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

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

“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 can accumulate, we 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 about how to use PSMA PET to choose the best patients to undergo a therapy such as Lutetium (177Lu) vipivotide tetraxetan. [Pluvicto]. There is still a lot to learn, but at least this is becoming a more used tool than it should be. Over time, we will begin to learn more and be able to answer these questions.”

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

In the interview, Koo, head 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 that he also highlighted in his presentation at u 17 Annual Interdisciplinary Congress of Prostate Cancer® and other genitourinary malignancies in New York, York.

OncLive: What advice did the RADAR group give in the latest RADAR VI guidance on precision imaging?

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

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

Then going to the setting of biochemical recurrence, my perspective has been to use very aggressive PSMA PET in patients with early biochemical recurrence. We have to be a little more thoughtful about how we use this tool in the setting of biochemical recurrence and now for those patients who are thinking of doing MDT, PSMA PET is an absolute must. In other settings, it’s a bit more debatable.

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

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

In the recurrent biochemical environment, studies such as phase 2 ORIOLE, SABR-COMET [NCT01446744], and the STOMP trials helped us understand how best to use PSMA PET to use MDT. But even here, there are many questions [whether] which data is compelling enough to use MDT in all these patients. You can hear different perspectives on this.

Regarding EMBARK, this study was designed years ago – I believe the first patient was enrolled in 2015. EMBARK is great because it is now starting to stratify patients with high-risk versus low-risk biochemical recurrence and this is significant because those who they have high-risk biochemical. Recurrence probably has a more aggressive biology. The way to manage that should not be the same for those who have a lower risk of biochemical recurrence. There is a challenge now to understand how PSMA PET, which was not used in the trial, has an impact on how we manage patients. I don’t think there is a clear or wrong answer here and that is why we collectively need to discuss these [findings] in multidisciplinary environments, design processes that incorporate [PSMA PET] to answer some of these questions – what is happening today – and understand what makes sense for our patients.

What challenges will clinicians face when considering the use of PSMA PET imaging versus conventional imaging techniques?

I don’t want to say that PSMA PET is a new technology, it has been around for many years. Having said that, some practitioners may not have much experience with it, and some do; even if you have a wealth of experience with it, you will always learn more and see unusual patterns of distribution of the diseases you have. [haven’t] seen in the past. We’ve seen a lot of discussion about patients who have solitary rib injuries or a solitary pelvic injury -[these are] bone findings that often may or may not be a metastatic disease and it is difficult to understand and difficult to prove that it could be because the biopsy is not always possible.

Reference

Crawford ED, Koo PJ, Shore N, et al; RADAR Group III. A clinician’s guide to next-generation imaging in patients with advanced prostate cancer (RADAR III). J Urol. 2019;201(4):682-692. doi:10.1016/j.juro.2018.05.164