F-PSMA-1007 PET in Biochemical Recurrent Prostate Cancer: An Updated Meta-Analysis. Ferrari Matteo,Treglia Giorgio Contrast media & molecular imaging Background:Prostate-specific membrane antigen- (PSMA-) targeted agents labeled with fluorine-18 (F) have recently become available to evaluate patients with biochemical recurrent prostate cancer (BRPCa) by using positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI). We performed a systematic review and meta-analysis about the detection rate (DR) of F-PSMA-1007 PET/CT or PET/MRI in BRPCa patients. Methods:A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through 17 May 2021 was carried out using the following search algorithm: "PSMA" AND "1007". Only studies providing data on the DR of F-PSMA-1007 PET/CT or PET/MRI in BRPCa were included. A random-effects model was used to calculate the pooled DR on a per scan basis. Results:Fifteen articles (853 patients) were selected and included in the systematic review, and ten were included in the quantitative analysis. Most of the studies reported a good DR of F-PSMA-1007 PET/CT or PET/MRI in BRPCa including also patients with low prostate-specific membrane antigen (PSA) values. The DR of F-PSMA-1007 PET/CT or PET/MRI was dependent on PSA serum values. The pooled DR was 81.3% (95% confidence interval: 74.6-88%) with statistical heterogeneity. A significant reporting bias (publication bias) was not detected. Conclusions:F-PSMA-1007 PET/CT or PET/MRI showed a good DR in BRPCa patients in line with other PSMA-targeted agents. The DR of F-PSMA-1007 PET/CT or PET/MRI is influenced by serum PSA values. These findings should be confirmed by prospective multicentric trials. 10.1155/2021/3502389

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. PloS one 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). 10.1371/journal.pone.0270269

Novel Framework for Treatment Response Evaluation Using PSMA PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0): An International Multicenter Study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Our objective was to develop version 1.0 of a novel framework for response evaluation criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) and a composite response classification that combines responses by prostate-specific antigen (PSA) measurements and by RECIP 1.0 (PSA + RECIP). This was an international multicenter, retrospective study. One hundred twenty-four men with metastatic castration-specific prostate cancer (mCRPC) who underwent Lu-PSMA therapy and received PSMA PET/CT at baseline and at an interim time point of 12 wk were included. Pairs of baseline interim PET/CT scans were interpreted by consensus among 3 masked readers for appearance of new lesions. Tumor lesions were segmented, and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which included classifications of complete response (RECIP-CR: absence of any PSMA-ligand uptake on interim PET/CT), partial response (RECIP-PR: decline ≥ 30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥ 20% in PSMA-VOL and appearance of new lesions), and stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 wk by Prostate Cancer Working Group Criteria 3 were recorded. PSA + RECIP results were defined as response (PSA decline ≥ 50% or RECIP-PR/CR) or progression (PSA increase ≥ 25% or RECIP-PD). The study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). The secondary outcome measure was the prognostic accuracy (C-index) of PSA + RECIP versus PSA responses. Patients with RECIP-PD ( = 39; 8.3 mo) had a shorter OS than patients with stable disease (RECIP-SD) ( = 47; 13.1 mo; < 0.001) or RECIP-PR ( = 38; 21.7 mo; < 0.001). In identifying responders and progressors, PSA + RECIP had C-indices superior to those of PSA only: 0.65 versus 0.62 ( = 0.028) and 0.66 versus 0.63 ( = 0.044), respectively. PSMA PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor early efficacy of Lu-PSMA in men with mCRPC. PSA + RECIP may be used as a novel composite endpoint in mCRPC clinical trial design. 10.2967/jnumed.121.263072

The impact of PSMA PET on the treatment and outcomes of men with biochemical recurrence of prostate cancer: a systematic review and meta-analysis. Prostate cancer and prostatic diseases BACKGROUND:Prostate-specific membrane antigen (PSMA) PET is highly sensitive in identifying disease recurrence in men with biochemical recurrence of prostate cancer (BCR) after primary therapy and is rapidly being adopted in clinical practice. The purpose of this systematic review and meta-analysis was to assess the documented impact of PSMA-PET on patient management and outcomes, including prostate-specific antigen (PSA) response, and intermediate and long-term outcome measures. MATERIALS AND METHODS:MBASE, PubMed, Web of Science, Cochrane and OVID databases were searched for studies reporting on the impact of PSMA-PET on the management and outcomes of patients with BCR after definitive primary therapy. Outcome measures assessed included biochemical response to therapy after PET and BCR-free survival (BRFS). The proportions of patients in whom management changed, and the proportion of patients in whom each outcome measure was obtained were tabulated and pooled into meta-analysis using DerSimonian-Laird method. RESULTS:A total of 34 studies with 3680 men reported change in management after PSMA-PET and 27 studies with 2639 men reported on at least one outcome measure and had follow-up data. PSMA-PET was positive in 2508/3680 (68.2%). The pooled proportion of change in management after PSMA-PET was 56.4% (95% CI, 48.0-63.9%). A decrease in serum PSA was documented in 72.4% of men (95% CI, 63.4-81.5%), and complete biochemical response in 23.3% (95% CI, 14.6-32.0%) at a median follow-up of 8.1 and 11 months, respectively. The pooled BRFS rate was 60.2% (95% CI, 49.1-71.4%) at a median follow-up of 20 months. CONCLUSION:In conclusion, PSMA PET is positive in more than 2/3 of men with BCR and impacts patient management in more than half of the men. BRFS after PET-directed management is 60% at a median of 20 months after salvage therapy, and complete biochemical response may be achieved in up to a quarter of men. 10.1038/s41391-022-00544-3