Bridget Koontz, MD: 18F-flotufolastat demonstrates high detection rate in low PSA setting

In this interview, Bridget F. Koontz, MD, FASTRO, highlights the study, “¹⁸F-Flotufolastat Detection Rates in the Pelvis Region for Patients with Prostate Cancer Recurrence after Radical Prostatectomy and PSA Levels <1 ng/mL: Data from the Phase 3 SPOTLIGHT Study,” which was recently presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting in Washington, DC.

Bridget F. Koontz, MD, FASTRO

Koontz is radiation oncologist and the medical director of radiation oncology programs at AdventHealth Cancer Institute in Orlando, Florida.

This transcription was AI generated and edited by human editors for clarity.

Could you highlight the background/rationale for this study?

This study is a secondary analysis of SPOTLIGHT. SPOTLIGHT was a study [evaluating the detection rates] of a new hybrid PSMA-targeted agent, ¹⁸F-flotufolastat. That study was used in the FDA approval [of ¹⁸F-flotufolastat] based on the ability to diagnose recurrent prostate cancer. The [current] study was a sub-analysis trying to look at how low [we] can go in the radical prostatectomy patients [with] very low PSAs, less than 1 ng/mL, and what the detection rate is using ¹⁸F-flotufolastat in that population.

The rationale for this study is as clinicians, we have ultra-sensitive PSA. So, after a prostatectomy, we are monitoring patients very closely for recurrence. We are finding recurrent disease with PSAs in the 0.2 ng/mL to less than 1 range. There's a lot of anxiety around that. [One of the] questions is, "How early should we start the next salvage treatment?" Being able to detect where the tumor is—the source of that PSA—can guide treatment decision-making, whether it's a radiotherapy approach or whether they have metastatic disease and we need to be thinking about systemic options. Being able to have an agent that has a high rate of detection at a low PSA level is really useful from a clinical standpoint.

What were the key findings that were presented at ASTRO?

[This analysis included a] subset of 119 men. The criteria was [men who underwent] radical prostatectomy and [experienced] biochemical recurrence with a PSA less than 1 ng/mL who underwent ¹⁸F-flotufolastat imaging in the SPOTLIGHT trial. In that study, the way that we evaluated whether the test was positive was we had 3 readers who looked at the scan and gave their vote as to whether they could see uptake signifying metastatic disease or not. It was best 2 out of 3 in terms of the readers to determine whether the scan was positive.

We broke [that cohort of men] it into [groups with] PSAs less than 0.2 ng/mL, PSAs from 0.2 to 0.3 ng/mL, PSAs from 0.3 ng/mL to 0.5 ng/mL, and PSAs from 0.5 ng/mL to 1 ng/mL. We found that as soon as we got to the range of biochemical recurrence-defined PSA—0.2 ng/mL and up—the detection rate was very high. In 69% of men, we were able to detect a source of recurrence.

The other interesting finding was that in [patients with PSAs] less than 0.2 ng/mL, we still had a 50% detection rate, which is striking, given that those men haven't met the technical definition of biochemical recurrence yet. [However,] the numbers were really small [in this cohort]. We only tested 2 men, and in 1 of them, we could find the disease. In that case, I would say that number just highlights that we can detect the cancer, even when the PSA is 0.2 ng/mL. I think we need more patients in that range to get a more accurate understanding of what the performance of ¹⁸F-flotufolastat really is with a PSA that low.

What are some potential avenues for future research based on this study?

This study does not compare ¹⁸F-flotufolastat with other PSMA agents. There is a study that is ongoing comparing this agent with PyL PSMA. I think that will be really interesting to be able to understand [if] there [are] differences between the 2. But at the moment, what this study does is highlight that there is good performance in being able to detect recurrent disease using ¹⁸F-flotufolastat. It highlights that, as we would anticipate, the location of recurrence does change as the PSA rises. We noticed that at lower PSAs, there was more recurrence in the prostate bed. As we got up in the 0.5 ng/mL to 1 ng/mL [range]—what we would still consider a low PSA across the board—there was an increased rate of pelvic or even metastatic disease. I think the main finding here is that this is an excellent agent for use in very low PSA ranges. Comparison is coming out in future data.

Besides the comparative study between the 2 PSMA agents, I think the other thing that's really interesting and will be a [future] study is that ¹⁸F-flotufolastat appears to have a longer time to urinary excretion. That's actually the hypothesis as to why we're seeing such good detection rates at low PSA levels. Because ¹⁸F-flotufolastat has a very high binding to PSMA, it's released more slowly back out into the bloodstream. That means that the urinary clearance is a little bit longer, and at the time of imaging, we don't have as much of it already building up in the bladder and in the bladder neck. From a post-prostatectomy standpoint, there's less likelihood that we're going to be seeing benign uptake in the bladder neck region. That may be why it we had such good detection rates in the prostate bed.

Again, we just know how ¹⁸F-flotufolastat functions; it's not comparative. A better understanding of how this agent compares to others will be useful to help physicians decide, based on the clinical scenario, [is there] 1 agent that's preferred for imaging over another. Right now, frankly, they all work very well. It's really a matter of what's available. At least we know here that there does seem to be value in this low PSA range,

What are the key takeaways from this study?

The key takeaway is that ¹⁸F-flotufolastat is a great agent. It has a very high detection rate of 69% once you hit biochemical recurrence in a PSA of 0.2 ng/mL. So, [there's a] 70% chance that we're going to be able to find the source of disease using this test. That really helps us in decision-making regarding how we counsel our patients on treatment options. Post-operative radiotherapy can be very effective; it can cure patients. It is more likely to be effective when we know where to target, and that helps us also reduce side effects from radiation. This just highlights the excellent performance of the test, and I think it makes it a good PSMA agent to be using in this post-prostatectomy, low PSA setting.