PSMA PET Academy - Case Discussion: PSMA for Biochemical Recurrence and SRT Planning: Early Biochemical Relapse in Patients - Jeremie Calais, Michael Morris, & Alberto Briganti

March 17, 2023

In this educational initiative, focusing on the knowledge of PSMA PET imaging and PSMA theranostics, Drs Jeremie Calais, Michael Morris, and Alberto Briganti discuss a biochemical recurrence patient case and the impact PSMA PET can have on radiation therapy planning or treatment. In this surgical case a 60-year-old gentleman who had radical prostatectomy in 2016 was pT2c node-negative, margin negative and a good PSA response after surgery. The PSA went to a nadir of negative of 0.03, but unfortunately rose to 0.12 a few months later. Since then, it increased to 0.22, with a PSA doubling time, close to two months. He underwent a PSMA PET scan. Drs. Morris, Briganti, and Calais review this patient case and talk through his treatment regime.

Independent Medical Education Initiative Supported by Novartis/Adacap and Point Biopharma


Jeremie Calais, MD, Sc, Director, Clinical Research Program, Ahmanson Translational Theranostics Division, UCLA

Michael Morris, MD, Prostate Cancer Section Head, GU Oncology, Memorial Sloan Kettering Cancer Center

Alberto Briganti, MD, PhD, Associate Professor of Urology, Universita Vita-Salute San Raffaele

Read the Full Video Transcript

Jeremie Calas: Hello everyone. Thanks for joining the PSMA PET Academy organized by UroToday, in partnering with the PCF, and our great partners POINT Biopharma and AAA. Today, it's my great pleasure to present a couple of cases, a couple of biochemical recurrence cases, and the impact of what can have PSMA PET on radiation therapy planning or treatment management. The two key experts that we discussed these cases with us today are Dr. Michael Morris and Dr. Alberto Briganti.

Michael Morris: My name is Michael Morris, I'm the prostate cancer section head at Memorial Sloan Kettering Cancer Center in New York City.

Alberto Briganti: Thank you, and thank you, Jeremie for this kind introduction. My name is Alberto Briganti. I'm full professor of urology at Vita-Salute University San Raffaele, Milan Italy, and responsible for the prostate cancer unit here.

Jeremie Calas: Great. It's great to have such experts with us to discuss a few cases I choose to show here. So the first case I want to show is a 60-year-old gentleman who had radical prostatectomy surgery for his prostate cancer in 2016, as you can see here. It was pT2c node-negative, margin negative. We had a good PSA response after surgery. The PSA went to a nadir of negative of 0.03, but unfortunately rose to 0.12 a few months later. Since then, it increased to 0.22, with a PSA doubling time, close to two months. He underwent a PSMA PET scan. So you can see, it was quite some time ago in 2017.

Here is the miT of the scan. You are probably all very familiar how these scans look like. And when you look at the scan at here, you don't see any clear targets. And in fact, indeed, the scan was judged as negative. Specifically in that scenario, what we are really looking at here is, any lesions just below the bladder here. For local recurrence, all these areas, and of course, the pelvic lymph nodes. The scan was negative here. So you have a biochemical recurrence early after surgery, PSA of around 0.2, and the PSMA PET scan negative.
Dr. Morris, Dr. Briganti, what would you do in that case?

Michael Morris: I'm happy to chime in first, and then Alberto, I'd love to hear what you have to say about this.

So I think this is a great case, because this is actually what happens very frequently with early biochemical relapse in patients. This PSA is relatively low, and from a performance characteristic standpoint, at 0.2 to 0.5. Between 35 and 45% of PSMA PETs will reveal some finding, but the rest will be negative. And what this really speaks to is, how to interpret the performance characteristics of PSMA PET. Now, PSMA PET does have false negatives, and so, the absence of a finding does not mean that there is no disease there. And I think, many patients and clinicians misinterpret a negative PSMA PET as not reflecting disease. I think that, one's approach to this is that, if this patient did not have a PSMA PET, he would be going for salvage radiation therapy.

I think it's entirely investigational, as to whether one should deintensify therapy with a negative PET. And so, I would interpret this as potentially, just this patient may well have disease that's simply under the threshold of detection for PET CT, and I would go ahead and treat this patient with salvage radiation therapy as though he had not had a PSMA PET at all. Because you have a curable opportunity here. We understand that the PSMA PET has a sensitivity of around 40%, and this may just be a situation where the disease is under the threshold of detection of the PET CT, and go ahead and give him salvage RT. Alberto?

Alberto Briganti: Yes, I fully agree with what Michael just said. There is little that I can add to the explanation, which was, I believe, very correct, in the sense that we have been assisting over the last month and years on patients who actually are not submitted to proper early salvage radiation therapy because of a negative scan. And this, I believe, is not the way to go. And this has been also reiterated by our EAU guidelines, which we follow in Europe, where, of course, it has been stated and it's recommended to go for local salvage therapy in presence of negative imaging if this is recommended, or if this is indicated, not to wait for the imaging being positive.

There is also another characteristics that came to my attention looking at these patients. He had very few nodes removed at the time of radical prostatectomy, only four lymph nodes. Which is not a real lymph node dissection, is rather a lymph node sampling, which might speak in favor of possible micrometastatic dissemination in the nodes, which has not been uptaken by the PSMA PET, despite the low PSA doubling time.

So in considerations of the early recurrence setting, low PSA doubling time, limited lymph node dissection, which may even define lymph node sampling, I would fully, even in presence of negative PSMA PET, I would fully agree with what Michael just said. These patients, I believe, would be candidate to early salvage radiation therapy.

Now, then we can discuss about the fields, and the concomitant additional of ADT. In our department, we actually would follow what has been just released by the RTOG 0534 study, and this guy would be suitable, in my opinion, to all pelvic radiation therapy in the salvage setting, plus short-term ADT.

Jeremie Calas: Okay. Very well. And here is what happened to the patient.

The patient got 50 Gy, the pelvic nodes, and 72 Gy, prostate beds, with ADT for six months, adjuvant. So let's say, pretty aggressive standard salvage therapy approach. I say pretty aggressive, because in the context of PSMA PET, many would start trying to kind of deescalate a little bit the treatment management, of course, without any proof, but that's something we observed either triggered by patients' will, or even some doctors.
So here, that's what the treatment was, and you can see the outcome four years later. PSA is still undetectable, so maybe it worked very well in that case. Okay.

I want to take that case to just put on the table some studies, retrospective series, looking at the outcome of SRT, when PSMA PET was incorporated into radiation therapy planning. And it seems really that, of course, because PSMA PET reflects the volume of the disease. Of course, when the PSMA PET scan is negative and these patients are being treated with salvage radiation therapy, they do better than when the PSM PET scan show a lesion somewhere. So the best thing you can hope for your patient when they come at BCR is to have a negative scan, actually.