[music]

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

In today's podcast, we will discuss new recommendations developed jointly by ASCO and the Society for Gynecologic Oncology on when women with newly diagnosed advanced ovarian cancer should receive neoadjuvant chemotherapy, which is chemotherapy given before surgery. These recommendations are intended to help guide doctors and their patients in making treatment decisions based on current research. This podcast will be led by Dr. Alexi Wright, an assistant professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, and Dr. Mitchell Edelson, a medical oncologist at the Hanjani Institute for Gynecologic Oncology at The Rosenfeld Cancer Center at Abington Hospital - Jefferson Health. ASCO will like to thank Dr. Wright and Dr. Edelson for discussing this topic.

Dr. Wright: Hi, I'm Dr. Alexi Wright and I'm a medical oncologist at Dana-Farber Cancer Institute. I'm here today with my colleague Dr. Mitchell Edelson who's from Abington Hospital - Jefferson Health. We're here to discuss ASCO and SGO clinical guidelines about neoadjuvant chemotherapy. To start it out, Mitch, what would you say are the main recommendations of these guidelines?

Dr. Edelson: Well, I think this was a very important collaboration between the Society of Gynecologic Oncology and the American Society of Clinical Oncology, to kind of look at the role of neoadjuvant chemotherapy for those newly diagnosed with advanced ovarian cancer, focusing on the role of primary surgery versus neoadjuvant chemotherapy. I think one of the key recommendations right off the bat was a very strong statement that all women who are suspected to have advanced stage ovarian, fallopian tube, or primary peritoneal cancer should be evaluated by a gynecologic oncologist prior to the initiation of therapy, to determine whether they are truly a candidate to undergo primary site or reductive surgery.

Dr. Wright: That's such a good point, Mitch. And just for some context for our listeners, one of the interesting things that has come out in the past several years is there have been two large randomized trials that compared for women who had advanced ovarian cancer, meaning stages 3C and 4, whether they should get chemotherapy first followed by surgery and then post-operative chemotherapy, or surgery followed by chemotherapy. And both of those studies suggested that the results - in terms of how long women lived - were the same, but some of the complications that happened from surgery differed a little bit between the two trials. And one of the things that the group looked at is, were there questions in these trials that raised red flags for the group? I guess I want to ask you that because that places the context of how we made some of the decisions.

Dr. Edelson: Some of the discussions and the criticism of some of the prior trials are, how extensive were the surgeries in those trials? Because gynecologic oncologists avow very strongly that some of the best data that we have in terms of overall survival has to do with trying to achieve a complete cytoreduction at initial surgery. And I think that's why the group felt very strongly about making a statement that somebody who has the expertise in doing these types of surgery, recognizing what is feasible and what is not, is very important in that initial evaluation as we look at which way to proceed.

Dr. Wright: Because the fear, Mitch, should be what? If someone didn't see a gynecologic oncologist…

Dr. Edelson: I think the concern is that every woman be given the opportunity to undergo complete removal of all disease in initial surgery if possible, and in some studies that might provide the highest survival rates. Now, that being said though, I think our group really did recognize that the best trials that have been done so far are randomized control trials, and the group looked at the randomized trials and looked at their data. Do you want to comment about what those trials showed, Alexi?

Dr. Wright: Yeah. What those trials showed was that women who were randomized to the studies and got either surgery first or chemotherapy first, lived the same amount of time. So it didn't seem to impact how people did ultimately. But patients who got chemotherapy first, in general, had fewer side effects or postoperative complications. So one natural conclusion might be, well, if women can get chemotherapy to shrink the disease and then get surgery, why not do that first if there are fewer complications? But one of the surprising things about these trials, that were done really outside of the United States, is that women didn't live as long as we expected them to, and the surgery seemed to be a little less extensive. So our group wrestled a lot with how to interpret these trials. And specifically in one study that was done in Europe, there was a finding that women who had low volume disease - a small amount of disease at the time of surgery - did live longer if they got surgery first, which made us really pause and think about the importance, as you said, of making sure that all women see a gynecology oncology surgeon first to see whether surgery makes sense or chemotherapy. Because that recommendation of whether to get surgery is a lot more complex than it seems.

Many women want to immediately and naturally, obviously, get the cancer out of their body as quickly as possible. But whether surgery is going to be helpful or not often depends on where the disease is located, what other kinds of medical problems the patient has, whether the surgery is likely to remove all visible disease, so that at the end of surgery, when the surgeon is looking inside the patient's abdomen and pelvis, you can't see any residual disease. Because as you said earlier, that's the thing that we know has the greatest survival benefit associated with it. So with those findings in mind, I think there is a little bit of a paradigm shift in our community in thinking that neoadjuvant chemotherapy may have more of a role. Neoadjuvant, giving chemotherapy before surgery, may have more of a role for women with ovarian cancer than we previously thought. Yet, the decision whether to do surgery or chemotherapy first is complex, and we don't think that the default decision should be just start everyone on chemotherapy.

Dr. Edelson: Yeah, I think you're right, and before we get into specifics, I think our group, as part of the guideline, while it's very complex, has provided some specific ways and even an algorithm of how to decide what to do. One of the other key points the group came up with is that truly when deciding about the surgical or medical care, they really should have an expert who understands these cancers, who's either a gynecologic oncologist or a medical oncologist with a gynecologic expertise. Because we know that there are in some situations, while the initial presentation looks like a very advanced cancer, and for some people, they may be counselled that any type of treatment is futile, we do know that these tumors are extremely responsive to the combination of chemotherapy and surgery. And we want to make sure that all women are offered the opportunity of some treatment, whether it may lead to palliation of their symptoms or lead to a longer term survival. So I think the group also really strongly recommended that people who have an expertise with this disease be available to those patients for consultation, in terms of making decisions about further treatment.

Dr. Wright: That's absolutely right. Just to underscore that, just as we want women to have the opportunity to have surgery, we also want them to have the opportunity to have chemotherapy and certainly not make a decision about not receiving treatment without really being informed about the potential benefits and risks of the treatment. Because, as you said, this is a very chemo-sensitive disease.

Dr. Edelson: Alexi, so which patients would you say, right outright, would be those who maybe should be considered to have neoadjuvant chemotherapy right off the bat instead of primary surgery?

Dr. Wright: Right. So first of all, I think, if there's a question of whether we're going to be able to really reduce the disease to virtually invisible, to the point that you can't see it with the human eye or certainly less than a centimeter, that's a group of women who should get chemotherapy. If we came to that, those women should get chemotherapy first. If there are extensive medical problems, like a patient's had what's called a pulmonary embolism, a blood clot that's traveled to the lungs, that's a situation where they're probably better served by getting chemotherapy first. Similarly, there are other areas like if the spleen is involved or pretty extensive involvement of the liver, or women are otherwise frail, have a lot of medical problems that would make it difficult or make surgery a risky thing before all of these conditions were under a little bit better control. Those are women who should first get chemotherapy, in general.

Dr. Edelson: Yeah. I think that those are very important points, and that's part of that extensive evaluation that needs to occur in terms of making those decisions.

Dr. Wright: I think another really key point, Mitch, as you were getting through, is for women who do get chemotherapy first, one of the things that we emphasize in the guidelines is it should really be three to four cycles of chemotherapy, and then there should be repeat imaging. We mentioned in the guidelines that every woman who's diagnosed with ovarian cancer should have pathologic confirmation of this, meaning that a doctor has confirmed that they have ovarian cancer, and they should also have a CAT scan so that we can see where the disease is present. And if chemotherapy is selected first, then after three or four rounds of chemotherapy, we want to make sure that it's working. One of the ways of doing that is to restage with CAT scans. The reason that's so important is if the disease is not responding to treatment, we want to take a different direction or consider another strategy. So in general, we want to make sure that women aren't treated indefinitely with chemotherapy before they are reconsidered for surgery.

Dr. Edelson: Yeah, I think those are very important points about the way to approach the neoadjuvant chemotherapy. Now, I think that the other point that we've emphasized are for those women who do have a high likelihood of having all of their cancer removed at surgery, or at least reduced to a very small volume of disease, and they are able to tolerate a surgery, then primary surgery is recommended over neoadjuvant chemotherapy. Again, this is based upon some other non-randomized trials that have given us some of our best data in terms of overall survival and cure using this type of approach. So in our guidelines we did specifically make this clear about that is one of the situations where we would recommend primary surgery instead of the use of neoadjuvant chemotherapy.

Dr. Wright: That's a really important point.

Dr. Edelson: And there are other times where we would, on the other hand, prefer to use neoadjuvant chemotherapy. Alexi, do you want to just mention what that situation would be?

Dr. Wright: Right. So if we think that we can't remove the disease and get it down to a very small volume by doing surgery first, or we think that surgery would be too dangerous right after diagnosis. Those are situations where chemotherapy is better used to shrink the disease to the point that it can be removed successfully, and also give women a chance to recover from other acute medical problems like blood clots, or get their other medical conditions under good control, like if they had a heart attack or something that really made surgery difficult. Similarly, if there's disease that makes it stage four, in that case neoadjuvant chemotherapy may be one of the things that we decided in this guideline that - and we should specify is for women with stage four -  either neoadjuvant chemotherapy or surgery is reasonable. Because we know that we're not going to be able to get women to a small volume disease in that setting, and in that setting particularly, we may be able to more safely perform the surgery after chemotherapy.

Dr. Edelson: Yeah, I think that these are all very important details, and one of the things that I think we realized is that this is still a moving target. So these guidelines will constantly be reviewed. There is a lot of interest research-wise in looking at the role for neoadjuvant chemotherapy. There are still a lot of questions that we have in terms of truly trying to fine-tune deciding between neoadjuvant chemotherapy and primary surgery. And I think this is something that both societies will constantly keep an eye on new data, and these guidelines will be revised over time as new data becomes available.

Dr. Wright: That's right. Mitch, if you had to say in a few sentences, what do these recommendations mean for patients? Is there anything that they--?

Dr. Edelson: I think the important points is, number one, that women with what looks to be an advanced ovarian cancer need to be evaluated by specialists who understand this disease, who have treated a number of patients, and can help make those decisions about which way to proceed, whether it's chemotherapy followed by interval surgery or whether whether is surgery upfront. That's one of the key things, and I think that we realize that there are different ways to approach and where these guidelines help to individualize for the patient which may be the best approach.

Dr. Wright: That's right, and I think just as it's important for patients to seek experts with specialization within gynecology oncology, it's also important to know that at this point it's a moving target, but at this point, neither surgery or chemotherapy should be a default. This is a decision that needs to be made after careful review, and something to discuss with your doctor. Our hope in doing these guidelines and bringing these two societies together it was really to try to make sure that all women are getting the best care possible, evidence-based care that can be - as you said - personalized to them. And our hope is that this will help women get the best care possible throughout the country.

Dr. Edelson: Well, thank you, Alexi. It's been a pleasure working with you on this and being able to bring these guidelines for all of our patients.

Dr. Wright: Yeah, Mitch, it's been a real pleasure too. We want to thank all the people on the committee who put tremendous work into this and finding consensus. Thanks so much.

ASCO: Thank you Dr. Wright and Dr. Edelson. To learn more about treatment for ovarian cancer, visit www.cancer.net/ovarian. And for more expert interviews and stories from people living with cancer, visit the Cancer.Net blog at www.cancer.net/blog.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high quality cancer care. Thank you for listening to this Cancer.Net podcast.

[music]