Identifying Castration Resistance in Prostate Cancer

In part four of this roundtable series, Drs. Irbaz B. Riaz, Chad Cherington, Roopesh Kantala, and James Ewing discuss castration resistant prostate cancer and the typical patterns of presentation from CSPC to CRPC in each doctor’s practice. The panelists consider the best times to utilize PSMA PET scans based on PSA levels and patient considerations, and discuss how to care for newly-diagnosed patients.

Watch part five of this series: The Landscape of Radiopharmaceuticals and PARP Inhibitors in CRPC

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Dr. Riaz:
So, I just wanted to hear your thoughts on how do you manage patients who have metastatic castration-resistant disease, somebody who’s progressed now from metastatic castration-sensitive disease to metastatic castration-resistant disease.

Dr. Ewing:
So when you’re looking at the time of progression, you look at what the patient’s performance status is, what they’ve previously been treated with, how well they’ve tolerated, those sorts of things. If they had ADT alone, that’s going to be a very different patient than the one that was treated with triplet therapy up front.

It also is a time where we reassess what the genomic markers are, what the NGS sequencing is, whether it’s an actionable target, and then ultimately we have a number of new options.

Dr. Cherington:
Along the same lines, I’ll look at what did they receive before? What is their health status? Comorbidities? And then what was the treatment response before? Were they on abiraterone for a couple of years or a few months or docetaxel before? And that can kind of help guide if we’re going to use chemotherapy. Docetaxel or cabazitaxel, or go to radioligand therapy like lutetium or even radium-223. And then of course if they haven’t had molecular testing, you are reviewing if there’s any options in that space.

Dr. Kantala:
Yeah, I agree. I mean there’s various options at this point and clearly the driver is what they’ve received before and what their performance status is.

Dr. Riaz:
Absolutely. I think this is a very complicated space and there’s several factors that we have to consider here. I think really the most important thing that all of us have really said is that what they received in the past. What’s their performance status? What is their molecular profile at this time? The nature of progression, whether it’s oligoprogression versus it’s fluid progression. Is it just bone only disease versus it also has visceral metastases. So, we have a menu to pick from and we have to consider all these factors.

So let’s maybe talk about the patients who have minimally symptomatic bone only disease. How do you think about pS3 data in this context in these patients?

Dr. Cherington:
I think the data is impressive as far as having a potential role in this space. I think in the past I haven’t used it a lot because of concerns of financial toxicity for the patient, but I think that’s improving with time. But certainly the overall survival is impressive with that trial.

Dr. Kantala:
I can’t agree more. I mean pS3 definitely has given that option to pursue that approach and overall survival and I think as a tolerability was also pretty good.

Dr. Ewing:
With some increased toxicity. There was a three-month progression free survivor, I believe, in that study and that’s impressive. Not the progression free, but the overall survival difference. So that got my interest. Certainly it is a new option we have available.

Dr. Riaz:
How do you put in the context the data of combination abiraterone and radium? Any thoughts on that?

Dr. Kantala:
I think and where I practice, I wasn’t even considering that because as I said in my previous comments, I have had patients mostly if I was going to do a doublet was going to be abiraterone, so I never even thought or was going to consider that. But again, for academic purposes, we can keep discussing about it, but for me it really is not even a moot point for me to consider.

Dr. Ewing:
I think it was interesting that in the two trials that the use of bone strengthening agents, the denosumab and zoledronic acid was far greater in the second trial. Now that’s something we usually look for in this space anyway, but that may have something to do with the differences.

Dr. Riaz:
I think this is a great point and I think this also brings us back to the emphasis of using bone strengthening agent in patients who have castration resistant disease and bone metastases. It’s critically important for us to emphasize the need of using these agents because there’s always a question that now with these radiums and rhodiums, do we still need to use these bone strengthening agents? In my mind, I think the answer is yes, and absolutely yes.