[18F]Fluciclovine PET/CT versus [18F]DCFPyL PET/CT in patients with biochemical recurrence of prostate cancer after robot-assisted radical prostatectomy: a prospective, single-center, single-arm, comparative imaging trial.

PURPOSE: The current EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines recommend radiolabeled prostate-specific membrane antigen (PSMA), choline, or fluciclovine PET/CT at biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy. While studies compared [68Ga]Ga-PSMA-11 and [18F]Fluciclovine, data on 18F-labelled PSMA-ligands versus [18F]Fluciclovine in patients with low prostate-specific antigen (PSA) levels (< 2 ng/mL) are limited. This study compared the detection rates of [18F]Fluciclovine and [18F]DCFPyL PET/CT in patients with BCR after robot-assisted radical prostatectomy (RARP). Secondary objectives included stratifying detection rates by PSA level, anatomical regions and assessing inter-observer agreement. METHODS: In this prospective, single-center study, patients with BCR (PSA 0.2-2.0 ng/mL) underwent both [18F]Fluciclovine and [18F]DCFPyL PET/CT within 15 days. Three blinded nuclear medicine experts independently reviewed all scans. Lesions were classified as positive or negative in predefined regions (i.e., prostate bed, pelvic and extra-pelvic lymph nodes, bone, and visceral). Discrepancies were resolved by consensus, defined as majority agreement (≥ 2/3 readers). Inter-observer agreement was assessed using Fleiss’ kappa. RESULTS: Overall scan positivity was 44% (22/50 patients) for [18F]DCFPyL PET/CT and 24% (12/50) for [18F]Fluciclovine PET/CT (p = 0.018). Detection rates increased with rising PSA levels for both tracers. Local recurrence was detected by both tracers in 16% (8/50) of patients. Metastatic disease detection rates for [18F]DCFPyL versus [18F]Fluciclovine were 22% vs. 8.0% for pelvic lymph nodes (p = 0.016), and 6.0% versus 2.0% for distant metastases (p = 0.50), respectively. Inter-observer agreement was moderate for both tracers (κ = 0.59 for [18F]DCFPyL and κ = 0.55 for [18F]Fluciclovine). CONCLUSION: This study demonstrated the superiority of [18F]DCFPyL over [18F]Fluciclovine in detecting pelvic lymph node metastases in patients presenting with BCR after RARP at low PSA levels. These findings suggest the potential of [18F]DCFPyL PET/CT to facilitate earlier and more personalized salvage treatment strategies.