Detection Rate of Prostate-Specific Membrane Antigen Tracers for Positron Emission Tomography/Computerized Tomography in Prostate Cancer Biochemical Recurrence: A Systematic Review and Network Meta-Analysis

Purpose: Restaging of prostate cancer in patients with biochemical recurrence after radical treatment remains a challenging clinical scenario as current imaging modalities are suboptimal. To date, prostate specific membrane antigen positron emission tomography/computerized tomography seems to represent a very promising diagnostic tool in this setting. Therefore, we evaluated the detection rate of several positron emission tomography/computerized tomography prostate specific membrane antigen based tracers in the restaging of prostate cancer in patients with biochemical recurrence. Materials and methods: According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, a systematic search was performed across MEDLINE®, Embase® and Web of Science™. PICOS (Patient, Intervention, Comparator, Outcome, Study Type), criteria consisted of P: patients with biochemical recurrence after radical prostatectomy and/or radiation therapy as primary treatment; I: studies using gallium-68-prostate specific membrane antigen-11, gallium-68-prostate specific membrane antigen inhibitor for imaging and therapy, gallium-68-trishydroxypyridinone-prostate specific membrane antigen, copper-64-prostate specific membrane antigen-617, fluorine-18-DCFPyL or fluorine-18-prostate specific membrane antigen-1007; C: no control group or positron emission tomography/computerized tomography comparative studies; O: patient specific overall detection rate; and S: retrospective/prospective studies. A meta-analysis of proportions and a network meta-analysis were performed. Heterogeneity was assessed using Cochran Q and I2 statistics. Quality was assessed by QUADAS-2 (University of Bristol, Bristol, United Kingdom). Funnel plots and Egger test were used for publication biases. Results: A total of 43 studies including 5,832 patients were identified and included in the analysis. An overall detection rate of 74.1% (95% CI 69.2%-78.5%) was found, with no differences between tracers. The overall detection rates were 33.7%, 50.0%, 62.8%, 73.1% and 91.7% % in prostate specific antigen subgroups of less than 0.2 ng/ml, 0.2 to 0.49 ng/ml, 0.50 to 0.99 ng/ml, 1.0 to 1.99 ng/ml, and 2.0 ng/ml or greater, respectively. No difference between tracers was found according to prostate specific antigen doubling time or prostate specific antigen velocity. No tracer proved superior to the others through network meta-analysis. High heterogeneity and inconsistency were found across all analyses. Included studies showed a low risk of bias. Conclusions: Prostate specific membrane antigen positron emission tomography/computerized tomography for prostate cancer restaging in patients with biochemical recurrence achieves best detection rates (over 70%) if prostate specific antigen is below 1 ng/ml. At lower prostate specific antigen levels the detection rate of prostate specific membrane antigen positron emission tomography/computerized tomography is lower (33.7% for levels below 0.2 ng/ml and 50% for levels 0.2 to 0.49 ng/ml), despite being better than "older" tracers such as choline based positron emission tomography or computerized tomography/bone scintigraphy. Furthermore, no prostate specific membrane antigen tracer can be currently considered superior to others. Further studies are needed to better define the diagnostic performance and role of these imaging techniques.