Advancements in the diagnosis and treatment of patients with prostate cancer

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Published: 11 Dec 2017
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Prof Heather Payne, Prof Kurt Miller, Ms Netty Kinsella and Prof David Dearnaley

Professor Heather Payne chairs a discussion with Professor Kurt Miller, Ms Netty Kinsella and Professor David Dearnaley around advancements in the diagnosis and treatment of patients with prostate cancer.

Discussions around diagnosis highlighted the results of the PROMIS trial; with multiparametric MRI allowing more men with clinically insignificant disease to avoid biopsy. Active surveillance was also discussed as an important tool for the treatment of men with early or low risk disease.

Conversations around diagnosis for advanced disease focused around PSMA scanning which is perceived by the experts to have provided significant advancements in terms of specificity and sensitivity of diagnosis.

The group also discuss data around treatment of oligometastatic disease and the potential use of biomarkers and next generation sequencing in precision medicine, as well as the use of chemotherapy and abiraterone in combination with ADT as a promising treatment for patients with castration sensitive disease.
Looking to the future of treatment of patients with prostate cancer, the experts discuss the treatment of locally advanced disease and the use of abiraterone and docetaxel in this patient group. The importance of further understanding optimal combinations of treatment modalities for individual patients is also highlighted.

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

Prof Heather Payne – University College Hospital, London, UK
Prof Kurt Miller – Benjamin Franklin Medical Centre, Berlin, Germany
Ms Netty Kinsella – The Royal Marsden Hospital, London, UK
Prof David Dearnaley – The Institute of Cancer Research, London, UK

HP: Hello and a big welcome to the ecancer learning session at the Prostate Cancer Roadshow in London. We’ve just had a really interesting session discussing advanced prostate cancer. I’m really happy to be joined by my colleagues this evening, Professor Kurt Miller who is a urologist in Berlin, Miss Netty Kinsella who is a nurse consultant at the Royal Marsden Hospital, and Professor David Dearnaley who is a clinical oncologist at the Marsden Hospital as well. We have a great panel here tonight and we would like to share with you some of the discussions that we’ve had this evening. Starting with diagnosis, Netty, how do you think this has changed over the past few years?

NK: Certainly the PROMIS trial has contributed to a big change in the way we think about diagnostics. Multi-parametric MRI and MRI fusion prostate biopsies have really been pushed to the forefront of diagnostics. Actually the emphasis is much more now on making sure that we can take men off of a diagnostic pathway earlier, that we’re not biopsying men that probably are going to be diagnosed with very indolent disease that possibly never needs diagnosing, and actually are concentrating on those men that need a diagnosis and need radical treatment.

HP: And how do you think active surveillance has changed our management of early prostate cancer?

NK: I definitely feel that active surveillance is still going to be an important part of the options that we give to patients. I certainly think that we’re closer to an idea of what safe active surveillance might look like in the future and that’s come about as we’ve got better diagnostic tests and we’re being more accurate with our diagnosis, certainly with staging disease. But active surveillance in general is one of those things that really as clinicians we need to be shouting about a lot more for patients with very low, low to intermediate risk disease to ensure that we are not suggesting that men have to live with the morbidity of some of these radical treatments for long periods of time, even if it is as more of a stop-gap to preventing people from being treated too early.

HP: A lot is happening in early localised disease. Kurt, what do you think about new diagnostics for more advanced disease, what’s happening there?

KM: Yes, we’ve seen similar developments for diagnosing more advanced disease. We had the first step with whole body MRI which probably was an intermediate tool, so to say, because the data are quite impressive but it has probably never been used very broadly, at least not in our surrounding. But then along came the PSMA, PET-CT PSMA, as a tracer and that gave us, in comparison with the older diagnostics like bone scan or cold [?] impact, a real step upwards in terms of sensitivity and also specificity. So we’ve been talking about oligometastatic disease so oligometastatic disease ten years ago with the bone scan is probably not the same as oligometastatic disease today with the PSMA scan. It also may, as we just have said about MRI, it may change the way we’re treating and looking at prostate cancer.

HP: Does everybody have access to PSMA scanning? Have you found it a useful tool?

DD: It’s not got universal coverage in the UK as yet. It’s not the easier tracer to handle; it’s got a short half-life etc. So it’s something that will develop and as it is more clearly shown to be beneficial, as it’s shown that it actually does change the management of individual patients, then it’s going to become a requirement, or something similar to PSMA.

HP: Because there are new tracers coming through, aren’t there?

DD: Yes, there will be new tracers. But it’s a step change in the diagnostic accuracy we’ve got for finding metastases in men who have high grade, locally advanced disease as well as in detecting very small volume disease in men who have recurrence after either surgery or radiotherapy.

HP: We’ve talked quite a bit this evening, or you’ve talked to us, about oligometastasis which has been fascinating. Could you just summarise for our audience how you think that’s going to change our practice in the next five years?

DD: Our practice will really only change if we do the proper studies to find out actually whether treating oligometastasis really works and has an impact.

HP: It’s very attractive, isn’t it, to think of that.

DD: It’s a very obvious idea and it’s a very attractive idea but does it really make a difference to patients? The data that we’ve got at the moment suggests that there will be about a quarter to a third of patients who will get long, long periods of disease control, perhaps even cure, just treating the oligometastasis without a need for systemic treatments either with hormonal therapy or with chemotherapy, both of which are associated with a much higher side effect profile. So it’s quite exciting and we are going to learn a great deal of interest but it’s also very important, as Kurt has been saying, that we use the diagnostic tests appropriately. This is going to impact on actually the proportion of patients who end up being curable or having long-term benefit. Very exciting time and we’ve got the tools to actually deliver the treatments. It used to be just CyberKnife, now a whole range of different radiotherapy equipment can do it. But we shouldn’t forget about other options – there will often be a surgical option – and there are other kids on the block, things like high intensity focussed ultrasound for treating bone metastases, for example. So it’s a range of focal modalities and we need to be able to choose the best one to suit the individual patient.

HP: Thank you very much. Radiology has almost become another biomarker now, hasn’t it, it’s a way that we’re going to determine treatment. Kurt, what are your thoughts on some of the other biomarkers? How are they going to change practice, do you think, over the coming years? Because at every meeting we talk about personalised medicine.

KM: Actually for the time being for prostate cancer we do not really have precision medicine, as it’s called, because none of the biomarkers we have so far, for example AR-V7 there was some hype two years ago and then it turned out that it’s not as good as a negative predictive marker as it seemed to be at the beginning. This is a nice role model.

HP: We were all so excited about it.

KM: Yes, we were excited and then it turned out, well, it’s not as good as we thought at the beginning. Anyway, this is definitely the way for the future. To mention DNA repair deficiency as a marker for PARP inhibitors like BRCA2, BRCA1, ATM, and we’ve seen in phase II studies that this is kind of predictive for certain types of therapy as PARP inhibitors. This is only one step and we certainly have made progress in terms of new generation sequencing but it’s not there yet. But it will change the way we treat this disease, I would also say, over the next 5-10 years or so because then it’s more like the genetic signature rather than the organ specificity in the way we treat the disease. We’ve been talking about this for a long time but we’re much closer now to that, I would think, than ten years ago.

HP: Netty, what do you think? These are very exciting times for men with advanced prostate cancer. What general advice would you give to patients when they are first diagnosed, they’re facing treatment with ADT and other therapies?

NK: The most important thing is to actually approach each of the treatments that you might be offered in bite-sized chunks because it’s very easy to think about the next treatment while you’re on one treatment. Because we do have this feeling that things have a shelf-life or there’s a timeline associated with the treatment so it’s all about putting things into perspective and actually trying to optimise and maximise your quality of life while you’re on each individual treatment. Certainly, for example, if a gentleman is starting ADT there is very key lifestyle associated advice that is really important for us to share with our patients. It’s a joint responsibility of nurses, oncologists, urologists, in order to be able to deliver that. It really helps patients to really feel a part of their care if they’re actually doing something proactive towards living a healthier lifestyle and being much more engaged in their cancer treatment.

HP: Definitely. David, what do you think about guidelines? We have lots of guidelines and guidance, which do you think are the best guidelines to look at to get advice for almost the menu of opportunities for patients?

DD: There are a variety and one of the important things is that they’re kept up to date. The European guidelines are pretty sound; the North American guidelines also have got a huge amount of merit to them. There are different flavours, of course, because different treatments are available in different places.

HP: That’s very sound advice and, as we’ve been talking about today, it’s also the individualised options for each patient and their own personal circumstances. But it’s good to have some basics from the guidelines on which we base our multidisciplinary discussion.

DD: Yes, I think it is. The problem with a guideline, of course, is it can’t become a guideline until there is adequate evidence to support it. So many of the things that we are very interested in discussing and speculating about for the future can’t be in a guideline, except that you can say, ‘We ought to be doing more research in this area,’ and that’s a great guideline.

HP: Yes, I think that’s good guidance for anybody really. Kurt, we were talking about new developments, at one stage hormone sensitive prostate cancer was orchidectomy, ADT, but we’ve had some great results in the last few years for changes in hormone sensitive disease. Could you summarise those for us?

KM: Yes, the first step was that the addition of chemotherapy, specifically docetaxel, to ADT proved to be much better than ADT alone.

HP: That was surprising, wasn’t it, really?

KM: Yes, there were some very old data comparing mitoxantrone or epirubicin with ADT and they showed similar things but that was twenty years ago. It started all with the GETUG study and it was negative. For me personally, I thought, ‘OK, that is gone. There is no more progress here.’ I turned out to be wrong. Then that was 2015 and then in 2016 we got the STAMPEDE data, in 2017 we got additional data with abiraterone plus ADT. So some kind of a super-combined hormone blockade for the patient and it showed pretty similar results as chemotherapy. So we’re now in the situation where we have really, really new options and the interesting thing is what David mentioned, that we have now the possibility to locally treat these patients, metastases and the primary, and we have also new options to systemically treat these patients. It’s hard to say who is good for what, it’s again about precision medicine currently. So the good thing for the patient is, anyway, we’ve made progress in both ways.

HP: Thank you. David, what’s your tip for the future? What do you think is going to be important in the next few years?

DD: I think bringing forward our new treatments into locally advanced disease. The new treatments we have are really good for patients but actually they don’t cure more patients. If you want to cure more patients you need to go for the group that are on the borderline of curability and that’s locally advanced high grade disease. I’ll just reiterate Kurt’s comments about the use of chemotherapy and abiraterone in this group where the results are truly spectacular in terms of reducing recurrence. We’ve never, ever seen anything like it. So there is going to be a new curable subgroup and this subgroup is going to be comprised of patients who had a very high risk of dying of prostate cancer, rather than very early prostate cancer where actually our treatments aren’t affecting mortality very much because the men are not destined to die of prostate cancer. So that’s very, very exciting. But what we need to do is to work out which modalities to combine in that group because we are, after all, curing quite a lot of them already so we don’t need any extra treatment but we don’t know what that group is. This is where the personalised treatment comes in and whether it can be done by the molecular marking of the primary tumour or whether it needs to be done using circulating tumour cells and enumerating the different types of cells that we can find and, for example, how androgen receptor expression varies in these cells, is something that we need to work on. But it shows great promise.

HP: So that’s a great note to end on because there is such promise and excitement for the future of advanced prostate cancer. I’d like to really thank my colleagues for sharing their wisdom and experience. I’d like to thank you very much for joining us this evening. Thank you.