title: Sensitivity, Specificity, and Predictors of Positive68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis.
abstract: Positron emission tomography (PET) of68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality introduced to assess the burden of prostate cancer, typically in biochemically recurrent or advanced disease.68Ga-PSMA PET provides the ability to selectively identify and localize metastatic prostate cancer cells and subsequently change patient management. Owing to its limited history, robust sensitivity and specificity data are not available for68Ga-PSMA PET-positive scans.
  
  
  
  A systematic review and meta-analysis of reported predictors of positive68Ga-PSMA PET and corresponding sensitivity and specificity profiles.
  
  
  
  We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta-regression of proportions were performed using a random-effects model with pre-PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.
  
  
  
  Sixteen articles involving 1309 patients were analysed. The overall percentage of positive68Ga-PSMA PET among patients was 40% (95% confidence interval [CI] 19-64%) for primary staging and 76% (95% CI 66-85%) for biochemical recurrence (BCR). Positive68Ga-PSMA PET scans for BCR patients increased with pre-PET PSA. For the PSA categories 0-0.2, 0.2-1, 1-2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive. Shorter PSA doubling time increased68Ga-PSMA PET positivity. On per-patient analysis, the summary sensitivity and specificity were both 86%. On per-lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively.
  
  
  
  In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive68Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques.
  
  
  
  Positron emission tomography using68Ga-labelled prostate-specific membrane antigen is an emerging radiological technique developed to improve the characterisation of metastatic prostate cancer. We summarised the data available to date and found that this new test provides excellent rates of detection of cancer spread in late-stage prostate cancer.
authors.affiliation: Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia.
authors.forename: Marlon
authors.initials: M
authors.lastname: Perera
authors.affiliation: Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Papa
authors.affiliation: Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Christidis
authors.affiliation: Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Wetherell
authors.affiliation: Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hofman
authors.affiliation: Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Victoria, Australia; Australian Prostate Cancer Research Centre, Epworth Healthcare, Richmond, Australia.
authors.forename: Declan G
authors.initials: DG
authors.lastname: Murphy
authors.affiliation: Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia; Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Bolton
authors.affiliation: Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Victoria, Australia; Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Victoria, Australia. Electronic address: lawrentschuk@gmail.com.
authors.forename: Nathan
authors.initials: N
authors.lastname: Lawrentschuk
mesh_terms: D004492:Edetic Acid / Q000031:analogs & derivatives; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D006801:Humans; D008297:Male; D009842:Oligopeptides; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D012680:Sensitivity and Specificity
chemical_list: D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D009842:Oligopeptides; C000718244:gallium 68 PSMA-11; D004492:Edetic Acid
keywords: Biochemical recurrence; Imaging; Metastases; Positron emission tomography; Prostate cancer; Prostate-specific antigen; Prostate-specific membrane antigen; Sensitivity