Jurgen J. Fütterer

Magnetic Resonance Imaging Guided Prostate Biopsy in Men With Repeat Negative Biopsies and Increased Prostate Specific Antigen

PURPOSE Undetected cancer in repeat transrectal ultrasound guided prostate biopsies in patients with increased prostate specific antigen greater than 4 ng/ml is a considerable concern. We investigated the tumor detection rate of tumor suspicious regions on multimodal 3 Tesla magnetic resonance imaging and subsequent magnetic resonance imaging guided biopsy in 68 men with repeat negative transrectal ultrasound guided prostate biopsies. We compared results to those in a matched transrectal ultrasound guided prostate biopsy population. Also, we determined the clinical significance of detected tumors. MATERIALS AND METHODS A total of 71 consecutive patients with prostate specific antigen greater than 4 ng/ml and 2 or greater negative transrectal ultrasound guided prostate biopsy sessions underwent multimodal 3 Tesla magnetic resonance imaging. In 68 patients this was followed by magnetic resonance imaging guided biopsy directed toward tumor suspicious regions. A matched multisession transrectal ultrasound guided prostate biopsy population from our institutional database was used for comparison. The clinical significance of detected tumors was established using accepted criteria, including prostate specific antigen, Gleason grade, stage and tumor volume. RESULTS The tumor detection rate of multimodal 3 Tesla magnetic resonance imaging guided biopsy was 59% (40 of 68 cases) using a median of 4 cores. The tumor detection rate was significantly higher than that of transrectal ultrasound guided prostate biopsy in all patient subgroups (p <0.01) except in those with prostate specific antigen greater than 20 ng/ml, prostate volume greater than 65 cc and prostate specific antigen density greater than 0.5 ng/ml/cc, in which similar rates were achieved. Of the 40 patients with identified tumors 37 (93%) were considered highly likely to harbor clinically significant disease. CONCLUSIONS Multimodal magnetic resonance imaging is an effective technique to localize prostate cancer. Magnetic resonance imaging guided biopsy of tumor suspicious regions is an accurate method to detect clinically significant prostate cancer in men with repeat negative biopsies and increased prostate specific antigen.

Standards of Reporting for MRI-targeted Biopsy Studies (START) of the Prostate: Recommendations from an International Working Group.

BACKGROUND A systematic literature review of magnetic resonance imaging (MRI)-targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy (STARD) recommendations for the full and transparent reporting of diagnostic studies. OBJECTIVE To define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START). DESIGN, SETTING, AND PARTICIPANTS Each member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Measures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist). RESULTS AND LIMITATIONS The strongest recommendations were to report histologic results of standard and targeted cores separately using Gleason score and maximum cancer core length. A table comparing detection rates of clinically significant and clinically insignificant disease by targeted and standard approaches should also be used. It was recommended to report the recruitment criteria for MRI-targeted biopsy, prior biopsy status of the population, a brief description of the MRI sequences, MRI reporting method, radiologist experience, and image registration technique. There was uncertainty about which histologic criteria constitute clinically significant cancer when the prostate is sampled using MRI-targeted biopsy, and it was agreed that a new definition of clinical significance in this setting needed to be derived in future studies. CONCLUSIONS Use of the START checklist would improve the quality of reporting in MRI-targeted biopsy studies and facilitate a comparison between standard and MRI-targeted approaches.

Prospective Assessment of Prostate Cancer Aggressiveness Using 3-T Diffusion-Weighted Magnetic Resonance Imaging–Guided Biopsies Versus a Systematic 10-Core Transrectal Ultrasound Prostate Biopsy Cohort

BACKGROUND Accurate pretreatment assessment of prostate cancer (PCa) aggressiveness is important in decision making. Gleason grade is a critical predictor of the aggressiveness of PCa. Transrectal ultrasound-guided biopsies (TRUSBxs) show substantial undergrading of Gleason grades found after radical prostatectomy (RP). Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be a biomarker of tumour aggressiveness. OBJECTIVE To improve pretreatment assessment of PCa aggressiveness, this study prospectively evaluated MRI-guided prostate biopsies (MR-GBs) of abnormalities determined on diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) maps. The results were compared with a 10-core TRUSBx cohort. RP findings served as the gold standard. DESIGN, SETTING, AND PARTICIPANTS A 10-core TRUSBx (n=64) or MR-GB (n=34) was used for PCa diagnosis before RP in 98 patients. MEASUREMENTS Using multiparametric 3-T MRI: T2-weighted, dynamic contrast-enhanced imaging, and DWI were performed to identify tumour-suspicious regions in patients with a negative TRUSBx. The regions with the highest restriction on ADC maps within the suspicions regions were used to direct MR-GB. A 10-core TRUSBx was used in a matched cohort. Following RP, the highest Gleason grades (HGGs) in biopsies and RP specimens were identified. Biopsy and RP Gleason grade results were evaluated using chi-square analysis. RESULTS AND LIMITATIONS No significant differences on RP were observed for proportions of patients having a HGG of 3 (35% vs 28%; p=0.50), 4 (32% vs 41%; p=0.51), and 5 (32% vs 31%; p=0.61) for the MR-GB and TRUSBx cohort, respectively. MR-GB showed an exact performance with RP for overall HGG: 88% (30 of 34); for TRUS-GB it was 55% (35 of 64; p=0.001). In the MR-GB cohort, an exact performance with HGG 3 was 100% (12 of 12); for HGG 4, 91% (10 of 11); and for HGG 5, 73% (8 of 11). The corresponding performance rates for TRUSBx were 94% (17 of 18; p=0.41), 46% (12 of 26; p=0.02), and 30% (6 of 20; p=0.01), respectively. CONCLUSIONS This study shows prospectively that DWI-directed MR-GBs significantly improve pretreatment risk stratification by obtaining biopsies that are representative of true Gleason grade.

MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study

BACKGROUND In patients with prostate cancer who are deemed to be at intermediate or high risk of having nodal metastases, invasive diagnostic pelvic lymph-node dissection (PLND) is the gold standard for the detection of nodal disease. However, a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect metastases in normal-sized nodes (ie, <8 mm in size) by use of MR lymphoangiography (MRL). In this prospective, multicentre cohort study, we aimed to compare the diagnostic accuracy of MRL with up-to-date multidetector CT (MDCT), and test the hypothesis that a negative MRL finding obviates the need for a PLND. METHODS We included consecutive patients with prostate cancer who had an intermediate or high risk (risk of >5% according to routinely used nomograms) of having lymph-node metastases. All patients were assessed by MDCT and MRL, and underwent PLND or fine-needle aspiration biopsy. Imaging results were correlated with histopathology. The primary outcomes were sensitivity, specificity, accuracy, NPV, and PPV of MRL and MDCT. This study is registered with ClinicalTrials.gov, number NCT00185029. FINDINGS The study was done in 11 hospitals in the Netherlands between April 8, 2003, and April 19, 2005. 375 consecutive patients were included. 61 of 375 (16%) patients had lymph-node metastases. Sensitivity was 34% (21 of 61; 95% CI 23-48) for MDCT and 82% (50 of 61; 70-90) for MRL (McNemars test p<0.05). Specificity was 97% (303 of 314; 94-98) for MDCT and 93% (291 of 314; 89-95) for MRL. Positive predictive value (PPV) was 66% (21 of 32; 47-81) for MDCT and 69% (50 of 73; 56-79) for MRL. Negative predictive value (NPV) was 88% (303 of 343; 84-91) for MDCT and 96% (291 of 302; 93-98) for MRL (McNemars test p<0.05). Of the 61 patients with lymph-node metastases, 50 were detected by MRL, of which 40 (80%) had metastases in normal-sized lymph nodes. The high sensitivity and NPV of MRL imply that in patients with a negative MRL, the chance of positive lymph nodes is less than 11/302 (4%). INTERPRETATION MRL had significantly higher sensitivity and NPV than MDCT for patients with prostate cancer who had intermediate or high risk of having lymph-node metastases. In such patients, after a negative MRL, the post-test probability of having lymph-node metastases is low enough to omit a PLND.

Accuracy of multiparametric MRI for prostate cancer detection: a meta-analysis

OBJECTIVE The purpose of this diagnostic meta-analysis was to determine the diagnostic accuracy of multiparametric MRI for prostate cancer detection using anatomic T2-weighted imaging combined with two functional techniques: diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS We searched electronic databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 3, 2012. We included diagnostic accuracy studies using a combination of T2-weighted imaging, DWI, and DCE-MRI to detect prostate cancer with histopathologic data from prostatectomy or biopsy as the reference standard. The methodologic quality was assessed with version 2 of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool by two independent reviewers. Sensitivity and specificity of all studies were calculated from 2 × 2 tables, and the results were plotted in a hierarchic summary receiver operating characteristic plot. RESULTS Seven studies that met the inclusion criteria (526 patients) could be analyzed. The pooled data showed a specificity of 0.88 (95% CI, 0.82-0.92) and sensitivity of 0.74 (95% CI, 0.66-0.81) for prostate cancer detection, with negative predictive values (NPVs) ranging from 0.65 to 0.94. Subgroup analyses showed no significant difference between the subgroups. CONCLUSION The high specificity with variable but high NPVs and sensitivities implies a potential role for multiparametric MRI in detecting prostate cancer.

Initial experience of 3 tesla endorectal coil magnetic resonance imaging and 1H-spectroscopic imaging of the prostate.

Rationale and Objectives:We sought to explore the feasibility of magnetic resonance imaging (MRI) of the prostate at 3T, with the knowledge of potential drawbacks of MRI at high field strengths. Material and Methods:MRI, dynamic MRI, and 1H-MR spectroscopic imaging were performed in 10 patients with prostate cancer on 1.5T and 3T whole-body scanners. Comparable scan protocols were used, and additional high-resolution measurements at 3T were acquired. For both field strengths the signal-to-noise ratio was calculated and image quality was assessed. Results:At 3T the signal-to-noise ratio improved. This resulted in increased spatial MRI resolution, which significantly improved anatomic detail. The increased spectral resolution improved the separation of individual resonances in MRSI. Contrast-enhanced time-concentration curves could be obtained with a doubled temporal resolution. Conclusions:Initial results of endorectal 3T 1H-MR spectroscopic imaging in prostate cancer patients showed potential advantages: the increase in spatial, temporal, and spectral resolution at higher field strength may result in an improved accuracy in delineating and staging prostate cancer.

Transition Zone Prostate Cancer: Detection and Localization with 3-T Multiparametric MR Imaging

PURPOSE To retrospectively compare transition zone (TZ) cancer detection and localization accuracy of 3-T T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging, with radical prostatectomy specimens as the reference standard. MATERIALS AND METHODS The informed consent requirement was waived by the institutional review board. Inclusion criteria were radical prostatectomy specimen TZ cancer larger than 0.5 cm(3) and 3-T endorectal presurgery MP MR imaging (T2-weighted imaging, diffusion-weighted [DW] imaging apparent diffusion coefficient [ADC] maps [b < 1000 sec/mm(2)], and dynamic contrast material-enhanced [DCE] MR imaging). From 197 patients with radical prostatectomy specimens, 28 patients with TZ cancer were included. Thirty-five patients without TZ cancer were randomly selected as a control group. Four radiologists randomly scored T2-weighted and DW ADC images, T2-weighted and DCE MR images, and T2-weighted, DW ADC, and DCE MR images. TZ cancer suspicion was rated on a five-point scale in six TZ regions of interest (ROIs). A score of 4-5 was considered a positive finding. A score of 4 or higher for any ROI containing TZ cancer was considered a positive detection result at the patient level. Generalized estimating equations were used to analyze detection and localization accuracy by using ROI-receiver operating characteristics (ROC) curve analyses for the latter. Gleason grade (GG) 4-5 and GG 2-3 cancers were analyzed separately. RESULTS Detection accuracy did not differ between T2-weighted and MP MR imaging for all TZ cancers (68% vs 66%, P = .85), GG 4-5 TZ cancers (79% vs 72%-75%, P = .13), and GG 2-3 TZ cancers (66% vs 62%-65%, P = .47). MP MR imaging (area under the ROC curve, 0.70-0.77) did not improve T2-weighted imaging localization accuracy (AUC = 0.72) (P > .05). CONCLUSION Use of 3-T MP MR imaging, consisting of T2-weighted imaging, DW imaging ADC maps (b values, 50, 500, and 800 sec/mm(2)), and DCE MR imaging may not improve TZ cancer detection and localization accuracy compared with T2-weighted imaging. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120281/-/DC1.

Prostate cancer: comparison of local staging accuracy of pelvic phased-array coil alone versus integrated endorectal-pelvic phased-array coils. Local staging accuracy of prostate cancer using endorectal coil MR imaging.

To compare the visibility of anatomical details and prostate cancer local staging performance of pelvic phased-array coil and integrated endorectal–pelvic phased-array coil MR imaging, with histologic analysis serving as the reference standard. MR imaging was performed in 81 consecutive patients with biopsy-proved prostate cancer, prior to radical prostatectomy, on a 1.5T scanner. T2-weighted fast spin echo images of the prostate were obtained using phased-array coil and endorectal–pelvic phased-array coils. Prospectively, one radiologist, retrospectively, two radiologists and two less experienced radiologists working in consensus, evaluated and scored all endorectal–pelvic phased-array imaging, with regard to visibility of anatomical details and local staging. Receiver operator characteristics (ROC) analysis was performed. Anatomical details of the overall prostate were significantly better evaluated using the endorectal–pelvic phased-array coil setup (P<0.05). The overall local staging accuracy, sensitivity and specificity for the pelvic phased-array coil was 59% (48/81), 56% (20/36) and 62% (28/45), and for the endorectal-pelvic phased-array coils 83% (67/81), 64% (23/36) and 98% (44/45) respectively, for the prospective reader. Accuracy and specificity were significantly better with endorectal–pelvic phased-array coils (P<0.05). The overall staging accuracy, sensitivity and specificity for the retrospective readers were 78–79% (P<0.05), 56–58% and 96%, for the endorectal–pelvic phased-array coils. Area under the ROC curve (Az) was significantly higher for endorectal–pelvic phased-array coils (Az=0.74) compared to pelvic phased-array coil (Az=0.57), for the prospective reader. The use of endorectal–pelvic phased array coils resulted in significant improvement of anatomic details, extracapsular extension accuracy and specificity. Overstaging is reduced significantly with equal sensitivity when an endorectal–pelvic phased-array coil is used.

Thirty-two-channel Coil 3t Magnetic Resonance-guided Biopsies of Prostate Tumor Suspicious Regions Identified on Multimodality 3t Magnetic Resonance Imaging: Technique and Feasibility

Objectives:To test the technique and feasibility of translating tumor suspicious region maps in the prostate, obtained by multimodality, anatomic, and functional 3T magnetic resonance imaging (MRI) data to 32-channel coil, T2-weighted (T2-w), 3T MR images, for directing MR-guided biopsies. Furthermore, to evaluate the practicability of MR-guided biopsy on a 3T MR scanner using a 32-channel coil and a MR-compatible biopsy device. Materials and Methods:Twenty-one patients with a high prostate-specific antigen (>4.0 ng/mL) and at least 2 prior negative transrectal ultrasound-guided biopsies of the prostate underwent an endorectal coil 3T MRI, which included T2-w, diffusion weighted and dynamic contrast enhanced MRI. From these multimodality images, tumor suspicious regions (TSR) were determined. The 3D localization of these TSRs within the prostatic gland was translated to the T2-w MR images of a subsequent 32-channel coil 3T MRI. These were then biopsied under 3T MR guidance. Results:In all patients, TSRs could be identified and accurately translated to subsequent 3T MR images and biopsied under MR guidance. Median MR biopsy procedure time was 35 minutes. Of the 21 patients, 8 (38%) were diagnosed with prostate cancer, 6 (29%) had evidence of prostatitis, 6 (29%) had combined inflammatory and atrophic changes, and only 1 (5%) patient had no identifiable pathology. Conclusions:Multimodality, 3T MRI determined TSRs could effectively be translated to T2-weighted images, to be used for MR biopsies. 3T MR-guided biopsy based on these translated TSRs was feasible, performed in a clinical useful time, and resulted in a high number of positive results.

Fast acquisition-weighted three-dimensional proton MR spectroscopic imaging of the human prostate.

The clinical application of 3D proton spectroscopic imaging (3D SI) of the human prostate requires a robust suppression of periprostatic lipid signal contamination, minimal intervoxel signal contamination, and the shortest possible measurement time. In this work, a weighted elliptical sampling of k‐space, combined with k‐space filtering and pulse repetition time (TR) reduction minimized lipid signals, intervoxel contamination, and measurement time. At 1.5 T, the MR‐visible prostate metabolites citrate, creatine, and choline can now be mapped over the entire human prostate with uncontaminated spherical voxels, with a volume down to 0.37 cm3, in measurement times of 7–15 min. Magn Reson Med 52:80–88, 2004.