Johannes Czernin: Tom asked me to talk about the role of nuclear medicine in prostate cancer. Initially, he said I should talk about my expectations, so consider this whole thing my bucket list here. When you think about it, there are three things that come to mind. The one is integration, I will talk about this, multidisciplinary collaboration, competence with specialized expertise, and then, of course, knowledge about current research and guidelines. There's an example of horizontal and vertical integration. I want to show this here. This is how we now set up our theranostic center leadership. That is, of course, nuclear medicine providing the director and one co-director, but urology providing one, that's Wayne Brisbane and Amar Kishan from radiation oncology, also serving as co-director. When you go the vertical way, you see that we integrate also with the basic sciences. That's something that I found incredibly important, that especially in academic centers, we need to continue to support the basic sciences from which everything that we do in the clinic really comes. In the end, all these competencies that we achieve should help us to create a meaningful multidisciplinary tumor board with the usual suspects, the urologists, oncologists, nuclear medicine people, research, scientists, nurse navigators, and so on, to really arrive at the most informed patient care decision by competent image review, lab review, treatment option selection, and a plan for execution of the therapeutic plan.

What do we need to know? One thing we need to know, we need to know the clinical trials and the treatment options. There's the standard of care, you see that at the bottom, treatments that have been around for quite some time. Then you have clinical trials in related fields, but not necessarily radiopharmaceutical therapies. Then you have the large clinical trials on radiopharmaceutical therapies that have been conducted and have been done. This we need to be really competent in explaining to our colleagues, but also to our patients. Then we need to know emerging radiopharmaceutical targets in prostate cancer. On the left side here, you see one example, the delta-like ligand three for the neuroendocrine phenotype. This is preclinical work from Sloan Kettering. In the middle, you see STEAP1. That's, again, an antibody approach to be used in adenocarcinomas and PSMA-negative disease maybe. Then Trop-2, which probably is very useful, again, in neuroendocrine phenotype, and can be applied to many different cancers. Then there's one that Philip Backhaus is here. It's an approach to image the activity of prostatic acid phosphatase. That's a very new compound that is being developed and it's under clinical investigation already in Europe. Where in this study that is coming out next week in European Urology, 11 out of 27 patients had a benefit from being imaged with this compound over conventional PSMA imaging. You will see sessions on emerging therapeutic approaches.

One, for instance, today at 1:30 PM. But we are not alone. There's a whole universe of drug development that use different approaches. We have to know the competitive or even synergistic landscape, and we have to know the alternatives. This here is a cartoon of the antibody-drug conjugate landscape in prostate cancer. In the middle, you see all the different targets that are attacked in prostate cancer, and they include PSMA, which you see on the right side, but there are many other targets that are being attacked and being explored. I think we need to be aware there's competition, and competition is definitely something that is positive and helpful. We need to understand and solve the resistance problem. That's something that is disappointing after the very euphoric and enthusiastic reports from Europe, that we actually haven't cured a single patient and that the duration of remission is fairly short. They're not that long and not that lasting, so I think we need to do better. There are many reasons for it, and again, there's a session talking about it today at 2:30 where many reasons for the high rate of non-response probably could be explained. Another topic that we need to be knowledgeable about is toxicity. We know it a little bit from PRT with myelodysplastic syndrome becoming a more important and known side effect of the treatment, but there are also reports in prostate cancer. I just put up one case report, a myelodysplastic syndrome related to successful treatment with lutetium PSMA.

That was after six cycles with a drop in hemoglobin to below six. Then in the end, the patient succumbed to leukemia. We need to understand the Prostate Working Group 4 recommendations that just came out in the Journal of Clinical Oncology, and this will be presented by Mike Morris tomorrow at 11:40 AM. I think it's critically important that we can tell our colleagues from other disciplines what these guidelines are and how imaging decisions should be based on these guidelines that are coming out. Respect. I think we need to develop more respect for the basic sciences. This is the paper that Philip just referred to before. We published that in '22 in the Journal of Nuclear Medicine. It's the history of prostate-specific membrane antigen as a theranostic target. The panel on the right is not supposed to be very readable, but it should show that it takes a long time, this is more than 30 years, to bring a compound from the bench to the clinic. There are no shortcuts. There are no bypasses. You have to go through the pain of discovery, and this discovery process needs to be supported. One person who can really attest to that and talk about this today is Owen Witte, a member of the National Academy. This is a treat. You all should be coming, listening to his presentation on his view on prostate cancer. There are, of course, other competencies before they chase me off the stage here. We have to create a safe environment. We created a theranostic center with eight treatment rooms where radiation safety, of course, is a high priority.

You need highly competent nursing and administrative staff. You need technologists. At the bottom on the right, you see, you need to have a clinical research coordinator group to really run all the research that helps to translate the basic science discoveries into the clinic. My last slide, the role of nuclear medicine in prostate cancer, my bucket list. Tom, you're happy now. Multidisciplinary care, I think that's one thing that we really, really need to subscribe to. Establish tumor boards, integrate urology, oncology, radiology, and nuclear medicine. Clinical knowledge is, of course, essential. Identify new radiopharmaceutical targets. Stay ahead of translational advances. Understand the resistance biology or the biology of resistance. Be aware that treatments are not as benign as we maybe have thought. We need to talk about side effects. I think we should learn how to characterize the toxicity profile and improve patient stratification. Then learn about the competitive landscape. Is this my bucket list? I thank you very much. I stayed on time. Thank you. Bye-bye.