Dan George, MD: I want to talk a little about the clinical setting first. Bertrand, maybe you can start us off with the clinical phenotypes of metastatic hormone-naïve or hormone-sensitive prostate cancer. What are some of the prognostic factors? What are some of the parameters we think of when we’re evaluating that population?

Bertrand Tombal, MD, PhD: What I’m impressed by is the fact that what we’re going to discuss now was already identified 15 years ago. When SWOG planned the intermittent androgen deprivation therapy, a very famous urologist, Mark Soloway, came with ... 4 or more bone metastases. Clearly, in terms of a prognostic marker, the volume matters. That’s clear. For the number of bone metastases and the presence or absence of visceral metastases, clearly volume matters. The problem is the ongoing discussion about changing this prognostic marker into a predictive marker. That’s going to be a different question. Besides that, there are factors that are less discussed because they’re probably more difficult to comprehend which is the ECOG performance status or the frailty level of the patient. We are very surprised that actually in most of these trials, the No. 1 exclusion criterion we’re facing every day is the frailty of these patients. There is a lot of work to be done.

If you look at the STAMPEDE trial, there was a push a few years ago by the STAMPEDE team to produce the result of the placebo group to get a better understanding of the prognostic marker. Clearly, that was size and location of metastases, ECOG performance status, and Gleason score, but you don’t need to be a genius to know that it correlates to some extent to AR sensitivity and presence or absence of pain.

On top of that, there are others that are not often measured but have been shown by the French as one of the No. 1 prognostic markers, at least in terms of power. This is alkaline phosphatase. This was shown in the GETUG-AFU 15 trial by Gwenaelle Gravis. She used an old model, the Glass classification. Clearly these are the most important. Anybody collecting data should report that because otherwise, we can’t clarify. This is because, to me, if you have 5 bone metastases, you have a Gleason 7, and you’ve got normal alkaline phosphatase, I would put you at less risk than if you have 2 bone metastases with alkaline phosphatase of 250 and a Gleason 9. Usually, when you do a whole-body MRI [magnetic resonance imaging] on these patients, you see a lot of them. We’re going to have to play with that. But the question that has been dominating the debate in the last 4 years has been volume centric.

Dan George, MD: Let me pick up on that. I think that’s a really good framing. Thank you, Bertrand.

Transcript Edited for Clarity