Recommendations Further Aid in Elucidating the Role of PSMA PET Imaging in Prostate Cancer

Phillip J. Koo, MD

Precision imaging with prostate-specific membrane antigen (PSMA) PET takes advantage of prostate cancer–specific markers making it an ideal tool for detecting metastatic prostate cancer, according to Phillip J. Koo, MD, who noted it should also be considered for patients at initial biochemical recurrence.

“There are a lot of clinical trials that are starting to incorporate PSMA PET into their design, which is wonderful, and based on a lot of the data that we’re able to accumulate we’ll know more about the impact [of PSMA PET] and how it will inform our treatment decisions,” Koo said in an interview with OncLive®. “There are other questions concerning how to use PSMA PET to pick the best patients to undergo a therapy such as Lutetium (177Lu) vipivotide tetraxetan [Pluvicto]. There’s still a lot to be learned, but at least this is becoming a more utilized tool which it should be. Over time, we’ll start learning more and be able to answer those questions.”

Koo cited the RADAR VI guidelines, which he is a co-author of, that present consensus recommendations for initial and subsequent targeted precision imaging and note that the optimal timing and frequency of serial imaging are unknown. The guidelines highlight findings in the prostate cancer space from the phase 2 ORIOLE trial (NCT02680587), which revealed increased 6-month progression-free survival rates with PSMA PET-guided metastasis-directed therapy (MDT; 95%) vs with CI-guided MDT (62%). Additionally, data from the phase 2 STOMP trial (NCT01558427) showed that the median androgen deprivation therapy (ADT)-free survival was 21 months with choline PET-directed MDT vs 13 months with surveillance.1

In the interview, Koo, chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Phoenix, Arizona, discussed the guidelines, how PSMA PET will be used in clinical trials, and more which he also highlighted in his presentation at the 17th Annual Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies in New York, York.

OncLive: What recommendations did the RADAR group provide in the latest RADAR VI guide on precision imaging?

Koo: RADAR has been a journey that started approximately 11 years ago talking about the various imaging modalities and we started in the castration-resistant prostate cancer space focusing on conventional imaging. For RADAR VI, we updated those recommendations to focus on how clinicians should use PSMA PET in various disease states whether it is [at] initial diagnosis, [at] biochemical recurrence, or in those with castration-resistant disease.

Our RADAR VI recommendations are very similar to what you see in other various published guidelines and recommendations. For patients at initial diagnosis, before definitive therapy, you’re looking at PSMA PET in those where there’s a higher suspicion of metastatic disease and you’re not focused on identifying the primary disease with PSMA PET. For those patients with unfavorable intermediate-risk, high-risk, or very high-risk disease, who have biomarker tests that might indicate a higher risk of metastatic disease, or where using nomograms might have a higher risk of metastatic disease, [PSMA PET] is a good tool that might be able to detect those sites of metastatic disease [which] could help with treatment planning before perhaps prostatectomy or radiation therapy.

Then moving on to the biochemical recurrence setting, my perspective has been to use PSMA PET very aggressively in patients with initial biochemical recurrence. We need to be a little more thoughtful about how we use this tool in the biochemical recurrence setting and right now for those patients who you’re considering doing MDT, PSMA PET is an absolute must. In other settings, it’s a little bit more debatable.

We have data from the phase 3 EMBARK trial [NCT02319837] showing that patients who have high-risk biochemical recurrences will benefit from systemic therapies such as enzalutamide [Xtandi] plus ADT or enzalutamide alone. For at least right now, that raises some questions regarding when to use PSMA PET. For patients with castration-resistant disease, the real sweet spot is using PSMA PET to select patients who should undergo radioligand therapy.

How is PSMA PET being used or not used in clinical trials?

In the biochemical recurrent setting, studies such as the phase 2 ORIOLE, SABR-COMET [NCT01446744], and STOMP trials have helped us figure out how best to use PSMA PET to [help inform the] use [of] MDT. But even there, there are a lot of questions on [whether] that data is compelling enough to use MDT in all these patients. You can hear varying perspectives on that.

Regarding EMBARK, this study was designed years ago—I believe the first patient was enrolled in 2015. EMBARK is nice because it’s now starting to stratify patients with high-risk biochemical recurrence vs low risk and that’s meaningful because those with high-risk biochemical recurrence probably do have a more aggressive biology. The way we manage that shouldn’t be the same as for those who have a lower risk of biochemical recurrence. It’s challenging us now to figure out how PSMA PET, which was not used in the trial, affects how we manage patients. I don’t think there’s a clear right or wrong answer here and that’s why collectively we need to discuss these [findings] in multidisciplinary settings, design trials that incorporate [PSMA PET] to answer some of these questions—which is happening today—and figure out what makes sense for our patients.

What challenges might occur when considering the use of PSMA PET imaging vs conventional imaging techniques?

I don’t want to say PSMA PET is a new technology, it’s been around for a few years. That being said, some practices may not have as much experience with it, and some do; even if you do have a wealth of experience with it, you’re always learning more and seeing unusual patterns of disease distribution that you [haven’t] seen in the past. We’re seeing a lot of discussions about patients who have solitary rib lesions or a solitary pelvic lesion—[these are] bony findings that oftentimes may or may not be metastatic disease and it’s tricky to figure out and hard to prove it might be because biopsy may not always be possible.

Reference

Crawford ED, Albala DM, Harris RG, et al. A clinician’s guide to targeted precision imaging in patients with prostate cancer (RADAR VI). JU Open Plus. 2023;1(1):e00003. doi:10.1097/JU9.0000000000000003