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

Abstract

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 [18F]PSMA-1007 to the existing standard of care [68Ga]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 [68Ga]Ga-PSMA-11 followed by an additional [18F]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 [68Ga]Ga-PSMA-11 and three for [18F]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 [68Ga]Ga-PSMA-11 with [18F]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).

Diverse Imaging Methods May Influence Long-Term Oncologic Outcomes in Oligorecurrent Prostate Cancer Patients Treated with Metastasis-Directed Therapy (the PRECISE-MDT Study)

“…used [ 68 Ga]Ga-PSMA-11 as part of a reference standard for [ 18 F]F-PSMA-1007 PET/CT bone-uncertain findings ( 24 ). An ongoing randomized comparative trial is assessing the noninferiority of [ 18 F]F-PSMA-1007 to [ 68 Ga]Ga-PSMA-11 ( 25 ). To the best of our knowledge, the present study is the first to observe a difference in clinical outcomes in patients managed under the guidance of the 2 tracers.…”

PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor?

“…However, since intense unspecific 18 F-PSMA-1007 uptake may be observed within healthy bone, this tracer needs to be treated with caution when used for staging [ 72 ]. In this context, Alberts and colleagues presented a protocol design to experiment a head-to-head comparison of 68 Ga-PSMA-11 and 18 F-PSMA-1007 for the detection of recurrent prostate cancer lesions (ClinicalTrials.gov Identifier NCT05079828) [ 73 ]. As with prostate cancer, further studies on intra-patient comparisons with different PSMA-targeted tracers are needed for all of the clinical settings in which PSMA radioligands will find an application.…”

PSMA Targeted Molecular Imaging and Radioligand Therapy for Prostate Cancer: Optimal Patient and Treatment Issues

“…Some reports suggest that it is advantageous in the diagnosis of recurrence after total prostatectomy because of its lower urinary excretion compared to other agents, but others report that there was no difference in diagnostic performance [ 22 ]. Although this drug has not been approved by the FDA and EMA, it is currently being compared to Ga-PSMA-11 [ 24 ] and is a promising agent for future approval.…”

“…The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. Primary endpoints have been achieved ( 177 Lu-PSMA-617 group vs. cabazitaxel group, PSA responses; 66 vs. 37% by intention to treat; difference 29% (95% CI: 16–42; p < 0·0001; and 66 vs. 44% by treatment received; difference 23% [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]; p = 0·001)). However, the study results require careful interpretation because the primary endpoint of the study was at least a 50% reduction in PSA; in addition, the dose of 20 mg/m 2 cabazitaxel was lower than the 25 mg/m 2 in the TROPIC [ 7 ] and CARD trials [ 50 ].…”