Volume 67, Issue 4, Pages 787-794 (April 2015) Magnetic Resonance Imaging–Transectal Ultrasound Image-fusion Biopsies Accurately Characterize the Index Tumor: Correlation with Step-sectioned Radical Prostatectomy Specimens in 135 Patients  Eduard Baco, Osamu Ukimura, Erik Rud, Ljiljana Vlatkovic, Aud Svindland, Manju Aron, Suzanne Palmer, Toru Matsugasumi, Arnaud Marien, Jean-Christophe Bernhard, John C. Rewcastle, Heidi B. Eggesbø, Inderbir S. Gill  European Urology  Volume 67, Issue 4, Pages 787-794 (April 2015) DOI: 10.1016/j.eururo.2014.08.077 Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 1 Schematic flow chart of the number of men who were suitable for study inclusion. RP=radical prostatectomy; HIFU=high-intensity focused ultrasound; EBRT=external-beam radiation therapy; HT=hormonal treatment; AS=active surveillance; PCa=prostate cancer. European Urology 2015 67, 787-794DOI: (10.1016/j.eururo.2014.08.077) Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 2 Results for a 57-yr-old man with prostate-specific antigen of 5.4 ng/ml and a normal digital rectal examination who previously underwent 12 random biopsies that were negative. (A) DWI MRI using b2000 suggests a low suspicious lesion localized in the left anterior apex (green arrows). (B) Nothing is visualized on T2-weighted images. (C,D) Magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fused targeted biopsies (red bars) revealed cancer of Gleason score 6 (3+3) with cancer core lengths of 5 and 2mm (36% and 13% per core). (E) Histological analyses of whole-gland step-sectioned prostate specimens revealed pT2c prostate cancer with Gleason score 6 (3+3). The index tumor (red arrow) was measured as 12mm×9mm×9mm (volume 0.49ml). The secondary tumor in the right anterior apex (white arrow) was measured as 6mm×2mm×3mm (0.18ml) and classified as Gleason 6 (3+3) cancer and was not visualized on MRI. The spatial distribution of targeted biopsies (red bars) and the targeted region (yellow circle) in (C) axial and (D) sagittal TRUS images corresponds with the 3D index tumor location in segment 11a (F). European Urology 2015 67, 787-794DOI: (10.1016/j.eururo.2014.08.077) Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 3 Results for a 64-yr-old man with prostate-specific antigen of 4.1 ng/ml, a normal digital rectal examination, prostate volume of 25ml, and a prior single biopsy positive for prostate cancer (PCa) with Gleason score 6 (3+3) and core length 1mm (5% core) in the right mid-lateral prostate. The patient was on ongoing active surveillance. (A) Follow-up magnetic resonance imaging (MRI) suggests a suspicious 25-mm ventral lesion visible on T2-weighted images. (B) This lesion has significantly reduced diffusion capacity, indicated by the red/white color on the apparent diffusion coefficient map. (C,D) Grayscale MR-transrectal ultrasound (TRUS) fused targeted biopsies (red bars) were directed toward the area of lowest diffusion (yellow circle) and revealed two cores of Gleason 6 (3+3) PCa of 16 and 5mm (71% and 69% per core, respectively). (E) Histological analyses of whole-gland sections revealed pT3a PCa with Gleason score 6 (3+3). The tumor was measured as 14mm×9mm×14mm (volume 0.9ml). The spatial distribution of targeted biopsies (red bars) and the targeted region (yellow circle) in (C) axial and (D) sagittal TRUS images corresponds with the 3D index tumor location in segment 13a (F). European Urology 2015 67, 787-794DOI: (10.1016/j.eururo.2014.08.077) Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 4 (A) Scatter plot showing correlation between magnetic resonance imaging (MRI)-estimated tumor volume (MTV) and histological tumor volume (HTV) in 128 patients. The red line indicates the regression line. Data are presented on a logarithmic scale because of asymmetry. (B) Bland-Altman plot showing the limitation of agreement between MTV and HTV. The orange line represents the linear regression line. The percentage difference between MTV and HTV is plotted against the average tumor volume (calculated from both MTV and HTV). All values above the zero line represent overestimation of MTV, and all values below the zero line represent underestimation of MTV. The average underestimation of HTV by MRI is 5.9% (95% CI [−6.4%, +18.2%]), and is constant throughout the measurement range. The limit of agreement ranges from −147% to +135%, which indicates clinically significant inaccuracy for MTV. The median (range) is 1.0ml (0.1–20.0ml) for MTV and 1.25ml (0.1–27.1ml) for HTV. Graphic generated using GraphPad Prism 6.0a (GraphPad Software, Inc., San Diego, CA, USA). (C) Scatter plot demonstrating correlation between the maximum cancer core length on targeted biopsy and HTV in 128 patients. The red line indicates the regression line. European Urology 2015 67, 787-794DOI: (10.1016/j.eururo.2014.08.077) Copyright © 2014 European Association of Urology Terms and Conditions