Comparing EMBARK vs EAU High-Risk Biochemical Recurrence Criteria in Prostate Cancer - Ugo Falagario
March 21, 2025
Zachary Klassen speaks with Ugo Falagario about identifying high-risk biochemical recurrence (BCR) after prostate cancer treatment. Dr. Falagario discusses findings from an analysis of the Stockholm-0 database comparing EAU high-risk and EMBARK criteria definitions. The study reveals significant differences in the cumulative incidence of high-risk BCR depending on the definition used. After radical prostatectomy, 25% of patients experience any BCR at 10 years, but only 4% meet the more stringent EMBARK criteria. The EMBARK population shows the highest prostate cancer mortality (30% at 10 years post-recurrence), suggesting these patients would most benefit from treatment intensification. Importantly, up to 50% of post-prostatectomy patients with rising PSA never develop high-risk BCR and likely don't need additional treatment. Dr. Falagario emphasizes the importance of risk stratification to guide personalized treatment decisions.
Biographies:
Ugo Falagario, MD, Urologist, Karolinska Institutet, Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Ugo Falagario, MD, Urologist, Karolinska Institutet, Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Read the Full Video Transcript
Zachary Klassen: Hi, my name is Zach Klassen. I'm a urologic oncologist in Augusta, Georgia. We are live in San Francisco at GU ASCO 2025 for UroToday. I'm delighted to be joined by Dr. Ugo Falagario, who is a urologist at the Karolinska Institute in Sweden. Ugo, thanks so much for joining us on UroToday.
Ugo Falagario: Thank you, Zach, it's a real pleasure to be here.
Zachary Klassen: Awesome. Well, we're going to talk about a poster you presented at GU ASCO. Really interesting data looking at how we define high‑risk biochemical recurrence, whether it's EMBARK, whether it's EAU high risk. So just tell us a little bit about the background of why we're looking into this and how you came up with this project.
Ugo Falagario: Yes, so I think this is a super hot topic since there is a lot of data coming out about this setting. And a lot of patients have biochemical recurrence after primary treatment for prostate cancer. So what is already known is that we have a lot of patients that have biochemical recurrence, but who will never develop a clinical recurrence and will never die from the disease. So if we want to intensify treatment or not intensify treatment, we need a very strong definition and risk stratification of biochemical recurrence patients.
Zachary Klassen: It's great. And I think you nailed it. I mean, with EMBARK coming out in the last year or so, and knowing that there's going to be some people that will really benefit from therapy—and, like you said, people that will never need treatment—really honing in on that definition is important. So maybe just take us through the study design, looking at EMBARK criteria as well as EAU high‑risk criteria.
Ugo Falagario: Yes, so we are looking at the epidemiology of the biochemical recurrence and the high‑risk biochemical recurrence. So we are looking in a population‑based database, a very good register from Sweden. This is the Stockholm‑0 data set, which includes all the PSA values that a patient has taken all his time during his life. And we have all the registers going with all other information about diagnosis, mortality, and cause of death in all these patients.
Zachary Klassen: Excellent.
Ugo Falagario: So our analysis was to mainly focus on people treated with curative intent, with radiotherapy, with or without an ADT, and with radical prostatectomy. And we looked at any high‑risk BCR according to the EAU criteria and high‑risk BCR according to the EMBARK criteria.
Zachary Klassen: Absolutely.
Ugo Falagario: And then we looked at the mortality from the endpoint to death.
Zachary Klassen: Excellent. Maybe just for our listeners, just to highlight again what the EMBARK criteria is, what the EAU high‑risk criteria is.
Ugo Falagario: Yes, so the EAU criteria is a combination of PSA endpoint and clinical variables. So after radical prostatectomy, a patient is at EAU high risk if they have a doubling time less than one year or a Gleason grade group at radical prostatectomy 4 and 5.
Zachary Klassen: OK.
Ugo Falagario: After radiotherapy, slightly different. You have to have a time to recurrence less than 18 months or a Gleason grade group 4 and 5.
Zachary Klassen: OK.
Ugo Falagario: The EMBARK criteria are more stringent. You need a PSA up to one after radical prostatectomy and a doubling time less than nine months.
Zachary Klassen: Right.
Ugo Falagario: And after radiotherapy, you need a PSA doubling time less than nine months, and a PSA above 2 plus nadir.
Zachary Klassen: Excellent. Great review of that. That was awesome. Tell us the key findings from your study.
Ugo Falagario: Yes, so first, according to the definition used, the cumulative incidence of the high‑risk BCR is completely different.
Zachary Klassen: Right.
Ugo Falagario: And also according to the primary treatment. So we looked at a patient population that underwent radical prostatectomy. The cumulative incidence of any BCR was 25% at 10 years. This was only 10% if you look at the EAU high‑risk BCR and only 4% if you look at patients that reached the EMBARK criteria.
Zachary Klassen: Wow.
Ugo Falagario: This is because EMBARK criteria are the most stringent, of course, because of the higher PSA level. For radiotherapy, it's a little bit different. We have 20% of patients at 10 years develop any BCR, and half of these—10%—will develop either EAU high‑risk BCR or EMBARK high‑risk BCR.
Zachary Klassen: I see. OK. So when we look at this in terms of clinical rationale—so this is basically trying to treat patients that are going to truly benefit from therapy, but not overtreat patients that are never going to need therapy. In your opinion, which one of these is better? Or maybe there's indications for both in terms of how we identify these patients ultimately that are going to benefit from treatment intensification.
Ugo Falagario: Yes, so this was what we actually tried to do looking at our secondary endpoint, which was the prostate cancer mortality.
Zachary Klassen: Yeah.
Ugo Falagario: And as we probably could imagine, the EMBARK population is the one that has the highest risk of mortality, with up to 30% of prostate cancer mortality at 10 years after the endpoint. And this is a population that probably benefits from treatment intensification, as the EMBARK trial showed. Also, from other studies, we have looked at how many patients are already metastatic in this setting, and this is probably a very late definition for a high‑risk BCR.
Zachary Klassen: Yeah.
Ugo Falagario: Conversely, we also look at the time that elapsed from treatment to the BCR. And we saw that most of the high‑risk BCR happened in the first three years after radical prostatectomy and in the first five years after radiotherapy. So this is the time period where we should intensify our surveillance to look at patients that need treatment intensification.
On the other side, up to 50% of patients that have recurrence or a PSA arising after radical prostatectomy will never develop EMBARK high‑risk BCR or EAU high‑risk BCR. And this is the population that probably doesn't need any other treatment.
Zachary Klassen: Yeah.
Ugo Falagario: Same for radiotherapy. Up to 30% of patients have a BCR but will never have a high‑risk BCR. And this is the population with the lowest prostate cancer‑specific mortality.
Zachary Klassen: That's great. I mean, I think this is beautiful work. Congratulations, because it's really given us some guidance on sitting there with the patient—are they in that group that never is going to need treatment? Are they in that really high‑risk group? And if they are, again, remembering we treat for roughly nine months, and if they get a good PSA response, we can stop therapy.
So it's really getting to the point of identifying the ones that need treatment versus those who don't, and then personalizing who we're going to treat, and seeing what their response is with treatment intensification. So I think this is really clinically relevant data. Congratulations on it. Any take-home messages for our listeners today?
Ugo Falagario: Yes, so I think the first take-home message is to risk stratify patients when they have a rising PSA. And this is of pivotal importance. And then for treatment intensification, we should look at patients that have slow doubling time and very fast-growing PSA after active treatment. And finally, we probably need a more strict definition for high‑risk BCR in order to allow also the design of future trials to guide us for treatment intensification in this setting.
Zachary Klassen: Excellent. Ugo, thanks so much for your time and for joining us on UroToday.
Ugo Falagario: Thank you. It was great. Thank you so much.
Zachary Klassen: Hi, my name is Zach Klassen. I'm a urologic oncologist in Augusta, Georgia. We are live in San Francisco at GU ASCO 2025 for UroToday. I'm delighted to be joined by Dr. Ugo Falagario, who is a urologist at the Karolinska Institute in Sweden. Ugo, thanks so much for joining us on UroToday.
Ugo Falagario: Thank you, Zach, it's a real pleasure to be here.
Zachary Klassen: Awesome. Well, we're going to talk about a poster you presented at GU ASCO. Really interesting data looking at how we define high‑risk biochemical recurrence, whether it's EMBARK, whether it's EAU high risk. So just tell us a little bit about the background of why we're looking into this and how you came up with this project.
Ugo Falagario: Yes, so I think this is a super hot topic since there is a lot of data coming out about this setting. And a lot of patients have biochemical recurrence after primary treatment for prostate cancer. So what is already known is that we have a lot of patients that have biochemical recurrence, but who will never develop a clinical recurrence and will never die from the disease. So if we want to intensify treatment or not intensify treatment, we need a very strong definition and risk stratification of biochemical recurrence patients.
Zachary Klassen: It's great. And I think you nailed it. I mean, with EMBARK coming out in the last year or so, and knowing that there's going to be some people that will really benefit from therapy—and, like you said, people that will never need treatment—really honing in on that definition is important. So maybe just take us through the study design, looking at EMBARK criteria as well as EAU high‑risk criteria.
Ugo Falagario: Yes, so we are looking at the epidemiology of the biochemical recurrence and the high‑risk biochemical recurrence. So we are looking in a population‑based database, a very good register from Sweden. This is the Stockholm‑0 data set, which includes all the PSA values that a patient has taken all his time during his life. And we have all the registers going with all other information about diagnosis, mortality, and cause of death in all these patients.
Zachary Klassen: Excellent.
Ugo Falagario: So our analysis was to mainly focus on people treated with curative intent, with radiotherapy, with or without an ADT, and with radical prostatectomy. And we looked at any high‑risk BCR according to the EAU criteria and high‑risk BCR according to the EMBARK criteria.
Zachary Klassen: Absolutely.
Ugo Falagario: And then we looked at the mortality from the endpoint to death.
Zachary Klassen: Excellent. Maybe just for our listeners, just to highlight again what the EMBARK criteria is, what the EAU high‑risk criteria is.
Ugo Falagario: Yes, so the EAU criteria is a combination of PSA endpoint and clinical variables. So after radical prostatectomy, a patient is at EAU high risk if they have a doubling time less than one year or a Gleason grade group at radical prostatectomy 4 and 5.
Zachary Klassen: OK.
Ugo Falagario: After radiotherapy, slightly different. You have to have a time to recurrence less than 18 months or a Gleason grade group 4 and 5.
Zachary Klassen: OK.
Ugo Falagario: The EMBARK criteria are more stringent. You need a PSA up to one after radical prostatectomy and a doubling time less than nine months.
Zachary Klassen: Right.
Ugo Falagario: And after radiotherapy, you need a PSA doubling time less than nine months, and a PSA above 2 plus nadir.
Zachary Klassen: Excellent. Great review of that. That was awesome. Tell us the key findings from your study.
Ugo Falagario: Yes, so first, according to the definition used, the cumulative incidence of the high‑risk BCR is completely different.
Zachary Klassen: Right.
Ugo Falagario: And also according to the primary treatment. So we looked at a patient population that underwent radical prostatectomy. The cumulative incidence of any BCR was 25% at 10 years. This was only 10% if you look at the EAU high‑risk BCR and only 4% if you look at patients that reached the EMBARK criteria.
Zachary Klassen: Wow.
Ugo Falagario: This is because EMBARK criteria are the most stringent, of course, because of the higher PSA level. For radiotherapy, it's a little bit different. We have 20% of patients at 10 years develop any BCR, and half of these—10%—will develop either EAU high‑risk BCR or EMBARK high‑risk BCR.
Zachary Klassen: I see. OK. So when we look at this in terms of clinical rationale—so this is basically trying to treat patients that are going to truly benefit from therapy, but not overtreat patients that are never going to need therapy. In your opinion, which one of these is better? Or maybe there's indications for both in terms of how we identify these patients ultimately that are going to benefit from treatment intensification.
Ugo Falagario: Yes, so this was what we actually tried to do looking at our secondary endpoint, which was the prostate cancer mortality.
Zachary Klassen: Yeah.
Ugo Falagario: And as we probably could imagine, the EMBARK population is the one that has the highest risk of mortality, with up to 30% of prostate cancer mortality at 10 years after the endpoint. And this is a population that probably benefits from treatment intensification, as the EMBARK trial showed. Also, from other studies, we have looked at how many patients are already metastatic in this setting, and this is probably a very late definition for a high‑risk BCR.
Zachary Klassen: Yeah.
Ugo Falagario: Conversely, we also look at the time that elapsed from treatment to the BCR. And we saw that most of the high‑risk BCR happened in the first three years after radical prostatectomy and in the first five years after radiotherapy. So this is the time period where we should intensify our surveillance to look at patients that need treatment intensification.
On the other side, up to 50% of patients that have recurrence or a PSA arising after radical prostatectomy will never develop EMBARK high‑risk BCR or EAU high‑risk BCR. And this is the population that probably doesn't need any other treatment.
Zachary Klassen: Yeah.
Ugo Falagario: Same for radiotherapy. Up to 30% of patients have a BCR but will never have a high‑risk BCR. And this is the population with the lowest prostate cancer‑specific mortality.
Zachary Klassen: That's great. I mean, I think this is beautiful work. Congratulations, because it's really given us some guidance on sitting there with the patient—are they in that group that never is going to need treatment? Are they in that really high‑risk group? And if they are, again, remembering we treat for roughly nine months, and if they get a good PSA response, we can stop therapy.
So it's really getting to the point of identifying the ones that need treatment versus those who don't, and then personalizing who we're going to treat, and seeing what their response is with treatment intensification. So I think this is really clinically relevant data. Congratulations on it. Any take-home messages for our listeners today?
Ugo Falagario: Yes, so I think the first take-home message is to risk stratify patients when they have a rising PSA. And this is of pivotal importance. And then for treatment intensification, we should look at patients that have slow doubling time and very fast-growing PSA after active treatment. And finally, we probably need a more strict definition for high‑risk BCR in order to allow also the design of future trials to guide us for treatment intensification in this setting.
Zachary Klassen: Excellent. Ugo, thanks so much for your time and for joining us on UroToday.
Ugo Falagario: Thank you. It was great. Thank you so much.