18FFluciclovine PET/CT versus 18FDCFPyL PET/CT in patients with biochemical recurrence of prostate cancer after robot-assisted radical prostatectomy: a prospective, single-center, single-arm, comparative imaging trial

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 68GaGa-PSMA-11 and 18FFluciclovine, data on 18F-labelled PSMA-ligands versus 18FFluciclovine in patients with low prostate-specific antigen (PSA) levels (< 2 ng/mL) are limited. This study compared the detection rates of 18FFluciclovine and 18FDCFPyL 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. In this prospective, single-center study, patients with BCR (PSA 0.2-2.0 ng/mL) underwent both 18FFluciclovine and 18FDCFPyL 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. Overall scan positivity was 44% (22/50 patients) for 18FDCFPyL PET/CT and 24% (12/50) for 18FFluciclovine 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 18FDCFPyL versus 18FFluciclovine 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 18FDCFPyL and κ = 0.55 for 18FFluciclovine). This study demonstrated the superiority of 18FDCFPyL over 18FFluciclovine in detecting pelvic lymph node metastases in patients presenting with BCR after RARP at low PSA levels. These findings suggest the potential of 18FDCFPyL PET/CT to facilitate earlier and more personalized salvage treatment strategies.