A comprehensive review of imaging modalities available to patients with prostate cancer who are suspected of recurrence.
Brian Helfand, MD, PhD: When we talk about next-generation imaging, we’re focused on PET [positron emission tomography]–CT imaging, which has revolutionized the field. This is something that has given us increased sensitivities, even at PSA [prostate-specific antigen] levels that are very low values, to localize where that recurrence is coming from. The concept started a long time ago and was investigated with FDG [fluorodeoxyglucose] imaging PET scans. These are glucose-based transporter type of PET-CT imaging. They didn’t move the bar all that much because they weren’t specific for many prostate cancer tumors. Prostate cancer, especially in the very early stage, doesn’t have a lot of glucose metabolism, so it didn’t have the initial specificity and sensitivity we were looking for to diagnose recurrence.
Subsequently, choline C-11 PET scans came into play. But those type of PET-CT scans were limited and localized to centers of excellence. The reason is that you had to mix up the agent quickly because it had such a short half-life. You have to give it to the patient within an hour of mixing it up. Then you’d hope for a good image, because at that time the image quality wasn’t crystal clear. Based on that, it helped us localize some of where that prostate cancer recurrence was.
Fast-forward, there was a revolution when fluciclovine F-18, which is an amino acid transporter-based molecule, came on the market. As this fluciclovine-based PET imaging modality came on the market, which was a lot more specific and sensitive for prostate cancer, we were able to see with clarity where a lot of those recurrences were happening. In fact, in this type of patient, who had relatively early recurrence after a surgery, we were able to pick up new pelvic lymph nodes, or distant lymph nodes, and bone metastases. When we looked at the studies using fluciclovine—they were at low levels, meaning less than 0.8 ng/mL—we were detecting 30% to 40% of recurrences within the pelvis or distantly with this modality. This was an excellent and certain change and defined how we should be thinking about patients who are experiencing a recurrence.
Shortly after that, PSMA [prostate-specific membrane antigen] PET-CT scans came on the market and potentially changed the market. That’s because there was increased specificity, meaning that if you had a negative scan, it wasn’t necessarily going to be there; a positive [scan] was a signal that it was recurring. When you looked at the performance—there were no true head-to-head studies of PSMA vs fluciclovine—we were able to start detecting the recurrences at a higher-frequency even at lower levels. Up to 60% of patients, depending on the study, could have a positive scan to help localize where that cancer was after definitive treatments such as surgery or radiation. This is a game changer because it allowed us to plan our subsequent treatments based on where the recurrence was happening.
This is where we are today and where we’re going. If you ask me, this is the standard of care, meaning that if patients are starting to recur after definitive therapy, then this is what we should be doing as our first-line therapy. If we can localize this, it will help us identify and make a plan that’s better for the patient.
Prospective studies have been done with the fluciclovine agent looking at how this changes management and if that prevents further recurrences. But the data highly suggest that when you make a plan based on that PET imaging study, whether it’s to widen the field if you’re going to do radiation, localize, do SBRT [stereotactic body radiation therapy], or totally change management because it’s a widespread recurrence, the fluciclovine or PET imaging or PSMA scans have changed that management and help significantly decrease the risk of recurrence. It’s very exciting in that way.
A common question, as in this patient example, is about what the PSA level we should look at. Is there an optimal level and time, when a patient has that recurrence, that [signals that] we should be obtaining any type of PET-CT imaging? The [answer is] a moving target. At lower levels, we have enough sensitivity and specificity, so it’s beneficial to get it at early time points. The studies and meta-analyses that have been done at low levels, even at less than 0.5 ng/mL, using a lot of the PSMA PET-CT scans, are going to detect up to 60% to 70% of the location where those tumors are recurring in cells. That’s important because we know from historical studies, the earlier you can intervene—meaning that the lower the tumor burden if you’re talking about a cell or 2—it’s much easier to treat than if you have many cells or a huge mass recurrence that you could detect on more conventional imaging. It’s important to start intervening at early time points because patient survival, according to historical studies, tends to be better.
The higher your PSA, the more likely you are to have a positive scan or find more metastases. That’s not wrong. If you get a patient who comes in and their PSA is 10 ng/mL, it doesn’t mean that these scans are useless. It still has increased sensitivity and specificity and helps us localize where those recurrences are. However, if we could intervene at earlier time points, when that recurrence is occurring, it’s going to benefit the patient. That’s what I believe, and that’s what the data are starting to demonstrate better. Those are the indications.
As urologists, our space tends to be more focused on post-surgery management. Once we do surgery and remove the prostate, we’re following PSA [levels]. At early time points, we should start obtaining imaging. I start getting imaging when the PSA looks as though it’s trending and rising. I’ll get that about 0.12 ng/mL, which is very early and not considered a recurrence. Because I’m not being held to this, institutional data suggest that at that low level, we’re seeing almost 50% of scans that are positive, and we’re able to adjust. Our data reflect what all the prospective studies have shown. It depends on how you define recurrence after radiation therapy. Three consecutive rises or 2 ng/mL above their lowest PSA are the most commonly used definitions of radiation failure. But as soon as patients start to trend there, if their primary modality was radiation, it’s not incorrect to obtain a scan and start looking for that recurrence. It may be localized to the prostate—these scans will demonstrate that—but it may be elsewhere in the pelvis or even become M0, meaning above the bifurcation of the aorta. If that’s the case, then your treatment plans are going to vary based on what you see.
Transcript edited for clarity.