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Background: Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of "unnecessary" prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy., Methods: This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥-2.8. Decision curve analysis (DCA) was performed to assess clinical utility., Results: Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%., Conclusions: SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy., (© 2021. The Author(s).)

Background: Grading prostate biopsies has an important role in determining treatment strategy. Histopathological evaluations suffer from interobserver variability and therefore biopsies may be re-evaluated., Objective: To provide insight into the extent of, characteristics associated with and clinical implications of prostate biopsy re-evaluations in daily clinical practice., Methods: Patients diagnosed with prostate cancer (PCa) by biopsy between October 2015 and April 2016 identified through the Netherlands Cancer Registry were included. The proportion of re-evaluations was assessed and characteristics were compared between patients with and without biopsy re-evaluation. Interobserver concordance of ISUP grade and EAU prognostic risk classification was determined by calculating Cohen's kappa., Results: Biopsy re-evaluation was performed in 172 (3.3%) of 5214 patients. Primary reason for re-evaluation in patients treated with curative intent was referral to another hospital. Most referred patients treated with curative intent ( n  = 1856) had no re-evaluation (93.0%, n  = 1727). Patients with biopsy re-evaluation were younger and underwent more often prostatectomy compared to patients without re-evaluation. The disagreement rate for ISUP grade was 26.1% and interobserver concordance was substantial ( κ -weighted = 0.74). Re-evaluation resulted in 21.1% ( n  = 14) of patients with localised PCa in a different prognostic risk group. More tumours were downgraded (57.1%) than upgraded (42.9%). Interobserver concordance was very good ( κ weighted = 0.85)., Conclusion: Pathology review of prostate biopsies is infrequently requested by clinicians in the Netherlands but in a non-negligible minority of patients with localised PCa the pathology review led to a change in prognostic risk group which might impact their treatment.

Background: Although urinary adverse events after treatment of prostate cancer (CaP) are common, population-based studies on functional outcomes are scarce. The aim of this study is to evaluate the occurrence of urinary incontinence (UI) and erectile dysfunction (ED) in daily clinical practice using a nationwide Dutch cohort of patients with localized or locally advanced CaP., Basic Procedures: Patients were invited to complete the EPIC-26 questionnaire before treatment (baseline) and at 12 and 24 months after diagnosis. We calculated the mean EPIC-26 domain scores, stratified by treatment modality (i.e., radical prostatectomy, external radiotherapy, and no active treatment), and the proportions of patients with UI (defined as ≥ 2 pads per day) and ED (defined as erections not firm enough for sexual intercourse). Logistic regression modeling was used to explore the factors related to UI and ED after surgery., Main Findings: In total 1,759 patients participated in this study. Patients undergoing radical prostatectomy experienced clinically relevant worsening in the urinary incontinence domain. After excluding patients who reported UI at baseline, 15% of patients with prostatectomy reported UI 24 months after diagnosis. Only comorbidity was associated with UI in surgically treated patients. Regardless of treatment, patients reported a clinically significant reduced sexual functioning over time. Before treatment, 54% of patients reported ED. Among the 46% remaining patients, 87% of patients treated with radical prostatectomy reported ED 24 months after diagnosis, 41% after radiotherapy, and 46% in patients without active treatment. Bilateral nerve-sparing surgery was the only factor associated with ED after 24 months., Principal Conclusions: UI and ED frequently occur in patients with localized and locally advanced CaP, in particular after radical prostatectomy. The higher occurrence rate of UI and ED, compared with clinical trial participants, supports the importance of real-world data, which can be used for local treatment recommendations and patient information, but also to evaluate effects of future initiatives, such as treatment centralization and research aimed at improving functional outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To provide insight in the treatment variation of very-low-risk prostate cancer patients and to assess the role of hospital-related factors., Methods: All patients diagnosed with very-low-risk prostate cancer (cT1c-cT2a, PSA < 10 ng/ml, Gleason score <7 and <3 positive cores) in 2015 and 2016 were identified through the population-based Netherlands Cancer Registry. Multilevel logistic regression analyses were performed to examine the crude and case-mix adjusted probability of immediate treatment vs. active-surveillance (AS) according to hospital of diagnosis and to evaluate the effect of patient-, tumour-, and hospital-related factors., Results: In all, 2047 (85.4%) of the 2396 patients with very-low-risk prostate cancer were managed with AS. The crude proportion of patients with AS varied from 33.3 to 100% between hospitals. Case-mix adjusted probability varied from 71 to 97%. Tumour stage cT2a vs. cT1c (OR 2.0, 95%CI 1.1-3.6), two vs. one positive core (OR 2.8, 95%CI 1.6-4.7), diagnostic MRI (OR 2.8, 95%CI 1.5-5.2), discussion of a patient in a multi-disciplinary team (OR 2.2, 95%CI 1.1-4.5), discussion of treatment options with the patient (OR 3.3, 95%CI 1.5-7.4) and type of hospital (non-university referral hospital vs. community hospital: OR 0.5, 95%CI 0.2-0.9) were associated with immediate treatment., Conclusion: The majority of Dutch very-low-risk prostate cancer patients is managed with AS but variation between hospitals exists. Part of the variation is explained by patient- and tumour characteristics but also hospital-related factors play a role. This implies that clinical practice could be improved.

Background: Active surveillance (AS) aims to reduce overtreatment of low-risk prostate cancer (PC). Incorporating multiparametric magnetic resonance imaging (mp-MRI) and MR-guided biopsy (MRGB) in an AS protocol might contribute to more accurate identification of AS candidates., Objective: To evaluate the value of 3T mp-MRI and MRGB in PC patients on AS at inclusion and after 12-mo follow-up., Design, Setting, and Participants: Patients with cT1c-cT2 PC, prostate-specific antigen (PSA) ≤10ng/ml, PSA density <0.2ng/ml/ml, and Gleason scores (GSs) of ≤6 and ≤2 positive biopsy cores were included and followed in an AS protocol including mp-MRI and MRGB. The mp-MRI and MRGB were performed at <3 and 12 mo after diagnosis. Reclassification was defined as GS >6, >2 positive cores at repeat transrectal ultrasound-guided biopsy (TRUSGB), presence of PC in >3 separate cancer foci upon both MRGB and TRUSGB, or cT3 tumor on mp-MRI., Outcome Measurements and Statistical Analysis: Reclassification rates, treatment after discontinuation, and outcome on radical prostatectomy after discontinuing AS were reported. Uni- and multivariate analyses were performed to identify predictors of reclassification after 1 yr., Results and Limitations: From 2009 to 2013, a total of 111 of 158 patients were consecutively and prospectively included. Around initial diagnosis, 36 patients were excluded from the study protocol; mp-MRI+MRGB reclassified 25/111 (23%) patients, and 11 patients were excluded at own request. Reasons for reclassification were as follows: GS upgrade (15/25, 60%); cT3 disease (3/25, 12%); suspicion of bone metastases (1/25, 4%); and multifocal disease upon MRGB (6/25, 24%). Repeat examinations after 1 yr showed reclassification in 33/75 patients (44%). Reasons were the following: GS upgrade upon TRUSGB (9/33, 27%); volume progression upon TRUSGB (9/33, 27%); cT3 disease upon mp-MRI (1/33, 3%); GS upgrade upon MRGB (1/33, 3%); volume progression upon MRGB (1/33, 3%); multifocal disease upon MRGB (2/33, 6%); and upgrade or upstage upon both TRUSGB and MRGB (10/33, 30%). On logistic regression analysis, the presence of cancer at initial mp-MRI and MRGB examinations was the only predictor of reclassification after 1 yr (odds ratio 5.9, 95% confidence interval 2.0-17.6)., Conclusions: Although mp-MRI and MRGB are of additional value in the evaluation of PC patients on AS, the value of mp-MRI after 1 yr was limited. As a considerable percentage of GS ≥7 PC after 1 yr was detected only by TRUSGB, TRUSGB cannot be omitted yet., Patient Summary: More aggressive tumors are detected if low-risk prostate cancer patients are additionally monitored by magnetic resonance imaging. However, some high-grade tumors are detected only by transrectal ultrasound-guided biopsy., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the ability of high field ex vivo magnetic resonance imaging (MRI) to localize prostate cancer (PCa) and to predict the margin status in fresh radical prostatectomy (RP) specimens using histology as the reference standard., Materials and Methods: This Institutional Review Board (IRB)-approved study had written informed consent. Patients with biopsy-proved PCa and a diagnostic multiparametric 3T MRI examination of the prostate prior to undergoing RP were prospectively included. A custom-made container provided reference between the 7T ex vivo MRI obtained from fresh RP specimens and histological slicing. On ex vivo MRI, PCa was localized and the presence of positive surgical margins was determined in a double-reading session. These findings were compared with histological findings obtained from completely cut, whole-mount embedded, prostate specimens., Results: In 12 RP specimens, histopathology revealed 36 PCa lesions, of which 17 (47%) and 20 (56%) were correlated with the ex vivo MRI in the first and second reading session, respectively. Nine of 12 (75%) index lesions were localized in the first session, in the second 10 of 12 (83%). Seven and 8 lesions of 11 lesions with Gleason score >6 and >0.5 cc were localized in the first and second session, respectively. In the first session none of the four histologically positive surgical margins (sensitivity 0%) and 9 of 13 negative margins (specificity 69%) were detected. In second session the sensitivity and specificity were 25% and 88%, respectively., Conclusion: Ex vivo MRI enabled accurate localization of PCa in fresh RP specimens, and the technique provided information on the margin status with high specificity., Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:439-448., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: Prostate cancer (PCa) diagnostics would greatly benefit from more accurate, non-invasive techniques for the detection of clinically significant disease, leading to a reduction of over-diagnosis and over-treatment. The aim of this study was to determine the association between a novel urinary biomarker-based risk score (SelectMDx), multiparametric MRI (mpMRI) outcomes, and biopsy results for PCa detection., Methods: This retrospective observational study used data from the validation study of the SelectMDx score, in which urine was collected after digital rectal examination from men undergoing prostate biopsies. A subset of these patients also underwent a mpMRI scan of the prostate. The indications for performing mpMRI were based on persistent clinical suspicion of PCa or local staging after PCa was found upon biopsy. All mpMRI images were centrally reviewed in 2016 by an experienced radiologist blinded for the urine test results and biopsy outcome. The PI-RADS version 2 was used., Results: In total, 172 patients were included for analysis. Hundred (58%) patients had PCa detected upon prostate biopsy, of which 52 (52%) had high-grade disease correlated with a significantly higher SelectMDx score (P < 0.01). The median SelectMDx score was significantly higher in patients with a suspicious significant lesion on mpMRI compared to no suspicion of significant PCa (P < 0.01). For the prediction of mpMRI outcome, the area-under-the-curve of SelectMDx was 0.83 compared to 0.66 for PSA and 0.65 for PCA3. There was a positive association between SelectMDx score and the final PI-RADS grade. There was a statistically significant difference in SelectMDx score between PI-RADS 3 and 4 (P < 0.01) and between PI-RADS 4 and 5 (P < 0.01)., Conclusions: The novel urinary biomarker-based SelectMDx score is a promising tool in PCa detection. This study showed promising results regarding the correlation between the SelectMDx score and mpMRI outcomes, outperforming PCA3. Our results suggest that this risk score could guide clinicians in identifying patients at risk for significant PCa and selecting patients for further radiological diagnostics to reduce unnecessary procedures., (© 2017 Wiley Periodicals, Inc.)

Purpose: To correlate treatment effects of MRI-guided focal laser ablation in patients with prostate cancer with imaging using prostatectomy as standard of reference., Methods: This phase I study was approved by the Institutional Review Board. Three weeks prior to prostatectomy, five patients with histopathologically proven, low/intermediate grade prostate cancer underwent transrectal MRI-guided focal laser ablation. Per patient, only one ablation was performed to investigate the effect of ablation on the tissue rather than the effectiveness of ablation. Ablation was continuously monitored with real-time MR temperature mapping, and damage-estimation maps were computed. A post-ablation high-resolution T1-weighted contrast-enhanced sequence was acquired. Ablation volumes were contoured and measured on histopathology specimens (with a shrinkage factor of 1.15), T1-weighted contrast-enhanced images, and damage-estimation maps, and were compared., Results: A significant volume correlation was seen between the ablation zone on T1-weighted contrast-enhanced images and the whole-mount histopathology section (r = 0.94, p = 0.018). The damage-estimation maps and histopathology specimen showed a correlation of r = 0.33 (p = 0.583). On histopathology, the homogeneous necrotic area was surrounded by a reactive transition zone (1-5 mm) zone, showing neovascularisation, and an increased mitotic index, indicating increased tumor activity., Conclusions: The actual ablation zone was better indicated by T1-weighted contrast-enhanced than by damage-estimation maps. Histopathology results highlight the importance of complete tumor ablation with a safety margin.

Background: To reduce overdiagnosis and overtreatment, a test is urgently needed to detect clinically significant prostate cancer (PCa)., Objective: To develop a multimodal model, incorporating previously identified messenger RNA (mRNA) biomarkers and traditional risk factors that could be used to identify patients with high-grade PCa (Gleason score ≥7) on prostate biopsy., Design, Setting, and Participants: In two prospective multicenter studies, urine was collected for mRNA profiling after digital rectal examination (DRE) and prior to prostate biopsy. The multimodal risk score was developed on a first cohort (n=519) and subsequently validated clinically in an independent cohort (n=386)., Outcome Measurements and Statistical Analysis: The mRNA levels were measured using reverse transcription quantitative polymerase chain reaction. Logistic regression was used to model patient risk and combine risk factors. Models were compared using the area under the curve (AUC) of the receiver operating characteristic, and clinical utility was evaluated with a decision curve analysis (DCA)., Results and Limitations: HOXC6 and DLX1 mRNA levels were shown to be good predictors for the detection of high-grade PCa. The multimodal approach reached an overall AUC of 0.90 (95% confidence interval [CI], 0.85-0.95) in the validation cohort (AUC 0.86 in the training cohort), with the mRNA signature, prostate-specific antigen (PSA) density, and previous cancer-negative prostate biopsies as the strongest, most significant components, in addition to nonsignificant model contributions of PSA, age, and family history. For another model, which included DRE as an additional risk factor, an AUC of 0.86 (95% CI, 0.80-0.92) was obtained (AUC 0.90 in the training cohort). Both models were successfully validated, with no significant change in AUC in the validation cohort, and DCA indicated a strong net benefit and the best reduction in unnecessary biopsies compared with other clinical decision-making tools, such as the Prostate Cancer Prevention Trial risk calculator and the PCA3 assay., Conclusions: The risk score based on the mRNA liquid biopsy assay combined with traditional clinical risk factors identified men at risk of harboring high-grade PCa and resulted in a better patient risk stratification compared with current methods in clinical practice. Therefore, the risk score could reduce the number of unnecessary prostate biopsies., Patient Summary: This study evaluated a novel urine-based assay that could be used as a noninvasive diagnostic aid for high-grade prostate cancer (PCa). When results of this assay are combined with traditional clinical risk factors, risk stratification for high-grade PCa and biopsy decision making are improved., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine transrectal ultrasound (TRUS) visibility of magnetic resonance (MR) lesions., Methods: Data from 34 patients with 56 MR lesions and prostatectomy were used. Five observers localized and determined TRUS visibility during retrospective fusion. Visibility was correlated to Prostate Imaging-Reporting and Data System (PIRADS) and Gleason scores., Results: TRUS visibility occurred in 43% of all MR lesions and in 62% of PIRADS 5 lesions. Visible lesions had a significantly lower localization variability. On prostatectomy, 58% of the TRUS-visible lesions had a Gleason 4 or 5 component., Conclusions: Almost half of the MR lesions were visible on TRUS. TRUS-visible lesions were more aggressive than TRUS-invisible lesions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine associations of metabolite levels derived from magnetic resonance (MR) spectroscopic imaging (ie, hydrogen 1 [(1)H] MR spectroscopic imaging) and apparent diffusion coefficients (ADCs) from diffusion-weighted imaging with prostate tissue composition assessed by digital image analysis of histologic sections., Materials and Methods: Institutional ethical review board approved this retrospective study and waived informed consent. Fifty-seven prostate cancer patients underwent an MR examination followed by prostatectomy. One hematoxylin and eosin-stained section of the resected prostate per patient was digitized and computationally segmented into nuclei, lumen, and combination of epithelial cytoplasm and stroma. On each stained section, regions of interest (ROIs) were chosen and matched to the corresponding ADC map and (1)H MR spectroscopic imaging voxels. ADC and two metabolite ratios (citrate [Cit], spermine [Spm], and creatine [Cr] to choline [Cho] and Cho to Cr plus Spm) were correlated with percentage areas of nuclei, lumen, and cytoplasm and stroma for peripheral zone (PZ), transition zone (TZ), and tumor tissue in both zones of the prostate by using a linear mixed-effect model and Spearman correlation coefficient (ρ)., Results: ADC and (Cit + Spm + Cr)/Cho ratio showed positive correlation with percentage area of lumen (ρ = 0.43 and 0.50, respectively) and negative correlation with percentage area of nuclei (ρ = -0.29 and -0.26, respectively). The Cho/(Cr + Spm) ratio showed negative association with percentage area of lumen (ρ = -0.40) and positive association with area of nuclei (ρ = 0.26). Percentage areas of lumen and nuclei, (Cit + Spm + Cr)/Cho ratio, and ADC were significantly different (P < .001) between benign PZ (23.7 and 7.7, 8.83, and 1.58 × 10(-3) mm(2)/sec, respectively) and tumor PZ tissue (11.4 and 12.5, 5.13, and 1.20 × 10(-3) mm(2)/sec, respectively). These parameters were also significantly different between benign TZ (20.0 and 8.2, 6.50, and 1.26 × 10(-3) mm(2)/sec, respectively) and tumor TZ tissue (9.8 and 11.2, 4.36, and 1.03 × 10(-3) mm(2)/sec, respectively)., Conclusion: The observed correlation of (Cit + Spm + Cr)/Cho ratio and ADC of the prostate with its tissue composition indicates that components of this composition, such as percentage luminal area, contribute to the value of these MR parameters.

Purpose: To retrospectively assess the use of the European Society of Urogenital Radiology (ESUR) Prostate Imaging Reporting and Data System (PI-RADS) criteria and 3-T multiparametric magnetic resonance (MR) imaging for detection of extraprostatic extension (EPE) of prostate cancer., Materials and Methods: The institutional review board approval requirement was waived. Consecutive patients with prostate cancer (n = 133) underwent 3-T multiparametric MR imaging before prostatectomy. Lesions were assessed by using ESUR/PI-RADS criteria for T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging, and by using the sum of these scores. Zonal dominant parameters corresponding to the score of diffusion-weighted imaging for peripheral zone lesions and to T2-weighted imaging scores for transitional zone lesions were calculated. In addition, the presence of EPE in each patient was evaluated on the basis of subjective multiparametric MR imaging features. Histopathologic examination of whole-mount radical prostatectomy specimens was used as the reference standard. Sensitivity, specificity, positive predictive, and negative predictive values; likelihood ratios; and areas under the receiver operating characteristic curve were calculated for each parameter on the basis of its usefulness for prediction of EPE., Results: EPE was found in 60 of 133 (45%) patients. Receiver operating characteristic curve analysis for the prediction of EPE revealed an area under the curve of 0.72 for T2-weighted, 0.67 for diffusion-weighted, and 0.64 for dynamic contrast-enhanced imaging; 0.74 for the dominant parameter; and 0.74 for the sum of the PI-RADS scores, and a score of 5 was defined as the best threshold for the individual parameters, with a score greater than or equal to 13 as the threshold for the sum of the PI-RADS scores. By applying these thresholds, sensitivity, negative predictive value, and negative likelihood ratio (ruling out EPE) were 77%, 77%, and 0.36, respectively, and specificity, positive predictive value, and positive likelihood ratio (ruling in EPE) were 64%, 64%, and 2.15, respectively, for the dominant parameter. Feature analysis showed an area under the curve of 0.72; sensitivity, negative predictive value, and negative likelihood ratio of 63%, 72%, and 0.56, respectively, and specificity, positive predictive value, and positive likelihood ratio of 78%, 70%, and 3.77, respectively., Conclusion: ESUR/PI-RADS criteria showed moderate overall accuracy for use in the prediction of EPE, and these results were similar to those of multiparametric MR imaging assessment of features in this study sample., ((©) RSNA, 2015)

Objective: The aim of this study was to determine and validate the optimal combination of parameters derived from 3-T diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for discriminating low-grade from high-grade prostate cancer (PCa)., Materials and Methods: The study was approved by the institutional review board, and the need for informed consent was waived. Ninety-four patients with PCa who had undergone multiparametric MR imaging (MRI) before prostatectomy were included. Cancer was indicated on T2-weighted images, blinded to any functional data, with prostatectomy specimens as the reference standard. Tumors were classified as low grade or high grade based on Gleason score; peripheral zone (PZ) and transition zone (TZ) tumors were analyzed separately. In a development set (43 patients), the optimal combination of multiparametric MRI parameters was determined using logistic regression modeling. Subsequently, this combination was evaluated in a separate validation set (51 patients)., Results: In the PZ, the 25th percentile of apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging and washout (WO25) derived from dynamic contrast-enhanced MRI offered the optimal combination of parameters. In the TZ, WO25 and the choline over spermine + creatine ratio (C/SC) derived from MR spectroscopic imaging showed the highest discriminating performance. Using the models built with the development set, 48 (74%) of 65 cancer lesions were classified correctly in the validation set., Conclusions: Multiparametric MRI is a useful tool for the discrimination between low-grade and high-grade PCa and performs better than any individual functional parameter in both the PZ and TZ. The 25th percentile of ADC + WO25 offered the optimal combination in the PZ, and the choline over spermine + creatine ratio + WO25 offered the optimal combination in the TZ. The ADC parameter has no additional value for the assessment of PCa aggressiveness in the TZ.

Objective: The purpose of this article is to identify histopathologically proven prostate cancer locations using MRI followed by MRI-guided biopsy in patients with elevated prostate-specific antigen (PSA) levels and at least one negative transrectal ultrasound (TRUS)-guided biopsy session. Our hypothesis is that in this patient group most cancers are located in the anterior portion of the prostate. This may have implications for the biopsy strategy regarding the location of sampling., Materials and Methods: This retrospective study consisted of 872 consecutive men who had undergone MRI-guided prostate biopsy. Inclusion criteria were PSA level greater than or equal to 4 ng/mL, one or more negative TRUS-guided biopsy session, the presence of suspicious lesions on previous multiparametric MRI, and prostate cancer histopathologically proven by MRI-guided biopsy. Thereafter, the location of intermediate- or high-risk cancers and cancers with a maximum cancer core length of 6 mm or longer were determined. The proportion of cancer locations was compared using a chi-square test. One-way ANOVA analyses were performed to compare patient characteristics., Results: Results were presented on both a patient and lesion basis because a single patient can have multiple lesions. In total, 176 of 872 patients met the inclusion criteria. Prostate cancer was detected in 202 of 277 (73%) suspicious lesions. In total, 76% of patients had cancer of the transition zone and anterior fibromuscular stroma. Peripheral zone cancers were found in 30% of the patients, and 6% had cancers in both zones. In 70% of cases (141/202; 95%, CI, 63-76%), lesions were located anteriorly; this included 75% (132/176; 95%, CI, 69-81%) of patients. Intermediate- or high-risk prostate cancer was found in 93% (128/138; 95%, CI, 88-96%) of patients. Of these patients, 73% (94/128; 95%, CI, 66-81%) had anterior involvement. Cancers with a maximum cancer core length of 6 mm or more were more likely to be located in the anterior part of the prostate than were cancers with a core length of less than 6 mm (66% vs 6%). Most cancers 58% (102/176; 95% CI, 51-65%) were found in the mid prostate. Anterior involvement of prostate cancer detected by MRI-guided biopsy was statistically significantly (p = 0.04) higher in patients with two or more negative TRUS-guided biopsy sessions (79%) than in those with one negative TRUS-guided biopsy session (55%)., Conclusion: Anterior involvement was high (76%) in patients with an elevated PSA level and one or more negative TRUS-guided biopsy session, and the majority of these cancers (93%) were intermediate or high risk.

Purpose: Serum PSA (sPSA) testing has led to the identification of patients with indolent prostate cancer, and inevitably overtreatment has become a concern. Progensa PCA3 urine testing was shown to improve the diagnosis of prostate cancer, but its diagnostic value for aggressive prostate cancer is limited. Therefore, urinary biomarkers that can be used for prediction of Gleason score ≥7 prostate cancer in biopsies are urgently needed., Experimental Design: Using gene expression profiling data, 39 prostate cancer biomarkers were identified. After quantitative PCR analysis on tissue specimens and urinary sediments, eight promising biomarkers for the urinary detection of prostate cancer were selected (ONECUT2, HOXC4, HOXC6, DLX1, TDRD1, NKAIN1, MS4A8B, PPFIA2). The hypothesis that biomarker combinations improve the diagnostic value for aggressive prostate cancer was tested on 358 urinary sediments of an intention-to-treat cohort., Results: A urinary three-gene panel (HOXC6, TDRD1, and DLX1) had higher accuracy [area under the curve (AUC), 0.77; 95% confidence interval (CI), 0.71-0.83] to predict Gleason score ≥7 prostate cancer in biopsies compared with Progensa PCA3 (AUC, 0.68; 95% CI, 0.62-0.75) or sPSA (AUC, 0.72; 95% CI, 0.65-0.78). Combining the three-gene panel with sPSA further improved the predictive accuracy (AUC, 0.81; 95% CI, 0.75-0.86). The accuracy of the three-gene predictive model was maintained in subgroups with low sPSA concentrations., Conclusions: The urinary three-gene panel (HOXC6, TDRD1, and DLX1) represents a promising tool to identify patients with aggressive prostate cancer, also in those with low sPSA values. The combination of the urinary three-gene panel with sPSA bears great potential for the early diagnosis of patients with clinically significant prostate cancer., (©2015 American Association for Cancer Research.)

Objectives: To correlate pharmacokinetic parameters of 3-T dynamic contrast-enhanced (DCE-)MRI with histopathologic microvascular and lymphatic parameters in organ-confined prostate cancer., Methods: In 18 patients with unilateral peripheral zone (pT2a) tumours who underwent DCE-MRI prior to radical prostatectomy (RP), the following pharmacokinetic parameters were assessed: permeability surface area volume transfer constant (K (trans)), extravascular extracellular volume (Ve) and rate constant (K ep). In the RP sections blood and lymph vessels were visualised immunohistochemically and automatically examined and analysed. Parameters assessed included microvessel density (MVD), area (MVA) and perimeter (MVP) as well as lymph vessel density (LVD), area (LVA) and perimeter (LVP)., Results: A negative correlation was found between age and K (trans) and K ep for tumour (r = -0.60, p = 0.009; r = -0.67, p = 0.002) and normal (r = -0.54, p = 0.021; r = -0.46, p = 0.055) tissue. No correlation existed between absolute values of microvascular parameters from histopathology and DCE-MRI. In contrast, the ratio between tumour and normal tissue (correcting for individual microvascularity variations) significantly correlated between K ep and MVD (r = 0.61, p = 0.007) and MVP (r = 0.54, p = 0.022). The lymphovascular parameters showed only a correlation between LVA and K ep (r = -0.66, p = 0.003)., Conclusions: Significant correlations between DCE-MRI and histopathologic parameters were found when correcting for interpatient variations in microvascularity., Key Points: • Normal prostate tissue shows strong heterogeneity in microvascularity. • Peripheral zone prostate cancer shows increased and less heterogeneous microvascularity. • Normal and tumour tissue shows considerable variation in microvascularity between patients. • DCE-MRI should take into account the interprostatic heterogeneity of microvasculature between patients.

Objectives: The objective of this study was to evaluate the role of 3-T multiparametric magnetic resonance imaging (MP-MRI) and magnetic resonance-guided biopsy (MRGB) in early risk restratification of patients on active surveillance at 3 and 12 months of follow-up., Materials and Methods: Within 4 hospitals participating in a large active surveillance trial, a side study was initiated. Pelvic magnetic resonance imaging, prostate MP-MRI, and MRGB were performed at 3 and 12 months (latter prostate MP-MRI and MRGB only) after prostate cancer diagnosis in 1 of the 4 participating hospitals. Cancer-suspicious regions (CSRs) were defined on prostate MP-MRI using Prostate Imaging Reporting And Data System (PI-RADS) scores.Risk restratification criteria for active surveillance discontinuance were (1) histopathologically proven magnetic resonance imaging suspicion of node/bone metastases and/or (2) a Gleason growth pattern (GGP) 4 and/or 5 and/or cancer multifocality (≥3 foci) in MRGB specimens of a CSR on MP-MRI., Results: From 2009 to 2012, a total of 64 of 82 patients were consecutively and prospectively included and underwent MP-MRI and a subsequent MRGB. At 3 and 12 months of follow-up, 14% (9/64) and 10% (3/30) of the patients were risk-restratified on the basis of MP-MRI and MRGB. An overall CSR PI-RADS score of 1 or 2 had a negative predictive value of 84% (38/45) for detection of any prostate cancer and 100% (45/45) for detection of a GGP 4 or 5 containing cancer upon MRGB, respectively. A CSR PI-RADS score of 4 or higher had a sensitivity of 92% (11/12) for detection of a GGP 4 or 5 containing cancer upon MRGB., Conclusions: Application of MP-MRI and MRGB in active surveillance may contribute in early identification of patients with GGP 4 or 5 containing cancers at 3 months of follow-up. If, during further follow-up, a PI-RADS score of 1 or 2 continues to have a negative predictive value for GGP 4 or 5 containing cancers, a PI-RADS standardized reported MP-MRI may be a promising tool for the selection of prostate cancer patients suitable for active surveillance.

Background: Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine., Objective: To evaluate the diagnostic and prognostic value of Progensa PCA3 and TMPRSS2-ERG gene fusions (as individual biomarkers and as a panel) for PCa in a prospective multicentre setting., Design, Setting, and Participants: At six centres, post-digital rectal examination first-catch urine specimens prior to prostate biopsies were prospectively collected from 497 men. We assessed the predictive value of Progensa PCA3 and TMPRSS2-ERG (quantitative nucleic acid amplification assay to detect TMPRSS2-ERG messenger RNA [mRNA]) for PCa, Gleason score, clinical tumour stage, and PCa significance (individually and as a marker panel). This was compared with serum prostate-specific antigen and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator. In a subgroup (n=61) we evaluated biomarker association with prostatectomy outcome., Outcome Measurements and Statistical Analysis: Univariate and multivariate logistic regression analysis and receiver operating curves were used., Results and Limitations: Urine samples of 443 men contained sufficient mRNA for marker analysis. PCa was diagnosed in 196 of 443 men. Both PCA3 and TMPRSS2-ERG had significant additional predictive value to the ERSPC risk calculator parameters in multivariate analysis (p<0.001 and resp. p=0.002). The area under the curve (AUC) increased from 0.799 (ERSPC risk calculator), to 0.833 (ERSPC risk calculator plus PCA3), to 0.842 (ERSPC risk calculator plus PCA3 plus TMPRSS2-ERG) to predict PCa. Sensitivity of PCA3 increased from 68% to 76% when combined with TMPRSS2-ERG. TMPRSS2-ERG added significant predictive value to the ERSPC risk calculator to predict biopsy Gleason score (p<0.001) and clinical tumour stage (p=0.023), whereas PCA3 did not., Conclusions: TMPRSS2-ERG had independent additional predictive value to PCA3 and the ERSPC risk calculator parameters for predicting PCa. TMPRSS2-ERG had prognostic value, whereas PCA3 did not. Implementing the novel urinary biomarker panel PCA3 and TMPRSS2-ERG into clinical practice would lead to a considerable reduction of the number of prostate biopsies., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We determined the positive and negative predictive values of multiparametric magnetic resonance imaging for extraprostatic extension at radical prostatectomy for different prostate cancer risk groups., Materials and Methods: We evaluated a cohort of 183 patients who underwent 3 Tesla multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted magnetic resonance imaging and dynamic contrast enhanced sequences, with an endorectal coil before radical prostatectomy. Pathological stage at radical prostatectomy was used as standard reference for extraprostatic extension. The cohort was classified into low, intermediate and high risk groups according to the D'Amico criteria. We recorded prevalence of extraprostatic extension at radical prostatectomy and determined sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging for extraprostatic extension in each group. Univariate and multivariate analyses were performed to identify predictors of extraprostatic extension at radical prostatectomy., Results: The overall prevalence of extraprostatic extension at radical prostatectomy was 49.7% ranging from 24.7% to 77.1% between low and high risk categories. Overall staging accuracy of multiparametric magnetic resonance imaging for extraprostatic extension was 73.8%, with sensitivity, specificity, positive predictive value and negative predictive value of 58.2%, 89.1%, 84.1% and 68.3%, respectively. Positive predictive value of multiparametric magnetic resonance imaging for extraprostatic extension was best in the high risk cohort with 88.8%. Negative predictive value was highest in the low risk cohort with 87.7%. With an odds ratio of 10.3 multiparametric magnetic resonance imaging is by far the best preoperative predictor of extraprostatic extension at radical prostatectomy., Conclusions: For adequate patient counseling, knowledge of predictive values of multiparametric magnetic resonance imaging for extraprostatic extension is of utmost importance. High negative predictive value, important for decisions on nerve sparing strategies at radical prostatectomy, is only reached in low risk subjects., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to evaluate the apparent diffusion coefficient (ADC) of diffusion-weighted magnetic resonance (MR) imaging for the differentiation of transition zone cancer from non-cancerous transition zone with and without prostatitis and for the differentiation of transition zone cancer Gleason grade (GG) using MR-guided biopsy specimens as a reference standard., Materials and Methods: From consecutive MR-guided prostate biopsies (2008-2012) in our referral center, we retrospectively included patients from whom diffusion-weighted MR imaging ADC values were acquired during MR-guided biopsy and whose biopsy cores had a (cancer) core length 10 mm or greater and originated from the transition zone. Two radiologists, who were blinded to the ADC data, annotated regions of interest on biopsy sampling locations of MR-guided biopsy confirmation scans in consensus. Median ADC (mADC) of the regions of interest was related to histopathology outcome in MR-guided biopsy core specimens. Mixed model analysis was used to evaluate mADC differences between 7 histopathology categories predefined as MR-guided biopsy core specimens with primary and secondary GG 4-5 (I), primary GG 4-5 secondary GG 2-3 (II), primary GG 2-3 secondary GG 4-5 (III) and primary and secondary GG 2-3 cancer (IV), and noncancerous tissue without (V) or with degree 1 (VI) or degree 2 prostatitis (VII). Diagnostic accuracy was evaluated using areas under the receiver operating characteristic (AUC) curve., Results: Fifty-two patients with 87 cancer-containing biopsy cores and 53 patients with 101 non-cancerous biopsy cores were included. Significant mean mADC differences were present between cancers (mean mADC, 0.77-0.86 × 10 mm/s) and noncancerous transition zone without (1.12 × 10 mm/s) and with degree 1 to 2 prostatitis (1.05-1.12 × 10 mm/s; P < 0.0001-0.05). Exceptions were mixed primary and secondary GG cancers versus a degree 2 of prostatitis (P = 0.06-0.09). No significant differences were found between subcategories of primary and secondary GG cancers (P = 0.17-0.91) and between a degree 1 and 2 prostatitis and non-cancerous transition zone without prostatitis (P = 0.48-0.94).The mADC had an AUC of 0.84 to differentiate cancer versus non-cancerous transition zone. AUCs of 0.84 and 0.56 were found for mADC to differentiate prostatitis from cancer and from non-cancerous transition zone. The mADC had an AUC of 0.62 to differentiate a primary GG 4 versus GG 3 cancer., Conclusions: The mADC values can differentiate transition zone cancer from non-cancerous transition zone and from a degree 1, and from most cases of a degree 2 prostatitis. However, because of substantial overlap, mADC has a moderate accuracy to differentiate between different primary and secondary GG subcategories and cannot be used to differentiate non-cancerous transition zone from degrees 1 to 2 of prostatitis. Diffusion-weighted imaging ADC may therefore contribute in the detection of transition zone cancers; however, as a single functional MR imaging technique, diffusion-weighted imaging has a moderate diagnostic accuracy in separating higher from lower GG transition zone cancers and in differentiating prostatitis from non-cancerous transition zone.

Background: A challenge in the diagnosis of prostate cancer (PCa) is the accurate assessment of aggressiveness., Objective: To validate the performance of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate at 3 tesla (T) for the assessment of PCa aggressiveness, with prostatectomy specimens as the reference standard., Design, Settings, and Participants: A total of 45 patients with PCa scheduled for prostatectomy were included. This study was approved by the institutional review board; the need for informed consent was waived., Outcome Measurements and Statistical Analysis: Subjects underwent a clinical MRI protocol including DCE-MRI. Blinded to DCE-images, PCa was indicated on T2-weighted images based on histopathology results from prostatectomy specimens with the use of anatomical landmarks for the precise localization of the tumor. PCa was classified as low-, intermediate-, or high-grade, according to Gleason score. DCE-images were used as an overlay on T2-weighted images; mean and quartile values from semi-quantitative and pharmacokinetic model parameters were extracted per tumor region. Statistical analysis included Spearman's ρ, the Kruskal-Wallis test, and a receiver operating characteristics (ROC) analysis., Results and Limitations: Significant differences were seen for the mean and 75th percentile (p75) values of wash-in (p = 0.024 and p = 0.017, respectively), mean wash-out (p = 0.044), and p75 of transfer constant (K(trans)) (p = 0.035), all between low-grade and high-grade PCa in the peripheral zone. ROC analysis revealed the best discriminating performance between low-grade versus intermediate-grade plus high-grade PCa in the peripheral zone for p75 of wash-in, K(trans), and rate constant (Kep) (area under the curve: 0.72). Due to a limited number of tumors in the transition zone, a definitive conclusion for this region of the prostate could not be drawn., Conclusions: Quantitative parameters (K(trans) and Kep) and semi-quantitative parameters (wash-in and wash-out) derived from DCE-MRI at 3 T have the potential to assess the aggressiveness of PCa in the peripheral zone. P75 of wash-in, K(trans), and Kep offer the best possibility to discriminate low-grade from intermediate-grade plus high-grade PCa., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To estimate the required spatial alignment accuracy for correctly grading 95 % of peripheral zone (PZ) prostate cancers using a system for multiparametric magnetic resonance (MR)-guided ultrasound (US) biopsies., Methods: PZ prostate tumours were retrospectively annotated on multiparametric MR series using prostatectomy specimens as reference standard. Tumours were grouped based on homogeneous and heterogeneous apparent diffusion coefficient (ADC) values using an automated ADC texture analysis method. The proportion of heterogeneous tumours containing a distinct, high Gleason grade tumour focus yielding low ADC values was determined. Both overall tumour and high-grade focal volumes were calculated. All high-grade target volumes were then used in a simulated US biopsy system with adjustable accuracy to determine the hit rate., Results: An ADC-determined high-grade tumour focus was found in 63 % of the PZ prostate tumours. The focal volumes were significantly smaller than the total tumour volumes (median volume of 0.3 ml and 1.1 ml respectively). To correctly grade 95 % of the aggressive tumour components the target registration error (TRE) should be smaller than 1.9 mm., Conclusions: To enable finding the high Gleason grade component in 95 % of PZ prostate tumours with MR-guided US biopsies, a technical registration accuracy of 1.9 mm is required., Key Points: • MRI can identify foci of prostatic cancer with reduced apparent diffusion coefficients • Sixty-three per cent of prostatic peripheral zone tumours contain high-grade tumour low ADC foci • The median volume of such foci is 0.3 ml • Biopsy targets are significantly smaller than whole tumour volumes • Simulated registration accuracy is 1.9 mm for correctly grading 95 % of tumours.

Background: The objective of this study was comparison of characteristics of the microvasculature in transition zone tumor (TZT) and benign nodular hyperplasia (BPH) with normal prostatic transition zone (NTZ), applying accurate and objective quantification based on digital image analysis. Results of this study may increase understanding of prostate dynamic contrast enhanced (DCE) MRI analysis., Methods: Radical prostatectomy specimens of 28 patients containing TZT ranging from pT2-pT4 were used. In 11 patients a concomitant peripheral zone tumor (PZT) was present. Microvessels were visualized by CD31 immunohistochemistry. Specimens were scanned using a computer-controlled microscope with automatic recognition of microvessels. Pseudocolor maps were produced displaying microvessel density, perimeter, and area of an entire prostate transection. Mean, 75th percentile (p75) and coefficient of variation (CV) were calculated automatically in manually indicated areas of the tumor and corresponding contralateral normal tissue, and BPH., Results: Large variability was seen in TZT microvascular parameters, indicating presence of patients having both hypo and hypervascularized tumors compared to NTZ. In contrast, areas of BPH showed a more consistent increase in vascular parameters, with decreased CV. Analysis of PZT confirmed results of our previous study, with mean and p75 of all vascular parameters being significantly increased and a decrease in CV. No correlation was found for clinicopathological parameters and microvascular parameters., Conclusion: Microvasculature of transition zone tumor showed increased heterogeneity compared to BPH and peripheral zone tumors, possibly explaining the difficulty of TZT detection on DCE-MRI., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: We aimed to determine whether diffusion-weighted magnetic resonance imaging, by means of the apparent diffusion coefficient (ADC), is able to guide magnetic resonance-guided biopsy in patients fit for active surveillance (AS) and identify patients harboring high-grade Gleason components not suitable for AS., Materials and Methods: Our study was approved by the institutional review board of all participating hospitals, and all patients signed informed consent at inclusion. Fifty-four consecutive patients with low-risk prostate cancer (PCa) underwent multiparametric magnetic resonance imaging (MP-MRI) at inclusion for AS. Cancer-suspicious regions (CSRs) upon 3-T MP-MRI were identified in all patients, and magnetic resonance-guided biopsy was performed in all CSRs to obtain histopathological verification. For all CSRs, a median ADC (mADC) was calculated. Wilcoxon signed ranks and Mann-Whitney tests was performed to detect differences between the groups. We used the area under the receiver operating characteristic curve to evaluate the accuracy of mADC to predict the presence of PCa in a CSR. Level of statistical significance was set at P < 0.05., Results: Mean mADC in the CSRs with PCa was 1.04 × 10⁻³ mm²/s (SD, 0.29), whereas the CSRs with no PCa displayed a mean mADC of 1.26 × 10⁻³ mm²/s (SD, 0.25; P < 0.001). Cancer-suspicious regions with a high-grade Gleason component displayed a mean mADC of 0.84 × 10⁻³ mm²/s (SD, 0.35) vs a mean mADC for the low-grade CSRs of 1.09 × 10⁻³ mm²/s (SD, 0.25; P < 0.05). A diagnostic accuracy of mADC for predicting the presence of PCa in a CSR with an area under the receiver operating characteristic curve of 0.73 was established (95% confidence interval, 0.61-0.84)., Conclusions: Median ADC is able to predict the presence and grade of PCa in CSRs identified by MP-MRI.

Purpose: To determine the effect of computer-aided diagnosis (CAD) on less-experienced and experienced observer performance in differentiation of benign from malignant prostate lesions at 3-T multiparametric magnetic resonance (MR) imaging., Materials and Methods: The institutional review board waived the need for informed consent. Retrospectively, 34 patients were included who had prostate cancer and had undergone multiparametric MR imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced MR imaging prior to radical prostatectomy. Six radiologists less experienced in prostate imaging and four radiologists experienced in prostate imaging were asked to characterize different regions suspicious for cancer as benign or malignant on multiparametric MR images first without and subsequently with CAD software. The effect of CAD was analyzed by using a multiple-reader, multicase, receiver operating characteristic analysis and a linear mixed-model analysis., Results: In 34 patients, 206 preannotated regions, including 67 malignant and 64 benign regions in the peripheral zone (PZ) and 19 malignant and 56 benign regions in the transition zone (TZ), were evaluated. Stand-alone CAD had an overall area under the receiver operating characteristic curve (AUC) of 0.90. For PZ and TZ lesions, the AUCs were 0.92 and 0.87, respectively. Without CAD, less-experienced observers had an overall AUC of 0.81, which significantly increased to 0.91 (P = .001) with CAD. For experienced observers, the AUC without CAD was 0.88, which increased to 0.91 (P = .17) with CAD. For PZ lesions, less-experienced observers increased their AUC from 0.86 to 0.95 (P < .001) with CAD. Experienced observers showed an increase from 0.91 to 0.93 (P = .13). For TZ lesions, less-experienced observers significantly increased their performance from 0.72 to 0.79 (P = .01) with CAD and experienced observers increased their performance from 0.81 to 0.82 (P = .42)., Conclusion: Addition of CAD significantly improved the performance of less-experienced observers in distinguishing benign from malignant lesions; when less-experienced observers used CAD, they reached similar performance as experienced observers. The stand-alone performance of CAD was similar to performance of experienced observers.

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., (RSNA, 2012)

Purpose: To determine the individual and combined performance of magnetic resonance (MR) spectroscopic imaging and diffusion-weighted (DW) imaging at 3 T in the in vivo assessment of prostate cancer aggressiveness by using histopathologically defined regions of interest on radical prostatectomy specimens to define the prostate cancer regions to be investigated., Materials and Methods: The local institutional ethics review board approved this retrospective study and waived the informed consent requirement. Fifty-four patients with biopsy-proved prostate cancer underwent clinical MR spectroscopic imaging followed by prostatectomy. Guided by the histopathologic map, all spectroscopy voxels that contained tumor tissue were selected, and metabolite ratios (choline [Cho] plus creatine [Cr]-to-citrate [Cit] and Cho/Cr ratios) were derived. For each spectroscopic voxel, 25th percentile apparent diffusion coefficient (ADC) of the region corresponding to that voxel was determined, representing the most aberrant tumor part on the ADC map, which was often smaller than spectroscopic imaging voxels. Maximum metabolic ratios and minimum 25th percentile ADC of each tumor were related to tumor aggressiveness and were used to differentiate aggressiveness classes. A logistic regression model (LRM) was used to combine data from both modalities., Results: Significant correlation was found between aggressiveness classes and maximum Cho+Cr/Cit ratio (ρ=0.36), maximum Cho/Cr ratio (ρ=0.35), and minimum 25th percentile ADC (ρ=-0.63) in the peripheral zone (PZ). In the transition zone (TZ), the correlation was significant for only Cho+Cr/Cit and Cho/Cr ratios (ρ=0.58 and ρ=0.60, respectively). For differentiation between aggressiveness classes, LRM use did not result in significantly improved differentiation over any individual variables., Conclusion: These findings enabled confirmation that MR spectroscopic imaging and DW imaging offer potential for in vivo noninvasive assessment of prostate cancer aggressiveness, and both modalities have comparable performance. The combination did not result in better performance. Nonetheless, the better performances of metabolite ratios in the TZ and of ADCs in the PZ suggest that they have complementary value., (© RSNA, 2012)

Background: Patients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)-guided biopsy (MRGB) has shown high prostate cancer (PCa)-detection rates in studies with limited patient numbers., Objective: Determine the detection rate of (clinically significant) PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one or more negative TRUS-biopsy sessions., Design, Setting, and Participants: Of 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection., Intervention: Patients underwent MRGB of MP-MRI CSRs., Measurements: (Clinically significant) MRGB cancer-detection rates were determined. Clinically significant cancer was defined by accepted (i.a. Epstein and d'Amico) criteria based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB., Results and Limitations: In a total of 117 patients, cancer was detected with MRGB (n=108) or after negative MRGB (n=9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. Clinically significant cancers were detected in seven of nine (78%) negative MRGB patients in whom PCa was detected during follow-up. Sensitivity analysis resulted in increased cancer detection (47-56%). Complications occurred in 0.2% of patients (5 of 265)., Conclusions: In patients with elevated PSA and one or more negative TRUS-biopsy sessions, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%)., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Diffusion-weighted magnetic resonance (MR) imaging (DWI) might be able to fulfill the need to accurately identify high-grade prostate carcinoma, in patients initially selected for active surveillance in the Prostate Specific Antigen (PSA) screening era based on transrectal ultrasound-guided biopsy Gleason score. We aimed to determine whether DWI is able to correctly identify those patients with a biopsy Gleason score of ≤ 3 + 3 = 6, but harboring Gleason 4 and/or 5 components in their radical prostatectomy (RP) specimen., Materials and Methods: Whole-mount RP specimens were used to identify regions of interest corresponding with tumor on the DWI-derived apparent diffusion coefficient (ADC) maps in 23 patients with a Gleason ≤ 3 + 3 = 6 on biopsy. ADC values were correlated with RP Gleason grades. Statistical analysis was performed by calculating area under the receiver operating characteristic curve for identification of prostate cancer with Gleason 4 and/or 5 components using DWI, and Mann-Whitney U testing was performed to detect differences in median ADC values for tumors with presence of Gleason grade 4 and/or 5 versus a highest Gleason grade of ≤ 3 on RP., Results: A diagnostic accuracy of median ADC values for identifying patients subject to transrectal ultrasound-guided biopsy undergrading with an area under the receiver operating characteristic curve of 0.88 was established using RP Gleason score as a reference. In patients harboring a Gleason 4 and/or 5 component, the median ADC was 0.86 × 10(-3) mm/s (standard deviation ± 0.21), whereas patients harboring no Gleason 4 and/or 5 component displayed a median ADC of 1.16 × 10(-3) mm/s (standard deviation ± 0.19) for the single tumor slice with the lowest median ADC (P < 0.002)., Conclusions: DWI is able to predict the presence of high-grade tumor in patients with a Gleason ≤ 3 + 3 = 6 on biopsy, providing important information for treatment decisions.

Background: One of the most important clinical challenges in prostate cancer (PCa) management is an in vivo assessment of cancer aggressiveness., Objective: To validate the performance of magnetic resonance (MR) spectroscopic imaging (MRSI) of the prostate at 3 T for the purpose of assessing tumour aggressiveness based on the ratio of choline plus creatine to citrate (Cho+Cr/Cit) and of choline to creatine (Cho/Cr), using the Gleason score of the radical prostatectomy (RP) specimen as the gold standard., Design, Setting, and Participants: A total of 43 biopsy-proven PCa patients with 53 clinically relevant tumour foci were retrospectively included in this study., Measurements: Patients underwent MR imaging and MRSI examination followed by RP. From MRSI, all spectroscopy voxels containing tumour were selected by a radiologist guided by the prostatectomy histopathology map only. For each tumour, two spectroscopists determined the maximum Cho+Cr/Cit, Cho/Cr, and malignancy rating using a standardised threshold approach, incorporating both metabolic ratios. The maximum Cho+Cr/Cit, Cho/Cr, and malignancy ratings showed a relation to tumour aggressiveness and so were used to differentiate among tumour aggressiveness classes., Results and Limitations: The maximum Cho+Cr/Cit ratio, maximum Cho/Cr ratio, and malignancy rating of a standardised threshold approach separated low-grade from higher-grade tumours, with areas under the receiver operating characteristic (ROC) curves of 0.70, 0.74, and 0.78, respectively., Conclusions: MRSI offers possibilities for an in vivo, noninvasive assessment of PCa aggressiveness. The combination of the different metabolite ratios was used with promising results for discrimination among different aggressiveness classes., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aims: Different methods to substage extraprostatic extension (EPE) were correlated with biochemical recurrence (BCR) after radical prostatectomy (RP)., Methods and Results:   A total of 157 consecutive RP specimens with EPE were completely embedded. Twenty-three patients with adjuvant therapy or detectable postoperative PSA levels were excluded, leaving 134 patients for BCR analysis. Data were analysed using Kaplan-Meier survival and Cox regression analyses. In univariate analysis, maximal radial distance (RD) was associated with BCR as continuous (P = 0.006) and dichotomous (P = 0.002) parameters. In multivariate analysis, independent predictors of BCR were preoperative prostate-specific antigen (PSA) (P = 0.006), Gleason score (P = 0.001), positive surgical margins (P = 0.005), maximal RD dichotomized at 0.6 mm [= one high-power field (HPF)]; hazard ratio (HR) 3.4; 95% confidence interval (CI) 1.48-7.85; P = 0.004), total RD (P = 0.009) and EPE quantification according to Epstein (P = 0.002) and to Wheeler (P = 0.004). The 5-year risk of BCR was 20% (95% CI 0.65-0.94) in patients with RD ≤ 0.6 mm and 47% (95% CI: 0.41-0.65) with RD > 0.6 mm. The restriction of focal EPE in no more than two slides (Epstein and Wheeler) gave no better results., Conclusions: Maximal RD dichotomized at one HPF is an objective method to subdivide EPE and a strong, independent predictor for BCR after RP. Its use is recommended for substaging pT3a in future TNM classifications., (2011 Blackwell Publishing Limited.)

Purpose: The purpose of this study was to compare the diagnostic performance of 3 Tesla, 3-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) in the localization of prostate cancer (PCa) with and without the use of an endorectal coil (ERC)., Materials and Methods: Our prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Between October 2004 and January 2006, 18 patients with histologically proven PCa on biopsy and scheduled for radical prostatectomy were included and underwent 3D-MRSI with and without an ERC. The prostate was divided into 14 regions of interest (ROIs). Four readers independently rated (on a 5-point scale) their confidence that cancer was present in each of these ROIs. These findings were correlated with whole-mount prostatectomy specimens. Areas under the receiver-operating characteristic curve were determined. A difference with a P < 0.05 was considered significant., Results: A total of 504 ROIs were rated for the presence and absence of PCa. Localization of PCa with MRSI with the use of an ERC had a significantly higher areas under the receiver-operating characteristic curve (0.68) than MRSI without the use of an ERC (0.63) (P = 0.015)., Conclusion: The use of an ERC in 3D MRSI in localizing PCa at 3 Tesla slightly but significantly increased the localization performance compared with not using an ERC.

Purpose: To retrospectively determine the relationship between apparent diffusion coefficients (ADCs) obtained with 3.0-T diffusion-weighted (DW) magnetic resonance (MR) imaging and Gleason grades in peripheral zone prostate cancer., Materials and Methods: The requirement to obtain institutional review board approval was waived. Fifty-one patients with prostate cancer underwent MR imaging before prostatectomy, including DW MR imaging with b values of 0, 50, 500, and 800 sec/mm(2). In prostatectomy specimens, separate slice-by-slice determinations of Gleason grade groups were performed according to primary, secondary, and tertiary Gleason grades. In addition, tumors were classified into qualitative grade groups (low-, intermediate-, or high-grade tumors). ADC maps were aligned to step-sections and regions of interest annotated for each tumor slice. The median ADC of tumors was related to qualitative grade groups with linear mixed-model regression analysis. The accuracy of the median ADC in the most aggressive tumor component in the differentiation of low- from combined intermediate- and high-grade tumors was summarized by using the area under the receiver operating characteristic (ROC) curve (A(z))., Results: In 51 prostatectomy specimens, 62 different tumors and 251 step-section tumor lesions were identified. The median ADC in the tumors showed a negative relationship with Gleason grade group, and differences among the three qualitative grade groups were statistically significant (P < .001). Overall, with an increase of one qualitative grade group, the median ADC (±standard deviation) decreased 0.18 × 10(-3) mm(2)/sec ± 0.02. Low-, intermediate-, and high-grade tumors had a median ADC of 1.30 × 10(-3) mm(2)/sec ± 0.30, 1.07 × 10(-3) mm(2)/sec ± 0.30, and 0.94 × 10(-3) mm(2)/sec ± 0.30, respectively. ROC analysis showed a discriminatory performance of A(z) = 0.90 in discerning low-grade from combined intermediate- and high-grade lesions., Conclusion: ADCs at 3.0 T showed an inverse relationship to Gleason grades in peripheral zone prostate cancer. A high discriminatory performance was achieved in the differentiation of low-, intermediate-, and high-grade cancer., (RSNA, 2011)

Background: The objective of this study was to analyze the characteristics of lymphatic vasculature in normal and (peri)tumoral prostate tissue, applying accurate and objective quantification techniques based on digital image analysis., Methods: Radical prostatectomy specimens of 27 patients were selected containing organ confined peripheral zone tumors, which were restricted to one side of the prostate (pT2a). Lymph vessels were visualized by immunohistochemistry against D2-40. Lymphatic vessel density, perimeter, and area were assessed over the entire tumor and corresponding contralateral normal tissue. Also, morphology (area, perimeter, and diameter) of individual lymph vessels were measured in (peri)tumoral and normal tissue., Results: No differences were found in the overall lymph vasculature between tumor and normal peripheral zone. However, the area, perimeter, and diameter of individual lymph vessel profiles were significantly decreased in (peri)tumoral as compared to normal tissue. No differences were seen for these parameters between peritumoral and tumoral area. Comparing the coefficient of variation between compartments (normal, (peri)tumoral), no differences were observed for any parameter., Conclusions: Although differences exist between the morphology of individual lymph vessels in tumor versus normal tissue, the overall vascular bed (number and summed area and perimeter of lymphatics per area unit tissue) is unaffected in tumor. Peritumoral lymphatics resemble lymphatics in tumor tissue rather than normal lymphatics., (© 2010 Wiley-Liss, Inc.)

Aims: To evaluate the prognostic role of the length of a positive surgical margin (+SM) for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostatic cancer., Methods and Results: Consecutive RP specimens (n = 267) with +SM were analysed. All RP specimens were sectioned at 4-mm intervals and completely embedded. Data were analysed using Kaplan-Meier survival analysis and proportional hazards models. In 267 patients the length of +SM ranged from 0.4 to 174.5 mm (median 11.2 mm) and correlated with preoperative prostate specific antigen (PSA) (P < 0.001), pathological stage (P < 0.001), tumour volume (P = 0.001), number of +SM (P < 0.001), Gleason grade at +SM (P < 0.001) and Gleason score (P = 0.015). Patients with detectable postoperative PSA levels (n = 34) or adjuvant therapy (n = 59) were excluded from BCR analysis. In the remaining 174 patients the 5-year risk of BCR was 29%; in patients with +SM 10 mm this was 21% and 39%, respectively. On multivariable analysis BCR was associated with an increasing length of +SM (10 mm; hazard ratio 2.15; 95% confidence interval 1.12, 4.15; P = 0.022)., Conclusions: The length of +SM is an independent prognostic factor for BCR in patients with undetectable PSA after RP.

Objectives: The objective of this study was to assess the feasibility of the combination of magnetic resonance (MR)-guided biopsy (MRGB) and diagnostic 3T MR imaging in the localization of local recurrence of prostate cancer (PCa) after external beam radiation therapy (EBRT)., Materials and Methods: Twenty-four consecutive men with biochemical failure suspected of local recurrence after initial EBRT were enrolled prospectively in this study. All patients underwent a diagnostic 3T MR examination of the prostate. T2-weighted and dynamic contrast-enhanced MR images (DCE-MRI) were acquired. Two radiologists evaluated the MR images in consensus for tumor suspicious regions (TSRs) for local recurrence. Subsequently, these TSRs were biopsied under MR-guidance and histopathologically evaluated for the presence of recurrent PCa. Descriptive statistical analysis was applied., Results: Tissue sampling was successful in all patients and all TSRs. The positive predictive value on a per patient basis was 75% (15/20) and on a per TSR basis 68% (26/38). The median number of biopsies taken per patient was 3, and the duration of an MRGB session was 31 minutes. No intervention-related complications occurred., Conclusions: The combination of MRGB and diagnostic MR imaging of the prostate was a feasible technique to localize PCa recurrence after EBRT using a low number of cores in a clinically acceptable time.

Objective: Small volume prostate cancers (<0.5 cc, svPC), and insignificant prostate cancers (<0.5 cc and Gleason scores <7, InsigPC) are considered clinically insignificant by some investigators. The aim of this study is to determine the biochemical recurrence rate (BCR) of svPC and InsigPC in prostatectomy specimens., Methods: In total, 502 patients with prostate cancer, treated with radical prostatectomy (RP) between 1992 and 2005 and with detailed pathological classification, were included in the present study. Patients were postoperatively followed for a median period of 39.5 months (0.6-150). A total of 82 specimens (16.3%) with svPC including 64 (12.8%) with InsigPC were identified. BCR was defined as 2 consecutive PSA levels >0.10 ng/ml., Results: In the total group, the median age at the time of surgery was 62.7 years (42.4-73.4) and the median preoperative PSA level was 8.0 ng/ml. Patients with InsigPC had Gleason scores of 4 in 7%, 5 in 37%, and 6 in 56%. Positive surgical margins were identified in 13 (15.9%) svPC and in 8 (12.7%) InsigPC specimens. The 5-year risk of BCR for the svPC group and the insigPC group was 10% (95% CI 2-18%, 7 and 5 patients, respectively) vs. 35% (95% CI 29-41%) in the rest of the cohort (log rank P = 0.001)., Conclusion: Patients with svPC and patients with InsigPC have a significantly lower risk of BCR. However, even in this seemingly very favorable patient group, 1 in 10 patients will develop a BCR after RP. Therefore, new studies are needed to examine what the prognostic relevance is of small-volume tumors.

Objective: To investigate whether body mass index (BMI) is a prognostic factor for biochemical recurrence (BCR) in Dutch men after radical prostatectomy (RP), as although epidemiological studies of obesity in relation to prostate cancer have provided conflicting results, recent studies from the USA suggest that a higher BMI is a risk factor for progression of prostate cancer., Patients and Methods: Of the 1417 patients with prostate cancer who had RP at two University hospitals, 1302 were included in the present study. BMI (kg/m(2)) classes were defined as normal (<25), overweight (25-30) and obese (> or =30). The median follow-up was 59 months and clinical data were obtained retrospectively from charts. BCR was defined as two consecutive prostate-specific antigen (PSA) levels of >0.1 ng/mL., Results: In all, 600 patients were classified as having normal weight (43.9%), 665 as overweight (48.6%) and 103 as obese (7.5%). Overall, 297 patients developed BCR after RP; the 10-year risk (95% confidence interval) of BCR was 31.9 (26.6-37.2)%, 30.5 (25.8-35.2)% and 23.9 (14.9-32.9)% for patients in the three categories, respectively (P = 0.836). Multivariable proportional hazard regression analyses of BMI and established prognostic factors for BCR did not change these results., Conclusion: BMI appeared to have no prognostic value for BCR in Dutch patients with clinically localized prostate cancer and treated with RP.

Background: Contrast enhanced imaging enables powerful, non-invasive diagnostics, important for detection and staging of early prostate cancer. The uptake of contrast agent is increased in prostate cancer as compared to normal prostate tissue. To reveal the underlying physiological mechanisms, quantification of tissue components in pathology specimens may yield important information. Aim of this study was to investigate whether microvascularity is increased in prostate confined cancer (pT2)., Methods: Radical prostatectomy specimens of 26 patients were selected for organ confined peripheral zone tumors which were restricted to one side of the prostate. Microvessels were visualized by immunohistochemistry against CD31. Specimens were scanned using a computer controlled microscope and scanning stage and vessels were recognized automatically. Pseudocolor mappings were produced showing number of vascular profiles (MVD), vascular area (MVA) and perimeter (MVP) in an overview of the entire prostate transection. MVD is a common measure for vascularity, whereas MVA represents the 3D vascular volume and MVP the perfused surface area. Mean, coefficient of variation and 75th percentile of these parameters were calculated automatically in manually indicated areas, consisting of the entire tumor area and the corresponding normal area in the contra lateral side of the prostate., Results: The mappings clearly indicate areas of increased vascularity in prostate transections. In tumor tissue an increase was found compared to normal tissue of 81%, 49%, and 62% for mean MVD, mean MVA and mean MVP, respectively (P < 0.001 for all comparisons). In contrast, the heterogeneity in tumor vasculature was significantly decreased as compared to normal prostate (P < 0.001)., Conclusions: Characteristics of microvasculature deviated significantly in pT2 prostate tumor as compared to normal tissue., (Copyright 2008 Wiley-Liss, Inc.)

Background: Due to the drawbacks of serum prostate-specific antigen, there is an ongoing search for new diagnostic and prognostic prostate cancer (PCa) markers. PCA3 has proven to be of value in the diagnosis of PCa. However, so far few attempts have been made to investigate the prognostic value of PCA3. Our objective was to further investigate the prognostic value of PCA3., Methods: In this study we correlated the PCA3 score in urinary sediments after digital rectal examination in 62 men with the classical prognostic parameters assessed in radical prostatectomy specimens (i.e. Gleason score, pathological tumor stage and total tumor volume) and moreover, with the expression of three immunohistochemical markers for PCa biological aggressiveness (i.e. E-cadherin, alpha-catenin and EZH2). The results from this study serve as a reflection on and a valuable adjunct to recently published results., Results: We did not find a significant correlation of the PCA3 score with the classical prognostic parameters assessed in radical prostatectomy specimens or the expression of the immunohistochemical markers for PCa biological aggressiveness. However, we did observe a trend for a higher PCA3 score in significant PCa versus insignificant PCa, aberrant E-cadherin staining versus normal E-cadherin staining and increased EZH2 staining versus normal EZH2 staining., Conclusions: In this study we could not prove the prognostic value of PCA3. Further research with large numbers of men and adequate follow-up is needed to provide a definitive answer to the question if PCA3 is not only a diagnostic but also a prognostic PCa marker., (Copyright (c) 2008 Wiley-Liss, Inc.)

Objective: To evaluate the prognostic role of the 2002 Tumour-Nodes-Metastasis (TNM) pT2 subclassification for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer., Patients and Methods: The 1997 TNM staging system is based on one subdivision for organ-confined prostate tumours (T2a, unilateral; T2b, bilateral involvement). The 2002 TNM staging system subdivides unilateral involvement into T2a (half of one lobe or less) and T2b (more than one half of one lobe), while bilateral involvement is classified as T2c. In all, 542 patients were treated with RP at our institute; the RP specimens were completely embedded and histopathologically evaluated for Gleason grade, tumour volume and anatomical extent, and were staged according to the 2002 TNM staging criteria. Patients were followed for a median of 39.5 months. BCR was defined as two subsequent increasing prostate-specific antigen (PSA) levels of >0.10 ng/mL. Kaplan-Meier and proportional hazards regression analyses were used to evaluate the univariable and multivariable prognostic effect of tumour stage., Results: According to the 2002 TNM staging system, 360 specimens were found to have pT2 tumours; 79 (22%) of the RP specimens were staged as pT2a and 281 (78%) as pT2c; no pT2b specimens were identified. Patients with unilateral involvement (pT2a) had a 5-year risk of BCR of 13%, while those with bilateral involvement (pT2c) had a risk of 23% (log rank test, P = 0.056). Patients with pT2c disease were more likely to have a larger tumour volume (Mann-Whitney U-test P < 0.001) and positive surgical margins (Fishers' exact test, P = 0.001)than those with pT2a tumours. Mann-Whitney U-tests showed no differences between the groups for preoperative PSA levels (P = 0.167). Also, the RP Gleason score was no different between groups (Pearson chi-square, P = 0.807). In the multivariable analyses, positive surgical margins appeared to increase the risk of BCR (hazard ratio 4.4, 95% confidence interval 2.5-7.9); pT2c vs pT2a had only a marginally (insignificant) additional effect (1.3, 0.6-2.7)., Conclusion: The absence of a true unilateral pathological T2b tumour in a series of 360 pT2 RP specimens questions the relevance of substaging unilateral disease. The limited differences in BCR and in pathological features of unilateral vs bilateral pT2 prostate cancer justify modifying the TNM staging system to one with no subclassification of pT2 disease, or at most as only one subdivision into unilateral (T2a) and bilateral (T2b) disease, combining the T2b and T2c substages.

A novel automated computerized scheme has been developed for determining a likelihood measure of malignancy for cancer suspicious regions in the prostate based on dynamic contrast-enhanced magnetic resonance imaging (MRI) (DCE-MRI) images. Our database consisted of 34 consecutive patients with histologically proven adenocarcinoma in the peripheral zone of the prostate. Both carcinoma and non-malignant tissue were annotated in consensus on MR images by a radiologist and a researcher using whole mount step-section histopathology as standard of reference. The annotations were used as regions of interest (ROIs). A feature set comprising pharmacokinetic parameters and a T1 estimate was extracted from the ROIs to train a support vector machine as classifier. The output of the classifier was used as a measure of likelihood of malignancy. Diagnostic performance of the scheme was evaluated using the area under the ROC curve. The diagnostic accuracy obtained for differentiating prostate cancer from non-malignant disorders in the peripheral zone was 0.83 (0.75-0.92). This suggests that it is feasible to develop a computer aided diagnosis system capable of characterizing prostate cancer in the peripheral zone based on DCE-MRI.

Purpose: To evaluate sensitivity and specificity of proton magnetic resonance (MR) spectroscopy of the prostate with external surface coil elements at 3 T for differentiation of cancer from healthy tissue within an acceptable measurement time, by using histopathologic findings as the reference standard., Materials and Methods: The study was approved by the institutional review board; informed consent was obtained. Forty-five men (age range, 51-70 years) underwent 3-T MR imaging with external radiofrequency surface coils for signal reception. MR spectroscopy was performed with acquisition-weighted three-dimensional water- and lipid-suppressed point-resolved spectroscopy pulse sequence. Voxels were classified into healthy peripheral zone, central gland, and periurethral zone and cancer tissue. Cancer voxels were classified according to cancer size and certainty in matching histopathologic findings with MR images. After visual inspection of automated fitting of classified voxels, the choline plus creatine-to-citrate (Cho + Cr/Cit) ratio was calculated for all tissues. Area under the receiver operating characteristic curves (A(z)) values were used to assess accuracy of discrimination of cancer from healthy tissues. P < .05 indicated a significant difference., Results: After exclusion of four patients with no voxels that passed visual inspection of the automated fit, a median of 82% of the classified voxels per patient was used in the analysis. Mean Cho + Cr/Cit ratios for healthy tissues were 0.22 +/- 0.12 (standard deviation) for peripheral zone, 0.34 +/- 0.14 for central gland, and 0.36 +/- 0.20 for periurethral area; all were significantly different from that of cancer (P < .001). A(z) for discrimination of probable and definite cancer tissue from healthy tissue for the peripheral zone (0.84) was significantly higher than that for the central gland (0.69) (P < .05)., Conclusion: Three-dimensional proton MR spectroscopy of the prostate, with a combination of only external radiofrequency surface coils at 3 T, can be used to discriminate cancer from healthy tissue.

Purpose: To prospectively compare image quality and accuracy of prostate cancer localization and staging with body-array coil (BAC) versus endorectal coil (ERC) T2-weighted magnetic resonance (MR) imaging at 3 T, with histopathologic findings as the reference standard., Materials and Methods: After institutional review board approval and written informed consent, 46 men underwent 3-T T2-weighted MR imaging with a BAC (voxel size, 0.43 x 0.43 x 4.00 mm) and an ERC (voxel size, 0.26 x 0.26 x 2.50 mm) before radical prostatectomy. Four radiologists independently evaluated data sets obtained with the BAC and ERC separately. Ten image quality characteristics related to prostate cancer localization and staging were assigned scores. Prostate cancer presence was recorded with a five-point probability scale in each of 14 segments that included the whole prostate. Disease stage was classified as organ-confined or locally advanced with a five-point probability scale. Whole-mount-section histopathologic examination was the reference standard. Areas under the receiver operating characteristic curve (AUCs) and diagnostic performance parameters were determined. A difference with a P value of less than .05 was considered significant., Results: Forty-six patients (mean age, 61 years) were included for analysis. Significantly more motion artifacts were present with ERC imaging (P<.001). All other image quality characteristics improved significantly (P<.001) with ERC imaging. With ERC imaging, the AUC for localization of prostate cancer was significantly increased from 0.62 to 0.68 (P<.001). ERC imaging significantly increased the AUCs for staging, and sensitivity for detection of locally advanced disease by experienced readers was increased from 7% (one of 15) to a range of 73% (11 of 15) to 80% (12 of 15) (P<.05), whereas a high specificity of 97% (30 of 31) to 100% (31 of 31) was maintained. Extracapsular extension as small as 0.5 mm at histopathologic examination could be accurately detected only with ERC imaging., Conclusion: Image quality and localization improved significantly with ERC imaging compared with BAC imaging. For experienced radiologists, the staging performance was significantly better with ERC imaging., ((c) RSNA, 2007.)

In a patient suspected of having recurrent prostate cancer after radiation therapy, we demonstrate the feasibility of noninvasive proton magnetic resonance spectroscopic (1H-MRS) imaging of the prostate and a lymph node at 3 T using a matrix of external surface coils. Written informed consent was obtained from the patient. With 1H-MRS imaging, high choline with low citrate signal was observed in the prostate, and in the lymph node a signal of choline-containing compounds was identified. The tissue level of the compounds in the enlarged lymph node was estimated to be 8.1 mmol/kg water. Subsequent histopathological analysis of systematic transrectal ultrasound-guided prostate biopsy and computed tomography-guided biopsy of the lymph node confirmed the presence of prostate cancer in both.

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.

Objectives: We sought to determine the localization accuracy using 3-dimensional (3D) proton magnetic resonance spectroscopic imaging (MRSI) of the entire prostate with a standardized thresholds approach in prostate cancer patients., Materials and Methods: In a prospective study, 32 consecutive patients were examined. Mean age and prostate specific antigen level were 61 years and 7.8 ng/mL, respectively. Median biopsy Gleason score was 6. T2-weighted MRI and 3D MRSI of the entire prostate were performed. Three readers recorded the location of suspicious peripheral zone and central gland cancer nodules on a standardized division of the prostate (14 regions of interest [ROI]) using a standardized thresholds approach. The degree of diagnostic confidence for each ROI was recorded on a 5-point scale. Reconstructed whole-mount section histopathology was the standard of reference. The sensitivity, specificity, positive, and negative predictive value, overall accuracy and interobserver agreement were calculated. Areas under the ROI-based receiver operating characteristic curve (AUC) and diagnostic performance parameters were determined., Results: The standardized thresholds approach had an accuracy of 81% and an AUC of 0.85-0.86 for differentiation between benign and malignant ROIs in the peripheral zone and an accuracy of 87% and an AUC of 0.86-0.91 for this differentiation in the central gland, respectively. Specificities of 81% to 88% were achieved with accompanying sensitivities of 75% to 92% for both peripheral zone and central gland, respectively. Moderate to near-perfect interobserver agreement was demonstrated (kappa=0.42-0.91)., Conclusion: Our data indicate that a standardized zone-specific threshold approach in MRSI of the prostate is able to prospectively differentiate between benign and malignant tissues in the peripheral zone and the central gland with good accuracy and interobserver agreement.

Purpose: To prospectively determine the accuracies of T2-weighted magnetic resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and quantitative three-dimensional (3D) proton MR spectroscopic imaging of the entire prostate for prostate cancer localization, with whole-mount histopathologic section findings as the reference standard., Materials and Methods: This study was approved by the institutional review board, and informed consent was obtained from all patients. Thirty-four consecutive men with a mean age of 60 years and a mean prostate-specific antigen level of 8 ng/mL were examined. The median biopsy Gleason score was 6. T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and 3D MR spectroscopic imaging were performed, and on the basis of the image data, two readers with different levels of experience recorded the location of the suspicious peripheral zone and central gland tumor nodules on each of 14 standardized regions of interest (ROIs) in the prostate. The degree of diagnostic confidence for each ROI was recorded on a five-point scale. Localization accuracy and ROI-based receiver operating characteristic (ROC) curves were calculated., Results: For both readers, areas under the ROC curve for T2-weighted MR, dynamic contrast-enhanced MR, and 3D MR spectroscopic imaging were 0.68, 0.91, and 0.80, respectively. Reader accuracy in tumor localization with dynamic contrast-enhanced imaging was significantly better than that with quantitative spectroscopic imaging (P < .01). Reader accuracy in tumor localization with both dynamic contrast-enhanced imaging and spectroscopic imaging was significantly better than that with T2-weighted imaging (P < .01)., Conclusion: Compared with use of T2-weighted MR imaging, use of dynamic contrast-enhanced MR imaging and 3D MR spectroscopic imaging facilitated significantly improved accuracy in prostate cancer localization.

Purpose: To prospectively investigate the local staging accuracy of 3-T endorectal magnetic resonance (MR) imaging for prostate cancer by using whole-mount-section histopathologic analysis as the standard of reference., Materials and Methods: This study was approved by the institutional review board, and informed consent was obtained from all patients. In 35 consecutive patients (median age, 62.3 years) with biopsy-proved prostate cancer, 3-T endorectal MR imaging was performed. High-spatial-resolution endorectal T2-weighted fast spin-echo images of the prostate were obtained in three planes. MR images were prospectively evaluated by two experienced radiologists and a third radiologist who was less experienced with regard to local disease extent by using five established extracapsular criteria. Whole-mount-section histopathologic analysis was the standard of reference. Evaluation was performed according to octant and patient. Sensitivity, specificity, positive and negative predictive values, overall accuracy, and interobserver agreement were calculated., Results: Thirty-two patients who underwent radical prostatectomy were enrolled in this study. Accuracy, sensitivity, and specificity of local staging were 94% (30 of 32), 88% (seven of eight), and 96% (23 of 24), respectively, for both experienced radiologists, and these values were 81% (26 of 32), 50% (four of eight), and 92% (22 of 24), respectively, for the less experienced radiologist. There was substantial agreement between both experienced readers (kappa = 0.42-0.79) and moderate agreement between the less experienced reader and the experienced readers with respect to all extracapsular criteria. In regard to the three cases of minimal capsular invasion, two were detected by both experienced radiologists., Conclusion: In this study, high accuracy for staging of prostate cancer at 3-T endorectal MR imaging, with moderate to substantial observer agreement, was demonstrated. In addition, minimal capsular invasion could be detected., (RSNA, 2005.)

Purpose: To prospectively determine the accuracy of experienced and less experienced readers in the interpretation of combined T2-weighted fast spin-echo (SE) magnetic resonance (MR) images and dynamic contrast material-enhanced MR images compared with T2-weighted fast SE alone, with respect to differentiation of stage T2 versus stage T3 prostate carcinoma, with histologic analysis serving as the reference standard., Materials and Methods: Institutional review board approval and informed consent were obtained, and 124 consecutive men (age range, 42-74 years; median age, 63 years) with biopsy-proved prostate cancer underwent MR imaging and were candidates for radical prostatectomy. T2-weighted fast SE MR images and multisection dynamic contrast-enhanced MR images with a 2-second time resolution for the whole prostate were obtained. The T2-weighted and fused color-coded parametric dynamic contrast-enhanced MR images with T2-weighted images were evaluated prospectively and scored with regard to local extent by one experienced reader and evaluated retrospectively by two less experienced readers working in consensus by using a five-point scale; images with a score greater than or equal to four were considered indicative of T3 disease. Results were correlated with whole-mount section histopathologic findings, and receiver operating characteristics analysis was performed., Results: Twenty-five patients were excluded because of positive findings in the lymph nodes (n = 16), preoperative biopsy-proved seminal vesicle invasion (n = 5), and an absent dynamic dataset (n = 4). Ninety-nine patients were included in this study. The overall sensitivity, specificity, and accuracy of MR staging performance in prostate cancer with dynamic contrast-enhanced MR imaging was 69% (24 of 35 patients), 97% (62 of 64 patients), and 87% (86 of 99 patients), respectively, for the experienced reader. This difference was not significant (P = .48) when results were compared with results from the T2-weighted images. Staging performance for the less experienced readers with parametric dynamic contrast-enhanced MR imaging, however, resulted in significant improvement of the area under the receiver operating characteristics curve (A(z)) compared with T2-weighted MR imaging alone (A(z) = .66 and .82, respectively; P = .01)., Conclusion: The use of multisection dynamic contrast-enhanced MR imaging in staging prostate cancer showed significant improvement in staging performance for the less experienced readers but had no benefit for the experienced reader.