Head-to-Head Comparison of 68Ga-PSMA-11 PET/CT and mpMRI with a Histopathology Gold Standard in the Detection, Intraprostatic Localization, and Determination of Local Extension of Primary Prostate Cancer: Results from a Prospective Single-Center Imaging Trial

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to mpMRI in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performances of PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI using 3 independent blinded readers for each modality and with histopathology as gold standard in the detection, intra-prostatic localization and local extension of primary prostate cancer. Methods: Patients with intermediate- or high-risk prostate cancer who underwent a PSMA PET/CT as part of the prospective trial (NCT03368547) and a mpMRI prior to radical prostatectomy were included. Each imaging modality was interpreted by 3 blinded independent readers unaware of the other modality result. Central majority rule was applied (2:1). Whole-mount pathology was used as the gold-standard. Imaging scans and whole-mount pathology were interpreted using the same standardized approach on a segment- and lesion-level. A “neighboring” approach was used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Accuracy in determining the location, extraprostatic extension (EPE) and seminal vesicle invasion (SVI) of prostate cancer foci was assessed using receiver operating characteristic (ROC) analysis. Inter-reader agreement was calculated using inter-class coefficient (ICC) analysis. Results: The final analysis included 74 patients (14/74 ( 19%) intermediate risk and 60/74 (81%) high risk). Cancer detection rate (lesion-based analysis) was 85%, 83% and 87 for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone for delineation of tumor localization (segment-based analysis) was statistically significant (p<0.001), but not between PSMA PET/CT and mpMRI (P = 0.093). mpMRI outperformed PSMA PET/CT in detecting EPE (P = 0.002) and SVI (P = 0.001). On a segment-level analysis, ICC analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range: 0.53 to 0.64). In the evaluation of T-staging, poor reliability was found among PSMA PET/CT readers and poor to moderate reliability was found for mpMRI readers. Conclusion: PSMA PET/CT and mpMRI have similar accuracy in the detection and intra-prostatic localization of prostate cancer foci. mpMRI performs better in identifying EPE and SVI. For the T-staging evaluation of intermediate to high-risk prostate cancer patients, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the co-registration/fusion of PSMA PET/CT and mpMRI (PSMA PET+mpMRI) should be used as it improves tumor extent delineation.