The latest updates in prostate cancer imaging using positron emission tomography (PET) with Andrei Iagaru, MD, Professor of Radiology – Nuclear Medicine and the Chief of the Division of Nuclear Medicine and Molecular Imaging at Stanford Health Care.
GU Oncology Now: Dr. Iagaru, you recently had a review published in Current Opinion in Urology that explored the clinical applications of fluciclovine, choline, and gastrin-releasing peptide receptor targeting PET imaging for prostate cancer. Could you give a brief overview of the clinical use of these imaging agents?
Andrei Iagaru, MD: This was part of a series of articles in a supplement that we’re looking at ways to image prostate cancer. Of course, these days, prostate-specific membrane antigen (PSMA) is the universally accepted standard of care, even before it’s FDA approved. And in my institution, we use it in research trials where participants don’t have to pay for their enrollment in these studies. However, given how complex prostate cancer is, like any other cancer, and despite how good PSMA is, we must have ac- cess to other targets for imaging and hopefully treatment of prostate cancer as well.
We have access in the United States to Axumin (fluciclovine), which is FDA approved and it works well. In some instances, it may outperform occasionally PSMA. Although in many cases, PSMA has been shown to be superior. Historically, choline, which is incorporated metabolism of cancer cells overexpressed in prostate cancer, has been used initially labeled with C11, carbon-11, but also as fluorine-18.
So like many of these, including PMSA, you can deal with some misnomer because it’s not prostate specifically, overexpressed in prostate cancer, but other entities can show this target as well. So my view is that the more biological targets we have access to the better our patients will be served. And gastrin-releasing peptide receptors are a similar biological target that allows us to interrogate yet another component of cancer metabolism. These receptors are overexpressed in 60 to 100 percent of prostate cancers, but also in more than 80 percent of estrogen receptors, positive breast cancers, ovarian cancers, GI stromal tumors, and others.
So I don’t think we have a silver bullet in PSMA. We have a great agent in PSMA, but we need to be ready to interrogate the cancer processes when PSMA is not useful.
What are the challenges to PET in other types of imaging for prostate cancer?
Before the introduction of PSMA, prostate cancer was a difficult one for nuclear medicine in the sense that the standard of care, FDG, the workhorse of nuclear medicine in the United States, was only useful at very advanced stages. The aggressiveness of the tumor was much increased. We see availability of C-level and choline at several centers, the pioneer in the US being Mayo Clinic. Afterward, with Axumin availability, the difficulty in prostate cancer and PET is becoming more of a regulatory one, let’s get approval for PSMA. And I’ve seen there are good news coming from that direction.
And then the reimbursement, we have a big issue here where after the initial pass-through period where most of the approval, the cost of the drug is covered for a number of years, afterwards it’s bundled together with everything else and institutions are losing money by offering this because they have to purchase the agent from a commercial pharmacy, and they only go get reimbursed for a certain part of the exam. And here is where advocacy from physician organization, patient groups, may result in legislation that will hopefully fix this issue.
What are some other areas that are being researched in prostate cancer imaging that are of interest to you?
At my institution, we have several trials where we want to expand the use of PSMA, as well as gastrin-releasing peptide receptor (GRPR) imaging, beyond biochemical recurrence and the pre-surgical setting, which are the two indications that have been submitted for FDA approval. We have trials where we evaluate both PSMA and GRPR PET to guide biopsy in men whose MRI are equivocal or negative that they have high suspicion for prostate cancer. That’s an area of unmet need. These men undergo serial imaging procedures, sometimes multiple biopsies, chasing where the PSA is coming from. And our preliminary results indicate that this combined approach may help urology’s guider therapy. We hope to have preliminary results from our pilot phase study published soon.
We are also using the combination of PSMA and GRPR imaging to guide targeted therapy, such as high-intensity focused ultrasound (HIFU) or high-dose rate brachytherapy. The high-dose rate brachytherapy trial is supported by an R01 from the National Cancer Institute. In addition to guiding these local therapies, we also repeat the scan six months after treatment. The hope there is that if we can show a decrease in signal that perhaps some of these men will not require re-biopsy of the lesion to demonstrate success of treatment. A limitation of MRI is in the post-treatment setting where inflammation, bleeding, et cetera, may make the interpretation more difficult. So I hope the combination of these two biological targets and PET together with SMR will allow us to have a more accurate guidance of treatment and a better evaluation of responsive treatment.