Benign Conditions

Benign Prostatic Hyperplasia

Bladder Cancer

Female Urology

Genitourinary Cancers

Genomic Testing

Hormone Therapy

Kidney Cancer

Challenging Anatomy

Innovative Techniques

Laser Lithotripsy

PCNL Tech & Devices

Ureteroscopy Tech & Devices

Kidney Stones

Men's Health

Next-Generation Imaging

Voiding Dysfunction

OAB and Incontinence

Pediatrics

Controveries in Urologic Cancer

Drug Therapy

Prostate Cancer

Sexual Dysfunction

UTUC

Cosmetic Surgery

Urologic Surgery

Business

Practice Management

Malpractice Consult

Health Law & Policy

Media

Case-Based Peer Perspectives

Investigator Perspectives 

Medical World News

Podcasts

Urology Medical Perspectives

UTv Videos

Peer Exchange

Special Report

Virtual Tumor Board

Insights

Medcast

Peers & Perspectives

Conferences

Conference Listing

Conference Previews 

Conference Recaps

Publications

Urology Times Journal

Editorial Advisory Board

Urologists in Cancer Care

Supplements and Featured Publications

Clinical Forums Recaps

CME/CE

Resources

Begin Your Journey: Tackling Burnout

Live Events

Interactive Tools

Job Board

Partners

Treatment Landscape Evolutions

Subscribe

Articles

Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

The phase 1 study is set to begin later this year. 

FDA greenlights phase 1 trial of theranostic radiopharmaceutical for mCRPC

The approval is supported by data from the pivotal phase 3 ARANOTE trial. 

CHMP recommends EU approval of darolutamide plus ADT in mHSPC

The approval is supported by several studies highlighting the efficacy of Rezūm Water Vapor Therapy in patients with larger prostates,

FDA approves label expansion for Rezūm Water Vapor Thermal Therapy for BPH

The conversation covers practical, case-based strategies for counseling MSM patients.

Pearls & Perspectives: Sexual Health in MSM, with Joshua R. Gonzalez, MD

Urology Times is the leading resource for urologists & allied health professionals offering clinical analysis, policy perspectives, & practical advice.

About Us

Advertise

Editorial

Contact Us

Terms and Conditions

Privacy

Do not sell my Personnal Information

Urology Times – News & Insights for Urologists & Health Professionals

Facebook

LinkedIn

Spotlight

Peers and Perspectives

Clinical

1rem

Clinical Focus

Glenn M. Chertow, MD, MPH; Anil K. Agarwal, MD, FACP, FASN, FNKF, FASDIN; Preethi Yerram, MD

Case-by-Case: Application of HIF-PHIs for the Treatment of Anemia in Patients With CKD

Jason Hafron, MD; Aaron D. Berger, MD; Arpeet Shah, MD

Medical Crossfire® in Adjunctive Testing: Charting a New Course in Prostate Cancer Risk Assessment

, highlights the recent FDA approval of flotufolastat F 18 (POSLUMA), a PSMA-PET imaging agent in prostate cancer. Schuster is a professor of radiology and imaging sciences and the director of the division of nuclear medicine and molecular imaging at Emory University School of Medicine in Atlanta, Georgia.

 in May 2023, and became commercially available in June 2023. The agent is indicated for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence. The approval was based off of findings from the phase 3 SPOTLIGHT and LIGHTHOUSE trials, which Dr. Schuster’s highlights during the discussion.

Don’t forget to subscribe to Speaking of Urology® on 

, or anywhere that podcasts are available.

"We're excited that the FDA approval of this radiotracer gives us yet more tools at our disposal to diagnose prostate cancer in all its forms, from early to late in the disease process," says David M. Schuster, MD, FACR. 

Dr. Schuster highlights the FDA approval of imaging agent flotufolastat F 18 in prostate cancer

The results from the SABRE trial are intended to support the design of a registrational trial of 64Cu-SAR-Bombesin. 

64Cu-SAR-Bombesin shows efficacy in detecting prostate cancer recurrence

Gozellix was approved by the FDA in March 2025.

PSMA-PET imaging product, Gozellix, launches on US market

"For every 1 unit increase in whole body tumor SUVmean, there was a 12% decrease in the risk of an rPFS event and a 10% decrease in the risk of death," says Phillip H. Kuo, MD, PhD, FACR.

Baseline 68Ga-PSMA-11 PET/CT parameters can predict response to 177Lu-PSMA-617

A recap of the FDA submissions and regulatory decisions in urology from March 2025.

FDA updates in urology: March 2025

"I think a take-home message there is that in the prostate/prostate bed, you have to take extra time and caution in reading that region," says Phillip H. Kuo, MD, PhD.

18F-flotufolastat PET/CT shows high inter- and intrareader agreement rates 

 (TLX007-CDx), a proprietary cold kit for the preparation of gallium-68 (

Ga) gozetotide injection, in March 2025. In a recent interview with 

, offers his thoughts on how this approval will impact the clinical workflow of PSMA-PET imaging.

According to Stratton, “The approval of Gozellix is likely to both streamline and expand access to PSMA-PET imaging, hopefully broadening the distribution and use of gallium 68.”

According to Telix, the developer of the agent, Gozelliz has a longer shelf life of up to 6 hours and provides an extended distribution profile compared with previously approved gallium-68 (

Ga) PSMA-PET imaging agents. Stratton touched on these benefits, explaining that the simplistic preparation and extended shelf life of Gozellix should enable better integration into clinical workflows, easier scheduling, and expanded access to sites that lack on-site radiopharmaceutical capabilities.

Stratton is an assistant professor of urologic oncology and an adjunct associate professor of medicine at the University of Oklahoma (OU) College of Medicine and the chair of urologic oncology at the OU Stephenson Cancer Center in Oklahoma City.

Kelly L. Stratton, MD, FACS, offers his thoughts on how the approval of Gozellix will impact the clinical workflow of PSMA-PET imaging. 

Kelly Stratton, MD, reacts to FDA approval of Gozellix for prostate cancer imaging

Expanding on the advantages of an extended shelf life, Stratton said, “This is especially important for sites that are in, for instance, rural areas or centers that don't have their own radiopharmaceutical pharmacy, and so they rely on deliveries from regional hubs.”

The hope, he says, is to expand access to PSMA-PET to patients in underserved populations, such as those in rural settings or veterans.

1. FDA approves new prostate cancer imaging agent Gozellix. News release. Telix Pharmaceuticals. March 20, 2025. Accessed April 8, 2025. https://telixpharma.com/news-views/fda-approves-new-prostate-cancer-imaging-agent-gozellix/

Videos

"“The approval of Gozellix is likely to both streamline and expand access to PSMA-PET imaging, hopefully broadening the distribution and use of gallium 68," says Kelly L. Stratton, MD, FACS. 

investigators sought to review data regarding combination therapies for the treatment of locally advanced and metastatic hormone-sensitive prostate cancer.

 In their paper, the authors touched on the integration of prostate-specific membrane antigen (PSMA) PET imaging leading to earlier detection of metastatic disease. In an interview with 

®, study author Dr Louise Kostos was asked whether she felt this might affect the balance between treatment intensification and de-escalation strategies, especially in terms of minimizing overtreatment and long-term toxicity.

“That's a really good question, and one we don't have a clear answer to at the moment. I guess what we know about PSMA PET scans is that they are more sensitive compared with conventional imaging, but they also have a lower false positive rate compared with CT and bone scan,” said Kostos, a medical oncologist and PhD candidate at Peter MacCallum Cancer Centre in Victoria, Australia.

Dr Louise Kostos discusses PSMA PET's effect on treatment intensification and de-escalation in mHSPC

PSMA PET and treatment intensification in mHSPC

She added, “The main challenge at the moment is patients are being diagnosed with metastatic disease far earlier than they would have been otherwise, and therefore [are being] considered for combination systemic therapy potentially years earlier than they would have been if we just looked at conventional imaging.”

During the interview, Kostos also made note of the LIBERTAS trial, “which is looking at patients with metastatic hormone-sensitive prostate cancer who go on to start ADT [androgen deprivation therapy] and apalutamide [Erleada], and use PSA [prostate-specific antigen] as a biomarker. [They’re looking] at the whether patients have an undetectable PSA at 6 months, and if they do, they get randomized to stop the ADT or continue with the doublet. And importantly, that study also incorporates PSMA PET into the baseline staging as well,” Kostos said.

1. Azad AA, Kostos L, Agarwal N, et al. Combination therapies in locally advanced and metastatic hormone-sensitive prostate cancer. 

. 2025 Feb 12:S0302-2838(25)00023-5. doi:10.1016/j.eururo.2025.01.010

“The main challenge at the moment is patients are being diagnosed with metastatic disease far earlier than they would have been otherwise, and therefore [are being] considered for combination systemic therapy potentially years earlier than they would have been if we just looked at conventional imaging," says Dr Louise Kostos.

Amar U. Kishan, MD, shares future research directions based on the MIRAGE trial.

Amar Kishan, MD, highlights ongoing research on reducing toxicity in SBRT 

, shares future research directions based on the MIRAGE trial (NCT04384770), which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT. Overall, the study showed that both short-term and long-term toxicity were reduced with the use of aggressive margin reduction with MRI-guided SBRT compared with CT-guided SBRT.

Kishan is a professor and executive vice chair of radiation oncology at the University of California, Los Angeles.

For the MIRAGE trial specifically, we're going to continue following patients and we'll look at [data at] 5 years as well. What are the outcomes at that point? Sometimes these numbers seem arbitrary, but they are benchmark indicators within oncology: 2-year patient reported outcome toxicity and 5-year patient reported outcome toxicity and clinical outcome as well. That will be the next step for the MIRAGE patients specifically.

Our group and others do a lot of work on reducing toxicity. Things that we're looking at are, are there ways to do 2 mm margins with the CT-guided? We are actively looking into that as well. Are there ways to improve on even the MRI-guided with 2 mm, using something called adaptive radiotherapy, where we make changes to the radiation plan on a daily basis based on the patient's anatomy of the day; [that's] the next level of technology. We'll be looking at that also. And then finally, an area of interest of ours is, is there a way to predict which patients are genetically more prone to toxicity after radiotherapy? Obviously, that would be great to be able to identify that beforehand. We're working on that as well. These are what are called germline biomarkers of toxicity, and so we're evaluating those too.

This transcript was AI generated and edited by human editors for clarity.

"For the MIRAGE trial specifically, we're going to continue following patients and we'll look at [data at] 5 years as well," says Amar U. Kishan, MD. 

Amar U. Kishan, MD, highlights some of the implications of findings from the MIRAGE trial (NCT04384770), which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT.

Amar Kishan, MD, on implications of MIRAGE trial data

, highlights some of the implications of the MIRAGE trial (NCT04384770), which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT. Kishan is a professor and executive vice chair of radiation oncology at the University of California, Los Angeles.

There's a couple of ways to think about how this could move forward. One is, now we have data right that going from 4 mm margins to 2 mm margins, strictly speaking—the MRI allowed us to do that—reduces both short-term toxicity and long-term toxicity. One implication would be if there is an uptake in MRI-guided radiation, that would allow a seamless move from larger margins to smaller margins. Thinking a little bit more broadly, perhaps there may be technological advances, even in the CT-guided, that allow us going from a 4 mm to 2 mm without MRI-guided; that's possible as well. Strictly speaking, it was a trial of reducing the margin. We just used the advanced technology to be able to do that. I would say both there could be an increase in MRI-guided [SBRT] and there may be increase in investigation into shrinking margins with CT-guided SBRT as well. MRI-guided radiation is great. It does require an expensive MRI-guided linear accelerator. CT-guided linear accelerators are, at this point, more common. There, I think, will be parallel streams of research there.

I think another implication is that it's important to note that dropping short-term toxicity did lead to less long-term toxicity, which is intuitive to most people, but it is a controversial point in the field whether short-term toxicity is meaningful in and of itself, because it gets better. These results are supportive, as well as some work that'll be coming out in a month or so, that there is a link between early toxicity and late toxicity. If we can do things to minimize the short-term toxicity, that may very well pan out later, and that's ultimately what we want to do. Ultimately, we aren't concerned about just short-term toxicity. We want to make sure that the whole survivorship, patient quality of life, many years down the line is improved.

“I would say both there could be an increase in MRI-guided [SBRT] and there may be increase in investigation into shrinking margins with CT-guided SBRT as well,” says Amar U. Kishan, MD.

Amar U. Kishan, MD, shares the initial and 2-year outcomes from the MIRAGE trial, which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT. 

Amar Kishan, MD, shares 2-year data on MRI-guided vs CT-guided SBRT

, shares the initial and 2-year outcomes from the MIRAGE trial (NCT04384770), which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT. Kishan is a professor and executive vice chair of radiation oncology at the University of California, Los Angeles.

The primary end point was short-term toxicity. That was known several years ago at this point. About 2 years ago, we published our primary end point analysis in JAMA Oncology, which found a significant reduction in acute urinary toxicity and acute bowel toxicity with the use of the MRI to reduce margins. Essentially, we reduced acute GU toxicity, grade 2 or greater, from 43.4% to 24.4% and acute GI grade 2 or greater toxicity went from 10.5% to 0% in the MRI-guided arm. We also saw some benefits in patient-reported outcomes. So urinary toxicity, specifically, patients that had a large increase in their IPSS score, which is a marker of lower urinary tract symptoms, the proportion of patients that had a big increase in that was less, and the proportion of patients that had a significant decrease in EPIC quality of life bowel metrics was significantly less as well. That was the acute toxicity, the 3-month end point. This current manuscript, which came out a couple of months ago now in November, was looking at the 2-year patient reported outcomes, so touching a little bit more on one of the comments and criticisms of the earlier report, which was that it was just this short-term toxicity. Now we're looking at longer term toxicity. This was a pre-specified secondary analysis. We had always wanted to look at this, we just didn't power the trial to be able to look at these longer-term end points.

We looked at physician scored toxicity as well. We looked at something called cumulative incidence, which is if a patient has the toxicity at some point, that's counted as an event. Essentially, physician scored GU toxicity grade 2 or greater at 2 years now was 51% with the CT-guided and 27% with the MRI-guided, so a significant reduction there. And GI toxicity grade 2 or greater was 9.4% with CT-guided, and down to 1.4% with the MRI-guided, so significant benefits in late physician score toxicity.

We also looked at patient reported outcomes, as I mentioned. When looking at EPIC bowel domain scores, we looked at the odds of experiencing what's called 2x the minimal clinically [important] difference (MCID), which is well established in patient reported outcomes literature to be a clinically significant decrease in function if you have 2 times the MCID. We saw that the odds of having that were about 60% lower with the MRI-guided radiation. We also looked at this interval at sexual health outcomes; there's something called the SHIM score, the sexual health inventory for men. In that subgroup of patients who had evaluable scores for this—so these are the patients that didn't have androgen deprivation therapy or had a short course androgen deprivation therapy—there was an improvement as well. There was about a 63% decreased odds of a significant decrease in sexual functioning by patient reported outcomes in the patients who had the MRI- guided SBRT.

"Physician scored GU toxicity grade 2 or greater at 2 years was 51% with the CT-guided and 27% with the MRI-guided," says Amar U. Kishan, MD.

Amar U. Kishan, MD, highlights the rationale for the initiation and design of the MIRAGE trial, which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT

Amar Kishan, MD, outlines the rationale for the MIRAGE trial 

, highlights the rationale for the commencement and design of the MIRAGE trial (NCT04384770), which compared the use of aggressive margin reduction with MRI-guided SBRT to standard CT-guided SBRT. Kishan is a professor and executive vice chair of radiation oncology at the University of California, Los Angeles.

When you're treating prostate cancer with definitive radiation, it's a highly effective treatment, but of course, one of the major concerns that patients and providers have is post-treatment toxicity. This arises from the organs that are close to the prostate when we're doing the radiation—that includes the bladder and the rectum and also the urethra, which is a tube that carries urine, running through the center of the prostate. All of these normal structures can get affected by the radiation leading to post-radiation toxicity. It's always an area of interest, from the radiation oncology standpoint to try to reduce the toxicity that's involved with radiotherapy.

Now, one important aspect that is intuitive but maybe not obviously apparent when you're treating the prostate with external radiation is you need to account for the fact that the prostate is a moving target. It moves side to side, up and down, front and back, about an average of 2 to 3 millimeters over a several minute time frame. Again, because of the close proximity to these critical structures, we want to make sure that we have a margin around the prostate to encompass that motion, but we don't want it to be so big that it's irradiating large portions of these nearby structures. It's very typical when we're delivering radiation to aim at the prostate with this margin around it but then use sophisticated imaging technologies to limit as best we can how big that margin needs to be. This is called motion management.

In the MIRAGE trial, what we looked at specifically was in the context of doing stereotactic body radiotherapy, which is a 5-day course of radiation for prostate cancer that already uses advanced technology to begin with. One group of patients had what we called CT-guided SBRT, which is our standard of care option that we had been delivering for over a decade at UCLA. Basically, these golden markers are placed into the prostate, and we use that as a proxy for the position of the prostate, and track those markers using an x-ray and a CT to help guide the radiation. We compared that approach with an MRI-guided radiation approach, where we used a newer MRI guided radiation device, linear accelerator, where patients were actually treated inside of an MRI tube. They're getting a continuous MRI, 4 frames per second. That's basically creating a movie that monitors the prostate itself and can start and pause radiation if the prostate is moving too much.

That was a 1:1 randomization, men getting CT-guided radiation and MRI-guided radiation. All the SBRT was 40 Gy in 5 treatments, 8 Gy per fraction, so high dose radiation. In the CT-guided arm, because of the type of monitoring that we were using for motion management, we'd used a 4 mm margin. So, the target plus a 4 mm margin. That's standard of care. If you look at other SBRT reports and ongoing SBRT trials, it's typically 5 mm margins, maybe reduced to 3 mm posteriorly in certain cases. But, 3-5 mm posteriorly; I think our 4 mm margin is well within that range. [In] the MRI-guided arm, that's where we leveraged the abilities of the machine to reduce that margin to 2 mm. So, 4 mm vs 2 mm.

The trial, then, was specifically looking at whether that aggressive margin reduction from 4 mm to 2 mm would lead to a reduction in physician-reported urinary toxicity, specifically in the first 90 days after radiation. A lot of people have asked me why was that the end point, as opposed to long-term urinary toxicity or long-term bowel toxicity, patient reported outcomes? Honestly, it was an issue of practicality. This was a single center randomized trial using a novel device that many other institutions, frankly speaking, had and were using, not on a trial. So, there was a small time window within which we could complete a trial like this in a single institution while we were still able to randomize between the 2 machines. We chose a toxicity that's common. Physician scored urinary toxicity within the first 90 days after radiation is fairly common, so we would be able to detect a difference.

Thankfully, radiation is pretty good when it comes to long-term toxicity. Though, I'm sure there'll be some discussion about that statement, but many men do quite well with radiation in the long-term. To be able to show a difference in long-term toxicity would have required a large multicenter trial with many fold more patients. That's just not practical. I think, to date, the MIRAGE trial, which has now finished accrual over 3.5 years ago, is the only randomized trial that looked at these 2 machines. So, I don't think it would have been practical to have a longer-term toxicity end point. It's also not something you can blind patients to, which is why it wasn't a blinded trial. And it was run in the height of the COVID pandemic, so there were some limitations in how frequently we could ask patients questionnaires and give them other things. We were able to eventually figure that out and do remote visits and electronic patient reported outcomes. But anyone who was practicing during that time knows that was a big shift to move to that format. So, we stuck with a hard end point—for us, physician scored toxicity—which was easy to do remotely if needed to.

“The trial was specifically looking at whether that aggressive margin reduction from 4 mm to 2 mm would lead to a reduction in physician-reported urinary toxicity, specifically in the first 90 days after radiation,” says Amar U. Kishan, MD.

Michael S. Cookson, MD, MMHC, FACS, touches on the current limitations of PSMA-PET imaging in prostate cancer. 

Michael Cookson, MD, on challenges with PSMA-PET imaging

, touches on some of the current limitations of PSMA-PET imaging in prostate cancer. Cookson, who is a professor and the Donald D. Albers Endowed Chair in Urology at the University of Oklahoma Health Sciences Center in Oklahoma City, is a co–editor in chief for Urology Times.

I think having the ability to monitor patients with imaging and using things like PSMA-PET is good, but yet we're we sometimes have pitfalls with PSMA-PET too. Patients can sometimes have false positives. Not everything that's small and shows up on a PSMA-PET is definitely metastatic disease, and some of these particularly low volume areas can be challenging to even get a diagnosis. An example would be a small isolated rib lesion that can also be a false positive. There's benign bone diseases such as Paget's disease, that can also show up in the pelvic area, for example, and lead to over-diagnosis of advanced cancer. So, you have to interpret it, of course, appropriately. But PSMA imaging is being used for staging patients with newly diagnosed advanced, high-risk disease, for locally advanced disease, for metastatic disease, and it's also being used in the monitoring. Then if you get further down the road with castration resistant cancer, and it can be used as the entry to deciding whether or not they be candidates for PLUVICTO, so theranostics. That's evolving too. So, it's an exciting time, and the imaging is really helpful, but it also needs to be interpreted, and then it can also be used in the treatment. There's a lot of ways in which we're learning to use it.

PSMA-PET imaging is a valuable tool in prostate cancer management, aiding in staging, monitoring, and treatment decisions. However, it has limitations, such as false positives, particularly in low-volume lesions, which can lead to over-diagnosis. Conditions like Paget's disease can mimic metastatic disease on imaging. Despite these challenges, PSMA-PET is crucial for assessing newly diagnosed advanced, high-risk, and metastatic prostate cancer. It also plays a role in evaluating candidates for theranostic treatments like PLUVICTO, highlighting its evolving role in prostate cancer care.

“I think having the ability to monitor patients with imaging and using things like PSMA-PET is good, but yet we're we sometimes have pitfalls with PSMA-PET too,” says Michael Cookson, MD. 

Eric Li, MD, shares the take-home message from The Journal of Urology paper “Clinical Factors Associated with Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed with Radical Prostatectomy including PSA <0.5 ng/mL.” 

Expert: PSMA-PET should be considered at lower PSA levels

 paper “Clinical Factors Associated with Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed with Radical Prostatectomy including PSA <0.5 ng/mL.” Li is a urology resident at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

What are the next steps for this research?

I think the main question is, how does PSA-directed therapy and metastasis-directed therapy affect recurrent metastasis-free survival and survival outcomes eventually? There are a number of trials and a number of studies looking at that currently. I do think that that's going to be an important step. I think our paper is just kind of getting the word out there that these patients with low PSAs do have suspicious PSMA findings. But really, the question is going to be, how does this affect longer term outcomes? There are a lot of trials ongoing in the area, and the question is, can metastasis-directed therapy also potentially improve quality of life and maybe decrease the amount of androgen deprivation therapy that patients need? These are all questions that are currently be investigated with other studies.

What is the take-home message for the practicing urologist?

I think the main takeaway is just that we can consider PSMA-PET at lower PSA values, below 0.2, certainly below 0.5. There are potentially PSMA findings that would change your management in this situation. I do think it's important to also emphasize that a negative PSMA-PET should not delay salvage therapy such as salvage radiation. It's been shown that these patients should get salvage radiation. But, I think that urologists can use PSMA-PET, along with other factors such as PSA doubling time, pathology, and radical prostatectomy and maybe genomics to just counsel the patient and to really personalize their treatment plan.

The discussion centers on the implications of using PSMA-PET imaging in patients with low PSA levels post-radical prostatectomy. It highlights the potential of PSMA-PET to influence management decisions even at PSA levels below 0.5 ng/mL. The conversation also touches on the importance of not delaying salvage therapies based on negative PSMA-PET results. Ongoing research is exploring how PSA-directed and metastasis-directed therapies impact metastasis-free survival and overall outcomes, including quality of life and the necessity for androgen deprivation therapy.

Eric Li, MD, on “Clinical Factors Associated with Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed with Radical Prostatectomy including PSA <0.5 ng/mL.” 

Eric Li, MD, on PSMA-PET imaging in men with low PSA levels

 describes the background and notable findings from the 

Please describe the background for this study.

We know that prostate cancer is the most common malignancy in men, and radical prostatectomy remains one of the primary treatments for patients with localized prostate cancer. In the US, we do about 90,000 radical prostatectomies every year. And as you were mentioning, prostate specific membrane antigen or PSMA PET has emerged as a superior modality, both for initial diagnosis before we decide what treatment we want to pursue, but also at the time of recurrence. So our paper focused on patients who got radical prostatectomy as their primary treatment for prostate cancer. Currently, there are limited data on low PSA values. Most of the trials only included patients above 0.2, and so we looked at PSAs below 0.2 and also PSAs below 0.5 just because there hasn't really been a lot of work done in that area.

As I mentioned, this was a retrospective cohort across the Northwestern system across our 11 hospitals for patients initially managed with radical prostatectomy. We had about 415 patients, and surprisingly, over half of them actually had a PSA value of below 0.5. We found that almost half of them had suspicious findings as defined by the radiologist, but also that the positivity rate for PSAs below 0.5 were around 35%, which is much higher than we thought it would be. We looked at what factors were associated with the suspicious PSMA activity, and for the cohort that was below PSA 0.5, we found that prior postoperative radiation was associated with PSMA positive findings. Now, when you look at the entire cohort, we found that age, Gleason grade at radical prostatectomy, and PSA at PSMA-PET were all associated as well.

And then we did a series of sensitivity analyses looking at various risk stratification tools such as PSA doubling time. We used a nomogram called the CAPRA-S, which has been previously published on, as well as the EAU risk stratification that's also been previously published. Those were all associated with suspicious PSMA activity. The part that really excites me is, well, how does this change patient management? And we looked at, of those with suspicion for metastatic disease, how many of those people received metastasis-directed therapy, and we found that about 40% in the overall cohort and about half of patients with PSA below 0.5 actually received metastasis-directed therapy where it changed the radiation plan and radiation field. So to me, that's really the most exciting part about this work.

The study investigates the use of PSMA PET imaging in prostate cancer patients post-radical prostatectomy, focusing on those with PSA levels below 0.5 ng/mL. It reveals that a significant portion of these patients exhibit suspicious PSMA activity, with a positivity rate of 35%. Factors such as prior postoperative radiation, age, Gleason grade, and PSA levels are associated with suspicious findings. The study highlights the impact of PSMA PET on patient management, with a notable percentage receiving metastasis-directed therapy, altering radiation plans and fields.

"We found that almost half of them had suspicious findings as defined by the radiologist, but also that the positivity rate for PSAs below 0.5 were around 35%," says Eric Li, MD.

Jitesh Dhingra, MD, FRCEM, discusses current and future research directions in the field of PSMA-PET imaging for prostate cancer. 

Expert shares anticipated research directions for PSMA-PET in prostate cancer

 discusses current and future research directions in the field of PSMA-PET imaging for prostate cancer. Dhingra is an attending nuclear medicine physician at Allegheny Health Network in Pittsburgh, Pennsylvania.      

What are the current and future research directions in the field of PSMA-PET imaging for prostate cancer, and what advancements can we expect in the coming years?

The tracer that is probably going to be coming soon is called Posluma. Once we have Posluma, which is also a PSMA-based tracer, we'll have a better assessment of patients who will be benefiting from PSMA-based therapies like Lutetium-based theranostics. That's one big thing that I'm looking forward to. The other thing that I think is going to be really, really helpful is the utility of dosimetry. At this point of time, we are not doing dosimetry on any of our patients, but once we start using Posluma, we'll get a better assessment of what lesions and tumor sites are present in a patient, and we'll be able to use and translate that information toward dosimetry and directing our theranostic or PSMA-based therapies in a much more precise manner. That's another thing. The third thing I'm already currently working on clinical trials with these patients is that we are trying to use PSMA-based therapies in an adjuvant setting. So patients who have prostate cancer with a highly aggressive variant, we are using PSMA-based therapies in an adjuvant setting much earlier to even using chemotherapy at this point of time. That's another area that we are very excited about. There are many more things that I can keep talking about, but I would basically look at these 3 things as the major things to be coming up.

The field of PSMA-PET imaging for prostate cancer is advancing with the introduction of new tracers like Posluma, which will enhance patient assessment for PSMA-based therapies such as Lutetium-based theranostics. The integration of dosimetry is anticipated to improve the precision of these therapies by accurately identifying lesions and tumor sites. Additionally, clinical trials are exploring the use of PSMA-based therapies in an adjuvant setting for aggressive prostate cancer variants, potentially preceding chemotherapy. These developments represent significant progress in prostate cancer management.

"I would basically look at these 3 things as the major things to be coming up," says Jitesh Dhingra, MD, FRCEM.

Michael S. Cookson, MD, MMHC, FACS, touches on the current and future applications of PSMA-PET imaging in prostate cancer.

Michael Cookson, MD, on potential future applications of PSMA-PET

, touches on the current and future applications of PSMA-PET imaging in prostate cancer. Cookson, who is a professor and the Donald D. Albers Endowed Chair in Urology at the University of Oklahoma Health Sciences Center in Oklahoma City, is a co–editor in chief for 

I think about the patients with say, radiation-recurrent disease, we usually get an MRI of their pelvis, and then we get a complimentary PSMA-PET for staging, but it's also showing us disease in the primary as well. In some ways, it can be used to help if you want to get a biopsy to prove or confirm—it can be used to help detect in that range, too. That's a new area. We're not quite to the point—we don't omit the biopsy currently. We still get a piece of tissue from that primary prostate if it does look like it's recurred. But it's starting to be to the point where, when you have an MRI lesion, say, post-radiation, with a rising PSA, and it correlates with the PET scan, then that disease is, for the most part, very real, and it's just confirmed with a biopsy, but you already knew it was there. Stay tuned on that. We're still using tissue to kind of make decisions on treatment in that setting.

“In some ways, it can be used to help if you want to get a biopsy to prove or confirm—it can be used to help detect in that range, too,” says Michael S. Cookson, MD, MMHC, FACS. 

Next-Generation Imaging

Latest News