Revolutionizing Prostate Cancer Imaging with PSMA PET-CT

The advent of PSMA PET-CT imaging in prostate cancer has impacted disease monitoring and detection, resulting in updated guidelines and practice standards. In this series, Naveen Kella, MD, a urologist from The Urology Place in San Antonio, Texas, offers his perspective on the evolution of PSMA PET-CT imaging and how it has impacted the real-world management of prostate cancer.

Urology Times®: What limitations or clinical challenges exist with conventional imaging modalities?

Naveen Kella, MD: With prostate cancer, there is conventional imaging that we use right now. Conventional imaging typically means bone scan and CT scan. With bone scan, we have problems with picking up prostate cancer recurrences at low PSAs [prostate-specific antigen levels]. It has a very low sensitivity for that. And with a CT scan, one of the problems is that it’s able to pick up lesions in the bone lymph nodes. But for soft tissue it becomes difficult, it has low sensitivity and specificity. MRI is something that we’re using more and more of for imaging for prostate cancer, but it’s limited to the arena of localized prostate cancer. We don’t use the study for metastatic evaluation. So those have been some shortcomings that we’ve had with conventional imaging that we’re addressing now with some of the next-generation imaging.

Urology Times: What impact has PSMA-PET had on prostate cancer imaging?

Naveen Kella, MD: PET-CT has been around for a long time. In prostate cancer, it hasn’t really been used that much. It hasn’t been very effective, nor has it been widely available. PSMA [prostate-specific membrane antigen] PET-CT has really changed that. In fact, in a short period of time since it’s been available, it’s becoming my go-to. I usually use it for indications where someone’s been diagnosed with prostate cancer, and I feel that there is a likelihood of metastatic disease or a potential likelihood. And what does that mean, exactly? I’m looking at patients who perhaps have unfavorable or intermediate-risk or high-risk disease features. That would mean a Gleason score [of] 4 + 3 or greater, and PSA over 10. More than 50% of their biopsy cores negative.

Another area where I’m using PSMA PET-CT is in patients who have biochemical recurrence after definitive therapy. [In] those patients, I can pick up disease much earlier and with more precision than I could with conventional imaging. And another indication where I’ve been using PSMA PET-CT is in patients who’ve had failure [of] or been through chemotherapy and they have a rising PSA, and they may be a candidate for some of the theranostics that incorporate PSMA. Usually, we’ll get a PSMA PET-CT diagnostic scan prior to getting the theranostic study done or the theranostic procedure done.

Urology Times: Are clinical guidelines generally in agreement or disagreement on the use of PSMA PET in prostate cancer? Are there any recommendations that differentiate between 68Ga and 18F tracers?

Naveen Kella, MD: So the different panels out there—AUA [American Urological Association], NCCN [National Comprehensive Cancer Network], RADAR [Radiographic Assessments for Detection of Advanced Recurrence]—with PSMA PET-CT, there’s actually a lot of agreement among the different panels. In fact, with NCCN, it’s considered the preferred alternative to conventional imaging for when you’re concerned about metastatic [disease] or a PSA rise after definitive therapy. There [are] 2 main tracers that are available right now. And the different panels have said that there’s not one clear tracer that should be used…that both of them can be used.

Now, there is some discussion. When they’ve looked at fluorinated tracers versus the gallium tracer, there is this issue of indeterminate bone lesions that we can see with the fluorinated tracers where basically, when the tracer is taken up, some of it breaks down and bone will take up the fluorinated molecules. So it shows up and can be confusing sometimes for interpretation by the radiologists. And so, it’s called [a]…bone lesion. But overall, the panels have been clear that PSMA PET-CT should be considered for imaging for prostate cancer when you’re concerned for metastasis or recurrence. And there’s not one clear tracer that you should be using right now.

Urology Times: What are some of the most critical remaining challenges and unmet needs in imaging of prostate cancer?

Naveen Kella, MD: PSMA PET-CT is a breakthrough, I think, for prostate cancer imaging. It’s not perfect. PSMA stands for prostate-specific membrane antigen, and we’re learning with looking at these PSMA PET-CTs that it isn’t as specific for prostate as we thought. The tracer can be picked up by different organs in the body, secretory organs. And so, you have to be careful in interpreting [results]. There is also a phenomenon where [with] benign conditions such as Paget disease, there can be an expression of PSMA PET-CT uptake, which could be confused for metastatic prostate cancer. So it’s something that we need to be careful about. PSMA PET-CT…as far as with the PET CT imaging modalities that we have, it’s the superior [option]. In fact, the one that we were using before that was good was fluciclovine. And in a head-to-head study, PSMA PET-CT using gallium was twice as effective as picking up lesions than the fluciclovine arm.

So, the data we have with PSMA PET-CT [are] that around 95% of prostate cancers can be picked up. The more aggressive the prostate cancer is, the more PSMA can be expressed. However, if you get to a certain point—for example, post chemotherapy—sometimes the expression of PSMA is not as much. Variants of prostate cancer, such as small cell, may not make PSMA. So overall, the test is very, very effective with [its] sensitivity. We’ve seen with [our] experience, it still takes interpretation, really as a team with the urologists and radiologists. The urologists bring in their clinical expertise and the radiologists their experience with reading lots of these scans. So, it’s really exciting right now in the world of PSMA PET.