Researchers Refining Role of Next-Generation Imaging in Prostate Cancer

Phillip J. Koo, MD, discusses the use of conventional imaging as well as the next-generation imaging tools that have the potential to change the management of patients with recurrent prostate cancer.

Phillip J. Koo, MD

18F-fluciclovine (Axumin)- and 68Ga-prostate-specific membrane antigen (68Ga-PSMA)—based PET imaging modalities have better sensitivity, specificity, and accuracy in detecting recurrent prostate cancer compared with conventional imaging tools, said Phillip J. Koo, MD.

“It’s pretty clear that 18F-fluciclovine and 68Ga-PSMA—based imaging tools perform better than conventional imaging in terms of identifying osseous metastatic disease and soft tissue disease,” said Koo. “There's no debate there.”

The challenge, he explained, is how next-generation imaging modalities will impact current management strategies. Although there is a growing body of evidence to suggest that using metastasis-directed therapy in conjunction with new-generation imaging could lead to improved outcomes for patients with smaller lesions, more data are needed before that approach replaces conventional imaging.

“It's very easy to fall in love with these great imaging tools, but we need to remember that 99% of all these clinical trials were done with conventional imaging modalities,” added Koo. “That's where we have the data.”

In an interview during the 2019 OncLive® State of the Science Summit™ on Genitourinary Cancers, Koo, division chief of Diagnostic Imaging, Banner MD Anderson Cancer Center, discussed the use of conventional imaging as well as the next-generation imaging tools that have the potential to change the management of patients with recurrent prostate cancer.

OncLive: Could you discuss the imaging modalities that are being used in prostate cancer?

Koo: [In my presentation], I talked about the use of next-generation imaging. I also discussed the appropriate use of these imaging tools and the impact they have had on the management of patients with prostate cancer.

For decades, next-generation imaging is something that the community has asked for. Our conventional imaging tools have been limited to bone scan and computed tomography (CT). However, we know that we’re probably missing a lot of lesions [with these conventional approaches]. It’s important [to be able to identify these lesions] because you want to know whether or not the disease is metastatic and where it might be confined to when you're considering therapy or potentially curative interventions.

Could you expand on the next-generation modalities that have emerged in recent years?

The one next-generation imaging tool that is most widely available and best performing is 18F-fluciclovine. It has been shown to be as good, if not a little better than choline C-11, which was the first novel radiopharmaceutical PET agent that was approved for use in the United States.

Are these modalities widely available?

18F-fluciclovine is widely available in the United States. I believe [it’s available] at over 300 sites in the United States. The future of next-generation imaging is going to be focused on PSMA-based imaging agents. The use of these agents varies across the globe. In the United States, we do not have any FDA-approved PSMA PET agent. That being said, several sites in the United States are offering these agents under new drug applications or clinical trials. Once the generic 68Ga-PSMA-11 PSMA, or the commercialized versions of PSMA are FDA approved, we'll see greater availability across the United States.

Is there still a role for conventional imaging in practice?

At this point, it's a little premature to say that we will no longer need conventional imaging. That being said, it's safe to assume that better and more accurate imaging tools will lead to improved outcomes in the future. Therefore, conventional imaging may play a smaller role in the future.

Could you highlight some of the data that we have seen with next-generation imaging tools?

The biggest debate right now is what to do with that information. Many studies have shown that your management decisions will change if you use one of these imaging agents. The biggest question that we need to answer is whether those new management strategies are going to lead to improved outcomes for our patients. Some signals suggest improved outcomes, but there is still a lot more that we need to learn before we alter our practice.

Could you shed light on some of these new management strategies?

The biggest disease state that comes to mind is oligometastatic disease. If a patient presents with biochemical recurrence and a low prostate-specific antigen (PSA) of 0.5 or 1, and you order conventional imaging, most likely the bone scan or CT will be negative. If you order one of these next-generation imaging tools, there's a high likelihood you might detect locally recurrent disease or local metastatic disease, potentially even oligometastatic disease outside the pelvis.

The question is, “How are we going to manage that patient?” According to surveys and consensus meetings, such as the Advanced Prostate Cancer Consensus Conference, it seems like many providers are treating patients with oligometastatic disease with metastasis-directed therapy. The data regarding the impact of this approach is growing. There's a study from The University of Ghent showing that the time to initiation of androgen deprivation therapy was longer in patients who had a C11-choline PET/CT and then received radiation or surgery on those identified lesions.

Where should research focus in the coming years?

Many clinical trials in the United States and globally are ongoing—more than I could list off during this interview. At The University of Texas MD Anderson Cancer Center, and here, [in Arizona], we have a basket trial looking at patients with oligometastatic disease who have difference disease sites. It's very encouraging to see more people trying to tackle this question [of how best to manage these patients]. In the next couple years, we'll have clearer answers. It's also encouraging to see more industry-sponsored efforts looking at ways to incorporate these imaging tools into their trials. These prospective studies will help us answer many remaining questions.

What are the biggest challenge in this space? What steps are being taken to address it?

The biggest challenge right now is getting these PSMA agents approved and into practice. Once PSMA-based therapies are approved, we’ll need some sort of companion diagnostic so that we can identify eligible patients. The second unmet need is that we need solid data to tell us that the changes we're making in how we manage our patients is making a significant difference. If it's not, then all we're doing is increasing the cost of care and potentially harming our patients. That information is vital to how we incorporate these tools into our practice in the future.

Is there anything else that is important to emphasize for these patients?

Whenever you order one of these tests, you want to know what you're going to do with the information before you order the test. An actionable result is needed in order for that test to be valuable. Based on a trial that enrolled a SPARTAN-like population, we know that 55% of patients with nonmetastatic CRPC had N1 disease when they were scanned with PSMA. The truth is those patients were actually included in the SPARTAN trial based on their bone scan and CT. However, they still had that 2-year improvement in metastasis-free survival. We need to make sure we stay true to the data.

The other message is that patients with CRPC have aggressive disease. PSA is a very important biomarker, but we know that patients will progress without a rise in PSA. We know this from the PREVAIL data that Alan H. Bryce, MD, of Mayo Clinic, authored that 25% of patients have radiographic progression without a rise in PSA. It's important for us to continue to closely monitor those patients as well.