Clinical data were part of a prospective on-going observational clinical study: “Diagnostic accuracy of target mpMRI/US fusion biopsy in patients with suspected prostate cancer after initial negative biopsy” approved by our Institutional Review Board (IRB) and Ethical Committee. Written informed consent was obtained from all individual participants included in the study. Patients with persistently elevated PSA, with or without ASAP and/or HG-PIN and negative DRE, after at least one negative biopsy (at least 12 cores for each biopsy course) and a negative mpMRI (PI-RADS v.2 < 3) or contraindications to MRI were included.
11C–choline PET/CT imaging technique
The radiopharmaceutical 11C–choline was synthesized using a General Electric TracerLab FXc module as previously described by (Pascali et al., 2000), and administered in a total amount of 250–400 MBq. Ten minutes after tracer administration, body axial images from the mid-thigh to the skull base were obtained with an integrated PET/CT Discovery 690, GE Healthcare. Low-dose CT images were acquired using an automated dose modulation (maximal 140 mA, 140 kVp), 64 × 3,75 mm collimation, 3.75 mm slice thickness, 0.5 s rotation time, and pitch 0,984:1. Emission images were obtained with a 3.0 min acquisition for bed position in the pelvis and 1.5 min for the remaining total body acquisition (axial FOV 1150 mm, matrix size 256 × 256) and subsequently reconstructed using an iterative algorithm (VUE Point FX, 3 iterations, 24 subsets). Reconstructed images of the pelvis were obtained separately and displayed for reading as sagittal, axial and coronal views on OsiriX MD Imaging workstation (Fig. 1). A correlation between PET/CT prostate volume and ultrasound prostate volume using the BK Medical, Analogic Ultrasound Group, Pro Focus, Transducer 8818, 6/9 MHz, was also performed. The ellipsoid formula was used (PV = p/6 x [length (cm)] x [width (cm)] x [high (cm)]). PET was considered positive when focal uptake of 11C–choline was superior to the background activity.
Software PET/TRUS fusion-guided target biopsy technique
For PET/TRUS fusion-guided prostate biopsy, the Bio-Jet™ fusion system and software (D&K Technologies, Barum, Germany) were used. Shoji et al. described the technical data and usage of this system and Tewes et al. showed that Bio-Jet™ fusion system and software facilitate diagnosis of PCa with high sensitivity and specificity (Shoji et al., 2015; Tewes et al., 2015).
PET/CT DICOM images were uploaded and prostate profile and ROIs were manually contoured. During the biopsy session the prostate and ROIs PET/CT derived image contours were fused in real time with the TRUS image stack and ROIs were targeted (Fig. 1). Biopsies, transrectal or transperineal according to the site of lesions, were performed with patients in dorsal lithotomy position, under antibiotic prophylaxis and local anaesthesia, using a 3D triplane transrectal ultrasound system (BK Medical, Analogic Ultrasound Group, Pro Focus, Transducer 8818, 6/9 MHz). Biopsy cores were numbered according to ROI number and topography. Specimens were processed and evaluated by a genitourinary pathologist. Foci of tumour were quantified (percentage and mean length in millimetres) and graded according to the 2005 consensus conference on Gleason grading of prostatic carcinoma of the International Society of Urological Pathology (Epstein et al., 2005). A second, independent, pathologist (PC), expert in urological pathologies, reviewed all the samples.
The primary endpoint was to assess the accuracy of 11C–choline PET/CT to determine the presence and the topographical distribution of the tumour foci.
Data were complemented by descriptive statistical analysis. For continuous data, differences between groups were compared by the T-test or the Wilcoxon-test, when appropriate. Pearson’s correlation coefficient was used for compare US and CT generated prostate volume. Statistical significance was set at p ≤ 0.05 for each evaluation. Study analyses were performed on MedCalc statistical software (MedCalc Software bvba © 1993–2014, http://medcalc.org/