Head-to-Head Comparison of the Diagnostic Accuracy of Prostate-Specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate to High Risk Prostate Cancer

The excellent diagnostic capabilities of prostate specific membrane antigen-positron emission tomography (PSMA-PET) are well established. Whether it should be offered to all patients with intermediate-high risk prostate cancer (PCa) for primary staging, and replace conventional imaging modalities (CIM) as the new standard-of-care, is however a question of whether it significantly outperforms CIM and thereby potentially improveing patient outcomes.

In this systematic review and meta-analysis (SRMA), 32 studies were included. Direct head-to-head comparisons of PSMA-PET and CIM were performed analysing the data of 2431 patients that underwent both PSMA-PET and CIM, with results confirmed against either histopathology or composite reference standards (CRS). Our pairwise analyses found PSMA-PET to have superior diagnostic capabilities as compared to multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) with or without single photon emission computed tomography (SPECT) across local, nodal and bone metastasis staging of PCa.

Two results are especially notable: Firstly, PSMA-PET/MRI was found to be more sensitive than mpMRI for extra-prostatic extension and seminal vesicle invasion while no significant differences existed between PSMA-PET/CT and mpMRI sensitivities. This suggests that the spatial resolution mpMRI cannot be replaced, but can be enhanced by the small lesion avidity accorded by PSMA-PET.

Secondly, our direct comparison of PSMA-PET and mpMRI for nodal staging of PCa which is the largest yet, including 13 retrospective and 6 prospective studies with 1190 patients, found PSMA-PET to be significantly more specific than mpMRI by 15.0 percentage points (95%CI 6.7 to 23.2, p<0.001). This crucially confirms PSMA-PET to have superior specificity as previous reviews had observed only limited differences between PSMA-PET and mpMRI.

The key strength of this SRMA lies in the robust methodology. In accordance to Cochrane guidelines on the gold standard methodology for diagnostic test accuracy (DTA), a direct comparison was performed, including only studies where the same patient cohorts have undergone both PSMA-PET and CIM concurrently. In contrast to previous indirect comparisons where studies on CIM alone are compared to those on PSMA-PET alone, direct comparisons eliminate confounding from patient selection that is unspecified or in the context of inconclusive CIM findings. Our heterogeneity analyses further found time interval between imaging modalities to be a significant source of heterogeneity which affirms the need for evaluation of different imaging modalities to be done within the same patient cohort, given that disease status can change with time.

Written by: Kenneth Chen, MBBS, DFD, MCI, FRCS, FAMS¹& Kit Mun Chow²

Singapore General Hospital, Duke-NUS Graduate Medical School, Yong Loo Lin School of Medicine, EXCO, Singapore Urological Association
YLL School of Medicine, National University of Singapore, Singapore

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