Prospective Comparison of ⁶⁴Copper [⁶⁴Cu]SAR-bisPSMA vs ⁶⁸Gallium[⁶⁸Ga] PSMA-11 PET/CT for Biochemical Recurrence of Prostate Cancer Following Radical Prostatectomy (Co-PSMA Trial).

Abstract

Prostate-specific membrane-antigen positron emission tomography (PSMA-PET) has transformed management of prostate cancer biochemical recurrence (BCR) with higher diagnostic accuracy than previous imaging modalities. ⁶⁴Cu-SAR-bisPSMA PET/computed tomography (CT) (⁶⁴Cu-bisPSMA) is a bivalent-PSMA-peptide with 12.7-hr half-life. The study objective was detection rate (per-patient) comparison between ⁶⁴Cu-bisPSMA and ⁶⁸GaPSMA-11 PET/CT (⁶⁸Ga-PSMA) in BCR post radical prostatectomy (RP) (NCT06907641). This prospective imaging trial enrolled 50 participants with BCR (PSA 0.2-0.75 ng/ml). ⁶⁴Cu-bisPSMA (1 and 24 hr) and ⁶⁸Ga-PSMA were acquired within 3-wk. Images were prospectively reported, and triple read for concordance. Management impact was evaluated after ⁶⁸Ga-PSMA and ⁶⁴Cu-bisPSMA. A reference standard (RS) for accuracy included biopsy, targeted treatment response (no androgen deprivation therapy), PSA increase/decrease on observation or repeat imaging (⁶⁴Cu-bisPSMA). The primary endpoint was mean per-participant lesional difference. Paired t tests and mixed-effects Poisson regression assessed lesion number differences between scans. Median prostate specific antigen (PSA) was 0.43 (interquartile range: 0.31-0.63). Mean per-participant lesions were higher in ⁶⁴Cu-bisPSMA (1.26) versus ⁶⁸GaPSMA (0.48), difference 0.78 (95% CI: 0.52-1.04), ratio 2.63 (95% CI: 1.64-4.20) (p < 0.0001). At a per-participant level 78% (39/50) were positive on 24-hr ⁶⁴Cu-bisPSMA compared to 36% (18/50) on ⁶⁸GaPSMA. Management changed between scans in 22/50 (44%). ⁶⁴Cu-bisPSMA were triple concordant in 84% (42/50) and ⁶⁸Ga-PSMA reads in 80% (40/50). RS-true positive was 71% (24/34) versus 29% (10/34) and RS-false negative rate was 21% (7/34) versus 65% (22/34) for ⁶⁴Cu-bisPSMA versus ⁶⁸Ga-PSMA, respectively. ⁶⁴Cu-bisPSMA-PET/CT identifies a higher number of disease recurrences than ⁶⁸Ga PSMA-PET/CT with substantial management impact and a high RS true positive rate in men with BCR post RP.