Stefano Fanti: Thank you, Amber. Good morning everybody. Great pleasure to be here again. Thanks to Aurelius and Silke for the amazing job that they did over the last year. Really incredible.

Those are my disclosures, as you can see are many. The main disclosures that I'm proudly a nuclear medicine physician, so I'm strongly in favor of what I'm doing, not because of just defending my very poor, let's say, pun the specialty, but because we are really doing something good, and the fact that we're coming more and more, it's really representative.

So, when Silke and Aurelius proposed it to me, this topic, well, I said, "Great. It's a piece of cake. It's so easy to talk about the advantage of PSMA." I remember first coming 4 years ago, talking about PET, the different tracer. I was really in trouble to convince you, but right now it's really super easy. So, I will go quite rapidly through the three main clinical indications for PSMA PET that everybody knows is staging, so presentation of high-risk patients, and then, biochemical recurrence, and therapy planning. 

I will, of course, take into account the guidelines, and for staging, as you can see, EAU guidelines do not even mention PSMA. That's correct. I'm part of the panel. I fully agree, of course, with those guidelines. The only mention is about, curiously, CT and bone scan, which are very old approach. Me and Anwar, we keep on struggling against those old approaches that have never been demonstrated to be useful, but they're still around.

Well, nonetheless, there are many paragraphs in the guidelines reporting the reason why PSMA PET is still not included in the guidelines. The fact is that there is a scarce literature with very variable results, in particular related to the fact that some studies have incorporated intermediate risk patient with high-risk patient. Of course, it makes a great difference, and the variability is mainly related to that. So, the conclusion is that we still need more data to incorporate PSMA PET into recommendation for staging high-risk patient.

But, I will show you a case that I steal from Alberto, which should be around. And, he presented that at EAU. That's a patient, a gentleman, 71 years old, PSA 12, as you can see, transrectal ultrasound, biopsy. Identified Gleason Score, eight, in four cores in the left and one core in the right lobe. So, with a family history of prostate cancer, he is definitely high-risk patient. So. it was conventionally stage the using bone scanning and CT and, of course, they were both negative. MRI was carried out and confirmed it clearly the lesion here, as you can see very clearly, but as part of a trial ongoing between Milan and Bologna, it was also scanned with PSMA, and here you can see the result. This confirmed the primary lesion, but you can see that there are also bone lesions here, and nodal lesion demonstrated. So, it completely changed the management of the patient.

And, that's clearly in line with the nice paper that has just been published by Australian colleagues, that in more than 1000 cases, they reported that in 12% of those, there are distant lesion that have not been seen by conventional imaging. So, I'm quite sure that in the very next future we will have more robust data to convince to incorporate the PSMA PET for staging high-risk patient. That are, of course, what we are talking about for advanced prostate cancer.

Biochemical recurrence is much easier. In this case, the guideline are recommended PSMA, as you can see, either after surgery or radiotherapy. PSMA is, indeed, the first choice in the scenario of biochemical recurrence. Fact is, that the strength recommendation is somewhat weak and that's related to the quality of the literature, and we will come back again on that.

Unfortunately, we don't have big strong pharma company behind us, so it's only single-center, frequently retrospective, or not multicentrical perspective, or randomized trial, because in many places where PSMA PET is there, nobody wants to randomize patients in the no PSMA arm.

So, that's one of the major problem. That's the largest publication published, so far, from Heidelberg. Again, one center only, 1000 patients. Sensitivity, but it's better to call a detection rate of around 80%, so very, very good. Much better than any alternative. Again, an example, I'm an imaging guy, so, I'm going to show you many images, of course. That's the gentleman already operated on. BCR, so relatively high value of PSA, and you can see the spread to the many lymph nodes here. And, of course, PSMA is the only method allowing you to study the local recurrence, the nodal spread that the liver, the bone very well, and that's clear the main advantage.

Another example, a patient's already operated. Salvage radiation therapy, early biochemical relapse, and one lesion only here in the bone. And again, PSMA clearly makes a difference. So, this is very consistent with the large literature data. Again, the panel in the guideline had to recognize that when you end up with more than 5000 patients in 40-something publication. Okay. Even if we don't have randomized multicentered, it's clearly robust data to suggest that to be incorporated into the guideline, again, and, the pooled sensitivity is around 70%. The good factor is that the detection rate is very good even in the early scenario. So, with PSA lower than two, that's where it makes more clinical difference to be used.

That's another systematic review in the early recurrence settings. So, below two of PSA, and the key point, I'm sorry, it's a little bit small, but they will just give you the detail. First of all, the number of studies about PET is incredibly superior to the number of study of any other methods. So, the data are more robust than CT NBS. And, what about gallium PSMA? The detection rate is higher than any other imaging modality, so there's no discussion. That's the most sensitive metals. That's the clear advantage. There's no advantage superior to that, it's simply the most accurate.

And, that's clear the same in the scenario of persistence of PSA. That's just if you want a little variation on that, but again, it's already recommended into the EAU guideline. Here, you can see an example. We did a comparison with the old-fashioned choline, a very young gentleman operated on in December last year, and then, a persistence of PSA. Choline is almost negative. There's just this very faint uptake here, and the impressive image of PSMA showing spread to the node, to the bone, and locally, of course.

Again, a nice meta-analysis from the group of Australia. Declan, that should be around. It's, again, 40000 patients with results confirming the best detection rate even at very low. They even consider the situation of PSA around .2 to .5, and again, there is a reasonably good, and definitely better than any other possible competitor.

Therapy planning. Well, the first very simple example is a gentleman suitable for salvage radiation therapy. And, of course, if you do a PSMA scan, you can rule out, or you can visualize, if there is any spread beyond the prostatic bed. And so, you can incorporate it into your treatment plan, or you can modify the treatment plan.

Again, several papers about that. There's also recently a publication reporting a very high number of patients, something like 70 to 80%, that has a change in the planning of the therapy. That does not, obviously, mean that you have a change in the result, but it's clear that the rationale is over there. If you see a lymph node that's positive at PSMA, it's a good idea to treat it.

But, the most amazing point about therapy planning is theranostic, and thernostic is a great, very simple concept that we hold in nuclear medicine since 50 years from the therapy of thyroid, to the therapy of a neuroendocrine tumor. It's very simple. In nuclear medicine, what you have is, that's the cancer cell, so this should be a target for you. It could be an enzyme, could be a receptor, and then, you have a ligand, that's the molecule, and that's you have here the radioactive isotope. That's the very simple principle of nuclear medicine of PET.

So, if you have here, and if you're using a positron emitter like gallium 68 or fluoride, then you will have a light, or you will have signal, an image, and you can see the cancer. You can see the tumor spread. But, if you replace the isotope with a killing isotope, just like lutetium, just like actinium, you will treat and you will treat essentially what you see.

So, what's hot in the image will be killed in the therapy. And, I really look forward to hear Michael Hofman, from Peter Mac, that will give us a beautiful lecture, I hope. And, I'm very sure about that, on Friday morning, about the great results that they're having on lutetium therapy. That's the paper that they just published last year on Lancet Oncology.

So, in conclusion, and I'm very proud that I'm the first guy not to having the bell ringing. Please take that into account. And, it's even more surprising because I'm Italian, and I'm in Switzerland, so, probably, you know what I'm talking about. We have a reputation here about that.

Now the key advantages of PSMA imaging are very simple. Well, it's a noninvasive, simple and reproducible method to study the patient. It's patient-friendly, it's very fast, it's not making you any pain, any problem. So, it's clearly available, and it allowed to study everything you need to study. So you can study the local recurrency, even if multiparametric MRI is better. But, PA... Okay. Come on. It was Amber. Was it Amber?

It allows you to study the nodes, as well as the bone, and the other parenchyma, if you need, all in one scan. It's more sensitive than any other imaging. Of course, in this scenario that I just mentioned, that is to say biochemical recurrence, and the planning of therapy is very important.

The rapid diffusion is impressive. Again, four years ago it was few centers in Germany. Then, it's spread out. Now, it's literally everywhere in the world, of course, apart from London, and it's easy to implement and easy to report. And, with that, I thank you very much for your attention. Thank you very much.