Charles Ryan: Hello from EAU 2019. I'm delighted to be joined by Dr. Maria De Santis, who is a Medical Oncologist and Chair of the Section for Interdisciplinary Genito-Urinary Cancer Medicine at Charité University Hospital in Berlin. Thank you for joining us, Maria. How are you doing?

Maria De Santis: I'm fine, thank you.

Charles Ryan: Always a pleasure to talk to you. We thought we'd talk today about locally advanced prostate cancer, and the changing treatment options, and how we approach patients in light of the STAMPEDE data, in light of data on radiation oligometastatic disease and the early use of abiraterone. So, if you will, just tell us a little bit about your approach to patients with locally advanced high-risk prostate cancer.

Maria De Santis: Okay, so as a medical oncologist, I'm involved in this discussion together with my urology colleagues. We are usually seeing together those patients who are node-positive on imaging. Usually, those patients have positive PSMA PET scans, which is quite common to do in Germany. The question always arises whether to use upfront systemic therapy or if the surgeons just go in and do surgery and remove the lymph nodes. If they are PSMA positive and not node-positive, usually we start with hormones and then the second question is of course, is to add something to the hormones. We have the data from STAMPEDE where patients that were not positive were also included and here we have positive data for docetaxel of course, and we have further data from abiraterone plus prednisone in that setting. Yeah.

Charles Ryan: Let's unpack that a little bit because what you mean by positive data... When we're talking about the STAMPEDE trial, there's a range of patients, right? There were patients with high-volume if you will, metastatic disease and then locally advanced disease. And so the STAMPEDE study has shown us data on the early use of abiraterone in these patients, the use of radiation in these locally advanced patients in combination with abiraterone, but are you referring to some data with docetaxel in the locally advanced patients as well?

Maria De Santis: Well, not really. But in the STAMPEDE trial-

Charles Ryan: In general.

Maria De Santis: In general, also the locally advanced patients with high-risk features were included and the node-positive patients were included. The ITT population was positive for overall survival. So you could extrapolate that the whole group was actually benefiting. However, when you go into the subgroups, you see that the M0 population actually had significant and really amazing benefit with regards to PFS. But the overall survival was not significant. But there were very few events. So maybe we just need to wait longer for more events to have to readout. But I think here it is too early to have a final conclusion.

Charles Ryan: Regarding docetaxel?

Maria De Santis: Regarding docetaxel. But the same you could actually apply for abiraterone in the STAMPEDE trial because the setup was the same. And also here you have very few events in the locally advanced and node-positive patient population.

Charles Ryan: So in most of Europe now of patients with locally advanced prostate cancer are not able to receive abiraterone because it has not received regulatory approval for that indication. Is that correct?

Maria De Santis: There is no regulatory approval and no reimbursement for those patients who are not kind of high-risk according to the LATITUDE data. So it is kind of linked to the high-risk definition there. And with this regard, it does not apply for most of the patients with only locally advanced disease or for the patients that are node-positive.

Charles Ryan: So a node-positive patient with a Gleason nine who's going to start ADT would get, based on the STAMPEDE data, would be likely to get docetaxel at this time? Or just ADT plus radiation therapy?

Maria De Santis: Well for those patients, ADT plus local radiotherapy would be the kind of standard way to go. Many patients of course, and also the families are asking for more treatment and for abiraterone. But as a matter of fact, this has not been approved because according to LATITUDE, the patient would have to show not only high Gleason score but a second high-risk feature. So either the bone mets or [inaudible 00:05:18] mets, and this is now a problem and even though we all think that those patients would derive a benefit, we don't have the approval and we don't have that one study showing the overall survival benefit in this patient population.

Charles Ryan: Right. And I don't think anybody's giving docetaxel to patients with really low-volume disease. Of course, the low-volume patients in the CHAARTED study didn't have a survival advantage and we really don't have any data on which to rely on the use of docetaxel. And I just want to clarify that point you made earlier because you said that in the intention to treat population from STAMPEDE, the docetaxel arm was superior in that the study did include patients with locally advanced disease, but that really hasn't become the standard of care.

Maria De Santis: That's very true. The docetaxel-

Charles Ryan: I just want to clarify that for our listeners.

Maria De Santis: Yeah. Docetaxel has not become the standard of care. Also as you said, and we know that all those patients were included in STAMPEDE, but it is definitely no standard of care and only metastatic patients, M1 patients would receive docetaxel.

Charles Ryan: Right, right, right. So with regards to across Europe, and you're always very interesting to talk to and now you have the perspective of someone who practiced in Austria, in the UK and now in Germany. Are you seeing, of course, this has been during the time that the treatments have evolved as well, but are the availabilities of therapies and sort of the approach to patients different in these three different environments where you've worked?

Maria De Santis: Well, that's an interesting question and I was for example, a little bit struggling with understanding how the UK system works and they were actually a little bit slower with adopting docetaxel even though STAMPEDE is the largest prostate cancer trial and it's a UK trial. So things that go a little bit slower sometimes in the UK and in other countries in Europe, treatments like docetaxel in the early hormone-sensitive metastatic setting is adopted right after the presentation next day. Which did not work as a matter of fact, in the UK.

Charles Ryan: That's the way we are in the US. We come back from ASCO and the next patient we see, we just do what we learned at ASCO, right?

Maria De Santis: Yeah, yeah, that's right. And it's easy when the drug is available and already part of standard of care in other indications. Yeah, it is not so easy if it's a new drug and still needs to come to the market, et cetera. And in such circumstances, we are usually, or we have to wait for the official EMA approval.

Charles Ryan: Yeah. Well it's a pleasure talking to you and it's an interesting topic and the more conversations we have on locally advanced disease and sort of how to manage patients, the clearer it becomes. But also it actually becomes, we find new questions, right? We find answers and we find new questions and we'll look forward to continuing the conversation on this topic. So thank you again for joining us Dr. De Santis from Charité Hospital in Berlin.

Maria De Santis: Thank you.