Incorporate Next Generation Imaging Tools Into Clinical Practice - Piet Ost

Piet Ost shares details of his recent presentation focusing on biochemical recurrent prostate cancer, specifically in the recurrent setting, and answering the question such as should we be investing in this novel imaging for all patients or should we dial back a bit and only have that for selected patients? Who should get this imaging? He expressed his intent to try to convince people to think before they do the scan, "What if it's negative, what will I do? What if it's positive and it shows this, what will I do? What if it only shows like this, but not that, will I act on it and how would I act on it?" Other questions they bring into discussion include, What should we do if we have a PSMA positive spots showing on the scan? Should you target it? Should you give systemic drugs? He addresses the uncertainties with novel imaging, highlights what the field learned from the STOMP trial and plans for the STORM trial – how to incorporate next-generation imaging tools into clinical practice.

Biography:

Professor Dr. Piet Ost works as Radiation Oncologist at Ghent University Hospital, Ghent, Belgium. He is a member of several national and international associations and is Vice Chairman of the EAU Young Academic Urologists Prostate Cancer Working Party. He is author and co-author of several papers published in peer-reviewed, indexed journals.

Phillip J. Koo, MD, is the Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Arizona

Read the Full Video Transcript

Phillip Koo: Welcome to the EAU 2019 coverage from UroToday. We're very fortunate to have with us Dr. Piet Ost, who is Assistant Professor at the Ghent University Hospital in Ghent, in Belgium and also Vice Chairman of the Young Academic Urologists' Prostate Cancer Working Group of the EAU. Very fortunate to have you with us and thank you for taking the time. Before we begin, can you tell us a little bit about something fun or some recommendations that you would give for people to do in Barcelona if you're visiting?

Piet Ost: Well, I hope they actually have the time to spend several days here because it's such a beautiful city. Actually, I did my Erasmus here a couple of years ago, so I spent three months, almost four months here, actually living here and going to the hospital back and forth, so I really got the ins and outs of the town. For me when I come back, it's always fun. You've got all those very historical places, but on the other hand, you've got your really spectacular food places which are just amazing. The mix of the vibe that is going on here of people living here, that mixed with students, tourists; it's a very lively atmosphere, very unique.

Phillip Koo: All right, favorite restaurant or favorite food?

Piet Ost: Ooh, favorite restaurant. The thing when you pick one, you always losing. The thing is when you pick one this year, it might have changed completely the next year, so it's virtually impossible to pick something here, but I'm a true fan of what the Spanish kitchen has to offer, even beyond the standard. Tapas, as everybody knows, they can really bring that to the next level, and that for me is always fun to actually indulge myself in what they have to offer here.

Phillip Koo: All right, let's get it down to business. You're here at EAU and you're speaking about the pros of PET with regards to prostate cancer. Can you tell us a little bit about your presentation?

Piet Ost: Yeah. Tomorrow, actually, there was the ideas of having a debate in the setting of the biochemical recurrent prostate cancer, so the focus will mainly be in the recurrent setting, and we will be debating on should we be investing in this novel imaging for all patients or actually should we dial back a bit and only have that for selected patients.

I'm going to approach my talk a bit conceptual and really try to think about who should get the imaging and why all of a sudden, how did we get here because a couple of years ago the guidelines were very strict. It was all about conventional imaging. When your PSA starts to rise in these patients, you need to wait at least until PSA levels go above 10, and then you can do your normal conventional CT and bone scan and maybe they will show something. All the levels lower, your scanning will be negative, so you will have patients that are on PSA rise for a long time until actually, they become positive, and there's nothing really you can do. Some did immediate ADT in some cases. Other waited it out until the scan became positive.

Then, there was the introduction, for example, of choline, and now with PSMA. We've seen these guidelines now switch completely. They are leaving more and more out the conventional imaging, it's getting to the background. Now, for example in the current guidelines from 2019, just published this week, they clearly state you should do a PSMA PET CT for the patients with a PSA above 0.2. If you read the small letters, it also clearly states, "But only if the outcome of this PET scan will change your actual management," and that is key.

The talk tomorrow, I will try to convince people already to think before they do the scan, "What if it's negative, what will I do? What if it's positive and it shows this, what will I do? What if it only shows like this, but that, will I act on it and how would I act on it?" I think it's important for clinicians to already think about that before they do the scan. When you look further down those guidelines, the question is what do you have to do with such a positive scan; they are less clear because we have a knowledge gap. There is almost no evidence what you should do if you have a PSMA positive spot somewhere. Should you target it? Should you give systemic drugs? The field is completely open, and the evidence especially for the field I love going after these metastasis with stereotactic body radiation therapy, the evidence is still very, very low. For me, the novel imaging is creating a space of uncertainty. That's a difficulty where we're in now and it's more confusing maybe.

Phillip Koo: You've actually taken a lot of steps to fill in that gap with STOMP and your future trial STORM or currently open trial. Can you talk a little bit about more about those two trials and how that's filling in the gap?

Piet Ost: What we wanted to do, we saw a rise in popularity of SBRT in different countries, so we started also experimenting and investigating the potential of targeting those metastasis, even started with FDG more than 10 years ago. We saw some very nice results in a minority of patients. Then, it got a little bit better and we got choline and our results improved again. But, then, at a certain point, we talked in our hospital and we said, "Well, actually we need to take this a step further and we should actually start thinking of a randomized trial."

In that specific setting for STOMP then, we thought, "What needs to be a control arm? Do we have no treatment whatsoever or is immediate ADT the standard?" We looked in the guidelines at that time, it's still currently stating the same. Immediate ADT is actually not recommended to give to all patients who have a PSA recurrence because there is no overall survival benefit. The data are just not there, so we said, "No treatment is actually the standard, you just follow your patients." That was a concept that that's how the concept of STORM was born.

Then we thought, "What do we want to aim for, a big Phase III that will need years and actually the field will evolve too fast or do we start small to create a signal and a Phase II and see if it's worthwhile to investigate?" That was our concept because I was at that point, not sure that we were actually doing the right thing. In my opinion, if our trial STOMP would have been negative, that SBRT actually didn't add anything over no treatment whatsoever, that would have been a great point to stop it. But, the trial was positive.

Now, we have to start looking into how can we further improve because if you look into the details, you see that approximately 50% of patients relapse is quite fast. Within the first two years, they have a PSA recurrence. If you re-image them, you will find new spots, so you keep on hunting those metastases or hunting down the Pokemons, as some say in literature, and they're actually true. Our sensitivity of the modern imaging is still not perfect.

Taking that, the ideas we got from STOMP, we are now moving to the next step, how can we further improve what we're doing with SBRT. In my opinion, that will be again, the combination with systemic drugs because we know we're dealing with metastatic disease, so there needs to be a combination of both. We didn't specifically do that in STOMP because we wanted to see if there was a signal, and that's how that trial should be regarded. It shouldn't be seen as final evidence or whatsoever. It's actually the basis to continue research and that's it.

For STORM, what we're going to do, we're going to randomize SBRT versus whole pelvis radiotherapy in combination with six months ADT in both arms, so short duration of ADT. Because what we've seen in Europe that's for nodal recurrences, that's where STORM is located, nodal recurrences on PSMA; we've seen people doing SBRT and we've seen in people doing actually a whole pelvis. The question is what is best there. We now have a poster at EAU already giving some retrospective evidence that whole pelvis might actually be the way to go, but we are now generating that evidence in STORM.

Getting to the other step, what about distant recurrences? How are we tackling that now? There, as well, I do believe that we need SBRT in combination with a drug. In that field, for me, the question is should that drug necessarily be standard ADT or now with the very interesting data we saw in the M0 CRPC. We've seen apalutamide and we've seen darolutamide, very potent drugs with little added toxicity, but so potent at the androgen receptor level. Why not think of using those in combination with SBRT? That we get their potency but keep on maintaining that quality of life because that for me is still very important in this field because those patients with a biochemical recurrence have a very long lifespan. We need to be aware that whatever we do, it should not harm the patient, and that's something we have to think about.

Phillip Koo: I think it's wonderful that we have investigators like yourself who are actually exploring and trying to answer this question. Kind of the last question is what advice would you have for the listeners with regards to how they should incorporate these next generation imaging tools into their practice because I think there's not as much good data with regards to outcomes, but clearly, the tide is turning.

Piet Ost: The first thing I think: be critical. As a urologist or as a radiation oncologist, challenge your nuclear physicians because they have to be on top of their game and give you solid, good standardized reports. They should be aware of the potential pitfalls, like, for example, the ganglia, presacral, a lot of so-called red metastasis aren't really metastases, so there are a lot of pitfalls. There are also false positives.

The sensitivity also, and that's very important, is not perfect. We've seen patients with negative PSMA, but if we radiate the prostatic fossa, we see a decline in PSA in 80 to 90%, so that means that sensitivity at the prostate bed level, at this time point, that these very low PSA levels is not good enough. Be critical and when you order the exam, already think of what you will be doing with the outcome.

For me, the ideal situation is find somewhere in whatever country you are, find someone who's doing a trial or trial to get a trial started. For example, STORM will now be, I started in Switzerland, Belgium, we will start up in the Netherlands, Spain, Italy, and also Australia, some sites. We're really trying to get that enthusiasm and work with that enthusiasm to get the data. I think that should be done right now, so find people to collaborate. The things we did in STOMP, it's not rocket science. Anyone can do that, so any group should try to get out their data. I think that would be, if that would be the result of STOMP, I would be so happy.

Phillip Koo: Well, that's wonderful. Thank you so much for joining us and I hope once you have some more data from STORM, we'd love to have you back on and share that data with us.

Piet Ost: Perfect. Love to be here.

Phillip Koo: Thank you very much.

Piet Ost: Thank you.