PSMA-PET Agents Poised to Advance Imaging in Prostate Cancer

Thomas Hope, MD

Thomas Hope, MD

Imaging agents for the detection of biochemical recurrent prostate cancer could move beyond computed tomography (CT) and magnetic resonance imaging (MRI) in the near future, with the emergence of prostate-specific membrane antigen (PSMA)-PET, particularly in oligometastatic disease, with a high-detection sensitivity rate, explains Thomas Hope, MD.

PSMA-PET uses small molecules that bind to PSMA, localizes a prostate cancer tumor, and allows radiologists to image patients after 1 hour to detect small sites of disease. Hope and researchers at the University of California, San Francisco (UCSF) are dedicated to bringing this imaging modality to the FDA for approval with diagnostic data as evidence.

One of these PSMA-PET agents, Ga-68-PSMA-11, is being investigated in a diagnostic phase II/III trial for patients with biochemically recurrent prostate cancer (NCT02918357). The study will determine the agent’s ability to detect metastatic disease in these patients, as they will undergo PET/CT or PET/MRI scans 50 to 70 minutes later after being administered Ga-68-PSMA-11.

OncLive: Please provide an overview of your presentation on the modern era of imaging in prostate cancer.

Hope, an assistant professor of abdominal imaging and nuclear medicine at UCSF, spoke on this new wave of imaging in the field during the 2017 OncLive^® State of the Science Summit^TM on Genitourinary Cancers. In an interview during the meeting, Hope spread the word about this novel technique and how, if approved, it will significantly alter detection of biochemically recurrent prostate cancer.Hope: I spoke about novel imaging techniques and how they impact the staging and treatment of patients with prostate cancer. I tried to highlight a couple of things; first, that there are some new FDA-approved agents, particularly fluciclovine (Axumin), which are available and are approved in patients with biochemical recurrent prostate cancer.

Can you hone in on the PSMA-PET approach, and why its approval would be practice changing?

Then, there are novel agents, such as PSMA-PET, which are coming to market soon, and they have a dramatic effect on detecting sites of oligometastatic disease, particularly in patients with low PSAs. That will change the way we treat patients with recurrent prostate cancer. PSMA-PET is [composed of] small molecules that bind to the prostate specific membrane antigen. It is an imaging agent—an agent that localizes the tumor in about an hour so that you can image the patient 1 hour later. It has a very high detection sensitivity because of the high sensitivity of positron emission tomography, or PET CT, for the detection of these radio-labeled ligands as they localize the tumor.

Have studies been conducted with this agent to demonstrate its efficacy and accuracy?

Therefore, imaging agents with PSMA-PET can really help us see where these very small sub-centimeter sites of disease are in patients whom we never would have known previously whether there was disease. The term trial has a slightly different meaning in radiology; you don’t do phase III trials as you would in an oncology setting. However, there have been lots of retrospective data that have been performed, particularly in Europe and Australia, which describe the term detection sensitivity. This is, if you have biochemical recurrent patients, what percentage of patients do you see an avid node of PSMA in? Most of the data show that when you have a PSA of less than 1, you can see a site of recurrence in about 60% to 70% of patients, which is much better than conventional imaging, such as CT or MRI.

Looking ahead, where would you like to see imaging advance even further in the prostate cancer field?

At UCSF, we just finished the first prospective phase II/III trial in the United States under an FDA registration trial. Hopefully, by the end of this year, we will have completed our data and published that. Where could we go beyond PSMA-PET? I'm not really motivated to find an agent that has a higher detection sensitivity than PSMA-PET. PSMA-PET functions very well, so it would be talking about a marginal improvement. What is more important is understanding how these novel imaging modalities affect care, so [we need to] incorporate these new imaging techniques into clinical trials, demonstrate when they should be used, and how you should manage patients if you do find sites of oligometastatic disease.

What other challenges are you still facing, from a radiology perspective?

Right now, we are shooting in the dark. We are doing what we think makes sense based on the imaging findings, but validating and demonstrating that it is appropriate in these patients is not trivial and is where the community should go. That’s not a radiology thing; you need people in oncology and radiation oncology to pick that up, which they are doing. That is what the next step is. We have to get PSMA-PET FDA approved, which is also not trivial. There are about 6 PSMA-PET agents out there that can be used for targeting prostate cancer. I think of them as a class; I don’t think one is better or worse than the other. They are all very similar and they target the same molecule.

However, we need to get these approved and covered by Medicare and private insurances so people can get it easily. Right now, it’s actually quite a struggle to have it made available. Unlike rare tumors, prostate cancer is very common. There is no way that UCSF can provide enough PSMA-PETs to image all patients with biochemically recurrent prostate cancer.

What I am working on is trying to get this approved by the FDA. There has only been one previously academically approved new drug application ever in the history of America, so it’s not a trivial endeavor, and, if we ever do succeed, I will be pretty happy.