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

Abstract

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to multiparametric MRI (mpMRI) in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performance of 68Ga-PSMA-11 PET/CT (PSMA PET/CT), mpMRI, and PSMA PET/CT + mpMRI using 3 independent masked readers for each modality and with histopathology as the gold standard in the detection, intraprostatic localization, and determination of local extension of primary prostate cancer. Methods: Patients with intermediate- or high-risk prostate cancer who underwent PSMA PET/CT as part of a prospective trial (NCT03368547) and mpMRI before radical prostatectomy were included. Each imaging modality was interpreted by 3 independent readers who were unaware of the other modality result. A central majority rule was applied (2:1). Pathologic examination of whole-mount slices was used as the gold standard. Imaging scans and whole-mount slices were interpreted using the same standardized approach on a segment level and a 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 curve analysis. Interreader agreement was calculated using intraclass correlation coefficient analysis. Results: The final analysis included 74 patients (14 [19%] with intermediate risk and 60 [81%] with high risk). The cancer detection rate (lesion-based analysis) was 85%, 83%, and 87% for PSMA PET/CT, mpMRI, and PSMA PET/CT + mpMRI, respectively. The change in AUC was statistically significant between PSMA PET/CT + mpMRI and the 2 imaging modalities alone for delineation of tumor localization (segment-based analysis) (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). In the segment-level analysis, intraclass correlation coefficient analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range, 0.53-0.64). 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 intraprostatic 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, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the coregistration or fusion of PSMA PET/CT and mpMRI (PSMA PET/CT + mpMRI) should be used as it improves tumor extent delineation.

Keywords: PSMA PET/CT; T staging; mpMRI; prostate cancer; staging.

© 2022 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

Graphical abstract

FIGURE 1.

Prostate segmentation template and imaging–pathology correspondence for lesion-based analysis. Twelve-segment subdivision of prostate gland was used for standardized reads (left). Examples are shown of imaging–pathology correlation for lesion-level analysis using neighboring approach. Arrows indicate adjacent or neighboring segments. (Example 1) One lesion described on pathology as involving segment MRP, and 1 lesion identified by imaging as involving segment BRP. Imaging–pathology correlation: true-positive finding because BRP and MRP are neighboring segments. (Example 2) One large lesion described on pathology as involving segments ARP, MRP, BRP, ALP, and MLP, and 2 lesions identified by imaging (lesion 1, involving ARP and MRP [yellow segments], and lesion 2, involving ALP and MLP [green segments]). Imaging–pathology correlation: true-positive because one single lesion was described on pathology and correctly identified as cancer by imaging, even though described differently. (Example 3) Two lesions described on pathology (lesion 1, involving ALP, MLP, BLP, ALA, MLA, ARP, and MRP [pink lesion], and lesion 2, involving MRA [red lesion]), and 1 large lesion described by imaging as involving segments ARP, MRP, MLP, BRP, and MRA. Imaging–pathology correlation: 2 true-positive findings because 2 lesions were described on pathology, and both were described as cancer on imaging.

FIGURE 2.

Study flowchart.

FIGURE 3.

Prostate cancer localization (segment-based analysis) and T3 staging. (A and B) Receiver-operating-characteristic curves for segment-level analysis obtained for PSMA PET/CT and mpMRI majority reads (A) and using 1–5 PSMA and PI-RADS score for each individual reader (B). Graphs show change in AUC between PSMA PET/CT and mpMRI (95% CI, −0.01 to 0.07; P = 0.093), between PSMA PET/CT + mpMRI and PSMA PET/CT (95% CI, 0.05–0.1; P < 0.001), and between PSMA PET/CT + mpMRI and mpMRI (95% CI, 0.03–0.06; P < 0.001). (C) Receiver-operating-characteristic curves for PSMA PET/CT and mpMRI majority reads in evaluation of T staging. Graphs show change in AUC for bilateral disease (0.65 vs. 0.54, DeLong test, P = 0.138), change in AUC for EPE (0.79 vs. 0.59; 95% CI, 0.08–0.32; P = 0.002), and change in AUC for SVI (0.84 vs. 0.63; 95% CI, 0.09–0.33; P = 0.001).

FIGURE 4.

Two case examples from our cohort. (A–D) A 68-y-old patient (patient 4) with biopsy-proven prostate cancer with Gleason score of 3 + 4 = 7 and PSA of 8.6 ng/mL at time of PSMA PET/CT. Transverse PSMA PET/CT image (A), T2-weighted MR image (B), and high b-value diffusion-weighted MR image (C) show right-posterior mid-gland lesion (arrows). Whole-mount slice (D) shows 1 lesion, with Gleason score of 4 + 3 = 7, in same segment (contoured in green), and lesion showed EPE. There was good imaging–pathology correspondence (true-positive finding for both imaging modalities). All 6 readers correctly identified and described lesion. (E–H) A 69-y-old patient (patient 5) with biopsy-proven prostate cancer with Gleason score of 3 + 4 = 7 and PSA of 11.4 ng/mL at time of PSMA PET/CT. Transverse PSMA PET/CT image (E) shows 2 foci of increased PSMA uptake in right-posterior apex (yellow arrow) and left-posterior apex (green arrow). PSMA reader 1 correctly described 1 lesion involving left- and right-posterior apex; PSMA readers 2 and 3 described left and right foci as 2 separate lesions. T2-weighted MR image (F) shows hypointense lesion, and diffusion-weighted image (G) shows diffusion restriction in right- and left-posterior apex (arrow). All MRI readers correctly described only 1 lesion. Whole-mount slice (H) shows 1 lesion encompassing both right- and left-posterior apex (contoured in green) with EPE. This is an example of same lesion being described differently by PSMA PET/CT and whole-mount slice (true-positive finding for both imaging modalities).