Impact of clinical factors on 18F-flotufolastat detection rates in men with recurrent prostate cancer: exploratory analysis of the phase 3 SPOTLIGHT Study

Background 18F-Flotufolastat (18F-rhPSMA-7.3) is a newly approved PSMA-targeting radiopharmaceutical for diagnostic imaging of prostate cancer (PCa). SPOTLIGHT (NCT04186845) evaluated 18F-flotufolastat in men with suspected PCa recurrence. Here, we present results of predefined exploratory endpoints from SPOTLIGHT to evaluate the impact of clinical factors on 18F-flotufolastat detection rates (DR). Methods The impact of baseline PSA, PSA doubling time (PSAdt), and ISUP Grade Group (GG) on 18F-flotufolastat DR was evaluated among all SPOTLIGHT patients with an evaluable scan, with DR stratified according to the patients’ prior treatment (radical prostatectomy ± radiotherapy [RP] or radiotherapy only [RT]).The patients underwent PET 50–70 minutes after receiving 18F-flotufolastat (296 MBq IV) and scans were read by three blinded central readers, with the majority read representing agreement between ≥2 readers. Results In total, 389 men (median PSA: 1.10ng/mL) were evaluable. By majority read, 18F-flotufolastat identified distant lesions in 39% and 43% of patients treated with prior RP or RT, respectively. The overall DR broadly increased with increasing PSA (<0.2 ng/mL: 33%; ≥10 ng/mL: 100%). Among patients with PSA<1 ng/mL, 68% had positive scans, and 27% had extra-pelvic findings. PSAdt was available for 145/389 (37%) patients. PSAdt did not appear to influence 18F-flotufolastat DR (77‒90% across all PSAdt categories). Among patients with prior RP, DR ranged from 70–83% across PSAdt categories, while 100% DR were reported for all post-RT patients. In total, 362/389 (93%) patients had baseline GG data. Overall DR were uniformly high (75‒95%) across all GG. When stratified by prior treatment, DR across all GG were 69‒89% in patients with prior RP, and ≥96% in patients with prior RT. Conclusions 18F-Flotufolastat-PET enabled the accurate detection of recurrent PCa lesions across a wide range of PSA, PSAdt, and ISUP GG, thus supporting its clinical utility for a broad range of patients with recurrent PCa.