Alicia Morgans: Hi, I am delighted to have here today a friend and colleague, Dr. Kala Sridhar, who is an Associate Professor at the University of Toronto, a GU Medical Oncologist at the Princess Margaret Cancer Center and the Chair of the GU Medical Oncologists of Canada. Thank you so much for talking to me today.

Kala Sridhar: Thanks for having me, Alicia.

Alicia Morgans: Of course. So we are here at APCCC 2019 and you've been actively attending, as we all have, and I just wanted to get your thoughts on some of the highlights of the meeting for those who can't be here.

Kala Sridhar: Sure. So this was my first APCCC meeting and I've really enjoyed it. I thought the talks were very focused, were very interesting. The debates, in particular, were nice because there was no right or wrong, but it was just learning two sides of the issue. So I really liked that. In terms of my key thoughts, I have a couple of them. So, the first is in the area of metastatic hormone-sensitive prostate cancer, which is an area that we both treat. I think the things that were really interesting or came out of this was the fact that there's a fair amount of heterogeneity within this setting. So we talk about low volume life expectancy, about eight years, high volume life expectancy, about three years. But within these categories there is indolent low volume, there's more aggressive high volume. So I think we have to be cautious about painting everybody with metastatic hormone-sensitive prostate cancer with the same brush. And I think we really have to consider the patient in front of us and how they fit into this. So I think that's one of the first things that was very evident from the presentations today.

Alicia Morgans: Absolutely.

Kala Sridhar: I think the other thing that we think about in this setting of metastatic hormone-sensitive prostate cancer, was discussed quite a bit, was the issue of what we do with the disease locally. Do we do radiation, do we do surgery? And I think we really need to understand the biology of what happens in this disease. So are the metastases coming from the local disease or the metastases coming from the metastases. And that, in turn, may help us to better understand what to do locally. And I think there'll be a number of trials that'll be really important in determining how we manage this disease. So I think that was sort of what the big points that I got out of the metastatic hormone-sensitive prostate cancer area and discussion.

Alicia Morgans: So, I completely agree. And the clinical trials, I think, are going to be so important in helping to figure this out. In the United States we have SWOG 1802, which is really looking at best systemic therapy for six months before we then use either radiation or surgery. And each of those are going to be randomized to no treatment of the primary, and there are a lot of correlatives embedded into this analysis to help us understand, as you said, the biology of the disease in a way that helps us really make smarter decisions in the future. And certainly, the volume issue continues to be an issue and we're really looking forward to continuing to see that unfold, both in terms of systemic therapy and treatment of the primary. So, what else really captured your attention?

Kala Sridhar: Yeah, so the other thing within the setting of the non-metastatic CRPC, I thought it was interesting, we have a new terminology, the SPA trials, so the trials looking at apalutamide, enzalutamide and darolutamide in the non-metastatic setting. I think it's important to think that it's non-metastatic by conventional imaging, that may not necessarily be non-metastatic, it may be micrometastatic. I think Dr. Hussain alluded to that. And I think the other thing that was interesting is these trials were similar but not completely identical in terms of their eligibility criteria, where one of the trials did allow the presence of pelvic lymph nodes. And I think this really brings up an issue that I think is really relevant and important in the field. And I think that's the issue of harmonization.

So as we do a number of trials, it would be nice to see trials in the same setting having a similar set of eligibility criteria. Because although we say we don't do cross-trial comparisons, I think in a sense we do. So I think it's really important for us to be able to come up with maybe a set of key eligibility criteria for trials in a similar setting, and I'm part of a larger initiative to look at harmonization across trials in prostate cancer.

Alicia Morgans: Absolutely. And I continue to follow your work in that area and definitely appreciate it. So what else have you been thinking about? Since I know we're all thinking, actually, quite a lot at this meeting.

Kala Sridhar: Yeah. We're all thinking. I think that's been a nice thing about this meeting is that it's really made us think, it's made us come up with ideas and things that we really want to look at further. There was some interesting work in terms of new therapies. So where are we going? I think one of the important things that came out is the fact that immunotherapy has not been a home run in this disease. We've seen it have a benefit in other diseases like melanoma, lung cancer, even kidney cancer within the GU space, but we're not quite there yet in prostate cancer and I know Chuck Drake is doing a lot of work and there's a lot of work going on, trying to understand where do we go with immunotherapy? Do we go somewhere with immunotherapy?

There's some interesting questions about combination therapy in prostate cancer, and not only do we combine them, how do we combine them and how do we sequence them? For example, do you start with a hormonal therapy and then add in the immunotherapy? Do you do them both together? A lot of unanswered questions, but I think it'll be interesting to see what the future holds for immunotherapy in prostate cancer, but I think we have a lot of work to do yet in that area.

Alicia Morgans: I agree. And I think as long as Chuck Drake's enthusiasm holds out, mine will hold out a little bit.

Kala Sridhar: Agreed.

Alicia Morgans: At least.

Kala Sridhar: Agreed.

Alicia Morgans: And these combinations are really exciting. I think there were some combinations that maybe even were involving lutetium or thinking about DNA repair defects and PARP. So really, where we go on the next level of this is that we need combinations. And I think that's something that we discussed here at the meeting and I really look forward to, though it's years away and they were very clear to say it, seeing some of that data come out. One of the other big areas that has been discussed, and it has been kind of a hot topic since we got the ERA 223 data maybe a year ago now, has been bone health.

And I really like to see a resurgence of attention to that because I think that that is something that's pretty easily left out of the care picture unless we are actively focusing for every single patient. Because in honesty, there are so many things that we're thinking about with these patients, that sometimes things that are not active problems today are hard to keep on that to-do list. So what were your take-home thoughts from a bone health perspective?

Kala Sridhar: Yeah, I think the ERA study did show us that the bone health is important, that using bone-targeted agents, especially as we're layering drugs that can impact on the bone, say ADT, the abiraterone, the prednisone, they can all affect what's happening in the bones, right?

Alicia Morgans: Yes.

Kala Sridhar: And so, I think as we're doing that, we need to make sure that we're cognizant of what's happening in the bone and make sure that we're using drugs appropriately in that setting. There remain questions as to dosing, as to how long we use these drugs, but I think it's an important consideration.

And along the same lines as treatment-related effects, there was a very good presentation on sexual health in our patients who are on ADT and other such treatments. And what was particularly interesting in the presentation was the thought that, for patients on these drugs, that it's often the partner that's more bothered by the effects of these drugs. And it's not so much, perhaps, physiologically what's happening, but more intimacy being compromised by these drugs. And how many patients may benefit, some patients may benefit from a referral to people who are dedicated in this area to help both the patient and the couple and move forward. So I think it's an important area that perhaps, like bone health, is a little bit underappreciated, and I think something that we should put some attention to.

Alicia Morgans: Absolutely. I think for a long time we've thought, "Well we're giving them these medications, the patients, that's really going to wipe out their erections and wipe out their libido". But we have to remember that men are, in some sense, a part of a couple and that we might actually be wiping out part of their interpersonal relationship. And it's not all about intercourse, that there can be other parts of that and that we can focus on supporting that as well. So I think it was really important to draw that to our attention.

Kala Sridhar: Yeah. Yeah. So I think that was important. The other thing where there was a lot of discussion about, as you know, is PSMA and the role of PSMA, and how it may be redefining disease. So disease that's negative on conventional imaging may now be positive by PSMA, but I think it's still early days for PSMA. I don't think we fully understand the clinical utility of PSMA. I think we have to keep in mind that our outcomes in prostate cancer have gotten better, much better, over the years, and should a test like PSMA change what we're doing, which may negatively impact on how patients are doing, we don't know. I think it's still early.

What I would say is I think we should start incorporating PSMA into trials. I think that there's a lot of heterogeneity in use of PSMA because not all countries, I know we don't have regular access to PSMA, the same thing in the US, whereas Australia and other centers might. But I think if we can, again, harmonize perhaps the incorporation of PSMA into our ongoing studies or new studies, we may learn more. We may be able to have more comparison between the PSMA and conventional imaging, and then we also would probably need to incorporate things like cost, like how expensive are these scans? Because conventional imaging, CTs and bone scans are perhaps not that expensive. Right?

Alicia Morgans: Absolutely.

Kala Sridhar: And again, I think it depends on where you are, but I think that that was a message that came out for me, that PSMA is exciting, it's interesting, but I don't know yet it's at a point where it should change what we're doing clinically.

Alicia Morgans: And I think there's a fear, too, that was raised that we don't want to do harm to our patients. We don't want to give up on therapies too early. We don't want to not start a therapy that could potentially be beneficial when patients appear to be a stage by PSMA, but actually, by conventional imaging, are a different stage. When all of the Phase III data that we have, the directs, the systemic therapy and the local therapy that we use, all of those trials are actually built on conventional imaging. So we really, there is a danger of over or undertreating some patients and potentially causing harm. And so, I appreciated that we discussed this exciting opportunity, but that we then took a step to say, "We have to make sure, still, that we don't cause harm by misinterpreting the data based on this new and exciting tool," which at this point isn't so new.

And so we, I think, in Canada and in the United States, we do need to start incorporating these into our trials. Finding the funding to do so may be an issue, but as you said, in order to really understand what we're doing, we're going to need this new modality and actually old modalities, too, so we can benchmark. And that's going to be really important.

Kala Sridhar: Yeah. Yeah. So I think, overall, it's been a really interesting meeting in different areas, right?

Alicia Morgans: Yes.

Kala Sridhar: We're learning, we're discussing, really good questions came up, and yeah, no, it was very enjoyable. I hope to come to Lugano next year.

Alicia Morgans: Yes. I think we're all very excited. Well, thank you so much for talking with me about these highlights and I appreciate your time and your insights, and I hope you have a great rest of the meeting.

Kala Sridhar: Thank you for having me.