Alicia Morgans: Hi. I am so excited to be at SOGUG 2022, where I have the opportunity to speak with the wonderful Dr. Elena Castro, recently moved back to Madrid. It's wonderful to talk to you today.

Elena Castro: Thank you, Alicia. I'm very happy to be here with you, and I'm very glad that you came all the way to Madrid to meet all my colleagues.

Alicia Morgans: Oh, wonderful. And such a wonderful group of people it is. You are speaking today, and giving a commentary on metastatic castration-resistant prostate cancer, and trying to help us put some sense to the madness that is the current clinical trial landscape. Lots of advances, and even some interesting advances here, specifically, I think in Spain, related to some trials that we'll talk about a little bit later. At least one trial we'll talk about later. How do you put this all together? What are you thinking about, when you first see a patient with metastatic castration-resistant prostate cancer?

Elena Castro: Well, there are many things that we need to take into consideration. First, what are the therapies that the patient has already received for the disease? Whether the patient presented with metastatic hormone-sensitive disease, and received hormonal agents, in combination or not with chemotherapy, or the patient presented with non-metastatic castration-resistant prostate cancer and again, has been treated with hormonal agents. And this is something that we need to take into consideration, and we don't really know for patients who have been treated with hormonal agents, we more or less know that sequential, or a second agent, perhaps will not be the best choice. But it's true, that for patients who have received a triplet therapy, we don't know yet which could be the best choice.

Alicia Morgans: Absolutely. I think there's so much influx, based on the prior lines. But there's a lot of other things to think about too. Whether you're in Spain or somewhere else in the world, genetic testing remains, I think, really important, as we think about potential for targeted treatments. That's part of what you discussed today too, right?

Elena Castro: Absolutely. And because alterations in BRCA1 and BRCA2 are early events that could have been investigated earlier on, even in the primary tumor, we will have those results by the time the patient becomes metastatic castration-resistant, and we could offer the opportunity of treating him or them with different PARP inhibitors.

Alicia Morgans: Wonderful. So I don't necessarily know the landscape here in Spain, but one of the things that we think about in other places is using radiopharmaceuticals, whether that's radium or maybe Lutetium-PSMA-617. How are you considering these agents when you have so many other options?

Elena Castro: Yes. Radium has been available for a number of years here, and we are quite used to it, and to treat our patients with radium-223. Also, I think perhaps, the use of radium-223 now is going down, and now that we are using Lutetium more and more, and we need to learn how to use both therapies. Because I think, this will provide us with more opportunities for our patients. I think we are all now very excited about the Lutetium, and 223 at present. We can use it in very late stages. We have different centers in the country are participating in many trials with Lutetium, and we are slowly learning how to use it in earlier stages. We, of course, have to wait to see the results of the trials.

Alicia Morgans: Absolutely. And to that point, clinical trials are something that we should always consider. I know that's really a focus of SOGUG, and a focus of your practice in Spain. Can you tell me how do you talk to patients? How do you think about moving patients, and giving them the opportunity to move into a clinical trial, if that's the right thing for them?

Elena Castro: Yeah, I think Spain usually does quite well in recruiting patients for clinical trials. It's not just for prostate cancer, but also for other tumor types. And I think our patients are really generous. So unlike in another countries, perhaps they are not so prone to contribute in other ways economically, but they are always very, very keen to participate in clinical trials. Because once we explain them the trials, and the different choices, they always feel like they will be given to the society, and they will be helping us to improve knowledge, and to cure them and also other patients. So my experience is that, most patients accept to participate in clinical trials.

Alicia Morgans: That's wonderful. And hopefully, that continues to maintain in Spain, and to increase around the world, because it is really that participation that gives us the data we need to move forward. There was a recent, you said a positive statement, I think, related to one of the recently reported clinical trials, the PROpel trial, which I think is really fitting, if we're talking about metastatic castration-resistant prostate cancer. Can you tell me a little bit about that?

Elena Castro: Yes. The European agency recently emitted a positive opinion on the use of olaparib in combination with abiraterone, for all patients with metastatic castration-resistant prostate cancer, who were not clinically eligible for treatment with taxanes. There has been recently released, and of course, we still need to wait to the final decision of the agency. But if this is finally approved, and in our country still has to be reimbursed, that will perhaps change the way in which we approach our patients, and investigate the presence of predictive biomarkers for PARP inhibitors. We still will need to see. I think it's very relevant, and something that needs to be discussed, because what we've learned from PROpel is that the benefit from the combination is very different, depending on whether the patient has a BRCA alteration or homologous recommendation defects, or no alterations at all. So I think, we will need to inform patients of the potential benefit, and the potential side effects that they may still get. And I guess, the conversation will be quite different from the three different groups, patients with alterations and without them.

Alicia Morgans: Yeah. I know that makes a lot of sense. And I think, the other thing that is important for us in clinic, is whether we still do germline genetic testing, somatic testing, what are your thoughts on that? What is the right way for us to move forward if there is a suggested approval across all patients?

Elena Castro: Yes. Well, perhaps it is true that tumor testing is a struggle, even when we are slowly learning how to overcome some of the difficulties, and the liquid biopsy will also come in our help. But germline testing is a totally different story. It's something that we should do, not just to learn whether a patient could benefit from a PARP inhibitor, but mostly, because there will help us identify alterations that maybe also be present in other relatives, who could be unaffected and benefit from early diagnosis or early detection programs.

Alicia Morgans: Absolutely. It's interesting, my patients still are not necessarily realizing that it is their daughters who may benefit most, because we can find early stage breast cancers, or ensure that they're aware of their ovarian cancer risk. Of course, for sons as well. But daughters in the screening programs, really do have implications, and it is so important. So I'm glad that this is something that you are maintaining in your practice. Certainly, we are maintaining, or I'm maintaining in mine. So if you had to sum it up, how do you make a choice in metastatic CRPC? What is it that you would recommend?

Elena Castro: We need to take into consideration previous therapies, avoid cross resistance between, for instance, hormonal agents. We need to take into consideration, if we can, predict the biomarkers, where is the patient's prognostic, the patient's preferences, comorbidities, drug interactions, and financial toxicity as well.

Alicia Morgans: Absolutely. And whenever possible, we should encourage clinical trial enrollment. And I sincerely appreciate all the work that you're doing. And I appreciate you taking the time to talk this through with me today. I hope you have a wonderful SOGUG 2022. Thank you so much.

Elena Castro: Thank you, Alicia.