Combined Prostate-specific Membrane Antigen Positron Emission Tomography and Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer.

Background and objective: More than half of men who undergo a prostate biopsy based on positive multiparametric magnetic resonance imaging (mpMRI) findings do not have clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) may complement mpMRI to better triage men with suspected prostate cancer (PCa) and reduce the number of unnecessary biopsies performed. A diagnostic test accuracy systematic review and meta-analysis was performed to determine the diagnostic accuracy of combined imaging for csPCa detection with pairwise comparisons with mpMRI and PSMA-PET alone. A decision curve analysis (DCA) compared the strategies of performing an upfront biopsy versus combined imaging for suspected PCa patients, across varying thresholds for accepting the risk of missing a csPCa diagnosis.

Methods: A search of the PubMed, Embase, Central, and Scopus databases, from inception to January 2024, was conducted. Twenty studies (2153 patients) that referenced combined imaging against histopathology were included. Bivariate meta-analyses and metaregression were performed to determine the diagnostic parameters and assess the differences between imaging modalities.

Key findings and limitations: Combined imaging had sensitivity, specificity, positive predictive value (PPV), and negative predictive value of, respectively, 92% (95% confidence interval [CI] 87, 95), 64% (95% CI 48, 77), 80% (95% CI 68, 92), and 82% (95% CI 68, 97) at patient-level, and 82% (95% CI 77, 94), 85% (95% CI 77, 94), 79% (95% CI 52, 97), and 81% (95% CI 74, 98) at lesion-level analyses. Head-to-head comparisons showed significantly higher specificity and PPV than mpMRI at patient- and lesion-level analyses. On the DCA, combined imaging outperforms upfront biopsy at risk thresholds of 8% onwards. Synchronous reading of PSMA-PET/computed tomography (CT) with mpMRI was significantly more sensitive but less specific than PSMA-PET/MRI.

Conclusions and clinical implications: Combined imaging improves the diagnostic accuracy of csPCa and may help better select patients for a prostate biopsy.