PSMA-targeted Radiotracers versus ¹⁸F Fluciclovine for the Detection of Prostate Cancer Biochemical Recurrence after Definitive Therapy: A Systematic Review and Meta-Analysis

Abstract

Background: National guidelines endorse fluorine 18 ( 18 F) fluciclovine PET/CT for the detection of prostate cancer (PCa) in men with biochemically recurrent PCa. The comparative performance between fluciclovine and gallium 68 or 18 F prostate-specific membrane antigen (PSMA) PET/CT, a newer examination, is unclear.Purpose: To compare the detection of biochemical recurrence using fluciclovine versus PSMA-targeted radiotracers in patients with a prostate-specific antigen (PSA) level less than 2 ng/mL. Materials and Methods:With use of the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy, or PRISMA-DTA, guidelines, a systematic review of PubMed and EMBASE databases between 2012 and 2019 was performed. Studies of fluciclovine PET/CT or PSMA PET/CT in biochemical recurrence were identified. PSA levels, clinical data, and reference standards were obtained when available. A random-effects model was applied to pooled estimates and 95% confidence intervals (CIs) around the prevalence of a positive examination, stratified according to PSA tier.Results: Quantitative analysis included 482 patients (median age, 67 years; interquartile range, 67-67 years) in six fluciclovine studies and 3217 patients (median age, 68 years; interquartile range, 67-70 years) in 38 PSMA studies. Pooled detection rates for PSMA and fluciclovine were 45% (95% CI: 38%, 52%) and 37% (95% CI: 25%, 49%), respectively, for a PSA level less than 0.5 ng/mL (P = .46); 59% (95% CI: 52%, 66%) and 48% (95% CI: 34%, 61%) for a PSA level of 0.5-0.9 ng/mL (P = .19); and 80% (95% CI: 75%, 85%) and 62% (95% CI: 54%, 70%) for a PSA level of 1.0-1.9 ng/mL (P = .01). A reference standard was positive in 703 of 735 patients (96%) in the PSMA cohort and 247of 256 (97%) in the fluciclovine cohort. Conclusion:Patient-level detection rates for biochemically recurrent prostate cancer were greater for prostate-specific membrane antigen-targeted radiotracers than fluciclovine for prostate specific antigen levels of 1.0-1.9 ng/mL.

11C-Choline PET/CT in Recurrent Prostate Cancer: Retrospective Analysis in a Large U.S. Patient Series

“…For instance, similar to choline, there are many potential reasons for nonspecific and false-positive PSMA uptake (40). Regardless, our results are in line with those from other studies on recurrent PCa, showing that scan positivity with choline is generally lower than that reported for PSMA (ranging from 70.2% to 79.5% (31,(36)(37)(38)(39)). However, differences were not as striking among patients with low PSA levels, as had previously been suggested (Fig.…”

“…PSMA PET imaging is gaining increasing recognition for its ability to detect recurrent PCa. Therefore, we also compared our results with data from some of the largest PSMA studies and metaanalyses in patients with biochemical recurrence (31,(36)(37)(38)(39). Similar to the literature on choline PET, studies on the utility of PSMA PET in recurrent PCa are heterogeneous, applying variable methods: in some studies, multiple independent readers were aware only of the initial treatment and the PSA level at the time of scan, and a majority vote was used in cases of interobserver disagreement (37); in other studies, multiple physicians classified scan findings during an interdisciplinary conference, with readers aware of clinical data (and possibly prior imaging studies) (36).…”

“…Similar to the literature on choline PET, studies on the utility of PSMA PET in recurrent PCa are heterogeneous, applying variable methods: in some studies, multiple independent readers were aware only of the initial treatment and the PSA level at the time of scan, and a majority vote was used in cases of interobserver disagreement (37); in other studies, multiple physicians classified scan findings during an interdisciplinary conference, with readers aware of clinical data (and possibly prior imaging studies) (36). Recent metaanalyses of PSMA in recurrent PCa (31,39) reported slightly lower detection rates than those published before (38), reflecting a general trend after the introduction of novel radiotracers (as well as other tests): as experience grows and verification becomes more rigorous, initially high sensitivity and specificity tend to decline to more realistic levels. For instance, similar to choline, there are many potential reasons for nonspecific and false-positive PSMA uptake (40).…”

The Diagnostic Power of the Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography-Computed Tomography in Biochemical Recurrence After Primary Curative Treatment in Patients with Prostate Cancer: A Single-center Experience

“…In a study conducted with patients with serum PSA values <5 ng/mL, Kabasakal et al (15) detected a PSMA positive focus in 58% of patients by 68 Ga-PSMA PET-CT imaging, and, this rate was reported to be 31% in patients with serum PSA <0.2 ng/mL and 54% in patients with 0.2-2 ng/mL. In patients with BCR, the major effective factor for detecting the focus with imaging methods is serum PSA, and as the PSA increases, the focus detection rate increases (10,16). In a study by Sanli et al (17) on the 68 Ga-PSMA PET-CT imaging performed due to BCR, at least one focus was detected in 83.4% of the patients.…”

“…Although adjuvant RT is the first and most important treatment option in patients with BCR, the efficacy of this treatment is related to the detection of the recurrent disease as early as possible and is limited to the prostate region (6). In a meta-analysis of Tan et al (10) which included 5113 patients with BCR who underwent 68 Ga-PSMA PET-CT to detect the recurrence focus, 68 Ga-PSMA PET-CT scan was reported to have a 70% focus detection rate, and, for the serum PSA values of <0.5 ng/mL, 0.5-0.9 ng/mL, 1-1.9 ng/mL and ≥2 ng/mL, these rates were reported as 44.9%, 61.3%, 78.2%, and 93.9%, respectively. In our study, at least one PSMA-positive lesion was detected in 21 of the 34 patients (61.7%) as the BCR focus, and this rate was 46.1% in the RP group and 71.4% in the RT group.…”