Prof Fred Saad - University of Montreal Hospital Centers, Canada.

Prof Joe O'Sullivan - Queen's University Belfast, Northern Ireland.

Prof Axel Heidenreich - University Hospital Aachen, Germany.

FS: Hello, I’d like to welcome you. My name is Professor Fred Saad, I’m a urologist, Chief of Urology, at the University of Montreal Hospital Center in Montreal, Canada.

I’d like to present my colleagues.

AH: My name is Axel Heidenreich.

I’m Professor of Urology and Director of the Department of Urology at the Aachen University in Germany.

JOS: And I’m Joe O’sullivan.

I’m Professor of Radiation Oncology at Queen’s University, Belfast and I’m also Clinical Director of Oncology at the Northern Ireland Cancer Centre, Belfast.

FS: So I welcome you because this is an important aspect of treating prostate cancer complex cases and this is a multidisciplinary team that’s going to discuss two cases of prostate cancer that we encounter in clinical practice.

These two cases are one in a pre-docetaxel setting and another one in a post-docetaxel setting.

So how we decide on treatment for patients with metastatic prostate cancer really depends on patient preference, the situation of the patient, the progression of the disease in different states.

I’d like to start with the first case that we will discuss.

The first patient that I’m going to present is a patient who is 75 years old, healthy for his age, still active, who was diagnosed recently with castration resistant prostate cancer with metastases to his bone.

No evidence of visceral metastases.

In May of 2014 he started on abiraterone therapy; prior to starting abiraterone his PSA was 15.

Three months later his PSA declined to two and he felt fine.

In November of 2014 he was progressing on abiraterone and became symptomatic, complaining of discomfort requiring anti-inflammatory drugs.

PSA was rising and on X-ray we noticed progression of bone metastases.

Alkaline phosphatase was measured and it was elevated at 200 with platelets at 250,000 and haemoglobin of 118.

So, Axel, what would we be able to offer this patient who is not keen on getting chemotherapy?

AH: That’s already, then, one exclusion criteria for one of the available treatment options, so basically docetaxel would have been one option.

On the other hand you might think about switching the type of endocrine manipulation from abiraterone to enzalutamide, however, since he only responded about 3-4 months to abiraterone he probably will not respond to second line hormonal treatment with enzalutamide.

So the third available option would be a bone targeted treatment with radium-223 which makes him suitable for this type of drug because he has symptomatic bone disease, his bone marrow function seems to be quite well with a basically normal platelet count and normal haemoglobin level.

So in this scenario I would opt for radium-223 treatment in this patient.

Then, later on, if he progresses after this type of treatment you still can discuss chemotherapy, for example.

FS: Thanks. Thoughts?

JOS: Yes, I agree.

Obviously docetaxel would have been a consideration for the next step but the patient has made a decision which I think is very reasonable.

A lot of patients do have considerations to avoid chemotherapy for as long as possible sometimes.

In the absence of chemotherapy then switching to enzalutamide is an option as well but I think it doesn’t have a lot of evidence with regards to survival benefit.

We’re uncertain as to the survival benefit, especially in a patient like this, as Axel has said, who had a relatively short duration of response to abiraterone.

So I think I would consider him as a suitable candidate for radium-223 because he’s showing evidence of progression in his bony metastatic disease, both in terms of his bone scan, his symptoms and his alkaline phosphatase.

So I think he’s a good candidate for bone targeted therapy.

The benefits for the patient in this situation would be avoiding chemotherapy, which is his wish, but giving access to a potentially life-prolonging treatment which could also help him with his symptoms and maybe delay the onset of more significant bone symptoms.

FS: What about the complications of bone metastases? Is radium effective in reducing the complications?

AH: Radium is definitely effective, this has been shown in the ALSYMPCA trial, that it reduces the number of events of skeletal related events and that it also significantly prolongs the time until the development of skeletal related events.

Since we know that the occurrence of skeletal related events has an impact on prognosis and on further treatment and the development of further symptomatic disease, this would be just an ideal drug for him to start with, just in the scenario that he doesn’t want to undergo chemotherapy.

FS: Excellent. What about the older radionuclides? Any thoughts as an oncologist? Should we still be using them?

JOS: I think they have less role nowadays, especially when you’re thinking about survival prolongation.

Because while these drugs were useful in terms of pain control there was never any evidence of prolongation of survival. So compared to radium-223, that’s a real weakness from that point of view.

As well as that, the side effect profile of the older beta emitters is such that it may prevent further chemotherapy, it may also damage the bone marrow in somebody whose bone marrow is challenged already, potentially by his prostate cancer.

FS: Excellent.

So I think we have consensus here in a patient who would like to have an alternative to chemotherapy, a drug that can maintain quality of life, delay complications and prolong his life.

I think that would be a very reasonable option and I’m glad we have a consensus here as a multidisciplinary team.

FS: So if we go on to the next patient.

This is a patient who is younger and is 59 years old, diagnosed with metastatic castration resistant prostate cancer.

At the time of diagnosis he was asymptomatic and wanted to avoid any treatment with side effects but accepted to take zoledronic acid.

His PSA went from 15 to 237 over the two years he was on zoledronic acid and he continued to refuse chemotherapy until he became symptomatic, requiring narcotics.

At that point we saw progression of bone metastases and lymph node metastases which were still under 3cm.

The patient received docetaxel between February and August of 2013 and he responded well with disappearance of pain and his PSA declined from 237 to 14.

In December of 2013 he progressed again, becoming symptomatic and abiraterone was then started with a PSA of 40.

He had a good response and within three months his PSA had gone down to 5.

In November 2014 he again progressed on abiraterone, his PSA is now at 50.

He has pain progression, bone scan shows progression in his bones.

Alkaline phosphatase is elevated, 320, but he remains with a good performance status of 0-1.

In terms of lymph node metastases there is really no progression, still lymph nodes of 2cm in his pelvis.

So the patient and his referring doctor want to know what would be the best option.

Joe, what would you consider as options for this patient?

JOS: Well, clearly a relatively young man who is developing symptomatic progression which is largely driven by his bone metastases. I think there are a number of evidence-based options which can prolong life.

I think cabazitaxel, radium-223 and potentially enzalutamide, although we are very uncertain about the survival prolongation in somebody who has had abiraterone and especially not a terribly good response to abiraterone.

So I think the choices for him with regard to evidence-based survival prolonging therapy would be cabazitaxel or radium-223.

Either are an option for this man.

He obviously had some problems with chemotherapy or at least wanted to delay chemotherapy before, so potentially radium-223 is a good option for him.

He has a relatively small amount of non-skeletal metastases, it sounds like he has got some small volume lymph nodes so it may be that radium-223 may be more acceptable to the patient because of the better toxicity profile, however I think cabazitaxel is the other clear option for him at this stage.

FS: So what’s your experience with radium followed by chemotherapy in this patient that would like to probably avoid chemotherapy at this stage?

AH: We had a good experience, we did not see an increased haematotoxicity profile if we use radium-223 following docetaxel or also the other way round, if we use chemotherapy following radium-223.

So in this case I guess it would be a good option to start with the bone targeted agents because, as you said, his lymph nodes are basically stable, there is no progression.

There is no evidence of visceral disease so there is really not a clinical need to start him on a systemic cytotoxic treatment again.

Knowing that the haematotoxicity profile has not deteriorated with his second line chemotherapy you still could add chemotherapy once he has received radium and he might progress.

If it comes to the decision making process second line chemotherapy you could use cabazitaxel as evidence based medicine and you also could think about docetaxel rechallenge because he reduced his PSA by basically more than 90% which would be a good prognosticator for also another good response for rechallenging with docetaxel.

So basically he has three different options but in this specific scenario we would start him on radium-223.

FS: And what could the patient expect in terms of benefits from radium-223?

JOS: I would explain to the patients that the aims of therapy were to try and get his disease under control and that the evidence would suggest a potential for prolonging his survival but also for delaying the onset of more serious bone complications, especially bone pain, pathological fracture.

So I would hope that the drug would result in prolonged overall survival and also prolongation of time where he has hopefully better, more manageable symptoms.

AH: There might be one more thing we have to discuss with the patient because he is symptomatic.

We have to discuss with him that radium-223 is not a pain treatment so he might expect some improvement in pain but it could be that pain remains stable or even increases.

So he just must be aware of the fact that we might have to add in some additional palliative treatments; medication could be a salvage radiation therapy, whatever, but this has to be just followed once he is on radium-223.

FS: So I think the consensus here is that this patient has different options.

Given that he’s young, healthy, we want to make sure that he gets all of the available options that can make a difference in terms of prolonging his life and maintaining his quality of life.

So the sequence is less important than the ability to get access to these agents.

I would tend to agree that starting with radium would make sense since this is still a window of opportunity without visceral metastases which might preclude him from getting radium later if he developed visceral metastases.

Since we’re able to tolerate chemotherapy after radium I think that would be a perfectly good option and I’m glad we have, again, consensus in a multidisciplinary setting.

FS: So I’d like to summarise by saying that patients in the situations that we presented have several options.

Some options, such as radium, cabazitaxel, docetaxel, can be life-prolonging and the decision of which one to use really should be based on the clinical scenario, also patient preference is quite important and the tolerability of radium makes it very attractive for many patients in these situations being able to tolerate an agent that can add quality of life, reduce bone complications and also prolong life is very attractive for our patients and their families.

Thank you very much.