Imaging of Prostate Specific Membrane Antigen Targeted Radiotracers for the Detection of Prostate Cancer Biochemical Recurrence after Definitive Therapy: A Systematic Review and Meta-Analysis

PURPOSE: Prostate specific membrane antigen targeted radiotracers are promising agents for imaging patients with prostate cancer biochemical recurrence after definitive therapy. We report the results of a systematic review and meta-analysis of the detection of biochemical recurrence after definitive therapy for prostate cancer stratified by prostate specific antigen levels and using prostate specific membrane antigen targeted radiotracers.

MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Diagnostic Test Accuracy guidelines, we searched for articles in PubMed® and EMBASE® databases in our systematic review from 2012 to July 2018. Studies evaluating men with prostate cancer biochemical recurrence after definitive therapy and without known metastatic disease who underwent prostate specific membrane antigen positron emission tomography/computerized tomography to detect recurrent disease were included in analysis. The risk of bias and applicability concerns were assessed by QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Statistical heterogeneity was assessed with the Cochrane Q and an I 2 estimate. The reference standard was pathology findings, followup imaging or a prostate specific antigen decline after salvage treatment. We calculated pooled estimates and the 95% CI around the prevalence of a positive examination in the study population using a random effects model.

RESULTS: A total of 5,113 patients in 43 studies were included in this systematic review. Of the studies 15 (34.8%) were prospective, 3 (6.9%) were multi-institutional and the remainder were done at a single center. A total of 18 studies (41.8%) were done in subjects after radical prostatectomy, 2 (4.6%) were in subjects after radiotherapy and 23 (53.5%) were in subjects after radical prostatectomy and radiotherapy. Median prostate specific antigen was 1.6 ng/ml (IQR 0.7-4.4) and median subject age was 68 years (IQR 67-70). Of the 43 studies 33 (76.7%) evaluated 68Ga prostate specific membrane antigen-11 (Ga-HBED-CC) positron emission tomography/computerized tomography. The pooled detection rate was 70.2% (95% CI 65.0-75.4) in the entire cohort. For prostate specific antigen less than 0.5, 0.5 to 0.9, 1 to 1.9 and 2 ng/ml or greater the pooled detection rate was 44.9% (95% CI 36.0-53.9), 61.3% (95% CI 52.3-70.3), 78.2% (95% CI 70.8-85.6) and 93.9% (95% CI 92.0-95.8), respectively. A reference standard was confirmed to be positive in 684 of the 715 patients (95.7%). There were significant study heterogeneity and publication biases (p <0.01).

CONCLUSIONS: Prostate specific membrane antigen targeted radiotracers are likely effective to detect biochemically recurrent prostate cancer at low prostate specific antigen levels. However, existing studies are limited by retrospective design, limited reference standards, publication bias and a lack of interagent comparison.