A randomised, prospective and head-to-head comparison of [(68)Ga]Ga-PSMA-11 and [(18)F]PSMA-1007 for the detection of recurrent prostate cancer in PSMA-ligand PET/CT—Protocol design and rationale

BACKGROUND: A number of radiopharmaceuticals are available for the detection of recurrent prostate cancer (rPC), but few comparative imaging trials have been performed comparing them. In particular, there are no prospective head-to-head comparisons of the recently introduced [(18)F]PSMA-1007 to the existing standard of care [(68)Ga]Ga-PSMA-11. The purpose of this trial is to establish the non-inferiority of the new radiopharmaceutical in terms of the rate of PET-positive findings and to obtain an intra-individual comparison of accuracy and radiopharmaceutical kinetics. METHODS: In this cross-over trial we will randomise 100 individuals to receive either first a standard-of-care PET/CT using [(68)Ga]Ga-PSMA-11 followed by an additional [(18)F]PSMA-1007 PET/CT within 2 weeks, or vice-versa. Inclusion criteria include patients 18 years and older with biochemical recurrence of prostate cancer following radical prostatectomy, defined as two consecutive prostate specific antigen (PSA) levels > 0.2 ng/ml. Detection rate at the patient-based level is the primary end-point. Each scan will be interpreted by a panel of six independent and masked readers (three for [(68)Ga]Ga-PSMA-11 and three for [(18)F]PSMA-1007) which consensus majority in cases of discrepancy. To confirm the PET-positivity rate at a patient based level, follow up at 6 months following the first scan will be performed to a composite standard of truth. Secondary endpoints shall include an intra-individual comparison of radiopharmaceutical-kinetics, per-region detection rate and positive predictive value. DISCUSSION: This is the first randomised prospective comparative imaging trial to compare the established [(68)Ga]Ga-PSMA-11 with [(18)F]PSMA-1007 and will determine whether the new radiopharmaceutical is non-inferior to the established standard-of-care in terms of patient-level detection rate. CLINICAL TRIAL REGISTRATION: Registered with and approved by the regional ethics authority #2020–02903 (submitted 09.12.2020, approval 16.12.2021) and the regulatory authority SwissMedic 2020DR2103. Registered with ClinicalTrials.gov Identifier NCT05079828 and additionally in a national language in the Swiss National Clinical Trials Portal (SNCTP).