Finn E von Eyben1, Maria Picchio2, Rie von Eyben3, Handoo Rhee4, Glenn Bauman5. 1. Center of Tobacco Control Research, Odense, Denmark. Electronic address: finn113edler@mail.tele.dk. 2. Department of Nuclear Medicine, IRCCS San Rafaele Scientific Institute, Milan, Italy. 3. Department of Radiation Oncology, Stanford University, San Francisco, CA, USA. 4. Department of Urology, Princess Alexandra Hospital, Brisbane, Australia. 5. Department of Radiation Oncology, University of Western Ontario in London, ON, Canada.
Abstract
CONTEXT: 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. OBJECTIVE: To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. EVIDENCE ACQUISITION: Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. EVIDENCE SYNTHESIS: Fifteen 68Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2-0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs 14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. CONCLUSIONS: 68Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. PATIENT SUMMARY: Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called 68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA PET/CT imaging.
CONTEXT: 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. OBJECTIVE: To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. EVIDENCE ACQUISITION: Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. EVIDENCE SYNTHESIS: Fifteen 68Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2-0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs 14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. CONCLUSIONS: 68Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. PATIENT SUMMARY:Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called 68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA PET/CT imaging.
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