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Disease Spotlight: Prostate Cancer

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RSNA 2023

Rad View: PSMA PET Imaging Recommendations

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Using a learning network model to discuss challenges and share insights among radiology departments from five different organizations, researchers noted that 87 percent of audited prostate MRI exams had PI-QUAL scores > 4 at the conclusion of the collaborative program.



ACR Collaborative Model Achieves 20 Percent Improvement in PI-QUAL Scores for Prostate MRI

In a study involving over 1,000 visible prostate lesions on biparametric MRI, a deep learning algorithm detected 96 percent of clinically significant prostate cancer (csPCa) in comparison to a 98 percent detection rate for an expert genitourinary radiologist.

MRI-Based Deep Learning Algorithm Shows Comparable Detection of csPCa to Radiologists

A point-based model that incorporates prostate MRI findings offered a sensitivity rate of 89.5 percent for detecting clinically significant prostate cancer and could prevent over 20 percent of biopsies, according to new research.

Predicting Clinically Significant Prostate Cancer: Can a Prostate MRI Point-Based Model Have an Impact?

In a recent interview, Kenneth J. Pienta, M.D., discussed the impact of piflufolastat F18, current directions in research with other PSMA-targeted radiotracers and future possibilities for the role of PSMA PET in the imaging paradigm for prostate cancer. 

Emerging Perspectives on PSMA PET Radiotracers: An Interview with Kenneth J. Pienta, MD

A recent meta-analysis found that multiparametric MRI and PET/CT had comparable detection rates for diagnosing prostate cancer recurrence.



PET/CT or mpMRI: Which is Better for Detecting Biochemical Recurrence of Prostate Cancer?

Overtreatment of patients with prostate cancer has been a significant issue and may have impacted between one to two million men with the disease, suggested Steven Raman, M.D., in a recent interview.

However, the emergence of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) appears to be a promising option for men with intermediate risk 

, a treatment that has a more favorable side effect profile than surgery and radiation, according to Dr. Raman, a professor of radiology, urology and surgery at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).

In research presented at the recent Society of Interventional Radiology (SIR) conference, Dr. Raman noted the use of MRI-guided TULSA led to a 92 percent reduction in median prostate volume (from 37.3 ml to 2.8 ml) and a 48 percent reduction in the presence of Gleason Grade (GG) 2 PCa at one year.

At five years after treatment with MRI-guided TULSA, Dr. Raman and colleagues found that 87 percent of patients had preserved erectile function and 92 percent had recovered pad-free continence.

Dr. Raman says the use of MRI guidance and thermometry are more advantageous than prior ultrasound monitoring of thermal ultrasound treatments and key to the success of the TULSA procedure.

“What I don’t like about (ultrasound monitoring) is you don’t know how hot (it is) getting and where exactly you are treating. With MRI, thermometry is an important tool. MRI images the entire prostate as you’re treating it and while you’re treating it, you’re seeing how hot things get in the prostate and outside the prostate,” explained Dr. Raman. “This is an important safety tool to minimize damage to the nerve, the sphincter, and other things, and that results in much better outcomes.”

(Editor’s note: For related content, see “

Emerging Insights on MRI-Guided Transurethral Ultrasound Ablation for Prostate Cancer

Can MRI-Guided Transurethral Ultrasound Ablation Have an Impact for Localized Prostate Cancer?

Can MRI Findings Help Predict Toxicity After Radiotherapy for Prostate Cancer?

For more insights from Dr. Raman, watch the video below.

In a recent interview, Steven Raman, M.D., discussed MRI-guided transurethral ultrasound (TULSA) in the treatment of intermediate risk prostate cancer. 

A Closer Look at MRI-Guided Transurethral Ultrasound Ablation for Intermediate Risk Prostate Cancer

In a recent interview, Steven Raman, M.D., discussed the use of MRI-guided transurethral ultrasound (TULSA) in the treatment of intermediate risk prostate cancer and key research findings with one- and five-year outcomes. 

Artificial intelligence (AI) is of course one of, if not the hottest topic at this year's 

, but how is all of the hype translating to clinical practice?

As exciting as new technology can be, actually using that technology requires a great deal of effort, especially for larger institutions that are faced with training dozens of radiology staff. 

User education is a key component to adoption and uptake, according to Nina Kottler, MD, MS, associate chief medical officer of clinical artificial intelligence at Radiology Partners. Dr. Kottler spoke with 

 at RSNA 2023, where she reflected on Radiology Partners hitting (and recently surpassing) an impressive milestone: utilizing clinical AI in more than 20 million patient exams. None of that would be possible without purposeful training programs to make sure that radiology end-users are comfortable with the new technology and understand the key benefits of use. 

Dr. Kottler, who is also an associate fellow at Stanford University's Center for Artificial Intelligence in Medicine & Imaging (AIMI), also spoke about what she has observed in terms of the affect that AI is having on radiology workflows. 

Watch the interview below for additional insights on AI. 

Nina Kottler, MD, MS, of Radiology Partners, discusses the importance of user education to improve uptake of AI technology and improve ROI. 

Nina Kottler, MD, MS on AI Adoption in Radiology

Click here for more coverage of RSNA 2023.

Dr. Kottler sat down with Diagnostic Imaging at RSNA 2023 to discuss AI imaging milestones and the potential impact of AI on workflows in radiology. 

Nina Kottler, MD, MS on Adoption and Impact of AI in Radiology

This content originally appeared on our sister site, 

Prostate cancer imaging is having its moment in the spotlight, with numerous advances in imaging agents for positron emission tomography slated to help improve diagnostics in a disease that's rife with recurrence. 

The most recent news comes from Blue Earth Diagnostics, whose radioactive imaging agent Posluma (flotufolastat F 18) was 

 for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or those with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.

While improved imaging will certainly move the needle on diagnosis, it's yet to be seen how this will ultimately impact patient outcomes. 

, Brian F. Chapin, M.D., associate professor of urology at the University of Texas MD Anderson Cancer Center in Houston, spoke about the potential impact of PSMA PET and some of the challenges the clinical community is facing in the wake of these advances. 

Click here for more of the latest research on prostate imaging

The approval of Blue Earth Diagnostics' Posluma (flotufolastat F 18) is a significant step forward for PSMA PET imaging, but will it actually help improve patient outcomes?

Brian F. Chapin, M.D. on the Uptake of PSMA PET in Prostate Imaging

Approximately 40 to 50 percent of men will have prostate cancer recurrence over a 15 to 20-year period but the sensitivity in pinpointing locations of recurrence remains a significant limitation for conventional imaging such as computed tomography (CT), bone scans and magnetic resonance imaging (MRI), noted Brian Helfand, M.D., in a recent interview from the American Urological Association’s (AUA) 2023 Annual Meeting in Chicago.

“The success of conventional imaging is directly associated with the level of PSA (prostate-specific antigen). The higher the PSA, the more likely the conventional imaging can detect those sites of recurrence. But in general, the PSA has to be greater than 10 or 20 (ng/mL) for those modalities to pick up those sites of recurrence,” said Dr. Helfand, chief of the Division of Urology for the NorthShore University HealthSystem, and a clinical professor at the University of Chicago.

F-rhPSMA-7.3 (Blue Earth Diagnostics/Bracco Imaging) may have promising utility for the diagnosis of prostate cancer recurrence in patients with lower PSA levels. In a subgroup analysis of 389 patients from the phase 3 SPOTLIGHT study who had been treated with primary radiation therapy, Dr. Helfand and colleagues found that out of 76 patients diagnosed with prostate cancer recurrence (with a median baseline PSA of 4.4 ng/mL), 

F-rhPSMA-7.3 had a detection rate of 76 percent for recurrence in the prostate bed and detected recurrence in distant extra-pelvic sites in 43 percent of patients.

Could a New PSMA PET Agent Improve Detection of Distant Metastatic Lesions in Patients with Prostate Cancer?

Is PSMA PET/CT More Beneficial than Bone Scintigraphy in Detecting Bone Lesions in Cases of High-Risk Prostate Cancer?

“The whole point of this scan is that it allows, at lower PSA levels, to detect where that (prostate recurrence) site is and helps us come up with a subsequent therapy that is most effective in those patients,” noted Dr. Helfand, who presented the research at the AUA conference. “It’s always a surprise when you have distant metastases … When that happens, that can definitely change how we think about treatment and the type of the treatment that patient will get.”

For more insights from Dr. Helfand, watch the video below.

In a recent video interview from the American Urological Association (AUA) 2023 Annual Meeting, Brian Helfand, M.D., discussed emerging research that shows the potential viability of the agent F18-rhPSMA-7.3 for enhancing the detection of prostate cancer recurrence and facilitating earlier intervention for patients with low prostate-specific antigen (PSA) levels.

Can an Emerging PSMA/PET Agent Improve Detection of Prostate Cancer Recurrence in Patients with Low PSAs?

Conventional imaging can be limited in the detection of metastatic lesions associated with prostate cancer. Specificity rates for computed tomography (CT) are “reportedly all over the map,” ranging from 40 to 60 percent, pointed out Brian Chapin, MD, in a video interview from the recent American Society of Clinical Oncology Genitourinary Cancers (ASCO GU) symposium.

“When there is lymph node involvement … , the lymph nodes themselves can be small and the deposits within those lymph nodes can be as small as 1 to 3 mm in size sometimes so it’s really hard to identify those with a conventional imaging approach,” explained Dr. Chapin, an associate professor, director of clinical research and fellowship program director in the Department of Urology within the Division of Surgery at the University of Texas MD Anderson Cancer Center in Houston.

However, in recent research presented at the ASCO GU symposium, Dr. Chapin and colleagues found the use of the radiopharmaceutical agent 18F-rhPSMA-7.3 (Blue Earth Diagnostics/Bracco Imaging) with positron emission tomography (PET) led to verified detection of distant metastatic lesions in 10 to 15 percent of 335 patients with newly diagnosed intermediate or high-risk prostate cancer.

“One in 10 patients that we had planned to bring to the operating room with presumed localized prostate cancer indeed had metastatic disease, which is quite substantial, especially when you’re looking at a population of men who had (negative conventional imaging with CT, MRI and bone scan),” emphasized Dr. Chapin. “Those were all negative and you’re identifying metastatic disease in one in 10 patients. That is pretty substantial because that can change our clinical decision-making in how we treat patients.”

Study Assesses PET Agent for Detecting Pelvic Lymph Node Metastases in Patients with Prostate Cancer

Could an Emerging PSMA/PET Imaging Agent Improve the Detection of Recurrent Prostate Cancer?

For more insights from Dr. Chapin, watch the video below.

In a video interview from the recent American Society of Clinical Oncology Genitourinary Cancers (ASCO GU) Symposium, Brian Chapin, MD, discussed emerging research that demonstrated the ability of the positron emission tomography (PET) agent 18F-rhPSMA-7.3 to diagnose distant M1 lesions prior to surgery for patients with intermediate to high-risk prostate cancer.

Emerging research suggests that magnetic resonance imaging (MRI) guidance may be more advantageous than computed tomography (CT) guidance for reducing the side effects of stereotactic body radiation therapy (SBRT) in the treatment of prostate cancer.

Results from the phase 3 randomized trial, recently published in 

, showed that MRI guidance for SBRT led to a significantly reduced acute grade 2 or greater genitourinary (GU) toxicity rate (24.4 percent) versus that of CT guidance (43.4 percent). Researchers also noted no acute grade 2 or greater gastrointestinal (GI) toxic effects with MRI guidance in comparison to a 10.5 percent toxicity rate for CT guidance.

In a recent video interview, lead study author Amar Kishan, M.D. called the MRIdian LINAC (ViewRay) a “major technological breakthrough” that allows physicians to combine continuous MRI imaging with a more targeted radiation delivery system for 

“(With) these advanced precision and accuracy capabilities, particularly that high degree of tracking during the treatment, we felt we could reduce the margins around the prostate that we need to treat from four millimeters to two millimeters,” explained Dr. Kishan, an associate professor, vice-chair of Clinical and Translational Research and chief of the Genitourinary Oncology Service within the Department of Radiation Oncology at UCLA.

For more insights from Dr. Kishan, watch the video below.

In a recent video interview, Amar Kishan, M.D., discussed a new study that demonstrated significant side effect reduction when utilizing magnetic resonance imaging (MRI) guidance instead of computed tomography (CT) guidance for stereotactic body radiation therapy (SBRT) to treat localized prostate cancer.

Emerging Insights on MRI-Guided Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer

Traditional imaging has limitations in the early detection of prostate cancer recurrence. Bone scintigraphy, computed axial tomography (CAT) and magnetic resonance imaging (MRI) “often are unable to detect small recurrences when they would be more responsive to salvage therapy,” noted Benjamin Lowentritt, M.D., in a recent video interview from the American Society for Radiation Oncology (ASTRO) Annual Meeting.

However, Dr. Lowentritt, the director of the Prostate Cancer Care Program at Chesapeake Urology, said the emergence of prostate-specific membrane antigen/positron emission tomography (PSMA/PET) imaging agents over the past year and a half has “truly transformed care” as they have allowed improved staging and detection of recurrent prostate cancer, facilitating more targeted use of therapies.

As a co-author on the phase III multicenter SPOTLIGHT trial, Dr. Lowentritt said the study findings demonstrated that the emerging PSMA/PET agent 18F-rhPSMA-7.3 (Blue Earth Diagnostics/Bracco Imaging) was a “strong performer across a variety of different clinical factors” in the detection of prostate cancer recurrence. According to the study of 389 patients, 18F-rhPSMA-7.3 had an overall majority read detection rate of 83 percent.

(Editor's note: For related articles, see "

Study Suggests Shorter Duration of Radiation Therapy is Effective for High-Risk Prostate Cancer

FDA to Review Blue Earth Diagnostics' Emerging PSMA/PET Agent for Prostate Cancer

While emphasizing that there are currently no comparative trials of PSMA/PET imaging agents for detecting prostate cancer recurrence, Dr. Lowentritt said a possible advantage of 18F-rhPSMA-7.3 is the agent’s potential for less urinary excretion.

“We know this is a disease that often recurs in the pelvis so having a cleaner looking pelvis we would hope might allow this (agent) to have possibly a better ability to detect disease and more definitively detect disease in the pelvis,” added Dr. Lowentritt, president of the MidAtlantic Region of the American Urological Association.

For more insights from Dr. Lowentritt, watch the video below.

In a recent video interview from the American Society for Radiation Oncology (ASTRO) Annual Meeting, Benjamin Lowentritt, MD discussed the challenges of conventional imaging in diagnosing prostate cancer recurrence and the potential of an emerging high affinity, radiohybrid prostate-specific membrane antigen/positron emission tomography (PSMA/PET) imaging agent.

One interesting question raised is, is the same going to hold true in gallium PSMA [68Ga-PSMA-11] as it is a PYL [18F-DCFPyL]? Obviously, PYL is going to be a lot more available to the general community. Louis, you can comment on that a little.

The literature so far when you look at CONDOR and some of the comparative studies with gallium-68 shows that these agents perform very similarly, whether they’re F-18 [18F-fluciclovine] or gallium-68 based. That’s 1 thing that’s been shown. Another question is, what does this paper tell us about disease heterogeneity within the world of prostate cancer? What are the potential implications that that heterogeneity may have for treatment of disease? Whether that’s small molecule-based theragnostics or the ability to identify low-volume disease, mono-metastatic or oligometastatic disease. We’re heading toward a world of theragnostics where we’re going to be able to use small-molecule targets to identify small volume of disease by a PSMA [prostate-specific membrane antigen] study because most agents being developed are PSMA based. How does that affect a patient who has a 18F-fluciclovine study that has positive lesions that the PSMA study doesn’t pick up? I believe these patients have some degree of heterozygosity. How that’s impactful for the patient is another question.

That’s excellent. For me, I find the same. As a radiation oncologist, the theragnostics are exciting. We’re able to take images where we see exactly where there’s evidence of cancer recurrence and provide the right personalized therapy that’s targeting those sites of disease using radiation modalities. [That’s regardless] whether it’s what I do as a focused radiation oncologist using linear accelerator-based approaches, or I’m doing theragnostic work, giving target agents as well as our nuclear medicine colleagues. One of the most important steps coming down the pike is the PYL part of the story, the fact that 68Ga-PSMA-11 scans are hard to get and the PYL scans are going to be much more available is a really exciting thing about how to incorporate that in the community patient.

The other thing that’s exciting for next steps is that PYL–AI [artificial intelligence] is approved to help readers detect and read these scans in a more reproducible way. There’s some belief that this could correct some of the hot bladder issues with respect to imaging, and that’s going to be a very exciting part of the story as it comes up.

As we land the plane and get to our conclusions, with respect to this study, the advantage of F18-fluciclovine was in detecting curable localized disease in close anatomic relation to the urinary bladder. Whereas PSMA PET [positron emission tomography]—in this case, 68Gallium-PSMA-11—fails because of accumulation of activity in the urinary bladder. The modalities are equivalent in detecting distant metastases, although you can see the advantage in most situations for using PSMA PET when we’re talking about the detection of distant sites of disease. Louis, I’m going to let you finish and get the last word.

From an imaging perspective, this is a new era. This is certainly a new world. When we look at where we were with conventional imaging techniques [and compare it with] where we are [and look] into the future of theragnostics and localized therapy for small-volume disease, we have new tools that are redefining how we care for patients with prostate cancer and the whole prostate cancer algorithm. We’re very lucky in many ways to have 2 outstanding radiotracers that allow us to identify disease. Both potentially have utility in the future, even in the world of tumoral heterozygosity or 1 agent being more focused toward local recurrent, the other 1 more distance disease. We’re still defining those features. We still have work to do with respect to PSA [prostate-specific antigen] demographics. We need to subcategorize patients into their PSA quartiles but also the subtypes of Gleason tumors that they have. It’s important because these tumors will perform differently. But equally, we have a horizon that’s going to save a lot of people’s lives. It’s going to be very impactful in the future for how we treat these patients.

With that, on behalf of Louis, thank you to the 

® [for allowing us to] go over this exciting work today. It’s an exciting time to be a cancer doctor trying to help patients with prostate cancer. I hope you had a good educational experience, and we look forward to another 

Interesting questions raised by a paper that compared the use of 18F-fluciclovine with 68Ga-PSMA-11 imaging modalities to detect biochemical relapse in prostate cancer and implications for integrating newer techniques into clinical practice.

Prostate Cancer: Integrating Newer Imaging Modalities Into Clinical Practice

As we get into some of the key takeaways from the paper, we’ll talk about some of the conclusions. The first was the advantage of 18F-fluciclovine in detecting curable localized disease in close anatomic relation to the urinary bladder, whereas gallium PSMA [68Ga-PSMA-11] fails because of accumulation of activity in the urinary bladder. However, 18F-fluciclovine is almost equivalent to 68Ga-PSMA-11 in detecting distant sites of prostate cancer. As we talked about on the previous slide, for most situations outside the urinary bladder area, 68Ga-PSMA-11 was superior. What key points resonate with you from this paper, Louis?

You asked about some nuance to reading it. That’s something that needs to be considered when we’re thinking about these radiotracers, because 1 radiotracer we believe outperforms the other when it comes to outside the bed. When we want to question the bed, 1 thing we need to do for any future study—we’ll talk about that when we think about things—is optimization of technique. How would we optimize gallium-68 or F18-fluciclovine PSMA [prostate-specific membrane antigen] to perform better locally? I can speak anecdotally. To optimize the ability to identify disease locally with PSMA, 1 thing you do is acquire images as some institutions have, like my own, beginning with the thighs going toward the vertex. You decrease the amount of radioactive tracer within the bladder. From a PSMA perspective, you also have the patient void when they come to the imaging facility and have the patient void right before getting onto the scanner. Those are 2 other things you can do to optimize the ability to visualize the prostate.

The other thing you need to do when you’re looking at these scans—and this is true when it comes to 18F-fluciclovine, from the ability to look at bone and with a nodal disease—is windowing. Windowing is crucially important. Everything in PET [positron emission tomography] is about background. If your background in the bladder is incredibly high, you’re not going to be able to see anything next to it. But if you’re able to window the bladder appropriately, you’ll have a higher likelihood of identifying local disease. One thing I was wondering about—Steve, I don’t know if you wondered this as well—is that I don’t believe the paper broke down the amount of local recurrence identified by prostatectomy vs radiation therapy. We have a number of patients we saw who had recurrent disease locally at the bed, but it wasn’t clear to me which number of patients were from the radiation therapy side vs the prostatectomy side.

Their numbers were so small that they were concerned that if they broke it in subset analysis down to such low numbers, they would not have favorable reviewing on the paper. Fifty-eight was obviously the largest series when this paper was published, and that in 2019. Obviously, there’s a lot more interest and a lot more availability of gallium-68 scanning in the way of PYL [18F-DCFPyL] PET, and you would imagine that there will be some United States–based publications doing this work. The limitation previously had been where you could get gallium scans. With the advent of doing PYL scans, you’d imagine that you might have some subset papers of postprostatectomy and postradiation therapy, and be able to tease out some of these answers about the differences between 18F-fluciclovine and PSMA PET to detect recurrences in prostate cancer.

Reactions to key findings from an article by Birgit Pernthaler, et al, that compared the use of 18F-fluciclovine with 68Ga-PSMA-11 imaging modalities to detect biochemical relapse in prostate cancer.

Key Takeaways: Head-to-Head Comparison of 18F-Fluciclovine and 68Ga-PSMA-11 in Prostate Cancer

Let’s get into some of the details of the paper. If we look first at the patient characteristics on this study. There were 58 patients with biochemical recurrence of prostate cancer after a definitive primary therapy. What’s that? That’s either surgery or radiation therapy. And both scans were performed within a mean interval of 9.4 days. There wasn’t a great stretch where some new development, some new metastasis, was probably going to happen. A very short interval between the 2 scans. All scans were visualized and analyzed independently on a patient, on a region, and on a lesion-based analysis. All exams were performed in the same medical department using identical scanners. It wasn’t like this place had this kind of scanner [and another place] had a different kind of scanner. The scanners are the same, and the people looking at it are the same. What changed is the 2 different modalities. Louis, do you want to walk through the patient characteristic slide a little?

One thing that you first have to look at when you look at this paper is that we weren’t dealing with a population that was stratified to a very low PSA [prostate-specific antigen]. This was a wide range of PSA, both at diagnosis and at the time of scan importantly. You had PSAs that varied from a very low 0.2 ng/mL to 230.4 ng/mL. That’s incredibly important from a perspective of understanding the data. We’re not localizing to a very low PSA.

The other thing that’s interesting is that we have a range of Gleason scores. Among those included were 4 patients who at the time of diagnosis had Gleason 3 disease, which is interesting that they went on to definitive therapy. That’s something that wasn’t clarified in the paper that I’d like to learn a little more about. Otherwise, we have patients who have a Gleason score anywhere from 7 to 10, so presumptively had clinically significant prostate carcinoma.

We had no patients who had metastatic disease. We had patients who at the time of diagnosis had nodal disease, but none who had disease within the bones. That’s important. The other thing that’s important is that, as you mentioned, there’s a difference in how these were treated. The majority of patients were treated with radical prostatectomy and a smaller number of patients were treated with radiation therapy.

That’s excellent. When I look at some of the patient characteristics, I echo your comments. When you look, typically people are going to present in the recurrent setting or with more advanced disease. There are very few patients who by their Gleason score would be thought of as low risk: classic D’Amico low risk or NCCN [National Comprehensive Cancer Network] low or very low risk. Most of the patients would be felt to be favorable, unfavorable, intermediate risk, or higher. However, some of the nuances you alluded to are still not known. When we look, this group of patients represents that 72% of the patients underwent radical prostatectomy, whereas only 28% underwent radiation therapy.

We know that from the American Cancer Society data that with older men, the overwhelming choice of therapy is radiation therapy at a 3:1 ratio. This doesn’t represent exactly what we’re seeing from a patient characteristics perspective with older men or people with recurrence. This is unique to their experience in Europe.

Let’s go on and talk about localization of positive lesions. Louis, do you want to kick us off about what we’re talking about and how they broke up where a recurrence might be?

They decided to determine where they were based on the 4 regional areas that you would think of when you think about recurrence. Of course, you’d think about disease locally in the prostate or prostate bed. Of course, it’s a prostatectomy, so we’re thinking about the prostate bed. If it’s local pelvic disease, so not nodes outside the pelvis. If it’s extrapelvic disease, extending in the other known target regions for disease, the retroperitoneum. And then of course the bone. Not viscera but the bone. In terms of positivity, in terms of localization, what they identified was that a greater number of patients were identified with 18F-fluciclovine at the bed compared with gallium PSMA [68Ga-PSMA-11]. But when we looked at other sites of disease, the pelvis itself, extrapelvic lymph nodes, and bone metastatic disease, gallium-68 demonstrated a higher percentage of positivity. That being said, when we look at the 

 value would be at the local bed, where 18F-fluciclovine in the context of this study did better at the local bed than PSMA [prostate-specific membrane antigen]. The numbers otherwise were close. They weren’t necessarily significant but did favor 68Ga-PSMA-11.

Perfect. I echo your comments about the previous slide. When we look at the number of patients who had radiation therapy, it’s only 1 of 4. When you’re looking at a local recurrence in the prostate, most patients don’t have prostates to recur. It does affect how we’re looking at the data set a little. Irrespective of that, when we look at local recurrence—i.e., in the postprostatectomy area, which represents over 75% of patients—you’re looking that there was more detection using Axumin [18F-fluciclovine] than there was for the PSMA scans. Why is that? This gets into some of the nuances of reading the scans. Louis, do you want to talk a little about when you’re looking locally in the bed vs looking for distant disease? What are some of the nuances—based on what happens in technique—that can throw off your ability to read?

That’s the crux of the argument in this paper. Let’s talk little about physiology: 18F-fluciclovine vs PSMA. If you have that image up, it helps to illustrate it a little. First and foremost, we talk about urine excretion. When we talk about PSMA agents, they’re genitourinary excreted. Therefore the amount of radiotracer that you’re going to find in the kidneys and the bladder is going to be greater than you will with 18F-fluciclovine. As an aside, I want to comment about uptake in other places. As I mentioned, there’s going to be more background marrow uptake with 18F-fluciclovine compared with PSMA agents. There’s going to be more uptake in muscle with 18F-fluciclovine than there’s going to be with PSMA agents.

What’s crucial is technique. When we look at the technique, and we’ll talk a little about this in the papers, how did [Birgit] Pernthaler do this, in terms of gallium-68 vs 18F-fluciclovine? Typically, when we do an 18F-fluciclovine study, we acquire those images approximately 4 to 5 minutes status post-injection of radiotracer. We’ll begin an acquisition from the thighs and head to the vertex. That’s your standard 18F-fluciclovine acquisition. What’s interesting is that there’s a debate about how to acquire PSMA or 68Ga-PSMA-11, or 18F-fluciclovine. How do you do that? In the Pernthaler article, they did dynamic images initially through the pelvis, which were about 5 or 6 minutes. Then they went back at 60 minutes and did an acquisition from the vertex to the thighs. They didn’t start from the thighs to the vertex, and I say that only because over the acquisition time you’re going to be accruing more radiotracer within the bladder. Many sites, and this is just anecdotal, will start from below and then head above.

The other thing that wasn’t done in the Pernthaler article, which some places do, was acquiring delayed images through the pelvis with high resolution. In other words they’ll acquire the images over a longer bed time. Interestingly, on the 18F-fluciclovine side, the number of minutes of bed acquisition for the prostate was 5 minutes for 2 beds within the pelvis. For the 68Ga-PSMA-11 agent, it was 2.5 minutes through the pelvis, so there was a difference in acquisition. Those things are crucially important.

Just as an aside, when you interpret the images, 1 thing that’s crucially important—and it’s pointed out on this slide—is that this is an example of a patient who had a recurrence that was identified with 18F-fluciclovine but not with PSMA. Why was that the case? In this case, we can see that here’s the standard grayscale imaging. This is the low-dose noncontrast CT scan. Here’s the PET [positron emission tomography] without the fusion, and of course we have the fusion images. What’s happened is that the bladder is obscuring the uptake within the region of concern or disease recurrence within the prostate. This is the crux of where a difference in local recurrence may occur. I’ll make some more comments, but what are your thoughts when you look at these images? [How are you] feeling about the way the images look?

The hardest area for us is around the bladder. They asked Willie Sutton once, “Why do you rob banks?” He said, “That’s where the money is.” Where the prostate was is probably the area with highest risk of recurrence. That’s why postprostatectomy radiation therapy has been so successful. When the RTOG [Radiation Therapy Oncology Group] put together a consensus about what to aim at, we created what’s called an RTOG atlas consensus statement—here’s where we need to aim. That was the area where the prostate was and into the bladder a little. That would represent what we’re seeing here: 1 of 6 patients with a positive local recurrence on Axumin [18F-fluciclovine] that wasn’t demonstrated on a 68Ga-PSMA-11 scan. Why? Because the bladder uptake obscures your ability to detect it.

In the old days, before we had this fancy next-generation imaging, we’d cover where we thought the prostate cancer occurrences could be based on historical data and historical information. We were somewhere between 40% and 70% of the time, but it would be much better to be able to target areas of specific recurrence. Then we were doing Axumin [18F-fluciclovine] scans, able to find where these sites of recurrence were. Some of them in the areas of the seminal vesicles remnants, some near the area of where the anastomosis was, but in general we were finally able to see where these areas of occurrences were and how that could potentially lead to improvements in outcome. In fact, EMPIRE-1 was a trial that looked to see if imaging could be a relevant biomarker to drive care and show that an improvement in care using next-generation imaging to guide radiation therapy in those patients. It’s obviously very exciting. PSMA unfortunately has its issues with being obscured by the bladder uptake. From my standpoint as a radiation oncologist, if it’s obscured and the radiologist or the nuclear medicine physician doesn’t read that there’s disease there, that could cause the patient to not have the best outcome with respect to getting the right next therapy.

As we go into the next slide, we’re going to see something that’s remarkable for PSMA imaging agents, which is the ability to detect bone metastases. Louis, talk me through a little about how you think the 18F-fluciclovine and PSMA agents have done from your experience and from this trial?

One thing you know when you look at the fused images and when you look at the PET-only images is the uptake that’s a baseline uptake within bone. When we look at this vertebra and the uptake in the bone, we see that there’s clearly some uptake within the marrow; therefore, that could easily obscure the identification of a small or not particularly avid metastatic focus. Whereas when we look at the PSMA study, we see a large difference in terms of the amount of uptake within bone. Clearly, when the background is very low, the ability to identify a lesion is going to be easier and become more overt.

One comment that you can make about 18F-fluciclovine before we had PSMA was that we did note that lesions that were particularly sclerotic could be very difficult to see and distinguish as being neoplastic. Anecdotally, in my experience with PSMA, the background of uptake in the marrow is so low. Perhaps 1 of many reasons why PSMA outperforms 18F-fluciclovine within the skeletal system is the absence of background uptake. That will make a huge difference.

There are other things that are at play, and we’ll talk about those. Sometimes, simply, it’s about density. With PET, we’re all about resolution. How small can something be identified as positive is dependent on the concentration of radiotracer within it. If something is on a micromolecular level, we’re not going to see it regardless of how good our radiotracer is because it doesn’t have enough resolution. But even very small lesions, because the density of PSMA is so high within these lesions, we can identify these very small lesions. In this case perhaps 18F-fluciclovine because it’s a different mechanism of an action, it’s an amino acid transporter, it doesn’t have the density of uptake to be shown as being positive outside the issue of background. Those are the 2 comments I would make when I look at this comparison.

That’s perfect. When we talk about this for the radiation oncologist looking at these images, unfortunately we’re seeing that where there’s probably a lesion, their PSMA is detecting that lesion but 18F-fluciclovine did not within a distant site of metastasis. With that, we’re getting better visualization of smaller amounts of disease using a PSMA-imaging agent.

What about lymph nodes? Our next image is a set of positive lymph node metastasis looking at 18F-fluciclovine on the top and 68Ga-PSMA-11 on the bottom. Both modalities are detecting the lymph nodes, but you can see a much more robust pattern. I’ll let Louis as the imager give a little more nuanced comment to it.

Here you get a good sense of it, just to talk about physiological uptake. Both radiotracers have physiological uptake within the liver, and you can see radiotracer uptake within the kidneys but notice the difference in the PSMA study of the kidneys compared with the 18F-fluciclovine study. Here we have negative uptake within a renal cyst. But we have positive nodes, which are in the retroperitoneum and are clearly more identifiable and more scintigraphically evident on the PSMA study. We have to wonder why that is. We have to look at the mechanism of the radiotracer and understand that perhaps it’s because of the density of radiotracer being accumulated. In other words, does this tumor that has metastasized the retroperitoneum have a higher concentration of PSMA on its surface, which is allowing the radiotracer to outperform the 18F-fluciclovine? Regardless of the ability of the 18F-fluciclovine to identify the nodes, it’s a matter of concentration of radiotracer based on the molecular behavior of the tumor. In general, we’ve seen that largely be the case, that nodes—especially extrapelvic nodes—are better identified with PSMA than they are with 18F-fluciclovine. But that’s not entirely the case. As you see from some of the data within this paper, there are cases where 18F-fluciclovine outperformed PSMA on individual patients within the nodal beds, which is an interesting commentary on disease heterogeneity; that’s interpatient heterogeneity. There’s a lot going on.

Let’s get a into some of the specific data of the study. When we talk about detection of local recurrence and metastasis, the first thing is the overall detection rate for prostate cancer recurrence in this study: 79.3% in the 18F-fluciclovine arm and 82.8% in the 68Ga-PSMA-11 arm. Local recurrence was detected in 37.9% of patients on the 18F-fluciclovine arm and 27.6% on the 68Ga-PSMA-11 arm. Local pelvic lymph node recurrence was detected in the 18F-fluciclovine arm vs the 68Ga-PSMA-11 arm in 46.6% of patients vs 50%, and in extrapelvic lymph node metastasis in 41.4% vs 51.7%. Finally, when we look at bone metastasis, we’re looking at 25.9% vs 36.2%. Louis, walk us through this slide, which shows it in graphical form. It shows us issues with respect to 1 study, the other study, both, or none.

We get back to the idea of local recurrence to start. First, we see that there were no patients where local recurrence was identified only by PSMA and not by 18F-fluciclovine, but the converse was true where 18F-fluciclovine was able to identify a local recurrence and PSMA could not. When we look at the other sites of disease—the pelvic lymph nodes, the extrapelvic spaces, within the bone—we see that there are patients for whom only PSMA could identify the disease within the pelvic nodes, within the bones, and within the extrapelvic lymph nodes. That gets you to the large conclusions we’ve made, which is that the radiotracers perform very admirably. They perform admirably, but PSMA outperformed 18F-fluciclovine when it came to spaces outside the local bed. In this case, the local bed favored 18F-fluciclovine in terms of the ability to identify disease.

Drs Steven Finkelstein and Louis J. Mazzarelli highlight data revealed in the article “A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT,” by Birgit Pernthaler, et al.

Disease Spotlight: Prostate Cancer

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