Advancements in the treatment and management of patients with castration resistant prostate cancer

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Published: 12 Dec 2017
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Prof Kurt Miller and Prof David Dearnaley

Professor Kurt Miller and Professor David Dearnaley discuss advancements in the treatment and management of patients with castration resistant prostate cancer.

The discussion focuses on standard treatment strategies for men with advanced disease as well as following relapse. The experts discuss approaches to the treatment of patients with bone only metastasis as well as talking around the use of PSMA-PET scans in patients with lymph node involvement.

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

Prof Kurt Miller – Benjamin Franklin Medical Centre, Berlin, Germany
Prof David Dearnaley – The institute of Cnacer Research, London, UK

KM: Welcome to ecancer here in London at the Roadshow in Advanced Prostate Cancer. We just had a very nice event covering all aspects of localised and advanced prostate cancer and I’m happy to have David Dearnaley here. Tell me again, David…

DD: From the Institute of Cancer Research.

KM: From the Institute of Cancer Research. My name is Kurt Miller, I’m a urologist from Berlin, Germany and we’re going to talk a little bit about advanced prostate cancer in that setting here. David, we’ve seen many changes in mCRPC treatment and also, very recently, in hormone sensitive metastatic disease. Now, let’s just go back to hormone sensitive metastatic disease. Chemo-hormone therapy has been introduced two years ago, is that now really standard here in the UK, giving it to 80%, 50%, 90% of metastatic patients?

DD: It’s very difficult to put a precise figure on that; figures are not complete. One has got to be cognisant of actually the average age of the patients who present with far advanced metastatic disease, certainly not all men are suitable for chemotherapy. In the way that our cancer services are organised here, going through multidisciplinary teams, that men should be given the opportunity to have chemotherapy if they wish it. I would like to be able to assure you that actually that happens.

KM: Are patients reluctant to accept actually chemotherapy in that sense?

DD: Not all men will want it because it does impact on them and the way they lead their lives more than just having the hormone treatment. So it’s this balance between what they think they might gain against the obvious immediate disadvantages.

KM: So the next step would be now that with this type of treatment now two years on the road, we see the first patients coming to mCRPC stage that have gotten chemo-hormone therapy. Does it make any difference for you if they now get to the CRPC stage? How do you treat them?

DD: So, if they’ve had their chemotherapy up front?

KM: Yes, chemo.

DD: And then they develop progressive disease. These men may well continue to respond to chemotherapy with the same chemotherapy, docetaxel. That is still a very valid option. However, in the majority of cases we would now move to what I think of as super-hormone therapy, so the addition of either abiraterone or enzalutamide.

KM: So in these typical mildly or asymptomatic patients abiraterone or enzalutamide is standard first line treatment?

DD: I think that is what most people would do in the UK. There continues to be discussion.

KM: And then what would be the next step, typically? Once the patient is progressing under abiraterone or enzalutamide what would be the next step typically here?

DD: Then the vast majority of patients would then move to docetaxel chemotherapy. If they had bone disease only then there would certainly be the possibility of using radium-223 before chemotherapy. Again, this sequencing of treatment is something about which there’s quite a lot of opinion and actually there’s relatively little fact. It comes down to the particular expertise of the treating clinician but also very much about what the patient will feel.

KM: We talked about imaging, for a patient that would be a candidate for radium-223 would you say, ‘Well, I’m happy with the bone scan and the CT,’ or would you say, ‘Well, if available,’ availability is still the issue, ‘PSMA-PET is better’? Although, in the ALSYMPCA trial there was no PSMA-PET and patients were still candidates.

DD: Yes, I’m not so concerned about that in that particular situation. If you know a man has got bone metastases and the CT is not showing very much in the way of soft tissue disease then actually you can do without a PSMA scan. If you turn that around and you’ve just got, for example, lymph node disease and you’re thinking of targeting that lymph node disease with radiotherapy or surgery, for example, it’s very important to know that there isn’t additional disease and that’s where the PSMA-PET scan would be very important.

KM: We had intensive discussion, now with the PSMA scan you see sometimes patients’ bone mets and multiple lymph node mets. So do these patients still benefit from radium? Actually we don’t know.

DD: We don’t know the answer. I think one has to use a little bit of common sense and actually if there are multiple small lymph node metastases…

KM: You would be reluctant to use it.

DD: I think you’d say, ‘Look, this doesn’t make a lot of sense.’

KM: So let’s say we’ve gone through radium and/or docetaxel, is there cabazitaxel, is that something that is used here in third or fourth line of treatment?

DD: Yes. Cabazitaxel is used quite extensively provided, of course, the patient is fit enough to have it. My own thoughts about cabazitaxel, actually, is it’s slightly easier to give than docetaxel.

KM: Using 20mg instead of 25mg?

DD: I use 20mg although some of my very close colleagues are much keener on sticking at 25mg/m2.

KM: Really?

DD: Yes.

KM: Although there are potentially much more side effects.

DD: There’s potentially a bit more efficacy as well but I’m a 20mg chap.

KM: OK, yes, because the FIRSTANA trial or so have not shown any evidence that 20mg is worse than 25mg. So what else? Let’s just look again at the future. You mentioned in a small sentence that you’d sometimes send patients to lutetium-177 abroad, to Germany or wherever it’s available. Where does that fit in?

DD: Honestly, the answer is we don’t know yet. But I have been impressed by the data coming out using isotope targeted therapy with PSMA. It’s a very neat concept to link an effective isotope to an effective targeting molecule and PSMA is a very good molecule for this purpose because it becomes expressed more as the disease becomes more advanced and more resistant to our standard therapies. So it’s probably a better agent or drug, whichever you prefer to call it, actually in the more advanced stages after failures of earlier treatment.

KM: Definitely, and it has a totally different mode of action than androgen receptor, than chemotherapy, so we have a different mode of action again.

DD: Yes, it’s actually a very targeted but non-targeted treatment. It’s targeted physically but it’s not targeted biologically.

KM: David, thanks very much. Excellent discussion here and I’m looking forward to next time.