank you for having me, Amber. Besides that, I also want to mention that I am the director for the genetics program for the Upstate Cancer Center. And I serve in that capacity as a board-certified geneticist. So this study that we are here to talk about and focus on is very near and dear to me from both avenues of my training.

[00:00:53] Host Amber Smith: It sounds like it ties together nicely because the study focuses on women who know they are at an increased risk for ovarian cancer. Can you explain how a woman would know what her risk is?

[00:01:06] Rinki Agarwal, MD: So women may come to get this information through multiple streams. Hopefully the way it would work for a majority of women at risk would be because they have familial risk that was identified. And that information was shared by family members, with patients at risk. And they go through testing.

[00:01:26] Rinki Agarwal, MD: The other way that women find out about the risk is because they've had cancer themselves, either breast cancer or ovarian cancer, and they are going to the process of evaluating the reason for getting the cancer and go through testing. And that's the other significant way.

[00:01:47] Rinki Agarwal, MD: In our practice, we see a very large number of patients who are coming to us for evaluation on the genetic side of my practice because of the strong family history, and we evaluate them, and then we end up identifying patients who are at risk, and then they are referred to the different specialties that would address those risks and help them manage that, understand the risk and manage it from there.

[00:02:13] Host Amber Smith: But let me ask you about which family members. So are we talking about a mother or a sister or an aunt or a cousin who had ovarian cancer? Is that it, or is it just your parents?

[00:02:26] Rinki Agarwal, MD: So really it can come from either side of the family. It can be maternal or paternal risk or through those lineages.

[00:02:34] Rinki Agarwal, MD: And you can have people who have known risk in siblings, either parent or in extended family, aunts, uncles, or cousins. And there is enough general awareness of the relationship between the genetic predisposition genes and the cancer risk to flag those for most practitioners so that patients will get that information.

[00:03:01] Rinki Agarwal, MD: And then we encourage them to share it with family members.

[00:03:06] Host Amber Smith: Now, why does this study look at surgery as a potential solution?

[00:03:11] Rinki Agarwal, MD: So to understand that, I would like for us to go back to some of the background and say, why is this study necessary and why is it surgery that's part of the study? OK, so where we are right now is essentially about 20 years of knowledge synthesized into development of the study.

[00:03:35] Rinki Agarwal, MD: So on one side, and we're going to talk about understanding ovarian cancer risk. And in that, with the identification of major riask-factor genes, such as the BRCA 1 and 2 genes, where mutations would give people increased risk, we've known that from going to the mid-'90s and, that has led to development of strategies for managing risk, and a number of things have been tried in the realm of screening, prevention or risk reduction using surgery. And of those, the most effective method has been to remove the ovaries and fallopian tubes. And the people have studied that, and the literature supports that there is tremendous value and a significant reduction in risk when you do the surgical interventions, whereas we're not great at screening and prevention using medical modalities. OK, so that's on one end.

[00:04:34] Rinki Agarwal, MD: Then, as we've gone on, biological assessments of the precursors for ovarian cancer, going back decades, have not really shown us a true precursor lesion in the ovary as you see in multiple other cancers; you can take examples of breast or colon cancer, and you see precursor lesions. We never really saw those in the ovary. And then in the last decade, decade and a half or so, we found that there are precursor lesions that are present in the fallopian tubes. So the that's led to the belief that the genesis may not be in the ovary at all, but maybe in the fallopian tubes to start with.

[00:05:15] Rinki Agarwal, MD: So, that now brings us to a functional understanding of what these organs are doing, where you can draw on our knowledge of the different organs. We're talking about two different things here, the fallopian tube, which is essentially connecting the uterus to the ovary and allowing for transit of egg and sperm and fertilization within the fallopian tube, but beyond that, it doesn't really have functions beyond fertility preservation. It doesn't have functions for hormonal activity for the female. On the other hand, the ovaries produce eggs, but they also produce hormones. And there, what we know now from drawing on large studies of things like the Women's Health Initiative that we've had now available to us for review for the last 20 years or so, that the hormones coming from the ovaries are significantly impactful in preserving health for women. And that's pretty much for every body system you can think of. In the short term, that can be things like mood, sleep disturbances, sexual function, and in the long term, it can range from cholesterol management, heart disease, cognitive function, bone health and other impacts.

[00:06:37] Rinki Agarwal, MD: So you are coming to the realization that there is risk source, maybe the fallopian tube. And the ovary is potentially a source, but may just be a bystander that gets involved in the cancer process. And then the ovary has significant functional benefit for the individual, and you're giving up on that when you take the ovaries out.

[00:07:08] Host Amber Smith: If you were able to let a woman keep her ovaries, you would like that, as long as you can assure her that her risk for ovarian cancer is removed by taking the fallopian tubes out?

[00:07:21] Rinki Agarwal, MD: Exactly. So you're basically taking all of this functional information, the pathologic information that we've gained over time to say we have risk, we have the source of risk, we have benefit of this other organ, can we truly preserve it or time its removal such that you get most of the benefit before it's surgically removed? And that brings us to the study, the salpingo-oophorectomy to reduce the risk of ovarian cancer study.

[00:07:49] Host Amber Smith: Let me ask you before we get into that...

[00:07:51] Rinki Agarwal, MD: Sure.

[00:07:51] Host Amber Smith: ... if we think that most ovarian cancers start in the fallopian tubes, will we stop calling it ovarian cancer?

[00:08:00] Rinki Agarwal, MD: It depends on what kind of philosophy you have. We're not going to walk away from calling it ovarian cancer for a long time. A lot of the studies that we know about treatment of the disease, literature's all going to call it ovarian cancer.

[00:08:15] Rinki Agarwal, MD: In the end, there is significant involvement of the ovaries with the disease, whether it's arising from the fallopian tube or the ovary, and we can't completely eliminate the ovary as a primary source of the cancer. So, in a purist sort of a way I would say that, yes, we may, at some point, get to a point where we can differentiate and call them for what they are, based on their genesis. So we may have fallopian tube cancers that are a major category and ovary cancer is a minor category, rather than the reverse, which is as it exists right now. They are similar enough in our understanding of how they behave that for the purposes of our current treatment and discussions, they are considered the same.

[00:09:05] Host Amber Smith: This is Upstate's "HealthLink on Air." I'm your host, Amber Smith, talking with Dr. Rinki Agarwal about a study that is looking for women at high genetic risk for developing ovarian cancer. So what can you tell us about this trial? I know it's sponsored by the National Cancer Institute. What is it set up to do?

[00:09:23] Rinki Agarwal, MD: In short, it's called SOROCk, which stands for Salpingo-Oophorectomy to Reduce the risk of Ovarian Cancer. And it is a study that is available currently for enrollment at Upstate. And it's sponsored by NRG Oncology (a research organization), which is part of the National Cancer Institute Community Oncology Research Program.

[00:09:43] Rinki Agarwal, MD: So it's a national study to evaluate the strategy for managing risk in patients who have an identified mutation in a BRCA1 gene for future development of ovarian cancer.

[00:09:59] Host Amber Smith: So how many women are you looking for, and what are their ages?

[00:10:03] Rinki Agarwal, MD: For the study nationally, they're looking to enroll just under 2300 women, between the ages of 35 to 50.

[00:10:14] Rinki Agarwal, MD: And they would be looking to have certain things to include patients in the study. They have to have a known mutation in the BRCA1 gene, and they still have their fallopian tubes.

[00:10:29] Host Amber Smith: And is there anything that would disqualify someone from participating?

[00:10:33] Rinki Agarwal, MD: Well, people who already have ovarian or fallopian tube cancer as the start of where they gathered this information would not be candidates for this study, but pretty much everybody else. And if the fallopian tubes have already been removed, as part of some prior surgical process, those patients would be excluded, but otherwise, everybody else is a candidate for it.

[00:10:57] Host Amber Smith: I want to let listeners know that they can call a local number to the Upstate Cancer Center to learn more about this trial at 315-464-8200, and if they have friends in other parts of the country, the National Cancer Information Center at 1-800-4CANCER, that's 1-800-422-6237, can also provide information. Can you walk us through what happens when someone joins the trial? Is this person going to meet with you or another doctor to help decide which surgery she'll have?

[00:11:32] Rinki Agarwal, MD: Absolutely. All four gynecologic oncologists in our practice are able to see patients and enroll them in the trial.

[00:11:41] Rinki Agarwal, MD: So they could certainly see me or one of the other physicians in the practice. And what would happen is that they would have an initial interview. They can come in with this information, or we're pretty much screening every patient that comes through that may be eligibile for this trial to be considered for the trial. They're given information and given some time to think about it.

[00:12:03] Rinki Agarwal, MD: Now, the time to think about it is something that I encourage patients to do in the context of this particular scenario: They have a BRCA1 mutation; they're trying to manage their risk of ovarian cancer. And, we're talking about risk management. So that time to think about the study is something that I would consider a standard of care anyways.

[00:12:27] Rinki Agarwal, MD: And once they've gone through the information and considered it, it's an option for them to proceed with enrolling for the trial. And then within the trial, it is patient choice on whether or not they would be in the arm of doing the current standard, which is to remove both tubes and ovaries after the age of 35, or if they were to choose the salpingectomy arm with a subsequent delayed oophorectomy at a later point, after the age of 40 to 45. So those would be the two arms that the patient would be enrolled in, but it would be patient choice.

[00:13:06] Host Amber Smith: Does the trial pay for the surgery ,or does the woman's health insurance cover the surgery?

[00:13:12] Rinki Agarwal, MD: So the trial's intent is to collect information. The billing for the service is done through insurance.

[00:13:22] Rinki Agarwal, MD: And the burden for the patient in terms of participating in the trial is predominantly that they are answering questions, they're allowing the trial to access their medical records, and they're allowing them to store a sample of blood for any biomarkers that we may find have utility for patients in the future.

[00:13:44] Rinki Agarwal, MD: So those things would be covered by the trial, the maintenance of those records, that they've collected, but the study would not cover the surgeries.

[00:13:53] Host Amber Smith: What is the follow-up like? Are there visits after the surgery?

[00:13:57] Rinki Agarwal, MD: There are visits after the surgery that are also considered standard of care.

[00:14:01] Rinki Agarwal, MD: And that would be the points where we would assess for outcomes how are they doing, by way of quality of life preservation and the future risk of cancer, and that's all collected as part of standard of care, but would also be then given to the trial as long as the patient consents, continues to consent to do so.

[00:14:25] Host Amber Smith: How would you counsel women who joined this study to be on the lookout for signs or symptoms of ovarian cancer after they've had the surgery?

[00:14:35] Rinki Agarwal, MD: So for lack of a better description, the signs and symptoms of ovarian cancer are relatively subtle. And it has been in the media called a silent disease.

[00:14:49] Rinki Agarwal, MD: I do not believe that it's silent. It's more that you have to be aware because there is such subtlety to the signs and symptoms that you can frequently attribute those symptoms to other diseases before you think of ovarian cancer as the potential problem in a majority of those instances. So first to specify that there are some characteristics and symptoms that patients will have, if they have the disease and then, for what those symptoms may be.

[00:15:20] Rinki Agarwal, MD: Frequently, more abdominal symptoms than symptoms elsewhere in the body. And those can range from bloating, which we would define as just a sense of being very full or getting full too quickly. They find that they can't eat as much, but their abdomen or the belly feels very full. Abdominal pain or pressure change in how they're moving their bowels.

[00:15:46] Rinki Agarwal, MD: And then other range of symptoms can be things like shortness of breath, loss of weight, and, these are persistent. Anything that's lasting over a couple of weeks is something that would suggest that it requires further evaluation, and they can stem from numerous other potential differential diagnoses.

[00:16:06] Rinki Agarwal, MD: But we, in this context, for this particular discussion, we're talking about patients who were at identified, increased risk of ovarian cancer. So for them to be thinking about this as a higher potential differential diagnosis would be important,

[00:16:24] Host Amber Smith: What would you say are the benefits of a woman participating in a trial like this?

[00:16:30] Rinki Agarwal, MD: So the benefit may not be evident to us for a few years, until these trial results are available to us. But the idea of the study is that with the counseling and with all of the information provided, the patients who choose something like the salpingectomy arm, by their own choice, are not committed to that alone.

[00:16:56] Rinki Agarwal, MD: They can cross over to the salpingo-oophorectomy arm at any point. And even if they were to stay with salpingectomy arm, have a planned oophorectoomy sometime in the future. We don't know what the answer of the ultimate findings of the trial is, but the trial has been carefully designed in order to minimize the risk of ovarian cancer or choose patients who are at the lowest risk of ovarian cancer and have the maximum benefit from retention of the ovaries. So if in fact, the findings of this study showed that the salpingectomy-alone arm was good, then those patients would have gained from choosing that option along the way.

[00:17:43] Rinki Agarwal, MD: OK. And then there is the larger benefit. We're at a point where this is the logical next thing that we have to evaluate to minimize the impact of our recommendations on women's lives. So they would be contributing to our understanding and management of the risk tremendously by participating in this study.

[00:18:04] Host Amber Smith: Once again, the local phone number, if people are interested, is 315-464-8200, and that goes to the Upstate Cancer Center. My guest has been Dr. Rinki Agarwal. She's an associate professor of obstetrics and gynecology and the medical director of the Upstate Cancer Center's gynecologic oncology program, as well as the director of the Upstate Cancer Center's genetics program.

[00:18:28] Host Amber Smith: I'm Amber Smith for Upstate's "HealthLink on Air."