Detection Rates of PSMA-PET Radiopharmaceuticals in Recurrent Prostate Cancer: A Systematic Review.

: To conduct a systematic review to evaluate the detection rates (DR) of the three FDA-approved PSMA-targeted radiopharmaceuticals in patients with recurrent prostate cancer. : Two individuals systematically searched MEDLINE, ScienceDirect, and Cochrane Libraries (February 2025), and independently reviewed all results to identify studies reporting patient-level Ga-PSMA-11, F-DCFPyL, or F-flotufolastat DR in ≥100 evaluable patients with recurrent prostate cancer. Sample-weighted means (SWM) of extracted DR were calculated. : Of 5059 published articles, 37 met our inclusion criteria, reporting data from 8843 patients undergoing Ga-PSMA-11 ( = 27), F-DCFPyL ( = 8), or F-flotufolastat ( = 2) studies. Heterogeneity was noted across enrolled populations, particularly in prior treatments. Ga-PSMA-11 studies recruited patients with marginally higher median PSA than F-DCFPyL or F-flotufolastat studies (median PSA ranged from 0.1 to 10.7, 0.2-2.5, and 0.6-1.1, respectively). Reported overall DR ranged from 25 to 91% for Ga-PSMA-11, 49-86% for F-DCFPyL, and 73-83% for F-flotufolastat, with SWM of 71%, 66%, and 79%, respectively. Post-prostatectomy DR were reported in 18 articles, resulting in SWM DR of 58% for Ga-PSMA-11 ( = 12), 55% for F-DCFPyL ( = 4), and 76% for F-flotufolastat ( = 2). Among post-radiotherapy patients, SWM were 87% for Ga-PSMA-11 ( = 4), 90% for F-DCFPyL ( = 2), and 99% for F-flotufolastat ( = 1). SWM DR at PSA < 1 ng/mL were 53%, 42%, and 66% for Ga-PSMA-11 ( = 13), F-DCFPyL ( = 5), and F-flotufolastat ( = 2), respectively. : Considerable heterogeneity exists across populations in studies of diagnostic PET radiopharmaceuticals. Despite a paucity of F-DCFPyL and F-flotufolastat studies compared with Ga-PSMA-11, the available data suggest that all three radiopharmaceuticals provide high overall DR in patients with biochemical recurrence of prostate cancer.