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Study on Metastatic Hormone-Sensitive Prostate Cancer Survival Trends - Neeraj Agarwal

November 6, 2025

Neeraj Agarwal discusses a Flatiron database analysis examining treatment intensification in metastatic hormone-sensitive prostate cancer. The study analyzed approximately 10,000 patients treated between 2015 and 2021, revealing that median overall survival remained static despite approvals of docetaxel, abiraterone, enzalutamide, and apalutamide during this period. Dr. Agarwal attributes unchanged survival outcomes to low adoption rates, with fewer than 40% of patients receiving combination therapy through 2021, though this improved to 70% by 2024. Chemotherapy utilization remained at approximately 10% throughout the study period. The discussion highlights that implementing phase III trial data into real-world practice required seven to eight years for androgen receptor pathway inhibitor combinations. Dr. Agarwal emphasizes the critical need for improved implementation strategies as the field moves toward triplet therapies incorporating PARP inhibitors, lutetium PSMA-617, or AKT inhibitors, stressing the importance of making practice-changing data accessible beyond paywalls.

Biographies:

Neeraj Agarwal, MD, FASCO, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program and the Center of Investigational Therapeutics (CIT), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

Pedro C. Barata, MD, MSc, FACP, Miggo Family Chair in Cancer Research, Co-Leader Genitourinary (GU) Disease Team, Director of GU Medical Oncology Research Program, University Hospitals Seidman Cancer Center, Associate Professor of Medicine, Case Western Reserve University, Case Comprehensive Cancer Center, Cleveland, OH

Related Content:

A SEER Database Analysis of Real-World Survival Trends in Metastatic Prostate Cancer - Pedro Barata

A US Real-World Study of Treatment Patterns and Outcomes in Localized or Locally Advanced Prostate Cancer Patients - Beyond the Abstract
Read the Full Video Transcript

Pedro Barata: Hello and welcome to another video for UroToday. We're covering ESMO 2025 in Berlin and I get the chance—I'm lucky to get the chance—to sit down with the one and only Dr. Neeraj Agarwal. Neeraj is of course a leader in prostate cancer. He leads the group, he leads the research at the Huntsman Cancer Institute out of Salt Lake City, really a key opinion leader who has developed a lot of practice-changing data that helps us make decisions every day for our patients with GU cancers, particularly prostate cancer. So thank you, Neeraj, for taking the time from your busy schedule to be with us.

Neeraj Agarwal: Thanks for having me.

Pedro Barata: Thank you. So we're taking the chance to talk to you for a few minutes on a very interesting and very timely topic around treatment intensification for metastatic hormone-sensitive prostate cancer. And I know that you have a huge team out of Huntsman, which is amazing. I know you work very closely with Dr. Umang Swami, who is really a star, particularly when it comes to real-world data evaluation of databases, which is not easy to do. And so what I would like you to summarize for us, if you can, is tell us a little bit about the work that you put together from the Flatiron database, you and Umang, and tell us what you are seeing in terms of trends, because I think it's really informative for the field.

Neeraj Agarwal: So I'll just focus on the ESMO data, and we looked at the overall survival of patients with metastatic hormone-sensitive prostate cancer from 2015 to 2021. And the reason for choosing this period, 2015 to 2021, was that docetaxel was shown to improve survival in a very remarkable fashion in 2013. So we waited one year for incorporation of those data, and then 2021 was the cutoff year because we wanted to have adequate survival follow-up for those patients. And just for our audience's recollection, Flatiron database means direct extraction of data from the electronic medical records of hospital databases. So there is no recollection bias here. Nobody was trying to answer a questionnaire based on their memory. So this is a direct extraction of data from electronic medical records. So these data are very accurate compared to many other real-world datasets which are not as nuanced.

You don't get as much in-depth data in those databases. And also many of the databases are based on recollection by physicians and providers. So that is a huge strength of the Flatiron database. So in this particular study that we presented at the ESMO meeting in Berlin, which was led by my outstanding colleague, Dr. Umang Swami, we looked at about 10,000 patients with metastatic hormone-sensitive prostate cancer, newly diagnosed metastatic prostate cancer, who were treated between 2015 and 2021. And each year there were hundreds of patients. What we found was quite surprising and sobering: the median overall survival of these patients treated in the United States has remained static.

It has not improved from 2015 to 2021. If you dissect the data and look at patients by race—Black patients, white patients, Hispanic patients—all of them, the overall survival with newly diagnosed metastatic hormone-sensitive prostate cancer remained the same from 2015 to 2021. And just to put things in perspective, we had docetaxel chemotherapy which improved survival by more than one year from the CHAARTED study and STAMPEDE. Then we saw abiraterone getting approved in 2018, enzalutamide and apalutamide getting approved in 2019. So all these are literally oral pills. You just have to take an oral pill in addition to androgen-deprivation therapy injections. So it was quite sobering that survival had not improved through at least 2021.

Pedro Barata: Neeraj, thank you for that summary. I agree with you. I perhaps would not have anticipated exactly those results. I'm wondering, because as you were walking us through the results, there came to mind a trial that you led within the SWOG group, US-only, randomizing patients with ADT with or without abiraterone, a trial with an active therapy arm, SWOG 1216. And interestingly, in that study, we do see a difference in overall survival—

Neeraj Agarwal: Of the control arm.

Pedro Barata: Yes, the control arm was over 70 months, 71 months or so, versus 80. And from a statistical perspective, it was not a positive study, but yet you do see that difference. So my question—

Neeraj Agarwal: So let me just rephrase that. In that study we looked at the control arm survival, ADT plus bicalutamide, starting from SWOG trials in 1985 led by Dr. Crawford and Dr. Eisenberger and team, leading to approval of leuprolide and bicalutamide and flutamide. So really seminal early trials, and the median overall survival of the control arm went from 48 months to 70 months. But that's a trial population. So I think, obviously, we did not get into the reasons for no improvement in survival—at least through 2021—which is likely because the majority of patients with newly diagnosed metastatic hormone-sensitive prostate cancer were not getting ADT intensification or combination therapy until 2021. And you have shown those data, Pedro, from real-world studies, that less than 50% of these patients—and this is not unique to the US, this is happening across the world—unless you treat the majority of patients, at least 50% of patients with these new combination regimens, you are probably not going to see a movement in median survival.

I think that's what is reflected in these results: that through 2021, we are still not treating more than 30 to 40% of patients with intensification therapy. Fortunately, that was starting to change—by 2020, at the 2024 ASCO-GU, or maybe it was the 2025 ASCO-GU, we showed that 70% of patients with mHSPC—still not 100% or 90%—are receiving ADT intensification or combination therapy. So I think this median overall survival will move in the next two to three years, but unfortunately it has not moved yet.

Pedro Barata: No, it's a fantastic point. I'm assuming also, to confound the survival gains, of course, for patients who did not get it, I'm sure the crossover or the exposure to ARPI in mHSPC first-line was probably significant, because it's what we see in real life. A good number of patients being treated with ADT alone or ADT and first-generation antiandrogen are getting to an ARPI later on, which, to your point, is now obsolete. You've been working now for over seven to eight years, to your point, trying to highlight multiple phase III trials demonstrating that the addition of an ARPI on top of ADT is really the standard of care.

I'm interested in digging into your data a little bit on the use of chemo and triplet therapy, because from other databases we've kind of seen the use of chemo to be reserved for a minority of the patients and really static—it didn't really change much. It was around 10 to 12% if I can recall. So I'm wondering, did you see that in your database? And tell me why. I would anticipate perhaps when the triplet therapy strategies came up with darolutamide with ADT in ARASENS and then abiraterone and docetaxel as well in PEACE-1, I would anticipate an uptake, some uptake of triplet therapy with chemotherapy incorporation. And of course from CHAARTED and STAMPEDE. Can you walk me through—

Neeraj Agarwal: Yeah, so you are right. Use of docetaxel chemotherapy in metastatic hormone-sensitive prostate cancer, at least in the US, has remained at about 10% or less. And there could be many reasons. We are having a hard time getting ARPIs, which are oral therapies, incorporated in more than 50% of patients until just last year. So I personally think there may be a reluctance to receive chemotherapy in newly diagnosed patients who are already experiencing great response to androgen-deprivation therapy, and they may not feel compelled to receive chemotherapy in that setting. So I think it's our job to convince them to do that.

Just extrapolating from these data, and a lesson for me from this project which we presented at ESMO, is that it took about seven to eight years, I would say, from abiraterone approval, apalutamide and enzalutamide approval in the metastatic hormone-sensitive prostate cancer setting to apply this to the majority of patients in the real world. And did we do a decent job with implementation of those data coming from the phase III clinical trials in our real-world patients? The answer is no. So how are we going to make sure that it doesn't take this long every time we present data from a phase III trial? So I think true implementation of medicine and benefit to our patients will only happen in the real world if we do not take this long to implement the phase III data in the real world.

Pedro Barata: That's a fantastic summary, Neeraj, particularly in the time that we're living in now, because it's a given to do combination with an ARPI, and the conversation is, should we be adding other therapies like a PARP inhibitor or—

Neeraj Agarwal: Lutetium.

Pedro Barata: Lutetium PSMA-617 or AKT inhibitor or chemotherapy as a triplet, et cetera. So as we are moving toward maybe triplet therapy for certain groups of patients presenting with metastatic disease, your message is truly valuable about how it took us a long time to get to ARPI with ADT. So we have to continue to push. Do you have any ideas on how to improve?

Neeraj Agarwal: I think this is what we are doing right now: digitizing the information, making it available beyond the paywall. Think about our colleagues who don't have time to come to these big meetings like ESMO or ASCO annual meetings. How do we get the data to them? How do we make it as easily available as possible? And not only in the US, but in different parts of the world. Our colleagues are struggling with how to get this information from these big meetings. Patients are patients; it doesn't matter where they are, everybody wants to live longer. And the true service to them will only occur when we are able to implement the data from phase III trials in the real-world setting.

Pedro Barata: Well, Neeraj, fantastic summary. I think we just have to do just that, what you just advised the community to do. Thank you so much. Very informative study. Congratulations for bringing the study to ESMO and thank you for taking the time to talk to us about this very relevant topic.

Neeraj Agarwal: Thank you. Thank you for having me.

Pedro Barata: Thank you.