GU Debates 2019: Changing treatment paradigms for hormone-naïve and castration-resistant prostate cancer (1/2)

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Published: 10 Apr 2019
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Dr Eleni Efstathiou, Prof Peter Goebell, Prof Joaquim Bellmunt, Prof Thomas Steuber

Dr Eleni Efstathiou chairs a discussion with Prof Thomas Steuber, Prof Peter Goebell and Prof Joaquim Bellmunt on the recent data presented at the 2019 GU Debates in Budapest, with a specific focus on patients with prostate and urothelial cancers.

In this video, the group examine the holistic management of GU cancers - which include the assessment of patient co-morbidities, bone health and polypharmacy.

They also highlight the use of geriatric assessments as a multi-disciplinary tool, for identifying effective treatments for patients in this population.

The group also discuss the latest data on hormone-naïve and castration-resistant prostate cancer and how this data can contribute to the changing treatment paradigms for this disease.

Watch part 2 of this video which covers practice-changing developments in urothelial cancer here.


This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).

 

Dr Eleni Efstathiou – MD Anderson Cancer Center, Houston, USA
Prof Thomas Steuber – University Medical Center Hamburg-Eppendorf, Hamburg, German
Prof Peter Goebell – Friedrich-Alexander University, Erlangen-Nürnberg, Germany
Prof Joaquim Bellmunt – Beth Israel Deaconess Medical Center, Boston, USA


EE: Hello from Budapest. We are very pleased to have you on this ecancer review of debates, a meeting that is ongoing as we speak, here in Budapest. Interestingly enough, we are in one of the most beautiful venues in the world where we are in this room ready to discuss genitourinary malignancies. I am here with esteemed colleagues that I will let actually introduce themselves, so Thomas.

TS: Thomas Steuber, I’m a urologist working in the Martini-Klinik Prostate Cancer Centre at the University Hospital in Hamburg, Germany.

PG: I’m Peter Goebell, urologist from the University of Erlangen in Germany, southern Germany, Franconia, to be precise, and I’m leading the study unit there.

JB: Joaquim Bellmunt, I’m a medical oncologist. I’m mainly dedicated to bladder and prostate cancer. I’m a professor at Harvard Medical School and also personally directing the IMIM Institute in Barcelona.

EE: Gentlemen, I actually need to introduce myself. I’m Eleni Efstathiou, I’m a medical oncologist as well focussed mainly in prostate cancer and I am Greek so I do still have affiliations with Greece. But it’s very interesting, the Germans are still in place but the Spaniard and the Greeks have moved over to the United States – political comment here. So, moving on, we’ve had a great session yesterday and we’re going to have an even more interesting today. But I wanted your views, since we are a mixed group – we do have a urology strong presence with a lot of interesting data coming from Germany in advanced imaging, how to do better for our patients, and medical oncology, of course, sometimes we are more conservative as medical oncologists. So I wanted your view first on a more bigger picture topic. Joaquim, yesterday you had a very interesting session on a holistic management for all types of GU cancers – can you give us some take-home messages and then, Peter and Thomas, your views on the holistic management?

JB: Yes, the first session, the title, as you mentioned, was holistic management and I explained to the audience holistic doesn’t mean a religious or magical way of treating patients, holistic means treating the patient as a whole. In this first session what we discussed mainly was comorbidities and the geriatric assessment, then we focussed on bone health and in the end on polypharmacy. So those are the things that we are all the time facing when treating GU patients and I think it was a really interesting discussion presenting the way that you need to score patients in terms of comorbidities or geriatric assessment using the G8 score and the way that this can be implemented in daily clinical practice. We turned then to the way to prevent bone loss and the interesting thing, it was not only for prostate cancer – we moved the topic to bladder. We know that bladder patients that are receiving neoadjuvant chemotherapy and also the bone loss is more and more important. Then polypharmacy was given by a pharmacist and it’s really something that we need to keep in mind because these patients are aged patients, it’s an aged patient population taking a lot of medications and the interactions with the other active treatments that we are giving are really relevant.

EE: So, Peter, at the end of the day I think we’re all busy in our clinics. Do you actually take the time to do the geriatric assessment or do you…?

PG: Yes, I do.

EE: You do?

PG: Actually, it’s called the Erlangen score. We actually evaluated all these different geriatric assessment scores and we figured out that they are not equal and we made up, actually, a new score; one of our colleagues is working on this.  A) It’s shorter than all the different other assessments, B) it’s easier to provide and we saw in the retrospective analysis that this is even superior, for example, to predict perioperative morbidity. So we actually evaluated each and every patient who is above 70 with this score.

EE: A very, very good point. Thomas, does it affect your practice?

TS: I think it’s a good way, or it’s easy to handle when you use it. It’s a quick job, it takes less than five minutes and the patients can fill it in themselves because the questions are quite easy about their daily life. If you have a score above 14 it’s straightforward because you can consider him being fit for any systemic treatment; if he is frail and to decide whether it’s reversible or not it’s getting more complicated because you need a back-up of a geriatric, you need internal medicine, so then it becomes more multidisciplinary. So you have to have a good network that you get the feedback and you will see the patient again to eventually assess whether he is amenable for systemic treatment or not.

EE: This was a good point. I think the important point for everyone who is watching is the assessment allows you to consult with others who are more specialist and it doesn’t add time, it actually takes less time at the end of the day, and you avoid the complications that may ensue if you have all the parties involved from the beginning. So this is the most important part of the holistic which, by the way, I didn’t think that people would perceive, as you said Joaquim, because being a Greek word I thought it was straightforward. But a great point. Of course, I’ll move quickly to something that’s dear to our hearts, Thomas, which is prostate cancer treatment. I wanted your view, yesterday there were two sessions, one on hormone naïve prostate cancer and one on the next topic that you two are very interested in – early castration resistance. So I want to start, because of the natural history of the disease, with hormone naïve prostate cancer and the explosion of data that’s coming through. And your thoughts, Thomas, how is it shifting and changing the treatment paradigm for prostate cancer? Yesterday there were concerns, for instance, if you use all these agents early, and you know my views on that, you’re not going to have them later. Would you like to comment on all these thoughts?

TS: I don’t agree because if you look at the tremendous overall survival benefit when you use early chemotherapy or you use early abiraterone the patient benefits. I think the discussion at the moment is more complicated – to see or to decide which drug to start – and it’s going to be even more complicated. Probably other potential drugs are going to move into this field as well, there are ongoing trials. We will in the future talk about even more intensive treatments or adding chemotherapy and abiraterone in the setting of hormone naïve metastatic cancer. So they are also running trials there and to make it even more complicated the role of local treatment. So the biggest shift of paradigm is happening in the hormone sensitive metastatic setting. The steps of advance in the castration resistant is very hard to reach a further survival but in the beginning it counts.

EE: But I think that the next big step is going to be high risk localised disease, right? We need to tackle it at some point.

TS: Definitely.

EE: And you two, as urologists, I know have a great interest in that. But I wanted to ask you, Joaquim, do you think we are reaching a time where prostate cancer is closer to breast cancer therapeutics with the advent of agents earlier or are we still far off?

JB: I think that’s a funny question. Despite the high incidence of prostate cancer we have been lagging behind breast cancer where the field of managing patients with hormonal therapy, chemotherapy, has advanced so quickly. In fact, we see that we are moving in the same direction, introducing earlier and earlier chemotherapy, different types of hormonal therapies, so it looks like we are getting there.

EE: But no biomarkers.

JB: That’s a critical issue but maybe we are going to get some in the future.

EE: So quite hopeful with that. We’re not there yet fully with hormone naïve but, Peter, as we were preparing for this session you expressed your interest in this continuum of castration resistance. There has been an explosion within one year of three trials and I bet there’s going to be more conflict moving on on how we’re going to best select the right agent. For practical considerations we have three novel antiandrogens of the second generation that are showing powerful data. In fact, it’s a triplicate – three trials showing precisely the same data. How do you view this shift and how do you think it’s going to contribute to a better treatment of those men who are now feeling androgen deprivation as we know it?

PG: I think that these trials clearly show that combination therapy is probably the way we are moving forward so there are two or three messages in there. The first message is that ADT alone is, as we’ve seen in hormone sensitive treatment high risk patients, combinations are earlier and earlier. What we are seeing there is that combinations are probably the way to go. So ADT alone is no longer the standard, it is more toward combinations. We see the same also in the field of castration resistance or early castration resistance even in the non-metastatic - an interesting question whether that exists. Non-metastatic but castration resistant, rising PSA patients, and even there we see the combinations and, as you said, new drugs there – enzalutamide, darolutamide and apalutamide – as possible options. There are three really convincing trials leading to a delay, actually, of measurable disease of almost two years and that’s huge progress. What it tells us is, a) combinations and early combinations also in this setting are relevant for the patients. It may delay progression for these patients. It actually showed also that there is an overall survival benefit, independent of all consecutive therapies. The third part I think is very important because it was a grey zone in the past. We were searching for all these mets, we were thinking they are there, so PSMA testing, for example, is a huge topic actually to really find out what is the disease, what is the status of the disease, irrespectively of the rising PSA.

EE: A very interesting point. Now, we’ve got the three trials, positive primary outcomes of delay in metastases; great data on quality of life, great data at least to understand better safety and try to overcome it and pick the patients. But you brought up the point of that continuum being disrupted, as it was defined in the past, structurally defined as Matt Smith said, with regards to whether it’s metastatic or non-metastatic by just conventional imaging. Yesterday you made some comments about what he brought up just now – PSMA or other advanced imaging. Does it really make a difference in the biggest continuum or should we just rely on PSA doubling time, high PSA at base line and you’re good to go? What do you recommend?

TS: I think it’s crucial, as you mentioned, to really identify the patient base on the high risk definition. So precisely calculate the doubling time, look at the PSA level, because you may have a very indolent course of the disease if you have a low PSA doubling time.

EE: So you wouldn’t treat that?

TS: Those patients won’t need treatment or maybe you can treat with vintage drugs like bicalutamide, flutamide, whatever.

EE: So you still use those?

TS: Yes, why not?

EE: It’s more emotional.

TS: Because they are worried because of the rising PSA.

EE: Yes, emotional for the patient.

TS: But if it comes then to a high risk like a rapid doubling time I would order conventional imaging, I would not seek for the metastases.

EE: Even though you’re the gurus of advanced imaging in Germany?

TS: Because still in Germany it’s not reimbursed.

EE: Oh, it is not?

TS: No, it’s just the private insurance that cover it and some public insurance but the vast majority doesn’t have access to PSMA PET scan and the price is about €1,800-2,500 so still expensive. So what do we do with a lesion that is invisible in conventional imaging but visible in the PET scan? We don’t know.

EE: That’s a big question that we need a trial.

TS: So I avoid the conflict. In the setting we have perfect drugs, they work, they delay metastasis and even symptomatic progression. I think that’s a good endpoint.