Alicia Morgans: Hi, I'm delighted to be here at the APCCC 2019 here with Dr. Declan Murphy, who is a Professor of Urology and Director of GU Oncology at the Peter Mac in Melbourne, Australia. Thank you so much for being here.

Declan Murphy: Pleasure.

Alicia Morgans: I wanted to talk with you a little bit about your talk, which was really focused on men who have node-positive but non-metastatic disease and how we think about approaching treatment and integrating new imaging modalities into that entire therapeutic paradigm. So can you share some of your thoughts?

Declan Murphy: We reviewed two aspects of managing these node-positive men with regards to surgery. The first was what sort of imaging technology we use to clarify if these men have nodes or not. And of course, the take-home message on conventional imaging for staging pelvic lymph nodes is that it performs really poorly with sensitivities of only about 15%. We already know that a lot of men with N0 status will have pathological N1 status. So that's one aspect. But let's take those men that do have nodes on conventional imaging. What do we do with these patients? And I can tell you the take-home messages on that session were number one, the quality of the evidence to suggest that surgery, for example, can be used for these men is low. However, the EAU guidelines do summarize by saying that surgery as part of a multimodal therapy in highly selected men has a role in these patients with node positive disease.

Alicia Morgans: How do you use that in your practice and how are you selecting these highly selected patients?

Declan Murphy: Well, in our practice in Australia, we actually have widespread access to PSMA PET imaging, which was the other really important dialogue we had at this session today. What is the impact of novel imaging in staging pelvic lymph nodes in newly diagnosed high-risk prostate cancer? So in Australia, we've been running a prospective randomized trial of PSMA PET imaging versus conventional imaging for exactly these types of patients, newly diagnosed high-risk. So the way the trial has run is, it's a 300 patient multicenter trial, as men get randomized to either have conventional imaging first or a PET scan first and then crossover. So we get accuracy as the primary endpoint but also management impact. Here's the key question for us is, if you've got an otherwise fit the patient with a high-risk cancer N0 by conventional imaging, we already know there are standards of care for these patients like surgery or radiation therapy.

But what if they're N1 or even M1A by PET imaging. And we see this all the time because we understand that PET imaging certainly has much better sensitivity as well as extremely high specificity for assessment of pelvic lymph nodes. I think in our practice in Melbourne, we very, very rarely are in a situation where we have an N1 patient on conventional imaging who has not had a PET scan to clarify the extent of disease and therefore we are rarely operating on N1 patients without them having at least had a PET scan.

Alicia Morgans: When you said the primary endpoints of this trial though, you said change in management and then are you looking at... Are you actually doing surgery on these patients regardless of the imaging and actually getting a pathologic diagnosis or what? What are you doing to confirm the extent of the disease?

Declan Murphy: Yeah, the proPSMA study is this study which is fully recruited and we've just locked the database for follow up actually and will present it at EAU 2020. But from an accuracy point of view, we're going to get that. That's going to be straight forward. What proportion of patients who are N0 or low volume N1 on conventional imaging are higher stage or maybe lower stage on novel imaging?

Alicia Morgans: By imaging alone or by pathology?

Declan Murphy: Both actually. But the primary endpoint is based only on imaging, a predefined criteria. But of course, many of these patients will go on and have treatment. They'll have surgery in many instances. The trial doesn't mandate what type of treatment these patients have because that's the whole conundrum of PET imaging is, what do you do with this information? We haven't got validated trials that will say what you should do. So for example, the classic situation, some of which we show today, our young, fit patient comes in with what looks like localized prostate cancer on conventional imaging. You do a PSMA PET CT and they've got retroperitoneal nodes or supraclavicular nodes. In the old paradigm, those patients went straight for surgery or some sort of radiotherapy. And yes, they're the high-risk patients who fail of course because when you see these very avid distant nodes on PET imaging, let me tell you, it's always right. You know the specificity is extremely high.

But what do we do? Do we change the whole paradigm? So the management impact is one of the things that we explore a lot of this meeting here today. And we report the management impact as part of proPSMA. I think what we will see in that management impact is a lot of confusion. What do we do? Do we ignore the novel imaging because it's a young fit patient that otherwise would have gone forward and had curative-intent treatment at least? Or do we embrace the novel imaging and say, hey look, this is what we really see. This is metastatic disease. Let's go for best systemic therapy plus or minus treatment of the primary in the context of metastatic disease. I think what I'm saying to you is, we don't have the answer to what the impact of better information on imaging is, but it's going to be very profound. The management impact in these high-risk cases when we do PET scanning is very significant indeed.

Alicia Morgans: Well and I think that allowing physicians to actually use their judgment and then make these choices, measuring that and then looking at the outcomes of those patients will at least allow us to generate hypotheses around what's the best approach so that we can then look at that prospectively, which is exactly what we need. I'm very excited to see the results of this trial and I have really appreciated hearing the surgeon's perspective on how to deal with these patients. What is your... If you had one message for clinicians who are trying to take care of patients with node-positive disease, as a urologist or as a medical oncologist trying to support the urologist, what would you say?

Declan Murphy: I think my main message is these patients have to be managed in a multidisciplinary manner because if they've got proven disease outside the prostate, they're not going to be cured by local treatment alone. So, therefore, don't be a urologist or a radiation oncologist on your own managing these patients, work with your other GU Oncology colleagues so you can refine a plan that's going to give a good outcome for these patients.

But I'll give you a second message if I can-

Alicia Morgans: Of course.

Declan Murphy: Which is that PET imaging is a really disruptive technology and I find even here at this meeting, key opinion leaders are almost dismissing it or trying not to see PET imaging, saying it's not validated. But let me say to you, this is very high-quality imaging that is not going to go away and in fact, it probably will become much more accessible in places like the US before too long actually. What we need to do is build novel imaging into the trials that we're currently running. It doesn't have to be that every single patient has novel imaging in both arms of a 1500 patient study, but we should build it in as a subset so that we understand better both the value of the imaging in terms of accuracy, but especially the management impact.

Alicia Morgans: I completely agree and I think that what we in the United States, at least caution each other is that we can't run away without the data, especially since many of our patients if they get these are paying out of pocket or are flying overseas to places like Melbourne to try to get these imaging studies done. But we don't really understand how to use the data. I know that that is definitely how some of the comments came across. But I really look forward to hearing the results of your study at EAU in 2020 and to the continued partnership around the world of all of these prostate cancer specialists trying to figure out how to best integrate PSMA and other novel imaging modalities into our existing data and data as we move forward. So thank you so much for your time.

Declan Murphy: Pleasure. Thank you.