ASCO 2026: Latest in prostate cancer
Prof Eleni Efstathiou – Houston Methodist Cancer Center, Houston, USA
Dr Mary-Ellen Taplin – Dana-Farber Cancer Institute, Boston, USA
Prof Boris Hadaschik – University of Duisburg-Essen, Essen, Germany
Prof Axel Merseburger – University Hospital Schleswig-Holstein, Lübeck, Germany
EE: Hello, I’m Eleni Efstathiou and I’m very excited to be here in Chicago at ASCO 2026. We are currently discussing with experts in the field the results that came out with regard to prostate cancer. I am joined by physicians, experts that need no introduction but I will let them present themselves and especially I will start with the star of the whole meeting.
MT: Hello, I’m Dr Mary-Ellen Taplin, I’m a genitourinary medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts.
AM: Hi, my name is Axel Merseburger, I’m a urologist and surgeon from Lübeck, Germany. Happy to be here.
BH: My name is Boris Hadaschik, I’m a urologist and surgeon as well from Essen in Germany.
EE: So we are going to discuss firstly some groundbreaking news that were presented by Dr Taplin, I will call you Mary-Ellen, that in a very big extent have been driven by her passion. It’s been a long time coming. It’s not just that she was a star because it was a presentation at the plenary session, but it was driven by passion that led to these results and we are all very grateful for your efforts. Now, all of us here, full disclosure, are participants in the trial, contributors in the trial, and we're very honoured to be working with Mary-Ellen. But, Mary-Ellen, I will let you talk to us about the PROTEUS trial.
MT: Eleni, thank you for the question. PROTEUS is a phase III trial that started in 2019 and took many years to accrue and read out. What PROTEUS is evaluating is perioperative use of apalutamide and ADT compared to placebo and ADT, given for six months before prostatectomy and then six months after prostatectomy. There were two co-primary endpoints, an early endpoint and a later endpoint. The early endpoint was the pathologic response of the tumour at the time of prostatectomy and the later endpoint was metastasis free survival. Both are unique, the pathology endpoint takes into consideration pathologic complete response, minimal residual disease and PROTEUS even did calculation of what’s called residual cancer burden, which is based on cellularity and size of the tumour. Then the metastasis free endpoint was a composite endpoint that included conventional imaging, which you know is a bit going out of style, and also PSMA-PET scan which is much more sensitive and approved to use for staging patients. So we’re excited about the co-primary endpoints and then the secondary endpoints and exploratory endpoints were very supportive of the positive primary endpoints.
EE: So you hit a home run, or I should say we hit a home run, with both. So do you want to give us a little bit the numbers from a more clinical perspective and their clinical significance, both of them? And which one, in your mind, is leading the change here.
MT: Yes, so the endpoints that are palpable to patients are the metastasis free survival, the event free survival and I would say the time to first subsequent therapy. So all of those endpoints are positive and show a benefit anywhere from 20% to 32%. Take, for instance, the… we’ll start with the first primary endpoint, metastasis free survival. So that takes into consideration whether a patient will develop a metastasis based on PET, based on bone scan, based on CAT scan, based on a clinical recurrence or a PET scan recurrence. 20% reduction and if you’re a patient meeting with your doctors in the clinic and you can say there’s a 20% chance you will never have metastatic disease, that’s very meaningful. The other secondary endpoint that really stands out for me for patients is the time to first subsequent therapy was three years difference for the apalutamide ADT. Can you imagine a patient going to their visits with their doctor and their PSA is zero every 3-6 months for three years compared to, ‘Oh, your PSA is up, we have to figure something else out.’
EE: And, if I may comment, off treatment for a big part of that.
MT: Correct, that’s all off treatment. All off treatment.
EE: Unlike the case for potentially radiation plus 2-3 years of…
MT: Yes, so there was a 29% reduction in any next systemic therapy or radiation, and Boris and Axel can comment, what I call double local therapy – surgery and radiation – is hard on continence. So I think those are very meaningful for patients and very easy for physicians to process and be able to explain when we’re choosing the initial treatment options for patients.
EE: Thank you for that and thank you for making it clinically actual. We’re all very passionate here because we’ve all tried in the past to run phase II trials, it was very difficult because there was a lot of hesitancy on the side of the urology community performing these surgeries after the exposure to hormones. So I want to turn to you, Axel, because you’re one, along with Boris, who spearheaded this effort as well with a lot of many other urologists. For me this is a huge victory for urology today. I know it’s presented by a medical oncologist but it was done thanks to you urologists as well and you believed in it. But they are still out there, physicians who are going to say, ‘Well, we cannot perform surgery after such treatment.’ You have now experience from this trial, both of you have, can you comment to that?
AM: Yes, I think there are some things in oncology and urology that are myth and I learnt them 25 years ago – don’t give ADT before surgery because then you cannot operate. And you hear this over and over and then you need some evidence, you need proof. And I’m so happy that we could fill, or that you could fill, the vacuum we have of evidence in this situation. For us surgeons, we experienced no difficulties, and this is also displayed by the data. It helps even when you have patients, and I think it was about 10%, 8%, pathological complete response, with high-risk aggressive cancer before in the pelvis. Now after the surgery you can say there was nothing in any more. We know this from breast cancer, how good the prognosis is. So this is really reassuring and a lot of colleagues were doing this somehow off label in some regions of the world, that they give ADT before surgery. We haven’t had any problems with the surgery so, from my perspective, but maybe I’m biased, I’m happy to hear what Boris is saying, it’s not influencing the surgical and also backed up by the data. So it’s a very modern approach, I’m happy to have the data now to discuss this with patients possibly in the future if we have a label extension. However, from my perspective I never had any issues since in Germany, as you know, urologists can also prescribe ARPIs, so we’re used to apalutamide and ADT. So from our experience, and also what is mirrored in the trial results, this is very important for our patients in treating this aggressive prostate cancer.
EE: And, again, to point out 2,000 patients. We’re not talking a 400… 2,000 patients. So, Boris, do you want to continue that point and then I’ll come to your thoughts.
BH: Yes. So I can fully support Axel – surgery is not more challenging because of that neoadjuvant treatment. The purists will say, ‘Well, this trial now has ADT plus prostatectomy versus ADT plus apa plus prostatectomy, so you cannot compare surgery only,’ but there is a sub-study that’s being reported next year where we can also, from a patient perspective and looking at outcomes of surgery, confirm what we expect – that surgery is not complicated by this novel approach. So this is one thing. The other part that is important is that we will have a dedicated analysis focussed on surgery that also will be presented next year because we collected so much data, thanks to Mary-Ellen. So we will look not only at post-operative pathology but also PSA. We can look at the imaging results – all men got imaging post-prostatectomy, this is something never been done before. We have the patient-reported outcomes, we can look at continence, incontinence, over time. So there is really a vast amount of data that is coming. So it’s such a data-rich study that we now lay a foundation.
EE: So, to that point, there was a very large amount of patients who did have novel imaging in this study. We all acknowledge that you also spearheaded that, you have a passion for that. I remember all these meetings where we were all rolling our eyes and you insisted, of course. But in the long run I think that we are all grateful that we have this data. There has been some scepticism already – ‘Well, this is new, it’s….’ I want your comments on that because I don’t understand the scepticism. Just to make it clear, we have plenty of information within the field of prostate cancer that earlier targeting is better and now we are trying to actually introduce PET imaging within our trials. So thoughts on that and what are your expectations?
BH: First of all I appreciate the scepticism because we want to practise evidence-based medicine. Most of the evidence we have right now is based on conventional imaging and we know that MFS, so metastasis free survival, on conventional imaging is a correlate for overall survival in prostate cancer. This is why it was chosen as co-primary endpoint. But the reality is that PSMA-PET is a more accurate imaging exam and that for patients with biochemical recurrence it is established as the new standard of care imaging all over the world. So now we have to be grateful that this novel imaging, which is standard of care, has been integrated into the PROTEUS study. So now we have the data as it is because the analysis for PROTEUS was based on events with MFS. So we will not have all data on conventional imaging, we have to accept that this is a novel endpoint and that comparisons to other studies with radiation oncology treatments, for example, which are based on conventional imaging, must not be compared one to one with our study.
The other part that we have to remember, which are important because primary staging with PSMA-PET is now also coming into clinical practice. The PROTEUS study patients have high-risk, operable disease which are M0 on conventional imaging because at that time we did not have PSMA-PET, 2019, for primary staging. So in our PROTEUS dataset of 2,100 patients there are certainly also patients that might have distant metastasis from the start and we now have to find out, looking at patterns of recurrence and things like that, how we can translate this brand new data to patients that we have in front of us today with novel imaging as primary staging. So there are challenges, challenges I think we have to embrace, and it’s really a novelty and good thing that now we have a good foundation, a standard of care and standard of care outcomes with now PET and we can work from there. Because it’s a start.
EE: So on that point I want to come back to you, Mary-Ellen. Under your leadership we conducted a trial where we brought together, you brought together, so many different disciplines and also, this is my take, you managed to lead a massive trial with the help of our sponsors but you really made it an investigator-initiated massive trial with an abundance of data that for years we will be analysing. So it’s not just, ‘Oh a phase III trial is going to move the needle tomorrow.’ It’s phenomenal what you achieved. What are your comments? Where are you leading us from now on? Where are we going?
MT: Thank you, Eleni. The data we have for PROTEUS now is fantastic but I think it’s just the start. Not only will we have the sub-study which will help answer the question about up-front surgery versus neoadjuvant/adjuvant therapy and prostatectomy, but the biomarker data. We have baseline biopsies and prostatectomy specimens on 2,000 patients so we’ll be able to do analysis that could answer the questions of what are the markers for cure – patients who are destined never to relapse in addition to the pathology? Who is destined to relapse or likely to relapse? The trials that we will be able to form, based on that data, to increase the cure rate even more is what I just think is fantastic because hormone therapy is an important therapeutic target in prostate cancer but we’re going to have to add to that with more directed therapy, more directed targets. Because prostate cancer is just so heterogeneous and we can figure that out with these tissues because 2,000 cases is a lot to see the variety of pathways that are in action and that we can take action.
EE: So, as you understand, we are all very excited for what is coming and what has, of course, been presented today. But I feel that we stole a little bit the thunder with your presentation from another trial that I’d like us to discuss a little bit that was presented at the same meeting, the TALAPRO-3 trial, that in its own right is moving the needle. It is a trial that I think is worthy of discussion as well. Boris, would you take the time to walk us through the trial?
BH: Sure. The TALAPRO-3 trial has not only been presented here at the meeting, it’s also published in the same journal. Yes, I think it will move the needle because it is a trial in metastatic hormone-sensitive or androgen pathway modulation naïve patients which were molecularly screened. So patients were tested for HRR mutations both in tissue biopsies as well as in blood. In most patients they were concordant results. So, for example, in Europe we use more tissue-based testing. So these patients with HRR mutations, most of them had de novo disease and most of them had higher volumes of disease. They were treated either with ADT plus enzalutamide or ADT plus enza plus talazoparib. The trial is positive, it showed that with a hazard ratio of 0.48, I think, there’s positivity with regards to radiographic progression free survival, an established endpoint in this disease space. The overall survival data is not ready yet.
What is important is it was not only greatly positive in patients with BRCA mutations but also in a broader panel. So this is what is changing practice pretty soon, that we should treat patients with HRR mutations, including ATM, for example, which was prevalent and with a positive hazard ratio, in a targeted intensified fashion, so a modern triplet for these patients with hormone sensitive disease. We don’t have overall survival data yet but that is trending in the right direction and it opens up more possibilities for these patients. So this is coming back to Mary-Ellen, that we need to characterise our patients early, better, and then we can select the components of treatment to increase in this setting of polymetastatic disease of a long duration of response, in the setting of localised disease hopefully we can increase the fraction of patients we can completely cure.
EE: So, Axel, I wanted to come to you because we in the United States have a different indication currently in the CRPC setting versus what you have in the combinatorial strategy of an ARPI with a PARP inhibitor. How will this new data, given the fact that we don’t have for an unselected population anything in the hormone sensitive space, it will probably come in a few years with a different PARP inhibitor, but for the current setting how is it going to impact practice in Europe and other parts of the world where you have the broader indication later?
AM: This broader indication was always a little bit the elephant in the room because as your label is on BRCA1 and 2, and Japan is also with some other mutations, and in Europe and Germany it has a very broad label, the two triplet PARPi combinations with ARPI. The TALAPRO-2 trial led to approval of a set, talazoparib and enzalutamide plus ADT, and for Europe, for Germany, regardless of the biomarker, it could be used in mCRPC. The elephant thing is that this classical mCRPC derived out of ADT failure we should not have any more, so I’m very happy that we have the ability now, and it started at the beginning of the year with the AMPLITUDE, you’re well aware of AMPLITUDE, trial that led to approval of niraparib and abiraterone plus ADT. So we can do the marker screening now in our men at this risk and this is very important. Now we have a second option with TALAPRO-3, potentially in the future when it comes to a label extension. So I think it’s good to have more options and then we have to decide which one to use. Maybe one is more active, maybe one traps more other biomarkers. So it is very good to have those options. For me, my personal take-home is that it’s like in the Swiss situation, we can, as said from the previous discussion, we do more PSMA-PET now, we detect more metastatic disease in the high-risk situation and we can do a more tailored precision approach for those men at risk.
EE: I love your comment because it gives me a segue to give you a little bit of a more tricky question. In the US, even though we have had guidelines to do the testing, we have been limited. I’m not speaking to academic institutions such as yours but more in the community. On the other hand, we are getting more and more indications in the hormone sensitive space, including having the triplet, and we might get radioligands in that space. Do you think with that abundance of wealth in this space still we will have the opportunity to make the most of the AMPLITUDE and the TALAPRO-3 data? Is there a mandate?
MT: Yes, there’s definitely a mandate and the mandate is testing. Every patient with serious prostate cancer should have germline testing and now should also have somatic testing. Because only if we do the testing can we consider our patients’ best treatment options. If you don’t test, you won’t pick up the 20-25% of patients who have either BRCA mutations or other HRR alterations. Yes, we just, as all treating physicians, need to work it into our algorithms. In fact, when I’m in my first patient visit, that’s when I discuss it – germline, have that conversation, somatic, are we going to do it on the prostate biopsy, are we going to do it on a blood test? Are we going to think about doing another biopsy if a patient has accessible metastatic tissue? So, yes, testing and early is better.
EE: Thank you very much for this clear message about testing. I know we didn’t have the time to exhaust all the intricacies of the risk associated with this combinatorial strategy, however, we all in this room believe in the ability of the art of medicine and that every practice has that ability to adjust to the needs of their patients. We look forward to many more discussions regarding these topics and thank you for your attendance.
