Sequential flotufolastat-F18 PSMA-PET scans to enhance detection of prostate cancer in patients with early PSA recurrence following radical prostatectomy.

25 Background: Flotufolastat-F18 is a novel radio hybrid PSMA PET imaging agent that is FDA approved for imaging in men with prostate cancer (PCa) who are candidates for initial definitive local therapy or suspected recurrence based on elevated PSA following local therapy. Given the potential of low urinary excretion to improve the interpretability and sensitivity of flotufolastat-F18 and the suboptimal sensitivity of PSMA-PET imaging at lower PSA <0.5, we hypothesized that the detection rate may be enhanced by using serial flotufolastat-F18 scans in post-radical prostatectomy (RP) patients (pts) with early PSA recurrence. Methods: A single-center prospective trial evaluating flotufolastat-F18 PET imaging was designed at AdventHealth including pts who displayed a post-RP PSA ≥ 0.1 ng/ml and <0.5 ng/ml. Those who exhibited a lesion defined as definite PSMA uptake >background blood pool on the initial scan proceeded to treatment. If the initial scan did not detect a lesion, pts were monitored off-therapy and offered a second 18F-flotufolastat-scan following the first subsequent PSA increase by ≥0.1 ng/ml. Other imaging, biopsy and therapy was per investigator discretion. The primary objective was PSMA+ lesion detection rate for those who underwent protocol-planned sequential double-scanning strategy and for those who underwent a single scan. The target accrual was 30 pts who underwent at least 1 scan. Results: 30 pts have been enrolled who underwent ≥1 flotufolastat-F18 PET scans. The median (range) age was 64 years (43-83), PSA at study entry was 0.21 (0.10-0.49) ng/ml and the PSA before second scan among evaluable patients was 0.37 (0.22-0.58) ng/ml. The first PET scan detected a PSMA+ lesion in 8 of 30 pts (26.7%). Of the remaining 22 patients with negative initial scans, 3 patients decided to start therapy without undergoing the second scan, 13 have undergone the second scan, of whom 6 exhibited a lesion (46.1%), and remaining 6 are undergoing PSA monitoring to trigger the second scan. Overall, a PSMA+ lesion was detected in 14 of 21 (66.7%) evaluable patients who underwent the protocol-planned sequential double-scan strategy. Of the 14 pts with a PSMA+ lesion with the double--flotufolastat-F18 scan strategy on trial, 5 pts (3 with PSMA+ lesion on first scan) with median PSA= 0.22 ng/ml had undergone a prior off-trial PSMA-PET scan using a different tracer and 4 of these had not revealed a lesion (1 other pt showed a possible lesion). Conclusions: In post-RP patients with early PSA recurrence ≥0.1 to <0.5 ng/ml, the PSMA+ lesion detection rate may be enhanced by employing a strategy of sequential double flotufolastat-F18 PSMA-PET imaging, which uses a tracer with low urinary excretion. Updates with further follow-up will be presented. Validation of these data in larger studies is warranted given the impact on informing potentially curative radiation therapy.