Navigating through the changing treatment landscape of advanced prostate cancer

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Published: 2 May 2018
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Prof Heather Payne, Dr Luis Martinez-Piñeiro, Prof Woet Gianotten, Prof Álvaro Pinto and Prof Anders Bjartell

Professor Heather Payne is joined by Dr Luis Martinez-Piñeiro, Professor Woet Gianotten, Dr Álvaro Pinto and Professor Ander Bjartell at the 13th Prostate Cancer Debate in Madrid.

The discussion opens with a conversation around the definition of advanced prostate cancer and the importance of taking into consideration disease volume and risk when categorising patients.

The panel discuss hormone sensitive prostate cancer and the latest advancements in the treatment of these patients. Dr Pinto talks around the lack of reliable biomarkers meaning that clinical factors and patient preference play a significant role in treatment selection.

The increased awareness of patients with non-metastatic castration resistant prostate cancer (nmCRPC) is also discussed and the ways in which this patient group are identified and characterised. The panel feel that results from the PROSPER and SPARTAN trials have provided more treatment opportunities for these patients; with PFS2 data highlighting the importance of subsequent treatments and the need for standardisation of monitoring this patient group.

Professor Gianotten also discusses the interplay between cancer and sexual relationships and the difference between sex and sexuality highlighting the need for a holistic approach to cancer therapy.

Disease volume and risk
Abiraterone or docetaxel in hormone sensitive disease?
PROSPER and SPARTAN trials in nmCRPC
New endpoints in daily practice and clinical trials
Sexual function and sexuality

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
Dr Luis Martinez-Piñeiro – La Paz University Hospital, Madrid, Spain
Prof Woet Gianotten – Centre for Physical Rehabilitation De Trappenberg, Amsterdam, Netherlands
Prof Álvaro Pinto – La Paz University Hospital, Madrid, Spain
Prof Anders Bjartell – Lund University, Lund, Sweden


HP: Hello everyone and a very warm welcome to this ecancer round table. We’ve just spent the last two days in the 13th Prostate Cancer Debate in a very sunny Madrid and we’ve had a very interactive meeting. There has been lots of discussion and it would be our pleasure to share some of the highlights with you. I have sitting next to me a very distinguished panel of experts who I’m going to ask each of them to introduce themselves and say a little bit about their areas of interest.

LMP: My name is Luis Martinez-Piñeiro, I’m the Chief of the Department of Urology at La Paz University Hospital in Madrid. My interest is in urological oncology and also reconstructive surgery.

WG: I’m Woet Gianotten from The Netherlands, I’m a retired MD and psychotherapist and my main area of interest is in the complexities of sexuality in chronic diseases and cancer. We call it nowadays onco-sexology.

HP: And we look forward to hearing more about that in a minute.

AP: My name is Álvaro Pinto, I’m a medical oncologist at the La Paz University Hospital here in Madrid.

AB: My name is Anders Bjartell and I’m Professor in Urology at the University Hospital in Malmö, Sweden, part of Lund University. I’m interested in prostate cancer, all different aspects from basic science, translational research and clinical trials and surgical procedures.

HP: Thank you very much. Going back to basics, Luis, we sort of thought we’d got advanced prostate cancer organised, didn’t we, it was advanced prostate cancer. But recently there have been so many definitions and subgroups and that caused quite a lot of conversation around the meeting. Could you tell us a bit more about that?

LMP: Yes, you know that advanced prostate cancer, metastatic castration naïve prostate cancer, can be divided into low risk, low volume, high risk, high volume. These definitions are important, or were important, to select a patient for the different trials that were finished quite recently. Also the treatment that is indicated for each patient group is a little bit different. If you read the guidelines, for instance NCCN guidelines, they differentiate very clearly the patients with high volume disease. So patients who are castration naïve can be treated up front with abiraterone and can be treated up front with docetaxel but only in the high volume setting. If the patient has low volume disease actually they don’t gain a lot receiving docetaxel. On the contrary, for instance the EAU guidelines, they say all the patients, all metastatic patients, can be treated with abiraterone up front and ADT, of course, and can be treated also with chemotherapy. So there are differences in different guidelines. Here at this meeting I talked with people from different countries, from Germany, from Eastern countries, and they really took into account how many mets had the patient. So they really take into account if it’s a low risk patient or a high risk patient in the treatment. Patients who have a low risk and low volume, they really try to increase the quality of life and they try not to give too much treatment to the patient because experience tells us that ADT may be enough in this group of patients. Patients with a higher burden of disease who have high risk disease, most of them would treat the patients with either docetaxel or abiraterone. So the risk of the disease and the volume of the disease is important to decide which type of treatment.

HP: Thank you. It’s been a bit of a minefield to work through that with the initial docetaxel studies looking at low volume and high volume and then with the abiraterone studies with LATITUDE having high risk and low risk. Álvaro , what was your take home message from this because we had a lot of debate – if you have both compounds available who do you choose abiraterone for, who do you choose docetaxel for in this hormone sensitive stage? What do you think the summary was?

AP: It was one of the most intriguing pieces of the meeting because until now treatment for patients with mHSPC has been relatively easy for decades – ADT and let’s see what happens. Now in the past four or five years we have two different weapons for the same patients, at least for the same group of patients – chemo, based on CHAARTED and STAMPEDE data; abiraterone based on LATITUDE and STAMPEDE data. As Professor Martinez-Piñeiro said, not exactly the same patients so that’s where things get more and more complicated. That’s good news, of course, because the prognosis of the patients has improved clearly. But we do not have reliable biomarkers to decide which patients would benefit more from chemo, would benefit more from abiraterone. That’s where clinical factors – a young age, number of mets, visceral mets, performance status – may play a role in selecting patients because we have to rely until now on clinical data because there’s nothing else to help guide us in the decision. Some colleagues, some delegates, we were speaking about it in that working area, say that they were afraid of longer treatment duration with abiraterone but some others were afraid of giving chemo when you have a less toxic regime that at least seemed to be equivalent. So, as I said at the beginning, the conclusion is that we have very good news for our patients, we must not lose that out of sight, and when things get more complicated it’s because we have better things to offer to our patients. We will select based on clinical factors mainly but now we have something better for our patients. That’s the main conclusion for the mHSPC part of the meeting.
HP: And the docetaxel and the abiraterone studies have both shown excellent results and equivocal results really. So it is all about matching the patient. One of the last comments on the meeting was somebody who typed in, ‘It’s the patient preference.’ I guess that is our job, to explain both of these approaches to our patients and give them some choice and it’s wonderful to give them a choice. Now, as if hormone sensitive prostate cancer wasn’t exciting enough, we moved on to a whole new topic, perhaps the topic of 2018, which is non-metastatic castrate resistant prostate cancer. This is an area where previously for those men who have a rising PSA after first line ADT but no metastases we had very few options for them. We’ve spoken today about the SPARTAN study and could I ask you, Anders, what do you think the highlights of that were?

AB: We really tried to increase the awareness of this group of prostate cancer patients. We haven’t really been thinking so much about it before but now when we have the new studies, which is the SPARTAN study and PROSPER earlier this year, now we have started to discuss how can we identify this group of patients, what are their characteristics? This is a high risk group of patients, high risk of developing metastatic disease but not yet any visible metastases we’ve been able to detect. We have discussed a lot about imaging – it will probably change when we have more sensitive PSMA-PET and other methods. What we do today is we have a bone scan, we have regular CT scans and then we don’t see any metastases but this group of patients may have metastases. And that’s exactly what has been studied with very good results in the new studies here, that we can delay the time until we detect metastases considerably. So, the new drugs used in this group of patients have shown very promising results and we need to discuss how to identify this group of patients, how to use the new drugs. We also discussed a lot about the availability of the drugs, when can they be available. Also we discussed what did we do before for this group of men? We haven’t really taken care of this group of men so very well before.

HP: We just had to wait until they became metastatic, didn’t we, and then there were other treatment opportunities. But to give that treatment early and to delay metastasis, what, for two years on average? And also to delay symptomatic metastases is something very important for all of our patients. Obviously the studies with both apalutamide and enzalutamide, SPARTAN and PROSPER, showing very, very similar, almost identical results which actually gives us a lot more credibility to both of these studies.

AB: And we had a really interesting discussion about endpoints in studies and endpoints to use in our clinical daily practice. There is something new coming up here, it’s the progression free survival 2, which means that a subsequent treatment after the first treatment, then we monitor the patient until the next progression in disease. So that’s a very interesting endpoint, I think we’re going to use that more in clinical trials but also in our daily practice in the future. So we need to better standardise how to monitor the patients and when to change treatment, that was a really interesting discussion we had.

HP: The PFS2 is very intriguing in the SPARTAN study with apalutamide and then the majority of patients having abiraterone after that. But it gives a feeling of a more prolonged benefit, doesn’t it? That we’re actually offering patients not something just now but for the future that they will benefit longer from that. Now, the patient, the man with prostate cancer, is the centre of everything and unfortunately nearly every treatment that we give, be it radiotherapy, surgery, hormone treatment, has an effect on their ability to get an erection and potentially on their sex life. But would you say sexuality is the same thing as sex? You gave this fantastic talk with lots of things to think about, I wonder if you could share some of that?

WG: Sex and sexuality, yes. What people do in their bedrooms, that’s sex, and we discuss sexuality. So we divide it in official names, we talk about desire, we talk about arousal or erection, we talk about orgasm or ejaculation. Each of those parts can be damaged and for us it’s important to understand a little bit the damage for each of the parts. But for the patients there are many more things which are important. A lot which we cannot discuss so much is male identity. I’m feeling a man and what, for instance, happens a lot in androgen deprivation is when you gradually change from being less and less male by having no erections, no desire, you get maybe breasts, you get a female deposition of fat, you can get bouts of crying, which is all less male. Now you see a real difference between, let’s say, the real macho male, the alpha male, that’s horrible for him. Some other men can deal better with that. So that’s one of the important things, especially in androgen deprivation. Another thing which is very important when we deal with patients with prostate cancer, special urologists started to focus on the penis and then gradually they are learning that behind every penis is a man. But we should also think that behind nearly every man is a partner and that partner, she or sometimes he, is forgotten so frequently and should be part of the treatment and should be part of also when we have to make decisions on what is the best treatment. They have to be informed about what could be the consequences of this treatment for the relationship and for sexuality. That is what is extremely different between one man or one couple and another man or another couple because with so much diversity among people. For some sex is, ‘You’re right, it’s eight weeks ago. We should do it again.’ And for other people it’s so important that sometimes they say, ‘If I can’t have sex then I want to die.’ You can’t see that on the faces of the people so we have to ask about that because it’s such an important topic for many of them. That’s one of the important things. The other thing which came up yesterday very clearly was about orgasm. When you’ve got nearly all treatments in prostate cancer give no ejaculation but nearly all men, or a lot of men, still can have an orgasm. It’s funny, for most men, because we’ve had thousands of orgasms after erection and now if you have no more erection because of treatment then a lot of men stop trying to continue to have an orgasm and many still could have it. That is somewhere if you focus on sexuality as only erection then you’re lost but sexuality is much more than only erection, it’s also intimacy. You can play a lot and have a lot of fun even without an erection, even without orgasm, even without desire. That’s a very important thing.

HP: I think you did a very good job in educating us as a group of oncologists and urologists on perhaps not just concentrating on… we tick a box with our consent form on erectile functioning but having a more holistic approach to sexuality in general. So thank you for that, it was a very different session for many of us but it was something that will be of great value to us in our future dealings with our patients, so thank you. Sadly, we have run out of time. These were the highlights of the meeting in Madrid of this prostate cancer debate. We hope that some of the thoughts have been useful to you and into your daily practice. We would like to say goodbye from sunny Madrid, thank you so much for joining us.