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Clinical Focus

Oncology Decoded Live! Advancing Peri-Operative Bladder Cancer Care: Integration of Emerging Evidence into Clinical Practice

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.

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"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 investigators found a positive correlation between PSA levels and SUVmax. 

PSMA-PET shows diagnostic accuracy in initial staging of prostate cancer

As the year comes to a close, we revisit some of this year’s top content on next-generation imaging agents in urology.

Enrollment goal met in phase 3 SOLAR-RECUR trial 

The primary objective is to compare the detection rate of sites of prostate cancer recurrence between the 2 agents. 

Head-to-head trial to compare 64Cu-SAR-bisPSMA and 68Ga-PSMA-11 PET/CT 

The phase 1/2a SECuRE trial is evaluating the safety and efficacy of 67Cu-SAR-bisPSMA in the treatment of patients with mCRPC.

Collaboration to support phase 3 SECuRE trial of 67Cu-SAR-bisPSMA

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.

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

Videos

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.

Jeremie Calais, MD, PhD, highlights the background and key findings from the study, “Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy"

Jeremie Calais, MD, highlights study of PSMA-PET vs bone scan in metastatic prostate cancer

, highlights the background and key findings from the study, “Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy,” (NCT04928820), for which he served as the senior author. Calais is a nuclear medicine physician at the University of California, Los Angeles.

Bone scan or bone scintigraphy is the main standard of care imaging method for decades to stage metastatic prostate cancer patients. The bone tropism of metastasis from prostate cancer made that bone scan was the method of choice. Bone scan is an indirect imaging method to detect prostate cancer metastasis because it detects the surrounding reaction of the bone, around the bone metastasis, but still using indirect methods. It was used for again, decades, with some strong correlation to outcomes with the Prostate Cancer Working Group Criteria 2+2 rules.

PSMA-PET has been in the landscape of prostate cancer staging now for about 5 to 10 years. So, [there is] a lot about how do we convert and translate from bone scan to PSMA-PET staging? Depending on the patient population, you will have different answers. In the primary staging setting, untreated disease, biochemical recurrence setting, for sure PSMA-PET scan has a lot of superiority of a bone scan. Much more specific, much more accurate. There is a lot of false positive findings on the bone scan. When the prevalence of the metastases is low, such as in the untreated disease stage, early disease, biochemical recurrence, hormone sensitive, you have a lot of false positive findings.

Now when you move to the more advanced patient population, metastatic castration-resistant, for example, then of course the prevalence of bone metastasis is much higher. So, the specificity of the bone scan increases, specifically on a per patient basis. So, that study was an attempt to answer to that question. How do these 2 imaging modality compare to stage metastatic prostate cancer patients who are progressing under hormonal treatment, getting castration-resistant. So, it's an early mCRPC disease stage that we choose here. These are not the super late stage advanced, and we wanted to see how these 2 scans compare.

At the time of the study design, PSMA-PET was not yet FDA approved, so it was an incentive for patients to get a PSMA-PET scan. They could get into the study if they would do also a pair bone scan within 2 weeks of the PSMA-PET. So, it enabled to recruit patients. But during the trial, PSMA-PET got FDA approved, so it got widely available to patients that could get it covered by insurances. At some point there was much more difficulty to recruit patient to the trial because they don't need to do a bone scan, they don't want to do specifically a research trial, they can just get the scan as first-line of care. So, we had to terminate the trial early, instead of having 100 patients—that was the initial study design. The initial study design was based on the hypothesis that there would be a 35% detection rate with PSMA-PET/CT vs bone scan/CT 23% detection rate.

In fact, the 2 imaging modalities were deemed quite equivalent in the study. I'm going to go back on that, but we had to end the study at 20 patients instead of 100. So, the study was underpowered because of difficulty to recruit patients. Also, we were able to show that in the first 20 patient sample we had, the statistical signal that we got would have probably made the study impossible to succeed in terms of detection rate difference because bones scans and PSMA-PET in that specific patient subset performed quite equivalently on a per patient basis. There was no patient with bone scan positive and PSMA-PET negative detection rates, and there was no patient with PSMA-PET positive and bone scan negative detection rates.

Both scans were read by 3 imaging blinded readers. We used 3 blinded readers for the bone scan reads, different than the 3 imaging readers for the PSMA-PET/CT reads. We used a majority score for each imaging modality, 2 vs 1 in case of disagreement. That's the result; at the end there was no major difference observed on a patient level. On a lesion level, there were still more lesions detected with PSMA-PET, but not on a patient level. So, because of that absence of sign of [a statistical difference,] even in the first 20 patient data sets, [and] because of the difficulty to recruit patients after FDA approval, we terminated the study early at 20 patients instead of 100, and that's what we reported here.

The study compared PSMA PET/CT and planar bone scan/CT in prostate cancer patients progressing on androgen deprivation therapy. Historically, bone scans have been the standard for detecting bone metastases, but PSMA-PET offers greater specificity and accuracy, especially in early-stage disease. The trial faced recruitment challenges after PSMA-PET received FDA approval, leading to early termination with only 20 patients instead of the planned 100. Results showed no significant difference in detection rates between the two modalities on a per-patient basis, though PSMA-PET detected more lesions overall.

“On a lesion level, there were still more lesions detected with PSMA-PET, but not on a patient level,” says Jeremie Calais, MD, PhD. 

Bridget F. Koontz, MD, FASTRO, discusses the integration of PSMA-PET findings into radiation treatment planning.

Bridget Koontz, MD, on PSMA-PET’s impact on treatment planning

, discusses the integration of PSMA-PET findings into radiation treatment planning. Koontz is radiation oncologist and the medical director of radiation oncology programs at AdventHealth Cancer Institute in Orlando, Florida.

PET for prostate cancer specifically, so markers that highlight prostate recurrence, have really changed the way we treat prostate cancer. As a radiation oncologist, we're sort of surgeons without the knife. We need that imaging. We aim the radiation beam at targets that we see on CT and PET-based imaging. For us, being able to know where the cancer is allows us to target it, and I think that lets us be much more effective with our treatment.

There was actually a study done at Emory, where they looked at radiation after prostatectomy based on what we've done over the years––looking at the tumor markers and looking at the stage based on pathology and the PSA––and compared that to guide-designed radiation based on a PET result. They found that the PET result improved progression-free survival, even considering that some men were found to have metastatic disease and not treated at all. What that suggests is that if we know where we're treating, we can fine tune the radiation and be much more effective with our treatment options.

We're using it now for diagnosis in high-risk disease, so that we're not operating or focusing just on the prostate when it turns out they have a lymph node involved. Then we're using it if they recur after original treatment to make sure we're effective with the secondary treatment, like the study for GU-011. Then, even being able to understand in the metastatic space, which patients might still benefit from radiation vs which really need a more aggressive systemic therapy. So, it's helped us across the board.

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

The integration of PSMA-PET imaging has significantly transformed prostate cancer treatment by enhancing the precision of radiation therapy. This advanced imaging allows radiation oncologists to accurately target cancerous areas, improving treatment efficacy. A study at Emory demonstrated that PET-guided radiation post-prostatectomy improved progression-free survival compared to traditional methods. PSMA-PET is now utilized for diagnosing high-risk disease, assessing recurrence, and determining treatment strategies in metastatic cases. This approach aids in distinguishing patients who may benefit from radiation versus those requiring systemic therapy.

“For us, being able to know where the cancer is allows us to target it, and I think that lets us be much more effective with our treatment,” says Bridget F. Koontz, MD, FASTRO.

Jitesh Dhingra, MD, FRCEM, discusses the impact of prostate-specific membrane antigen (PSMA)-PET imaging in prostate cancer.

Jitesh Dhingra, MD, FRCEM, on PSMA-PET imaging’s impact on treatment decisions in prostate cancer

 discusses the impact of prostate-specific membrane antigen (PSMA)-PET imaging in prostate cancer. Dhingra is an attending nuclear medicine physician at Allegheny Health Network in Pittsburgh, Pennsylvania.

How does PSMA-PET imaging impact treatment decisions for patients with prostate cancer, and can it help guide therapy options?

This is basically another [area where PSMA supersedes other imaging]. As I said earlier, PSMA is prostate-specific membrane antigen. So it is basically targeted to prostate cancer cells. When we are using different modalities, we are trying to look for PSMA expression going up or down, and seeing whether the PSMA expression is going down, does that mean response to treatment? Now, having said that, there are multiple studies done, and I'll just give you a brief summary of how studies are being done is that if, whenever we are using androgen deprivation therapy, which is basically like the first line of treatment for patients with prostate cancer, because whenever the prostate cancer is detected, they get a prostatectomy, they get radiation, and are eventually placed on androgen deprivation therapy. Androgen deprivation therapy is supposedly going to lead to an over expression of PSMA in the first 6 months, which is also known as a flare response. But after 6 months of using the same androgen deprivation therapy, we will start seeing a reduction in PSMA levels. Once we start seeing that reduction in PSMA levels, that basically confirms that our treatment is going in the right direction. But instead, if, even after like, 6 months of using androgen deprivation therapy, the PSMA expression keeps going up, that is basically a time for the oncologist or urologist to say, this is time for me to change treatment, because this treatment doesn't seem to be working at this point of time. That's just for androgen deprivation therapy. Now the second thing that was the utility of Pluvicto. So when we are using radionuclide therapies, which are lutetium-based PSMA therapies, we should expect the PSMA expression to go down every time we treat them. But there are patients where I personally have had a decent amount of patients where we are treating patients with Pluvicto, and there are patients where the PSMA expression keeps going up, so now PSMA expression, if it keeps going up on Pluvicto treatment may be a situation and a discussion for the oncologist, urologist, as well as the nuclear medicine physician, to come to a point where they may think, okay, the PSMA is going up with giving Pluvicto. I should start thinking about stopping treatment or trying to do other diagnostic imaging at this point of time. Now, PSMA expression can also go down during Pluvicto. When it goes down, it is usually considered a reassuring step that the patient is getting treated. But then also, I would also like to introduce here another thing that the urologist and the oncologist should be aware of, which is that PSMA expression coming down on Pluvicto doesn't always mean that the patient is doing well. It could also mean that the patient is undergoing neuroendocrine differentiation of prostate cancer, and that's basically where our imaging modalities of clubbing PSMA paired with CT come into the picture, and we just come to a decision that this patient is not progressing on imaging, PSMA expression is coming down, so this means that the patient is doing well vs PSMA expression is coming down, but the patient is progressing on imaging, so I'm concerned about neuroendocrine differentiation, and I need to do other imaging or tissue relation.

PSMA-PET imaging significantly influences treatment decisions in prostate cancer by monitoring PSMA expression levels. Initially, androgen deprivation therapy may cause a PSMA flare, but a subsequent decrease indicates effective treatment. Conversely, persistent PSMA elevation suggests treatment inefficacy, necessitating a change. In radionuclide therapies like Pluvicto, decreasing PSMA levels are reassuring, but persistent elevation requires reevaluation. However, a decrease in PSMA during Pluvicto treatment might also indicate neuroendocrine differentiation, necessitating further imaging to confirm disease progression or response.

Dhingra discusses the utility of PSMA-PET imaging when treating patients with prostate cancer.

Jitesh Dhingra, MD, FRCEM, discusses the sensitivity and specificity of prostate-specific membrane antigen (PSMA)-PET imaging in prostate cancer

Expert on sensitivity and specificity of PSMA-PET in prostate cancer

 discusses the sensitivity and specificity of prostate-specific membrane antigen (PSMA)-PET imaging in prostate cancer. Dhingra is an attending nuclear medicine physician at Allegheny Health Network in Pittsburgh, Pennsylvania.

How sensitive and specific is PSMA-PET in detecting recurrent prostate cancer, particularly in patients with a rising PSA level but negative conventional imaging?

This is basically where PSMA-PET imaging supersedes any other modality. When we are treating prostate cancer, some patients get radiation, some patients get prostatectomy. In patients with prostatectomy, there are different cut-off levels for PSMA positivity with a PSA level. In patients who have had a prostatectomy, they usually have a low PSA level. They have a PSA below 1 ng/mL. Now in these patients, detecting an MRI abnormality becomes a challenge, and this is where PSMA-PET is basically [superior]. [That is] because even at molecular level, at a PSA of less than 1, PSMA-PET is able to detect lesions, which MRI may be missing at this point of time, and that's basically where many studies have been done, and they have come to an algorithm where the sensitivity of PSMA-PET with the PSA level of less than 1, is somewhere in the range of 60% and in PSA above 2, the sensitivity is almost in the range of 95% to 97%, so that means that above 2 and between 2 to 5, a PSA level can be detected with positive PSMA imaging, which may be missed on MRI.

PSMA-PET imaging demonstrates superior sensitivity and specificity in detecting recurrent prostate cancer, especially in patients with rising PSA levels and negative conventional imaging. It is particularly effective in post-prostatectomy patients with low PSA levels, where MRI may fail to identify abnormalities. PSMA-PET can detect lesions at a molecular level, with sensitivity ranging from 60% for PSA levels below 1 ng/mL to 95-97% for PSA levels above 2 ng/mL. This makes it a valuable tool in identifying prostate cancer recurrences that might be missed by MRI.

Jitesh Dhingra, MD, FRCEM, outlines advantages of prostate-specific membrane antigen (PSMA)-PET imaging compared with conventional imaging methods. 

Jitesh Dhingra, MD, FRCEM, on the advantages of PSMA-PET in prostate cancer

 outlines advantages of prostate-specific membrane antigen (PSMA)-PET imaging compared with conventional imaging methods. Dhingra is an attending nuclear medicine physician at Allegheny Health Network in Pittsburgh, Pennsylvania.

What are the specific advantages of PSMA-PET imaging over conventional imaging methods in the diagnosis and staging of prostate cancer?

This is a very exciting time for nuclear medicine and molecular medicine. Basically, PSMA stands for prostate-specific membrane antigen. When we are using PSMA, we are actually able to image specific cells which should have prostate cancer in them, under the camera. This is basically where PSMA imaging is superseding any other imaging modality like CT or MRI, because we are at the molecular level, figuring out where the prostate cancer cells are, and ideally, molecular medicine usually precedes radiology. So whenever you have prostate cancer cells enough to express PSMA, you start seeing it, but you may not even see a CT or MRI abnormality at that time. There have been many studies done about sensitivity and specificity comparisons between PSMA and PSMA-PET/CT and MRI, and they have come to a conclusion that utility of PSMA-PET/CT and MRI usually come and meet together in numbers, but PSMA is superseding MRI in many other areas. For example, like when we are using PSMA-PET/CT for patients with the recurrent prostate cancers...the sensitivity of PSMA is around about 86% with the PSA level of above 2 nanograms per ml, but above 5, the sensitivity actually goes higher and is like 97%. The specificity, on the other hand, for recurrent disease and prostate cancer is pretty high. It is in the ranges of 95% to 97% in multiple studies. It's difficult to give a number because there are so many studies that have been done, but the numbers are pretty reassuring with the sensitivity and specificity of about 90% in recurrent prostate cancers. Overall summary sensitivity and specificity of PSMA in patients with initial staging as well as recurrent disease is again in the range of 85% to 90%, which is again a pretty good number, and it's pretty comparative to MRI.

PSMA-PET imaging offers significant advantages over conventional imaging methods like CT and MRI in diagnosing and staging prostate cancer. It allows for molecular-level imaging, identifying prostate cancer cells before abnormalities appear on CT or MRI. PSMA-PET/CT demonstrates high sensitivity and specificity, particularly in recurrent prostate cancer cases, with sensitivity reaching up to 97% and specificity between 95% to 97%. These metrics are comparable to MRI, but PSMA-PET often surpasses MRI in certain areas, making it a valuable tool in nuclear and molecular medicine.

"This is a very exciting time for nuclear medicine and molecular medicine," says Jitesh Dhingra, MD, FRCEM.

Shyam Natarajan, PhD, discusses future research involving Unfold AI. 

Next steps in research for AI prostate cancer mapping

 discusses future research involving Unfold AI. He is an author of the recent 

study, “Extracapsular extension risk assessment using an artificial intelligence prostate cancer mapping algorithm.” Natarajan is the founder and CEO of Avenda Health.

What are the next steps in developing and refining AI-generated cancer maps for prostate cancer?

[Although] we were very excited about the finding in this study showing that Unfold AI could be superior to MRI in detecting extracapsular disease, our next step is to validate this in a multi-institutional, prospective manner. [Although] Unfold AI was trained on multi-institutional data, this particular study was concerning a single institution's experience, and so the next research phase for AI cancer maps and technologies like Unfold AI really is to understand, now we have a way to map prostate cancer, sort of within and potentially around the prostate, what other types of correlates or covariates can we predict? Can we predict biochemical recurrence? Can we predict long-term success or failure? I think those are very fruitful avenues of research.

This is exciting because Unfold AI is one of the first multimodal AI systems for patients with prostate cancer. I think it's a testament to our collaborators and the senior author of the study, Dr. Wayne Brisbane, of being able to acquire a very robust and large data set to perform this kind of unique analysis, because typically, AI-based systems use consensus panels of experts as their sort of final ground truth or gold standard, and that can only show you, are you as good as an expert clinician? Whereas in this study and other studies of this nature, we actually use the surgical pathology, sort of the ground truth, tissue information as our gold standard, showing that we could potentially be superior to the standard of care.

"[Although] we were very excited about the finding in this study showing that Unfold AI could be superior to MRI in detecting extracapsular disease, our next step is to validate this in a multi-institutional, prospective manner," says Shyam Natarjan, PhD. 

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. 

Jeremie Calais, MD, PhD, highlights the key components of the report, “Standardized template for clinical reporting of PSMA PET/CT scans.” 

Jeremie Calais, MD, highlights key elements of PSMA-PET reporting template

, highlights the key components of the report, “Standardized template for clinical reporting of PSMA PET/CT scans.” Calais is a nuclear medicine physician at the University of California, Los Angeles.

It's a table, basically, with boxes. It encompasses and contains the miTNM, PROMISE, PRIMARY, RECIP, PSMA-RADS, and E-PSMA concept and criteria all together. On this you have the relevant prostate cancer history, the indication for the scan, primary staging, BCR, PSMA expression assessment before PSMA targeted therapy, some technical parameters that are important, date of scan, the comparison to prior scans, the treatments the patient is on at the time of the scan, [and] how the CT was made. Then some measurement in the salivary glands, in the liver for tumor to background ratio assessments. Then you go by TNM staging. So, you start from the prostate. Both sides, we divided by left, right, apex, midline-based, anterior, posterior. You can check boxes wherever you see uptake or you find suspicious uptake. Number of lesions, seminal vesicles, then the pelvic lymph nodes, extra pelvic lymph nodes, bone metastasis, 1- 2- 3- oligo vs poly, visceral metastasis, the presence or absence of PSMA-negative lesion noted on CT. All that are all summarized into a table that I personally find quite nice to use. These are the main parameters that you can find in these templates.

“It encompasses and contains the miTNM, PROMISE, PRIMARY, RECIP, PSMA-RADS, and E-PSMA concept and criteria all together,” says Jeremie Calais, MD, PhD. 

, highlights the development process for the report, “Standardized template for clinical reporting of PSMA PET/CT scans.” Calais is a nuclear medicine physician at the University of California, Los Angeles.

We had medical oncologists, radiation oncologists, radiologists, nuclear medicine physician that are experts in their domain. They sat together, review what was available in the literature. We looked at all the guidelines, the guidelines from, for example, ASCO guidelines, ENM, SNMMI, NCCN, RADAR, AUA, ASTRO. So, all the main guidelines from Europe and North America, and we summarized them in the table. Then we look at the specific PSMA-PET criteria that were published out there. So, it's mostly PROMISE criteria, PSMA-RADs criteria, ePSMA, PRIMARY. These are the main attempts to classify PSMA-PET/CT reading in a standardized manner.

So, we summarized all that we discussed, and we came up with a template. It's kind of a to-do list. We check boxes to make sure that everybody talks the same language, put the information at the same place and do not forget relevant information. I don't think it has to be followed religiously, but specifically, when you do high volume of PSMA-PET scan or if you're learning and you're new to that technique, it's a great help to make sure you don't forget anything. So, you have these templates that you can use to help you to refine you PSMA-PET/CT reading. I hope that the community will use it. We find it of interest. It's just an attempt; it's just a draft. Maybe over time, we'll get some feedbacks, and we can improve it with new data coming in, new findings that can improve and refine such templates.

The standardized template for clinical reporting of PSMA PET/CT scans integrates multiple criteria and concepts, including miTNM, PROMISE, PRIMARY, RECIP, PSMA-RADS, and E-PSMA. It provides a comprehensive framework for documenting prostate cancer history, scan indications, staging, PSMA expression, and technical parameters. The template includes detailed assessments of tumor to background ratios, TNM staging, and lesion characterization. It allows for systematic documentation of prostate and lymph node involvement, metastasis, and PSMA-negative lesions, facilitating a structured and efficient reporting process for clinicians.

“It encompasses and contains the miTNM, PROMISE, PRIMARY, RECIP, PSMA-RADS, and E-PSMA concept and criteria all together,” says Jeremie Calais, MD, PhD.

Jeremie Calais, MD, on development of a prostate cancer imaging reporting template

Jeremie Calais, MD, PhD, describes the rationale for the report, “Standardized template for clinical reporting of PSMA PET/CT scans.” 

Jeremie Calais, MD, on rationale for reporting template for PSMA-PET scans

, describes the rationale for the report, “Standardized template for clinical reporting of PSMA PET/CT scans.” Calais is a nuclear medicine physician at the University of California, Los Angeles.

Since the FDA approval of PSMA-PET/CT back in 2020 then subsequently followed by [18F]DCFPyL PET/CT and other PSMA-PET agents that became commercially available in 2021, even 2022—now we have 5 or 6 of them available. PSMA-PET/CT got widely available and spread out in the community, which is great for patient care and urologists. But as you get out of expert centers and academic sites that did it for years under research protocols, the level of the quality of the reads decreases, of course, because not everybody can be experts in prostate cancer in the radiologists or nuclear medicine physicians. Not everybody knows what exactly to look for when you need to talk to radiologists. Maybe some imaging readers are experts in other cancers, in non-oncological disease. So, you decrease, of course, the level of expertise as you go out and spread out in the community.

And of course, by doing that, you get more false reads, which can be false negatives, but most importantly, false positives. The false negatives are not so important at the end, just that often you cannot go really beyond the limitation of the PET technique and the detector, the spatial resolution. I think it's okay to miss a lesion—if it's small, if it's faint, it's probably either not super clinically relevant, yet, at least. What is more problematic is to have false positive findings that the urologist, the oncologist act on and treats, whereas it was not a prostate cancer-related lesion. The false positive, the main example are the bone, false positive findings that you can have all along the skeleton. But the main example are the ribs, because the ribs can be the site of unknown trauma. Some frail patients, just by coughing, they can have a little trauma on the ribs. Each trauma that will enhance a little bit of inflammation, create a bit of revascularization and healing processes can light up on a PSMA-PET scan and mimic a prostate cancer metastasis at early disease stage, when you don't see anything on the CT yet. These things are important to know. They can be also early-stage prostate cancer metastasis that when you treat it focally with radiation therapy, actually hurting the patient. You have this line; you have to make a call—is it a lesion? Is not a lesion? Should I follow it? Should I treat it? This is really something important.

Then, this is the case also for the intraprostatic reads. The overall PSMA-PET uptake in the prostate is sometimes not easy to read. You don't have the spatial resolution, the tissue resolution you get with MRI, very refined features. Here it's just blurry signal in the whole prostate. Sometimes the whole prostate is lighting up, so it's not always easy. So, you also have some techniques to use on how to read and extract information in the prostate gland itself, from the PSMA-PET information. You can still get relevant information: seminal vesicle invasion, extracapsular extension—so T3 disease—bilateral secondary lesions. You can get all that. These are, I would say, probably the main 2 pitfalls, caveat that I see in the community, when I have to do some overreads.

Then you want to make sure that everybody reports the same thing. Do not forget to look at some specific areas, even the lungs, the penile area, the brain in advanced metastatic prostate cancer patients; these can be the sites of metastasis. In fact, we rediscovered that on PSMA-PET scans. How to report the SUV, the value, talking the same language—TNM score classification is great, but some [are] not using specifically the same language, so we have criteria for that.

The widespread availability of PSMA-PET/CT scans has improved patient care but also introduced variability in scan interpretation quality, especially outside expert centers. False positives, particularly in bone scans, pose significant challenges, potentially leading to unnecessary treatments. Accurate interpretation of intraprostatic reads is also complex due to limited spatial resolution. Standardized reporting templates are essential to ensure consistent communication and interpretation across different sites. This includes using uniform criteria for reporting SUV values and TNM classification to minimize discrepancies and improve diagnostic accuracy.

"But as you get out of expert centers and academic sites that did it for years under research protocols, the level of the quality of the reads decreases," says Jeremie Calais, MD, PhD. 

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