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Diagnostic Performance of 68 Ga Prostate-specific Membrane Antigen PET/MRI Compared with Multiparametric MRI for Detecting Clinically Significant Prostate Cancer

  • David Margel,
  • Hanna Bernstine,
  • David Groshar,
  • Yaara Ber,
  • Orian Nezrit,
  • Niv Segal,
  • Maxim Yakimov,
  • Jack Baniel,
  • Liran Domachevsky

Publication: Radiology, August 2021

Gallium 68 prostate-specific membrane antigen PET/MRI improved specificity for clinically significant prostate cancer, with a similar sensitivity to multiparametric MRI.


Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/MRI may improve detection of clinically significant prostate cancer (CSPC).


To compare the sensitivity and specificity of 68Ga-PSMA PET/MRI with multiparametric MRI for detecting CSPC.

Materials and Methods

Men with prostate specific antigen levels of 2.5–20 ng/mL prospectively underwent 68Ga-PSMA PET/MRI, including multiparametric MRI sequences, between June 2019 and March 2020. Imaging was evaluated independently by two radiologists by using the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. Sensitivity and specificity for CSPC (International Society of Urological Pathology grade group ≥ 2) were compared for 68Ga-PSMA PET/MRI and multiparametric MRI by using the McNemar test. Decision curve analysis compared the net benefit of each imaging strategy.


Ninety-nine men (median age, 67 years; interquartile range, 62–71 years) were included; 79% (78 of 99) underwent biopsy. CSPC was detected in 32% (25 of 78). For CSPC, specificity was higher for 68Ga-PSMA PET/MRI than multiparametric MRI (76% [95% CI: 62, 86] vs 49% [95% CI: 35, 63], respectively; P < .001). Sensitivity was similar (88% [95% CI: 69, 98] vs 92% [95% CI: 74, 99], respectively; P > .99). For PI-RADS 3 lesions, specificity was also higher for 68Ga-PSMA PET/MRI than for multiparametric MRI: 86% (95% CI: 73, 95) versus 59% (95% CI: 43, 74), respectively (P = .002). Decision curve analysis showed that biopsies targeted to PSMA uptake increased the net benefit of multiparametric MRI only among PI-RADS 3 lesions. The net benefit of targeted biopsy for a PI-RADS 3 lesion with PSMA uptake was higher across all threshold probabilities over 8%. The net benefit of targeted biopsy was similar for PI-RADS 4 and 5 lesions, regardless of PSMA uptake.


Gallium 68 prostate-specific membrane antigen PET/MRI improved specificity for clinically significant prostate cancer compared with multiparametric MRI, particularly in Prostate Imaging Reporting and Data System grade 3 lesions.

Commentary by Prof. Igor Tsaur

The advent of multiparametric (mp)MRI for the prostate has recently revolutionised the diagnostic workflow in the field of prostate-specific antigen (PSA) testing. This has even resulted in guidelines’ recommendations of its standard use before biopsy. Indeed, this imaging modality has significantly improved the accuracy of detecting clinically significant prostate cancer (CSPCa). However, its impressive sensitivity of roughly 90% to diagnose CSPCa contrasts with its limited specificity of ca. 40% which is associated with a high false-positive rate and consequently many unnecessary biopsies. In order to overcome this drawback, further imaging options are currently investigated, including inter alia, 68Ga-prostate-specific membrane antigen (PSMA) PET/MRI.

Margel and collaborators assessed the value of this modality in a prospective within-subject trial in men with PSA levels of 2.5-20 ng/ml without previous biopsy as well as those under active surveillance to improve the performance of mpMRI to detect CSPCa. 78 participants received PET/MRI with an mpMRI component and underwent either systematic (no PI-RADS finding ≥ 3 or SUVmax≥2.5 g/ml) or targeted + systematic biopsies (in cases of an abnormal mpMRI and/or PET/MRI). The findings of the prostate biopsy thus served as a reference standard test.

The authors demonstrated that PET/MRI has a superior specificity to detect CSPCa as compared to mpMRI alone (76% vs. 49%), whereas the sensitivity was similar in both imaging modalities. Importantly, stratification by PI-RADS score demonstrated that only males with PI-RADS 3 lesions benefitted from a PET/MRI utilisation, while in this subgroup only 8% of the participants without PSMA uptake were diagnosed with CSPCa as opposed to 40% of those with PSMA uptake. This was supported by a decision-curve analysis yielding an increased net benefit of adding PSMA uptake to mpMRI for patients with PI-RADS 3 lesions only. In addition, the specificity of using PI-RADS 3 only at mpMRI for CSPCa detection was 59% as compared to 86% when combining PI-RADS 3 with a positive PSMA uptake. Using PI-RADS 3 as a threshold for prostate biopsy together with a positive PSMA uptake would result in a higher number of avoided biopsies in comparison with utilising PI-RADS 3 alone (PET/MRI vs. mpMRI: 55% vs. 36%). Besides, PET/MRI did not aid in detecting more CSPCa in men with a negative mpMRI. Subgroup analyses excluding 24 men under active surveillance yielded similar results.

This analysis is one of the pioneer prospective data shedding light on the performance of PET/MRI compared to mpMRI in CSPCa diagnosis. One of the main limitations of the study is that in some CSPCa cases the reference standard test is prostate biopsy and not radical prostatectomy. Furthermore, the analysis had a limited generalisability to other centres due to the lack of trained staff and costly equipment. An improved specificity of PET/MRI observed mostly in males with a PI-RADS 3 lesion, along with a similar detection rate as mpMRI’s, will not immediately change the current practice, even if it will spare unnecessary biopsies.

A routine use of 68Ga-PSMA PET/MRI in the diagnostic pre-biopsy setting is not affordable for healthcare systems and stakeholders and not feasible for radiology centres taking into account the number of potential candidates for this type of imaging. Since mpMRI is being offered in many outpatient radiology units, it will currently remain the backbone of the diagnostic schedule in men with elevated PSA or suspicious digital-rectal examination. Further prospective research is warranted to classify the value of additional imaging to mpMRI to detect CSPCa. Of note, the recent PRIMARY trial demonstrated an improved sensitivity but reduced specificity in combining 68Ga-PSMA PET/CT with mpMRI as compared to mpMRI alone. PSA density might help select patients at higher risk for CSPCa, thus paving the way for additional imaging and/or biopsy.