Metastatic Prostate Cancer: A Practical Review of Therapy - Episode 12

Bone-Targeted Therapy for Prostate Cancer: Radium-223


Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: I’d really like to move the discussion on to bone-targeted therapy for metastatic castration-resistant prostate cancer. Chris, I’ll start with you, as an expert in the field and as the leading author of one of the major papers in the field. Just thinking about the patient selection for radium-223, how do you choose a patient for radium-223? What’s your approach to that?

Chris Parker, MD, FRCR, MRCP: Obviously, patients need to fulfill the eligibility criteria. So, they have to have bone metastases and they’re not allowed to have visceral disease, but that includes a large proportion of patients. It seems to me the most important mistake one can make is not to use radium-223 at all. It always amazes me when you hear about meetings like this and they have a lot of discussions about the treatment of CRPC, but they’re always talking about abiraterone, enzalutamide, and chemotherapy. And so, many of them don’t even mention radium-223, and yet the survival benefit is in the same order of magnitude. The safety profile is just as good, if not better.

My first message would be to think about using it, and then secondly, as to when to use it, we don’t know. We don’t have evidence to support that, but, as I was saying earlier, my preference is to use it earlier rather than later. I’m particularly mindful of the fact that visceral disease becomes more common as time goes by, and if you put it off for too long then you won’t use it at all. And then, I do have this hunch that it’s going to be used best in combination with an AR-targeted drug. It seems obvious that there should be some sort of beneficial interaction, a synergistic interaction, between radiation and AR targeting.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: What about the symptomatology? The license states, “symptomatic patients.” What’s your approach to the symptoms of these patients regarding their presence, their absence, or their definition?

Chris Parker, MD, FRCR, MRCP: Well, it’s no accident I didn’t mention symptoms.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Yes, I know that.

Chris Parker, MD, FRCR, MRCP: There seems to be no biological reason why radium-223 would work in men with symptomatic disease and not work in men with asymptomatic disease. I’m very mindful of the fact that many men, if you ask them whether or not they’ve got symptoms, will say no, but in actual fact they are symptomatic. Many men that I’ve treated with radium-223 after a month or so will say, “Oh, my pain has gone away. I’ve had it for months and months, and I thought it was just because I was getting older.” So, I really don’t find it a very helpful distinction to make.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Yes, I completely agree. I think, obviously, the reason it is on the license is because the trial mandated symptoms, which was really to have, I suppose, a worse bunch of patients with potentially a quicker readout. Is that right?

Chris Parker, MD, FRCR, MRCP: You’re absolutely right. So, the trial did say symptomatic, because the sponsors wanted an early readout. But the definition of symptomatic was extremely broad and included patients who were just taking 1 paracetamol a day, and who, on that, were pain-free.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: I suppose, like you said, there’s no optimal timing, but I agree with you. The earlier use has the other advantage of getting it in there and potentially moving on to other therapies afterwards. One of the concerns that’s sometimes expressed is the use of external beam radiation, either as an alternative to radium-223 or in combination with radium-223. Have you thought on that based on the data?

Chris Parker, MD, FRCR, MRCP: Yes. I find it a rather strange question, because in my practice, the question never arises. So, I would always use radium-223 long before a patient might need to have external beam radiotherapy. Really, I regard external beam radiotherapy as an admission of failure, because you should keep patients asymptomatic, or essentially asymptomatic, until they’re quite close to death.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Yes. I completely agree with that. I think it’s safe to use external beam radiation in somebody who potentially has a large soft tissue component to their bone metastases at the same time as radium, perhaps.

Transcript Edited for Clarity