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In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18 F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18 F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18 F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18 F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18 F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18 F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0-72.4 y), and the median PSA at 18 F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3-0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive 18 F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96-16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive 18 F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18 F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)