Evan Y. Yu, MD:Andy let's stick with you and this theme that we've been talking about as to how often would you image this patient; you have somebody with a rising PSA, they have M0 CRPC, how often would you image? What are your triggers to maybe start treatment?

Andrew J. Armstrong, MD, MSc: This guy has a fast doubling time. He meets the NCCN [National Comprehensive Cancer Network] level 1 evidence criteria for getting a potent AR inhibitor he's got 3 choices; apalutamide, darolutamide and enzalutamide. Now I don't want to throw up years of bicalutamide. It's not a bad drug, 50% of the patients can still respond to that.

Evan Y. Yu, MD: When do you use bicalutamide?

Andrew J. Armstrong, MD, MSc: I wouldn't be opposed to using it in this guy.

Evan Y. Yu, MD:Even with the short PSA doubling time?

Andrew J. Armstrong, MD, MSc: That's right.

Evan Y. Yu, MD:Can you remind everybody what is that PSA doubling time cut-off you use?

Andrew J. Armstrong, MD, MSc: It's 10 months. But bicalutamide had about a 50% success rate lasting about a year, that's not bad and these drugs still work afterwards if you follow a patient carefully you could still use a potent AR inhibitor.

Evan Y. Yu, MD:You just declared yourself as old school, Andrew. All right I like old school.

Andrew J. Armstrong, MD, MSc: It's not level one evidence but I hate throwing out old drugs because I could use bicalutamide and then a potent AR inhibitor and maybe extend the life of that patient even further. That's how PROSPER, ARAMIS and SPARTAN did. They were mostly post-bicalutamide trials to be evidence-based.

Evan Y. Yu, MD:Now you're not starting people immediately once their PSA rises, you're watching them a little bit right just to kind of get a sense as to what their PSA doubling time is?

Andrew J. Armstrong, MD, MSc: This guy's PSA is up to 17.

Evan Y. Yu, MD:This guy was quick.

Andrew J. Armstrong, MD, MSc: It meets the indication. If you did a PSMA PET, 98% of the time you're going to see something so they're really metastatic.

Evan Y. Yu, MD: Let's say it was rising a little slower, how often would you image and what would you use to image?

Andrew J. Armstrong, MD, MSc: The PSMA PET is changing how the world is doing our imaging. In the United States it's very expensive to order this. It's frequently met by denials and peer to peers and that's a headache and we don't know that ordering that test is going to improve the outcome of that patient but if I had it as a cheap test to order like most of the world, I would probably order it. It could be informative. It might lead to metastasis directed therapy like pelvic radiation that could possibly improve the outcome of the patient. I might still layer on top of that a level one evidence-based AR therapy as a radio sensitizer and for long term therapy to delay the risk of metastasis and death.

Pedro C. Barata, MD, MSc: If I may comment, I take your point. The way I see the data once you have level one data obviously to see support any anti-androgens that you are part and help develop of course and you look at what happened where we have been talking about hormone sensitive and then we’re going to be talking later about metastatic CSPC and you also mentioned it in the adjuvant setting. To me, what is clear is moving these agents early on improves outcomes, that to me is argument not against the first-generation anti-androgens. When I see patients that do meet or fit the bill for novel whether it is darolutamide, apalutamide, enzalutamide, in my mind 98% will be metastatic. To me it just a matter of scan for me to prove the point or not but because I have all that story together showing me that if I do it earlier probably going to help those patients, that to me would be an argument towards using in that scenario. And then the other comment to your question which is a great question, will you do if you have doubling time of 11 months and do you hold tight or not. The approval doesn’t specify that, so you can do it. I don’t get anxious because a lot of times you’re treating numbers for that matter. In that case I tend to wait for patient to be eligible for one of these three trials, PROSPER, ARAMIS, SPARTAN to actually put them on but I would not be shocked if I have a PET scan upfront which could be Fluciclovine or PSMA, which are both available to us and then if I see metastatic disease despite not meeting the criteria for one of these three drugs, does one of those cases where I still consider adding it because then the goal of care is control of disease and not cure.

Andrew J. Armstrong, MD, MSc: And just because you see metastasis on PSMA PET doesn’t mean you can’t give darolutamide for example even though darolutamide doesn’t have the metas mCRPC in its label, that’s by conventional imaging. There has been a lot on social media about that.

Evan Y. Yu, MD:I like this conversation because we have all pretty much agreed on everything but slightly subtle differences and that’s the way it should be, we should have slight subtle differences in practices with interpretation of the data, so I like this.

Andrew J. Armstrong, MD, MSc: One other point though, once you started that therapy, we still see the same PSA radiographic disconnect. There are some patients published on this from PROSPER when they progress radiographically, they have a low PSA, even with visceral progression, imaging is recommended. Whether it’s 3 months, 6 months, or 9 months, it depends on your patient and your level of worry.

Evan Y. Yu, MD:And how fast PSA is rising.

Andrew J. Armstrong, MD, MSc: Any rise.

Transcript edited for clarity.