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Sensitivity, Specificity, and Predictors of Positive 68Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis

Eur Urol. 2016 Dec;70(6):926-937

Abstract

Context

Positron emission tomography (PET) of 68Ga-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 for 68Ga-PSMA PET–positive scans.

Objective

A systematic review and meta-analysis of reported predictors of positive 68Ga-PSMA PET and corresponding sensitivity and specificity profiles.

Evidence acquisition

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.

Evidence synthesis

Sixteen articles involving 1309 patients were analysed. The overall percentage of positive 68Ga-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). Positive 68Ga-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 increased 68Ga-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.

Conclusions

In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive 68Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques.

Patient summary

Positron emission tomography using 68Ga-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.

Take Home Message

68Ga–Prostate-specific membrane antigen positron emission tomograpy is a novel imaging modality used to assess disease extent in advanced prostate cancer. Our study highlights excellent utility in primary staging for high-risk prostate cancer and secondary staging for biochemical recurrence. The pooled data outline acceptable sensitivity in detecting prostate cancer with low prostate-specific antigen (PSA) levels and PSA doubling times.

Keywords: Biochemical recurrence, Prostate cancer, Imaging, Positron emission tomography, Prostate-specific membrane antigen, Metastases, Sensitivity, Prostate-specific antigen.

Footnotes

a Department of Surgery, Austin Health, The University of Melbourne, Victoria, Australia

b Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

c Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Victoria, Australia

d Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Victoria, Australia

e Australian Prostate Cancer Research Centre, Epworth Healthcare, Richmond, Australia

Corresponding author. Olivia Newton-John Cancer and Wellness Centre, Austin Health, 210 Burgundy Street, Heidelberg, Victoria 3084, Australia. Tel. +61 4 88088240.