Diagnostic performance of 68Ga-PSMA-11 PET/MRI-guided biopsy in patients with suspected prostate cancer: a prospective single-center study

Abstract

Purpose: Ultrasound-guided biopsy (US biopsy) with 10-12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)-guided biopsy is recommended, despite a low specificity for lesions with score 3-5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with 68Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy.

Methods: Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard.

Results: SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy.

Conclusion: PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy.

Trial registration: This trial was retrospectively registered under the name "Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in Men with Elevated PSA" (NCT03187990) on 06/15/2017 ( https://ichgcp.net/clinical-trials-registry/NCT03187990 ).

Keywords: Imaging-guided biopsy; PET/MR; PSMA-PET accuracy; Prostate biopsy; Targeted biopsy; Template biopsy.

Conflict of interest statement

I. A. B. has received research grants and speaker honorarium from GE Healthcare, research grants from Swiss Life, and speaker honorarium from Bayer Health Care and Astellas Pharma AG. M. M. received speaker fees from GE Healthcare. The Department of Nuclear Medicine holds an institutional Research Contract with GE Healthcare. N. J. R. has provided consultancy services (advisory board member) to F. Hoffmann- La Roche AG. A. S. B. received research grants from the Prof. Dr. Max Cloëtta Foundation, medAlumni UZH, and the Swiss Society of Radiology. All other authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1

Patient selection and inclusion in the study

Fig. 2

Distribution of patients with clinically significant prostate cancer (sigPCa), clinically insignificant prostate cancer (insigPCa), and no evidence of disease on biopsy in correlation to PIRADS classification on multiparametric resonance magnetic imaging (a) and 68Ga-PSMA-11 PET/MRI result (b)

Fig. 3

Distribution of patients with clinically significant prostate cancer (sigPCa), clinically insignificant prostate cancer (insigPCa), and no evidence of disease on biopsy according to 68Ga-PSMA-11 PET/MRI results (a) and according to 68Ga-PSMA-11 PET/MRI results in correlation to PIRADS classification on multiparametric resonance magnetic imaging (b). The single false-negative case and the three false-positive cases shown in part “a” are shown in part “b” under PIRADS 5/negative PSMA-PET/MRI and PIRADS 3/positive PSMA-PET/MRI (two cases) and 4/positive PSMA-PET/MRI (one case), respectively

Fig. 4

All three patients with a false-positive PSMA-PET/MRI. From left to right, prostate MRI sequences T2-weighted and diffusion-weighted images (b value 1000), fused PET/MRI, representative pathology map with biopsy results, and radical prostatectomy (RPE) specimen with tumor outlined on hematoxylin and eosin staining (H&E) and PSMA-IHC (overview and magnification). Bars represent 2.5 mm in the H&E and PSMA-IHC images and 100 μm in the PSMA-IHC magnified images. Blue dots in the pathology map correspond to location of needles with clinically insignificant cancer diagnosed. a 67-year-old patient, with a PSA of 7.3 ng/ml and a PIRADS 4 lesion on mpMRI. PSMA-PET/MRI shows one targeted lesion (arrow) in the posterior right peripheral zone, where biopsy found ISUP grade group 2 tumor with up to 1.5-mm length. RPE specimen shows a PSMA-positive ISUP grade group 3 tumor in the PSMA uptake area. b 65-year-old patient, with a PSA of 7.18 ng/ml and a PIRADS 3 lesion on mpMRI. PSMA-PET/MRI shows one targeted lesion (arrow) in the anterior zone, where biopsy found ISUP grade group 2 tumor with up to 1.5-mm length. RPE specimen shows a PSMA-positive ISUP grade group 2 tumor in the PSMA uptake area. c 65-year-old patient, with a PSA of 48.5 ng/ml and a PIRADS 3 lesion on mpMRI. PSMA-PET/MRI shows two targeted lesions (arrows) in the transition zone corresponding on biopsy to ISUP grade group 2 tumor up to 5 mm length, and in the posterior left peripheral zone, where biopsy was negative. RPE specimen shows a PSMA-positive ISUP grade group 3 tumor in the PSMA uptake area of the posterior left peripheral zone

Fig. 5

The only patient with a false-negative PSMA-PET/MRI in our cohort. A 62-year-old patient with a PSA of 11.38 ng/ml. Top images from left to right are prostate MRI sequences T2-weighted and diffusion-weighted images and fused PET/MRI showing a PIRADS 5 lesion in the anterior transition zone (arrows) with no PSMA uptake. Bottom left image shows the representative pathology map with biopsy results including two cores with clinically significant cancer in the lesion area (red dots, ISUP grade group 2 tumor with length up to 10 mm) and many cores with clinically insignificant cancer (blue dots). Remaining bottom images show one of the biopsy cores with clinically significant cancer. The tumor is outlined in hematoxylin and eosin staining (H&E) and PSMA-IHC (overview and magnification), showing a virtually PSMA-negative tumor. Bars represent 2.5 mm in the H&E and PSMA-IHC images and 100 μm in the PSMA-IHC magnified image