Dr. Stefano Fanti on the Importance of PSMA-PET Imaging in Prostate Cancer

GU Oncology Now delved into an article that was published this week in European Urology Oncology, titled ‘Contemporary Imaging Technologies for Men with Rising Prostate-specific Antigen After Radical Prostatectomy and Before Early Salvage Irradiation: Where Do We Stand?’ We spoke with Dr. Stefano Fanti, Director of the Specialty School of Nuclear Medicine, University of Bologna, Bologna, Italy, and one of the authors of this article. See what he had to say.

GU Oncology Now: Can you give us some brief background of yourself?

Dr. Stefano Fanti: Oh, sure. I’m a nuclear medicine physician. I was born and trained and spent all of my career in Bologna. Bologna University probably is not so famous, but it’s the oldest academic institution in Western Europe. I’m Director of the Nuclear Medicine Department here in Bologna, which is one of the largest in Europe. We are doing especially PET examinations. My personal interest in recent years is about PET imaging of prostate cancer.

GU Oncology Now: Can you detail for us what this article is about, and its significance?

Dr. Stefano Fanti: Yeah, sure. I would say in the last 20 years, there’s been an incredible growth in the imaging capabilities of prostate cancer and, in particular, nuclear medicine contribution has been terrific because we started almost 20 years ago with choline PET, which was interesting, even if not perfect. And thereafter, there was PSMA-PET that came was this been also fluciclovine in the meantime, so we have a number of new tracers and they have completely changed the imaging approach to the patient of prostate cancer.

So, this has been largely used and established in the setting of biochemical recurrence and it led to incorporation into the guidelines. Now, there’s more and more evidence for the importance of PSMA imaging for staging high risk and for many other indications. And in the recent article that you just mentioned it, we try to address it, which is the role of PET as a whole, but in particular PSMA-PET in those gentlemen in which it’s planned to have [inaudible] radiation therapy. So patients that have already been operated on with an early increase of PSA, so early biochemical recurrence, and for which there is a potential of a radical re-treatment with external beam radiation therapy.

GU Oncology Now: How big a role has current imaging technologies played in enhancing prostate cancer detection/staging?

Dr. Stefano Fanti: Well, detection, if you mean identification of the primary cancer, is mostly done with multiparametric MRI. There are other methods that could have been proposed, but the main technique is multiparametric MRI. PET imaging comes a little bit later, that’s to say when you have to stage the patients and where the cancer has already been detected. So for staging, especially high risk patients, then PSMA-PET has a very relevant role because, of course, in those high risk patients that you want to exclude that there is an extension, which may prevent your intervention from bringing a [inaudible], so that’s an indication.

And for sure, when you have biochemical recurrence, so when the patients have already been treated, and there is a rise in PSA, and you want to see where the recurrence has occurred, now it’s well-established that PSMA-PET makes a clear difference in our standard of care because it’s incorporated into either the European and the North American guidelines.

So the change has been really dramatic. If you think that something like 20 years ago, there was almost no imaging; it was only CT and bone scanning. Both techniques are very well known to be poorly diagnostic accurate. That’s to say the prostate can barely be seen or not at all. For bone scintigraphy, it’s all about bone. CT is not a great matter to study prostate, not to study the lymph node, not to study the early recurrence. So it’s been really a revolution and the impact has still to be fully established. That was about our article.

Because when you have already, they operated on a gentleman and unfortunately there is a recurrence, now the very typical approach is to perform a radiation therapy in the prostatic bed because you suppose that the recurrence has occurred there. But with imaging, you can definitely demonstrate that if the recurrence is there, so you are sure that you are irradiating the recurring disease and you see the extent. So, if there is some lymph nodes, for example, that will not be involved in your field of treatment, and now you can make that with the PSMA-PET.

The point is that the rationale is very strong. That’s to say, given that you are sensitive, for example, in seeing the lymph nodes, you can better identify the volume that you need to treat, or if there is a need for some systemic therapy, or whatsoever. Unfortunately, what we don’t have are robust randomized multi-center trial that do demonstrate an impact on major clinical outcomes and, in particular, an impact on overall survival. So, it’s something that is in the domain, let’s say, at present of discussion because you don’t have any ABM trial that can demonstrate to other extent that having imaging will prolong the survival.

But the rationale is very strong because if with PSMA you can identify any other area of recurrence, it’s clear that you can personalize; you can take on the treatment and the patients will have a benefit from that. We have to be patient and wait for a while that some good trials will finish. Those have trials, of course, that are long-lasting because the expectancy of life of those gentlemen is very long. Its trials which are not usually supported by big pharma companies because there’s no drug beyond it, so essentially, you will have to run and investigate or promote the trial and that’s not easy in nowadays’ scenario.

GU Oncology Now: With the ongoing proliferation of technology in the medical space, how big a role will technology have on impacting prostate cancer outcomes in the future?

Dr. Stefano Fanti: Again, that’s a major issue which stands between medicine, philosophy and ABM, and so on. Because medicine has been largely driven again by the ABM movement towards some demonstrations, which are easily run for drug intervention. All the trials promoted with the introduction of new therapies, new pills, can easily be done if you have a control group and you have your investigational group with an intervention, which is directly modifying something that will lead to an increase, hopefully, in overall survival. But when your intervention is not just a simple intervention like adding a new drug, or replacing the standard of care with something else, but you have an intervention which is adding an imaging, and the consequence of imaging could be different because you can have several options as a consequence of what you see, then designing such trial is incredibly complicated, in some cases, almost impossible, especially when there is a long survival of the patients and the standard of care may change over time.

So, this is one very methodological reason why it’s difficult to have trials that can ultimately demonstrate that adding a diagnostic technique will immediately impact on overall survival. So we have surrogate endpoint, just like impacting, for example, on time to radiological progression; it’s a surrogate endpoint. Or you have this logic of the rationale, as I just told you. If you have demonstrated that irradiating every pathological lymph node is a benefit for the patients, you cannot pretend that identifying better. Those lymph nodes will have a benefit to the patient’s survival, but it’s not a direct demonstration of that.

I’m sorry, it’s quite methodological and I have to admit I’m not full expert on methodology, but it’s just to justify there’s a long-lasting debate between the imagers, let’s say nuclear medicine, and radiologist versus the urologist oncologist and radiation oncologist. Let’s just say, they say, “Okay, you are showing me one more hotspot, one more lesion, but treating that is really beneficial for the patient. I’m treating the patient for the survival or am I treating the hotspot for itself?”

And they are right because we have no final robust data in many cases to demonstrate that. But at the same time, the information that we provide are unique, are clear, are very accurate because of false negative and false positive are the minority, and the rationale is in favor of that. So, we should collaborate to build some scientific evidence supporting that and, in turn, this will lead to incorporation into guidelines, and daily practice, and whatsoever.

GU Oncology Now: Closing thoughts?

Dr. Stefano Fanti: No. I mean, this is a perfect example, the salvage radiation therapy, of an intervention, which is cheap, it’s a relatively safe from side effects, it’s done for many of us, and we need a better strategy to drive it. And PSMA-PET could be exactly the perfect strategy to make this salvage radiation therapy at its best to customize the treatment for the patient and, of course, increase the quality and duration of the results.