The Use of Novel Imaging Methods in Prostate Cancer - Stefano Fanti

Stefano Fanti joins Phillip Koo at the 2019 European Associate of Urology to discuss the use of novel imaging methods in the prostate cancer space. Their discussion highlights the excitement and limitations around imaging including the methods of MRI and PET, and its impacts on patient care.

Biographies:
Stefano Fanti, Professor Department of Experimental, Diagnostic and Specialty Medicine - DIMES at the University of Bologna. He is Director of Nuclear Medicine Division of the PET Unit at the Policlinico S. Orsola and Director of Speciality School of Nuclear Medicine at the University of Bologna.

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



Read the Full Video Transcript

Phillip Koo: Welcome, my name is Phillip Koo, and welcome to the conference coverage of EAU 2019 here in Barcelona, Spain. We're very fortunate to have with us today, Dr. Stefano Fanti, who is Professor of Imaging at the University of Bologna. Clearly a leader in the fields of imaging and therapies with the use of nuclear medicine radiopharmaceuticals. Welcome, Dr. Fanti. 

Stefano Fanti: Thank you very much it's my pleasure.

Phillip Koo: Great. So there's a lot of excitement clearly about imaging in the prostate cancer space, and I think with that excitement comes a little bit of a reality check. And I think one of the limitations that's been identified with prostate cancer imaging is what is really the truth? Can you comment on your thoughts about the truth in these tests?

Stefano Fanti: Absolutely, it's a very interesting topic because as you said, there is a lot of excitement about the use of novel imaging methods including MRI and PET. Being a nuclear medicine physician I'm mostly interested in PET being involved. One question, which is frequently raised up by the clinicians or by any expert, let's say of Cochrane Literature of ABM, is which is the standard of truth. That's to say, if you see something on your imaging method, how can you document and prove that ultimately a lesion related to the disease that you're studying. 

So sometimes they complain that we should have a biopsy to confirm ultimately every finding. Which is not feasible. By the ethical point of view, it would be very expensive, time-consuming, almost impossible to run an appropriate trial because the patient properly wouldn't be happy to be submitted in any case to multiple biopsies. And it wouldn't be ethical if you have 10 findings to make 10 biopsies. 

But on the other side, it's very correct, that if you have no proof at all, then you are self-referring. So you can call the positivity rate as something which is true, which definitely is not. Because if something for example in a PET scan is hot, you cannot automatically call that as a lesion. 

So I guess that we have to be more and more keen to accept some composite standard of truth. That's to say if possible, a biopsy. Because if you have just one lesion, and you will decide how to treat the patient on the basis of that, then you should do a biopsy. But alternatively you can have correlative confirmatory imaging, that's to say if I see something on the PET and I can have, let's say an MRI or a CT scan, confirming the finding, then it makes sense to call that as a true positive. 

But even something like, if you're starting a clinical trial to have a treatment which is focused on that finding, you will have a benefit for the patient with a PSA reduction rapidly related for example, with an external beam radiation therapy, pointed at what you have seen. Well, then it's in my view, an adequate surrogate that can be considered as a standard of truth. I guess we need more and more of this. More open-minded approach. 

Phillip Koo: Great. I completely agree with this idea of being open-minded and not using limitations as a reason why to throw something out, but just understand what the limitations are. And as you mentioned, being open-minded. 

Another area that seems to be misconstrued is the idea of using a lot of these advanced imaging agents for treatment response. And all of these different agents have different mechanisms of action, but the space of treatment response really hasn't been elucidated. Can you comment on that with regards to what is going on and what we might see in the future?

Stefano Fanti: I guess again, it's very articulated because we have a number of variables. So different treatments targeted to different pathways or different mechanisms, and at the same time, imaging methods completely different because you can have MRI, which is exquisitely morphological. For example, whole body MRI is a very nice method to document bone lesion, and you can use that for proving that there is a benefit in the bone lesion response to therapy. 

But for example, whole-body MRI will not document lymph node lesion, that you can do with PET. But PET at the same time could be targeted just like PSMA, which is very popular in Europe, to some receptor that is overexpressed, but maybe a function of the treatment that you are using, the expression of that. 

So it's very complicated. Probably we need much more trials in which you will incorporate the imaging methods, which is more appropriate for the treatment that you're using in order to see if you can have a surrogate response again. It can predict the final ultimate response, that is always the overall survival or something clinical endpoint. 

Phillip Koo: Great. So right now there's a lot of focus on these advanced imaging tools in patients who are biochemically recurrent. What's sort of the next area that we're going to see the biggest impact on patient care? 

Stefano Fanti: Well, for prostate cancer it's definitely staging of high-risk patients. I guess that for example, in the guidelines of EAU PSMA-PET has been widely incorporated in the setting of biochemical recurrence. There are still discussions for the staging, but there is someone going trial and in particular the PROSPECT from Australia, which is going to possibly bring a final response on the role. 

Of course, not in every gentleman diagnosed with prostate cancer, because we have to focus when it could be relevant, by the clinical point of view, for the management of the patients to identify further lesion. And that's clearly the high-risk patients, that presentation. 

Phillip Koo: What are your thoughts on the use of some of these tools in patients with more advanced of these who are castration-resistant? I've seen some renewed interest in FDG as a tool for patients with castration-resistance disease. And also the thoughts of using PSMA in those patients as well. What do you think about that?

Stefano Fanti: It's completely different from the possible role. I mean, FDG, which has long not been used, because of the poor sensitivity in prostate cancer, can indeed have a role as a prognostic indicator. Because if you have an avid FDG lesion, then, unfortunately, the prognosis is very bad, so you have to be very let's say, aggressive in the treatment of such patient. 

PSMA can provide you different information because in castration-resistant, for example, the category of M0 castration-resistant is very questionable. Because most likely, recent data coming jointly from Germany and the U.S., they demonstrated that probably is a category not even existing. Because 90 something percent of the patients have a positive PSMA scan.

So, you change the paradigm of treatment because if you see that there is no M0 then everybody should have a systemic approach. Or you may discuss if it's worth if you document a real oligometastatic disease, try to cure the very few lesion that you see, just to delay their approach to a next treatment. 

Phillip Koo: I agree. I think this is really complicating a lot of our understanding of these various disease states. And it's encouraging to see more people tackling those issues with those trials such as STOMP and STORM that are going to ... and I know you're working on some trials as well that will help us understand more about how we treat oligometastatic disease and what impact it'll have on outcomes. 

From your expert opinion, where do you think all this will sort out? Right now the practice patterns across the world are so different. In the U.S. we have access to fluciclovine, the PSMA agents are not FDA approved. In Europe, it's clearly different. South America it's different. Australia it's very different. How do you think this will all shake out worldwide in terms of what the gold standard will be? 

Stefano Fanti: It's very difficult to make a prediction because every country, of course, has the right to decide its own legislation. And definitely, again in Australia, it is almost routine to have a PSMA scan for a great majority of patient with prostate cancer. That's not the case in the U.S. or in North America. 

The good point to me is that it's a really very exciting moment because you have many different options in imaging so rapidly entering into the field and providing opportunity in staging evaluation of response to therapy, to some extent. Biochemical recurrence for sure. At the same time, a number of treatment options. 

The problem is that you have to cope them. That's to say, to see which is the most effective strategy for that individual patient. So that the long known term of personalized medicine is possible now coming to reality because finally, you have the tools. Because before you have few treatments and just a couple of diagnostic approach. Quite obsolete, just like CT and bone scanning. Right now you have many options.

I have to go step by step, demonstrating when it works, what works better, because we don't want to do everything in every single patient. But it's really a great, great excitement to be in this field at this moment because the promises are really great. 

Phillip Koo: I agree. Your comments about personalized medicine I think, are spot on. I think imaging has sort of lagged behind a little, especially with prostate cancer. Now that we've reached to this level I think it does unlock a lot of possibilities with regards to getting the right patients to the right therapies at the right time. 

Thank you so much Dr. Fanti, it was a pleasure having you here, and hopefully, we'll be able to host you again sometime in the near future. 

Stefano Fanti: Again, it was my great pleasure. Thank you, Phillip.