Philip Koo: Hello, welcome again to APCCC here in beautiful Basel, Switzerland. We're very fortunate to have with us today, Dr. Robert Reiter, who is Professor of Urology and Director of the Urologic Oncology Program at UCLA. Welcome.

Robert Reiter: Thank you.

Philip Koo: Thank you very much for that amazing lecture on oligometastatic disease. I think a lot of questions exist in the community with regards to that whole disease space. So for those who weren't able to attend APCCC, could you sort of clarify whether or not that disease state actually exists and if it does, what is it defined as in your opinion?

Robert Reiter: I do think it exists. I'm not sure that we have a very good handle on what it is compared to widespread metastatic disease. But there certainly does appear to be an intermediate state of metastasis wherein there might be less than five visible metastases and less than five metastases does seem to be associated with better overall survival, suggesting that there is, for some patients, kind of a window of opportunity to target oligometastatic disease.

Philip Koo: For the time being, for the viewers out there, you would use five as that cutoff regardless of distribution.

Robert Reiter: Distribution is a big question. And even in my own mind, after really reviewing all the literature, number seems to be consistently less than five, less than or equal to five visible metastases. Obviously, as I talked about, this very much depends on what technology you're using to actually identify or visualize those metastases, so it may very much differ for somebody undergoing a PSMA PET scan versus an MRI, CT scan, et cetera. In terms of location, I think the trials really encompass the spectrum. In some cases, it's really bone-only metastases. In some, nodal is okay, in others it's a combination of them totaling five. It seems that bone is what really drives survival to a large extent. So perhaps that's the most important subset.

Philip Koo: You've done some sentinel work with regards to next-generation imaging, PSMA, PET, CT with regards to the management of prostate cancer. Can you talk about the impact that it's had and how you translate NGI data into how you manage patients with oligometastatic disease?

Robert Reiter: In the context of clinical trials, we really don't know. I think that's what I would say. I think there's both a good and a bad to PSMA imaging. On the one hand, there are many men who have classically been thought to have non-metastatic disease, even hormone-sensitive disease, that now we find have quote-unquote oligometastatic disease based on PSMA imaging. In other cases there are patients who have oligometastatic disease with conventional imaging and then with PSMA imaging we're able to see that it's truly not oligometastatic, they have widespread metastases. And I think that the sweet spot is there are some patients for whom the conventional imaging and the PSMA imaging agree with each other. And I think that that probably is a better estimate of what the truth is in terms of the degree of spread. On the one hand, we're creating more oligometastatic disease with PSMA imaging, but we may be able to identify those who truly don't have that disease state using imaging, so I think there's on both sides of the issue, there's probably some advantage to next-generation imaging.

Philip Koo: Acknowledging that there's no real good data with regards to clinical outcomes, how do you manage those patients where there's that discrepancy? So if you have a patient who's M0 with conventional imaging but shows a few on a PSMA, PET-CT, how do you manage those patients?

Robert Reiter: It's always a discussion because we have, if it's truly metastatic, we've got drugs available so we have systemic therapy, but we do discuss it as perhaps this is an opportunity to actually get a significant amount of time off of a systemic therapy or without systemic therapy or perhaps even occasionally maybe we can actually change the course of the disease. So like many, we're kind of, we're doing it on an ad hoc basis but not really on the basis of clinical trial evidence.

So certainly we are using a lot of say, SBRT to patients who have oligometastatic disease, usually with a short course of hormonal therapy and then essentially seeing where we are and then if they fail, I personally don't favor doing it again and again and again, but rather at some point then transition to what's really standard of care. I think the danger is we have to remember we do have standards of care that actually have been proven to improve survival and just reiterating everything that we see, while it might feel good, we have to make sure that we're actually not doing harm by essentially withholding a treatment that can actually help that. So this is a discussion we have every day.

Philip Koo: Yeah. And I think that's a great reminder for a lot of the listeners, the fact that there are standard of care that's been tried and true and proven and I think it's a little too early to sort of throw that stuff away. A great point that you brought up in your talk was the idea of clinical trials and developing meaningful endpoints. So if you were speaking with someone who was planning a trial to incorporate this in the NGI and the oligometastatic disease space, what recommendations would you have with regards to meaningful endpoints?

Robert Reiter: In terms of endpoints, I think that the only really valid endpoints we have, historically, are survival. More recently we have time to progression or metastasis-free survival, which has been validated through Ice-CAP, mostly in the CRPC space, not so much in the hormone-sensitive space. So we need to, I think work to define what endpoints are actually valid. Kind of like was done with Ice-CAP to define metastasis-free disease so that we can actually identify endpoints, surrogate endpoints, so we could use within a reasonable period of time. I think the most important thing is consistency within, among trials as much as possible, but certainly within any given trial that the imaging is always done the same for within that trial so that we know what we're actually, the subset of patients that we're actually taking care of.

Philip Koo: So for the time being, you would think time to progression-

Robert Reiter: In time, I think, I think time to progression. I mean I think the STOMP trial would suggest a time to progression and time to systemic therapy is a starting point, but it will have to be validated with longer follow-up to see does that translate into either survival? Because it could be the opposite. We could be delaying systemic therapy and actually decreasing survival. We don't know.

Philip Koo: Great. Well thank you very much for your time and sharing your knowledge with us. It was a great experience for me personally as well. So thank you very much.

Robert Reiter: Pleasure to be here. Thanks.