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Zach Klaassen: Hi, my name is Dr. Zach Klaassen. I'm a Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. We are here in San Francisco at GU ASCO 2024. I'm pleased to be joined today by Dr. Peter Goebell at the University of Erlangen in Germany, who is a urologist there and presented some very awesome data today looking at a systematic review among treatment intensification for metastatic hormone-sensitive prostate cancer. So Peter, thanks so much for joining us.

Peter Goebell: Thanks for having me here.

Zach Klaassen: I look forward to discussing your paper today. Just take us through... We have trials, we have other systematic reviews. Yours was a little different in just the scope and the size. Just take us through what was the genesis for putting this together.

Peter Goebell: Well, the major purpose actually was to look at the treatment reality we are facing. We have all these new compounds, we have the new combinations, we have doublets, we have triplets. We have a whole change in the landscape, especially in metastatic hormone-sensitive prostate cancer. And what we wanted to know is does the research data, does the scientific evidence we have, which is depicted in the guidelines, does that convert into changes in routine practice?

Therefore, we really scanned all available data, which was looking at this, real-world data, and lumped this together, harmonized the data set to be able to compare things, to be able to look at endpoints, to be able to look at the patient populations which were part of these registries, part of these scientific publications, to get an idea of what really is happening in the real world, and also to be able to see maybe changes over time. Does scientific evidence really come to the patient? Is it translated into a change of routine practice?

And therefore, we gathered all available data, looking also at duplicates in data sets. Some registries are ongoing, and they report an update, but we wanted to avoid duplicates of these patients in there. And we ended up with some 340-something-thousand patient data sets, which we were able to then really dissect and look at the trials, the comparison cross-trial comparisons, the regional disparities of these populations, to look into detail also of the population composition, age distribution, comorbidities. But the main focus on this very first glimpse actually was to see how does the use of doublets and triplets really convert into the community.

Zach Klaassen: Yeah. And it really was a global systematic review. I think you had, what, 29 studies, 343,000 patients across. And you broke it down nicely between the US, Canada, Europe, and Asia.

Peter Goebell: Exactly.

Zach Klaassen: And so, just tell us a little bit about some of the key results. And I really liked how you compared it by region because there's some very interesting regional variation in the results.

Peter Goebell: I think it also reflects the title, The Underutilization of Intensified Treatment. So actually, looking at the guidelines and the evidence, the vast majority of our patients should not receive ADT alone. As you can see, depending on the region, depending on the reimbursement system, depending on the country, depending on the history over time, this still is some 30% to 40% where you see ADT usage alone. And this is one of the key messages actually.

And then the second finding is actually to see how these results change over time. So we see some appearance actually of the doublets and the change, but the change is not dramatic. Then we have a very interesting finding, looking, for example, at the IRONMAN cohort, which is actually, usually, should be centered and well-educated physicians, oncologists, urologists. There we would expect to have a very low ADT-alone treatment. But still in this cohort, you can see over time, depending also on the sites, that there is up to 35% of ADT-alone usage, which is also a surprising result.

Zach Klaassen: In a very well-defined registry even at that point.

Peter Goebell: Exactly. Which is mainly done by centers of excellence, by very well-trained people who are actually part of all these pivotal trials, also part of this scientific community really leading guidelines, leading the new evidence. And still, we see the ADT-alone use in a substantial proportion of the patients.

Zach Klaassen: Yeah. Did you find anything in terms of differences between, let's say, ADT plus docetaxel or ADT plus ARPIs? What was the take-home from... Or Abi plus ADT? Was there one that was being used more or less than the others?

Peter Goebell: Yeah, I think that the new hormonal agents, as we call them, depending on the nomenclature, are probably more used. We see a diminish actually of the chemotherapy, which is kind of surprising, because if you think of the doublets and the first pivotal trial for the doublets by Chris Sweeney was... I mean, this was a game-changer, really showing us that the combination including docetaxel is superior.

And somehow this did not translate into higher use of docetaxel or taxanes in general in the sequence. Now, we are only looking at the first line of course, but I think the value of introducing docetaxel into these doublets or triplets like the PEACE-1 or ARASENS, these are good examples where we know that this is a very important part of a combination therapy, but still, it doesn't translate into daily use.

Zach Klaassen: I'm going to ask you a two-part question. So the first part is the $64,000 question, which we probably won't be able to answer, but I'm going to ask it anyways.

Peter Goebell: $64,000. Okay.

Zach Klaassen: How do we get that number from 40%, 50% up to 80% to 90%, just in terms of treatment intensification? And we have great data from ARASENS against a very good control group, which was the standard of care in 2015, 2016 of ADT plus docetaxel.

Peter Goebell: Exactly.

Zach Klaassen: So how do we treatment intensify in general and how do we get to the triplet therapy if we can't even get to the doublet therapy?

Peter Goebell: I think the first problem is probably that we do not convey this message, this scientific message, not only to the physicians but also to the patients.

Zach Klaassen: That's a good point.

Peter Goebell: I think patients are driving many treatment decisions because patients would like to get the best and most intensified treatment. And we already know from all these doublet trials, we know that especially in the first line, the effect of the first line, the first hit is so important. Any PFS-2, for example, you're looking at, is maintaining the effect which we see in the first line. So also in the sequence we know exactly in those patients where we hit harder the first time, this benefit will be translated into later lines. And if you haven't done it in the first line, you will not get it-

Zach Klaassen: You'll lose that opportunity.

Peter Goebell: Exactly. So we know about the importance of an intensified treatment in the first line. So patient education is first, I think very important. Second is to really translate this trial data into something which is reportable, which helps the physician to really translate this into patient's language. So for counseling, if you look at a Kaplan-Meier curve or any survival data or clinical endpoints like radiographic progression-free survival, if I were a patient sitting there and you tell me something about radiographic progression-free survival, it doesn't mean anything to me.

So what I would like to hear as a patient in simple language is something which translates into key messages that are easy to understand. And I think in the scientific community, we all look at these curves, we all look at the data. Even at this congress, you're looking at all Kaplan-Meier curves, at hazard ratios, but we do not have the language to translate this into something a usual physician, not a specialist, can use for counseling.

So the translation, which is one of the themes of this year's ASCO GU, is translation doesn't only mean to bring it from the lab to the bed, but it also means to translate scientific evidence into counseling language into something which is understandable and then can be used for the patient. Who reads guidelines? Who is looking into the details, into the background texts, and really dense information which is in there, but who reads it and uses it for counseling?

And I think what we need to do is to increase this number and really to have an effect on survival, which is the case, to really get this done. I think it is important to translate this language into something that is meaningful to the patient. So really referring to the patient needs. Does it translate into something the patient is able to consent to? And I like the term, the English term... In Germany, it's not the case... In the English language, it's informed consent. And informed consent to me means that the patient has enough information in his mind setting, enough information to really consent to something, to make a decision, or at least to agree to a decision.

So we have the obligation to inform the patient as much to a point where the patient is able to make a decision or at least to agree to a decision. And I think we often, if you look at scientific papers and scientific messages also from congress meetings, it's not in the language a patient can understand. So I think their patient education and translation into something which is counseling language to, if this word exists, but to enable us to get this information to the patient so the patient will decide then that, for example, chemotherapy is not something which is bad. It's a transient side effects part of his life, but it's very effective. There are side effects which can be managed. So we need to tell this story more often, I think, as we did in the past.

Zach Klaassen: That's great. Great answer. It's been a great conversation. Anything we haven't hit on that you want to talk about? Any take-home messages for our listeners today?

Peter Goebell: I think what we need to do is to really use real-world data and real-world evidence to also put these pieces of data, not only to look at evidence in phase 3 trials but also to use real-world data to be put in our guideline thoughts to really see this is what we do in practice and this needs to be implemented in our thinking in the guidelines.

It is not valuable if we only have phase 3 trials, highly evidence, highly published papers with high impact, but also to refer to what is happening in the community and to add this to our knowledge in the guidelines so we can really bring benefits to the patients.

Zach Klaassen: That's great. Peter, thanks so much for your time. I know it's a busy meeting. We appreciate you taking some time and sharing your expertise today.

Peter Goebell: Thank you so much.

Zach Klaassen: Thank you.