Marlon Perera1, Nathan Papa2, Matthew Roberts3, Michael Williams4, Cristian Udovicich5, Ian Vela6, Daniel Christidis2, Damien Bolton7, Michael S Hofman8, Nathan Lawrentschuk9, Declan G Murphy10. 1. Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia; Department of Urology, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia. Electronic address: marlonlperera@gmail.com. 2. Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia. 3. Department of Urology, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia. 4. Department of Urology, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 5. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 6. Department of Urology, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Center QLD, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. 7. Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia; Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Victoria, Australia. 8. Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 9. Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia; Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Victoria, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia. 10. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
Abstract
CONTEXT: Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of 68Ga-PSMA PET in this setting. OBJECTIVE: To perform a systematic review and meta-analysis to update reported predictors of positive 68Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles. EVIDENCE ACQUISITION: We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. EVIDENCE SYNTHESIS: A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive 68Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed. CONCLUSIONS: Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings. PATIENT SUMMARY: Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
CONTEXT: Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of 68Ga-PSMA PET in this setting. OBJECTIVE: To perform a systematic review and meta-analysis to update reported predictors of positive 68Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles. EVIDENCE ACQUISITION: We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. EVIDENCE SYNTHESIS: A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive 68Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed. CONCLUSIONS: Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings. PATIENT SUMMARY:Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Authors: Mark A Green; Gary D Hutchins; Clinton D Bahler; Mark Tann; Carla J Mathias; Wendy Territo; Justin Sims; Heather Polson; David Alexoff; William C Eckelman; Hank F Kung; James W Fletcher Journal: Mol Imaging Biol Date: 2020-06 Impact factor: 3.488
Authors: J Kopp; D Kopp; E Bernhardt; L Manka; A Beck; H Gerullis; P Karakiewicz; W Schoerner; P Hammerer; Jonas Schiffmann Journal: World J Urol Date: 2020-02-26 Impact factor: 4.226
Authors: Lars J Petersen; Julie B Nielsen; Niels C Langkilde; Astrid Petersen; Ali Afshar-Oromieh; Nandita M De Souza; Katja De Paepe; Rune V Fisker; Dennis T Arp; Jesper Carl; Uwe Haberkorn; Helle D Zacho Journal: World J Urol Date: 2019-06-12 Impact factor: 4.226
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