18F-flotufolastat, a PSMA-targeted PET imaging agent, demonstrates a high detection rate in prostate cancer patients experiencing recurrence after radical prostatectomy, even at very low PSA levels (<1 ng/mL). This finding, presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting, suggests that 18F-flotufolastat can be a valuable tool for early detection and treatment planning in this patient population.
The study, a secondary analysis of the Phase 3 SPOTLIGHT trial, focused on a subset of 119 men who had undergone radical prostatectomy and experienced biochemical recurrence with a PSA level below 1 ng/mL. According to Dr. Bridget F. Koontz, radiation oncologist and medical director of radiation oncology programs at AdventHealth Cancer Institute, the rationale behind the study was to determine the agent's efficacy in detecting recurrence at the earliest possible stage, guiding decisions on salvage treatment.
Key Findings
The analysis revealed that 18F-flotufolastat detected a source of recurrence in 69% of men with PSA levels of 0.2 ng/mL or higher, which is the range defining biochemical recurrence. Notably, even in patients with PSA levels below 0.2 ng/mL, the detection rate was 50%, although this was based on a very small sample size. These results suggest that 18F-flotufolastat may be able to identify recurrence before it is typically detected by PSA testing alone.
Clinical Implications
The ability to detect recurrence at low PSA levels can significantly impact treatment decisions. As Dr. Koontz explained, identifying the source of the rising PSA allows clinicians to determine whether a radiotherapy approach is appropriate or if systemic options should be considered. Post-operative radiotherapy can be very effective and can cure patients and is more likely to be effective when we know where to target, and that helps us also reduce side effects from radiation. The high detection rate of 18F-flotufolastat in this setting can therefore lead to more targeted and effective treatment strategies.
Future Research
While this study demonstrates the effectiveness of 18F-flotufolastat, further research is needed to compare it directly with other PSMA-targeted agents. A study comparing 18F-flotufolastat with PyL PSMA is currently underway. Additionally, research is ongoing to investigate the hypothesis that 18F-flotufolastat's longer time to urinary excretion contributes to its high detection rates, potentially due to reduced benign uptake in the bladder neck region.
Mechanism of Action
18F-flotufolastat's high binding affinity to PSMA and slower release into the bloodstream may explain its superior detection rates at low PSA levels. The slower urinary clearance means that less of the agent accumulates in the bladder at the time of imaging, potentially reducing interference from benign uptake in the bladder neck region, a common challenge in post-prostatectomy imaging.
