Hot needles can confirm accurate lesion sampling intraoperatively using [18F]PSMA-1007 PET/CT-guided biopsy in patients with suspected prostate cancer

Abstract

Purpose: Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling.

Methods: In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC).

Results: In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUVmax 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm).

Conclusions: [18F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy.

Trial registration number: NCT03187990, 15/06/2017.

Keywords: Biopsy guidance; PSMA PET; Primary staging; Targeted biopsy; Template biopsy.

Conflict of interest statement

IAB 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. NR has provided consultancy services (advisory board member) to F. Hoffmann-La Roche AG. All other authors declare no competing interests with this work. Funding sources had no involvement in study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.

© 2021. The Author(s).

Figures

Fig. 1

Illustration of the study workflow with time line for [18F]PSMA-1007 PET/CT-guided biopsy and uptake quantification

Fig. 2

A Bar graph for the number of needles for each biopsy ISUP grade. B Box plot illustrations for cpm distribution (logarithmic scaling) according to the absence (0) or presence (1) of PCa. C Box plot illustrations for cpm distribution in needles according to biopsy ISUP grade

Fig. 3

A Gamma spectrometer assessment of the background. B True negative: patient 1, needle 11; low uptake on [18F]PSMA-1007 PET/CT (SUVmax 5.8) and low counts per minute (cpm = 30) were also negative for PCa on histopathology. C True positive: patient 1, needle 1; intense uptake on PSMA PET/CT (SUVmax 17.0) leads to a target biopsy with high counts per minute (cpm = 568), with confirmed PSMA-positive ISUP GG 3 PCa on histopathology. D False positive: patient 4, needle 8; focal uptake on PSMA PET/CT (SUVmax 8.7), corresponding to high counts per minute (cpm = 167) without PCa but inflammation and PSMA-positive benign glands on histopathology. E False negative: patient 2, needle 22; no increased PSMA uptake on PET/CT (SUVmax 5.65), corresponding to low counts per minute (cpm = 35) but confirmed ISUP GG 3 PCa on histopathology without PSMA expression on IHC

Fig. 4

Fifty-year-old patient 5 with a PSA of 66.5 ng/ml. A mpMRI detected a suspicious lesion with hypointense signal on T2-weighted imaging on the right peripheral zone (yellow arrow). B–C PET/CT confirmed high [18F]PSMA-1007 tracer uptake (SUVmax 104.5) in the same lesion. D The fused PSMA PET/CT DICOM file prepared by the nuclear medicine physician who outlined the suspicious lesion on PET for biopsy targeting that was loaded to the BiopSee system. E Corresponding histopathology prostate map with biopsy targeted lesions delineated in blue and green according to the DICOM file. Each number in E represents a biopsy sample; the position of needles with clinically significant cancer is marked by black dots. The red circle highlights the first needle detecting sigPCa, with the corresponding high cpm (2079) from the spectrometer (F)

Fig. 5

Summary images of patients 1–4. In the first column, the regular fused [18F]PSMA-1007 PET/CT images are given, using a PET window of 0–10. The second column represents the selected PET/CT DICOM set to be loaded to the BiopSee system. In the third column, the histopathology prostate map with targeted lesions is given. Biopsy needles with clinically significant cancer are marked by black dots. In the last column, the corresponding spectrometer results from the red circled biopsy in column three are given. A Patient 1 with tracer high tracer uptake on PET/CT (SUVmax 17.0). Underlined in red are the 5 not measured biopsy cores; the red circle highlights the first needle detecting sigPCa, with the corresponding high cpm (568) in the spectrometer. B Patient 2. PET/CT with moderate tracer uptake (SUVmax 8.26). The red circle highlights the first needle detecting sigPCa, with the corresponding high cpm (156) from the spectrometer. C Patient 3. PET/CT confirmed high tracer uptake (SUVmax 17.15). The red circle highlights the first needle detecting sigPCa, with the corresponding high cpm (224) from the spectrometer. D Patient 4 with inflammatory changes only: PET/CT showed moderate tracer uptake (SUVmax 8.71) in the transition zone, anterior to the mpMRI suspicious lesion. The red circle highlights the 8th needle with corresponding spectrometer results, showing some increased cpm (167) but no PCa