Disadvantages of Using Novel Imaging in nmCRPC APCCC 2022 Presentation - Alberto Briganti

August 11, 2022

At the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting, Alberto Briganti presents the disadvantages of using novel imaging in the management of non-metastatic castrate-resistant prostate cancer (nmCRPC) patients.

Biographies:

Alberto Briganti, MD, PhD, Associate Professor of Urology, San Raffaele, Milan, Italy


Read the Full Video Transcript

Elena Castro: The next presenter is Alberto Briganti. He's a Professor of Urology at Universita Vita-Salute San Raffaele in Milano, Italy. When you're ready.

Alberto Briganti: So thank you very much. I would like to thank the scientific committee for this kind invitation to talk about disadvantages of the using of novel imaging approaches in nonmetastatic CRPC. These are my disclosure, but my real disclosure is that I really simple-mind surgeon, so many of my consideration will be a little naive for you, but at least I will try to be as practical as possible when we deal patients with nonmetastatic CRPC.

You have seen this slide already. We know now that we have three big trials that showed a survival benefit of three drugs, in patient with high risk nonmetastatic CRPC, high risk defined based on short PSA doubling time, since the PSA doubling time is a strong predictor of outcomes in patients with CRPC.

You have seen this slide already. If we scan these patients with a novel imaging approach like PSMA PET/CT, the same patients resulted to be negative, turned out to be positive in the vast majority of the case. But the real question is not if these patients are positive or negative, the real question is, is it advantageous for these patients to know whether there is a positive imaging if we applying, for example, PSMA PET-CT. And in many case, I do believe that improved identification metastatic sites does not justify abandoning standard of care treatments, especially in 2022, and in the presence of the data we have available today.

Let's start with a clinical case, very practical information about the guy that I see some weeks ago, this patient was 72 years old, he had incidental prostate cancer diagnosed at TURP in another institution, Gleason 4+4 equal 8, very low PSA when it was diagnosed for unknown reason because no major comorbidities. He had untreated primary. He was put on hormones and after one year actually he had progressive increase on PSA, with testosterone suppressed, and initial imaging was negative. So this guy had CRPC based on testosterone suppression and PSA increase above 2, and the PSA doubling time which was very short. This guy was staged initially with CT and bone scan that was negative. This guy was a physician and he decided to prescribe himself another imaging, which was the old fashioned choline PET/CT, which showed uptake in the prostate in the seminal vesicle and in one common iliac node. The guy was proposed to undergo radical prostatectomy plus extended pelvic lymph node dissection, and the guy refused.

The real question is not to prescribe an examination. The real question is what to do with a positive imaging, what to do with a positive test. I do endorse the guideline definition or the guideline statement about the fact that if you do imaging, that should in a way change the way we manage your patients.

And this is in the early biochemical recurrence setting after the primary therapy. And these can be all supplied in the setting of nonmetastatic CRPC.

Again, you have a patient coming in your office with castration-resistant prostate cancer. You decide not to propose any conventional imaging. The guy is the redacting stage with PSMA PET/CT. Well, if he has high risk, nonmetastatic CRPC so negative imaging, but low PSA doubling time he is candidate anyway, to the three drugs we mentioned earlier, but what to do if this guy has a positive PSMA PET/CT? That's the problem. It's very simple to prescribe examination. It's very difficult to know what to do if we have a positive test. Should these patients actually be treated with systemic therapy as if he was diagnosed at conventional imaging? Should we perform metastasis-directed therapy in case of oligoprogressive disease? Should we treat the primary as it was the case the guy I showed you in case of uptake in the prostate, or shall we simply use the information for outcome predictions? The things are even more complicated since you actually have other parameters to stratify your patients according to PSA doubling time. So more questions than answer, as I will show you in a minute.

In the absence of data, what we can rely on is consensus conferences, and these are consensus conference that we recently had last year. And in this consensus conference, there was actually the opposite statement that Michael told you in other consensus conference. So we reached a consensus of uncertainty about the use of PSMA PET/CT in nonmetastatic CRPC. Why this uncertainty in using that? Because of patient heterogeneity, because of the lack of long-term data regarding the benefit of MDT in patients with CRPC, the lack of data on treatment response, how to follow these patients, and how to define response to therapy, the lack of data about the proper sequencing of treatments, and the lack of data about cost-effectiveness. Altogether, what we can state today, I believe that using novel imaging approach has an unproven clinical benefit in nonmetastatic CRPC patients.

These are just a list of some of these studies in which after a functional imaging approach, patients were actually treated with metastasis-directed therapy. I don't want to get into the results. Pierre will touch upon these studies, but just to show you that we are talking about oligoprogressive patients with a heterogeneous PSA at this time of treatment initiation with lack of information about PSA doubling time, which is the main predictor of outcome, and actually without for more or less any control group. We are talking about evidence, which to me is not yet ready to change our practice. And in the same studies again, not talking about the results, just methodology, many of these studies that we actually know exact definition of what is defined as disease progression, indications for new treatment initiations, very heterogeneous. In one of these studies, which is quite scary, the treatment initiation of another systemic therapy was given only if a second metastasis-directed therapy was not feasible implying in a way that metastasis-directed therapy might be one of the standard of care of these patients, which I believe is not the case nowadays.

Then we need to be very careful when you examine these results. We might have indeed flare after initiation of monomanipulation using PSMA PET/CT. This very small study that we published at European Urology Oncology, but it was a nice study because there was actually a repeated PSMA PET after enzalutamide initiation. And in 41% of the lesion, there was an early increased PSMA uptake, even among those patients who then responded to therapy. So again, talking about consensus conferences, we need to rely on what experts say, and it has been agreed upon that three months is the minimal timing for performing PSMA PET/CT after initiation of hormonal intervention.

We need to again be very cautious and very careful. We need to apply strict definition to responses. Otherwise, actually we need to classify our patients in the wrong way. And again, PSMA PET/CT, if done, should be always coupled with clinical evaluation and laboratory data and response assessment may be performed in patients with inconsistent laboratory findings. In a way, novel imaging approaches are not yet ready to be actually nowadays implemented in practice in this setting. The same panel again, agreed on the fact that PSMA PET/CT should not be performed in a majority of patients who are diagnosed with metastatic CRPC.

Then last questions about treatment sequencing. If we use PET and we find something, what to do? For example, should we add or should precede metastatic-directed therapy to androgen receptor targeted agents? If in fact CT is done, how to follow these patients and when to eventually add conventional imaging, if of any rationale? Is it beneficial for example, to perform reiterate metastasis-directed therapy due to the low toxicity, but what is the efficacy? Not always what is feasible should be done, again.

So in conclusion, I'm trying to convince you that novel imaging approaches certainly are sensitive options in this setting. However, the proven benefit of using novel imaging approaches is unclear, given all the considerations done so far. We do need for standardizing our reports, which is crucial if you want to implement these in clinical practice. However, being honest, I need to restate what say yesterday, that the train has left the station, even in the setting, hopefully is not an Italian, old-style fashion train, which starts from the station, but you never know when and if gets to the next destination. Thank you very much for your attention.