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Background: Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway "PEOPLE: PatiEnt prOstate samPLes for rEsearch" to collect high-quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue., Methods: Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset., Results: Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture., Conclusion: Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue., (© 2019 Wiley Periodicals, Inc.)

Objectives: To evaluate the feasibility of a novel multiparametric MRI (mpMRI) and cognitive fusion transperineal targeted biopsy (MRTB) led prostate cancer (PCa) diagnostic service with regard to cancer detection and reducing time to diagnosis and treatment., Design: Consecutive men being investigated for possible PCa under the UK 2-week wait guidelines., Setting: Tertiary referral centre for PCa in the UK., Participants: Men referred with a raised prostate-specific antigen (PSA) or abnormal digital rectal examination between February 2015 and March 2016 under the UK 2-week rule guideline., Interventions: An mpMRI was performed prior to patients attending clinic, on the same day. If required, MRTB was offered. Results were available within 48 hours and discussed at a specialist multidisciplinary team meeting. Patients returned for counselling within 7 days PRIMARY AND SECONDARY OUTCOME MEASURES: Outcome measures in this regard included the time to diagnosis and treatment of patients referred with a suspicion of PCa. Quality control outcome measures included clinically significant and total cancer detection rates., Results: 112 men were referred to the service. 111 (99.1%) underwent mpMRI. Median PSA was 9.4 ng/mL (IQR 5.6-21.0). 87 patients had a target on mpMRI with 25 scoring Likert 3/5 for likelihood of disease, 26 4/5 and 36 5/5.57 (51%) patients received a local anaesthetic, Magnetic resonance imaging targeted biopsy (MRTB). Cancer was detected in 45 (79%). 43 (96%) had University College London definition 2 disease or greater. The times to diagnosis and treatment were a median of 8 and 20 days, respectively., Conclusions: This approach greatly reduces the time to diagnosis and treatment. Detection rates of significant cancer are high. Similar services may be valuable to patients with a potential diagnosis of PCa., Competing Interests: Competing interests: HUA’s research is supported by core funding from the UK’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre. This paper is independent research funded by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC). HUA currently receives funding from the Wellcome Trust, Prostate Cancer UK, Sonacare Inc, Trod Medical and Sophiris Biocorp for trials in prostate cancer. HUA is a paid medical consultant for Sophiris Biocorp for trials work. ME’s research is supported by core funding from the UK’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. He was awarded NIHR Senior Investigator in 2015. ME receives funding from NIHR-i4i, MRC, Sonacare Inc, Trod Medical, Cancer Vaccine Institute and Sophiris Biocorp for trials in prostate cancer. ME is a medical consultant to Sonacare Inc, Sophiris Biocorp, Steba Biotech, Exact Imaging and Profound Medical. CMM receives funding from the National Institute for Health Research, The European Association of Urology Research Foundation, Prostate Cancer UK, Movember and the Cancer Vaccine Institute, for clinical prostate cancer research. She has received advisory board fees for Genomic Health. HUA, ME, and CMM are all proctors for HIFU and are paid for training other surgeons in this procedure. ME and AF have loan notes/stock options in Nuada Medical Ltd (UK)., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: T 2 -weighted imaging (T 2 -WI) information has been used in a qualitative manner in the assessment of prostate cancer. Quantitative derivatives (T 2 relaxation time) can be generated from T 2 -WI. These outputs may be useful in helping to discriminate clinically significant prostate cancer from background signal., Purpose/hypothesis: To investigate changes in quantitative T 2 parameters in lesions and noncancerous tissue of men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo daily for 6 months., Study Type: Retrospective., Population/subjects: Forty men randomized to 6 months of daily dutasteride (n = 20) or placebo (n = 20)., Field Strength/sequence: Multiparametric 3T MRI at baseline and 6 months. This included a multiecho MR sequence for quantification of the T 2 relaxation times, in three regions of interest (index lesion, noncancerous peripheral [PZ] and transitional [TZ] zones). A synthetic signal contrast (T 2 Q contrast) between lesion and noncancerous tissue was assessed using quantitative T 2 values. Signal contrast was calculated using the T 2 -weighted sequence (T 2 W contrast)., Assessment: Two radiologists reviewed the scans in consensus according to Prostate Imaging Reporting and Data System (PI-RADS v. 2) guidelines., Statistical Tests: Wilcoxon and Mann-Whitney U-tests, Spearman's correlation., Results: When compared to noncancerous tissue, shorter T 2 values were observed within lesions at baseline (83.5 and 80.5 msec) and 6 months (81.5 and 81.9 msec) in the placebo and dutasteride arm, respectively. No significant differences for T 2 W contrast at baseline and after 6 months were observed, both in the placebo (0.40 [0.29-0.49] vs. 0.43 [0.25-0.49]; P = 0.881) and dutasteride arm (0.35 [0.24-0.47] vs. 0.37 [0.22-0.44]; P = 0.668). There was a significant, positive correlation between the T 2 Q contrast and the T 2 W contrast values (r = 0.786; P < 0.001)., Data Conclusion: The exposure to antiandrogen therapy did not significantly influence the T 2 contrast or the T 2 relaxation values in men on active surveillance for prostate cancer., Level of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1646-1653., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy., Methods: All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm., Results: Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98-9.50), median (IQR) number of previous biopsies 1 (1-2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92-99), specificity 21.9% (15.5-29.5), negative predictive value (NPV) 91.4% (76.9-98.1) and positive predictive value (PPV) 46.7% (35.2-47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6-87.7), specificity 68.5% (60.3-75.9), NPV 83.3% (75.4-89.5) and PPV 64.3% (55.4-72.6)., Conclusions: In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied.

Purpose: Dutasteride, which is licensed for symptomatic benign prostatic hyperplasia, has been associated with a lower progression rate of low risk prostate cancer. We evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted magnetic resonance imaging., Materials and Methods: In this randomized, double-blind, placebo controlled trial, men with biopsy proven, low-intermediate risk prostate cancer (up to Gleason 3 + 4 and PSA up to 15 ng/ml) who had visible lesion of 0.2 ml or greater on T2-weighted magnetic resonance imaging sequences were randomized to daily dutasteride 0.5 mg or placebo for 6 months. Lesion volume was assessed at baseline, and 3 and 6 months with image guided biopsy to the lesion at study exit. The primary end point was the percent reduction in lesion volume over 6 months. This trial was registered with the European Clinical Trials register (EudraCT 2009-102405-18)., Results: A total of 42 men were recruited between June 2010 and January 2012. In the dutasteride group, the average volumes at baseline and 6 months were 0.55 and 0.38 ml, respectively and the average reduction was 36%. In the placebo group, the average volumes at baseline and 6 months were 0.65 and 0.76 ml, respectively, and the average reduction was -12%. The difference in percent reductions between the groups was 48% (95% CI 27.4-68.3, p <0.0001). The most common adverse event was deterioration in erectile function, which was 25% in men randomized to dutasteride and 16% in men randomized to placebo., Conclusions: Dutasteride was associated with a significant reduction in prostate cancer volume on T2-weighted magnetic resonance imaging compared to placebo., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether patients with Gleason 3 + 4 cancer on transrectal biopsy are upgraded after undergoing transperineal magnetic resonance imaging (MRI)‐targeted biopsy and whether this has implications for current clinical practice. Patients and Methods: In this retrospective analysis we examined 107 consecutive patients presenting at a single tertiary referral centre (July 2012 to July 2016) with prostate cancer of Gleason score 3 + 4 on transrectal ultrasonography (TRUS)‐guided systematic non‐targeted biopsy who then underwent a multiparametric MRI followed by MRI‐targeted transperineal prostate biopsy for accurate risk stratification and localization. Results: The patients' mean (sd) age was 67.0 (8.0) years, and they had a median (interquartile range) PSA concentration of 6.2 (4.7–9.6) ng/mL. Of the 107 patients, 84 (78.5%) had Gleason 3 + 4 on both transrectal systematic biopsy and transperineal MRI‐targeted biopsy. Nineteen patients (17.8%) were upgraded to Gleason 4 + 3, three patients (3.0%) to Gleason 4 + 4 and one patient (1.0%) to Gleason 4 + 5. These differences were significant (P = 0.0006). Likewise, 23/107 patients (22%) had higher‐risk disease based on their targeted biopsies. Conclusion: The use of targeted biopsy in men with impalpable cancer, ultimately upgraded one in five patients from favourable‐intermediate‐ to unfavourable‐intermediate‐risk disease or worse. This has significant clinical implications for men considering active surveillance or radical treatment. Our risk calculators must now be validated using these data from targeted biopsy as the technique becomes widely adopted. [ABSTRACT FROM AUTHOR]

Objective: To report medium‐term oncological outcomes in men receiving primary focal treatment with high‐intensity focused ultrasonography (HIFU) for prostate cancer (PCa). Patients and Methods: Consecutive patients with PCa treated with primary focal HIFU at two centres by six treating clinicians were assessed. Patients were submitted to either focal ablation or hemi‐ablation using HIFU (Sonablate 500). The primary objective of the study was to assess medium‐term oncological outcomes, defined as overall survival, freedom from biopsy failure, freedom from any further treatment and freedom from radical treatment after focal HIFU. The secondary objective was to evaluate the changes in pathological features among patients treated with focal HIFU over time. We also assessed the relationship between year of surgery and 5‐year retreatment probability. Results: A total of 1032 men treated between November 2005 and October 2017 were assessed. The median age was 65 years and median prostate‐specific antigen level was 7 ng/mL. The majority of patients had a Gleason score of 3 + 4 or above (80.3%). The median (interquartile range) follow‐up was 36 (14–64) months. The overall survival rates at 24, 60 and 96 months were 99%, 97% and 97%, respectively. Freedom from biopsy failure, defined as absence of Gleason 3 + 4 disease, was 84%, 64% and 54% at 24, 60 and 96 months. Freedom from any further treatment was 85%, 59% and 46% at 24, 60 and 96 months, respectively. Approximately 70% of patients who were retreated received a second focal treatment. Freedom from radical treatment was 98%, 91% and 81% at 24, 60 and 96 months. During the study period, we observed an increase in the proportion of patients undergoing focal HIFU with Gleason 3 + 4 disease and with T2 stage disease as defined by multiparametric magnetic resonance imaging. Finally, there was a reduction over time in the proportion of patients undergoing re‐treatment within 5 years of first treatment. Conclusions: Focal HIFU for PCa is a feasible therapeutic strategy, with acceptable survival and oncological results and a reduction in the 5‐year retreatment rates over the last decade. Re‐do focal treatment is a feasible technique whose functional and oncological outcomes have still to be evaluated. [ABSTRACT FROM AUTHOR]

Purpose We evaluated the detection of clinically significant prostate cancer using magnetic resonance imaging targeted biopsies and compared visual estimation to image fusion targeting in patients requiring repeat prostate biopsies. Materials and Methods The prospective, ethics committee approved PICTURE trial (ClinicalTrials.gov NCT01492270) enrolled 249 consecutive patients from January 11, 2012 to January 29, 2014. Men underwent multiparametric magnetic resonance imaging and were blinded to the results. All underwent transperineal template prostate mapping biopsies. In 200 men with a lesion this was preceded by visual estimation and image fusion targeted biopsies. As the primary study end point clinically significant prostate cancer was defined as Gleason 4 + 3 or greater and/or any grade of cancer with a length of 6 mm or greater. Other definitions of clinically significant prostate cancer were also evaluated. Results Mean ± SD patient age was 62.6 ± 7 years, median prostate specific antigen was 7.17 ng/ml (IQR 5.25–10.09), mean primary lesion size was 0.37 ± 1.52 cc with a mean of 4.3 ± 2.3 targeted cores per lesion on visual estimation and image fusion combined, and a mean of 48.7 ± 12.3 transperineal template prostate mapping biopsy cores. Transperineal template prostate mapping biopsies detected 97 clinically significant prostate cancers (48.5%) and 85 insignificant cancers (42.5%). Overall multiparametric magnetic resonance imaging targeted biopsies detected 81 clinically significant prostate cancers (40.5%) and 63 insignificant cancers (31.5%). In the 18 cases (9%) of clinically significant prostate cancer on magnetic resonance imaging targeted biopsies were benign or clinically insignificant on transperineal template prostate mapping biopsy. Clinically significant prostate cancer was detected in 34 cases (17%) on transperineal template prostate mapping biopsy but not on magnetic resonance imaging targeted biopsies and approximately half was present in nontargeted areas. Clinically significant prostate cancer was found on visual estimation and image fusion in 53 (31.3%) and 48 (28.4%) of the 169 patients (McNemar test p = 0.5322). Visual estimation missed 23 clinically significant prostate cancers (13.6%) detected by image fusion. Image fusion missed 18 clinically significant prostate cancers (10.8%) detected by visual estimation. Conclusions Magnetic resonance imaging targeted biopsies are accurate for detecting clinically significant prostate cancer and reducing the over diagnosis of insignificant cancers. To maximize detection visual estimation as well as image fusion targeted biopsies are required. [ABSTRACT FROM AUTHOR]

Background: T2 -weighted imaging (T2 -WI) information has been used in a qualitative manner in the assessment of prostate cancer. Quantitative derivatives (T2 relaxation time) can be generated from T2 -WI. These outputs may be useful in helping to discriminate clinically significant prostate cancer from background signal.Purpose/hypothesis: To investigate changes in quantitative T2 parameters in lesions and noncancerous tissue of men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo daily for 6 months.Study Type: Retrospective.Population/subjects: Forty men randomized to 6 months of daily dutasteride (n = 20) or placebo (n = 20).Field Strength/sequence: Multiparametric 3T MRI at baseline and 6 months. This included a multiecho MR sequence for quantification of the T2 relaxation times, in three regions of interest (index lesion, noncancerous peripheral [PZ] and transitional [TZ] zones). A synthetic signal contrast (T2 Q contrast) between lesion and noncancerous tissue was assessed using quantitative T2 values. Signal contrast was calculated using the T2 -weighted sequence (T2 W contrast).Assessment: Two radiologists reviewed the scans in consensus according to Prostate Imaging Reporting and Data System (PI-RADS v. 2) guidelines.Statistical Tests: Wilcoxon and Mann-Whitney U-tests, Spearman's correlation.Results: When compared to noncancerous tissue, shorter T2 values were observed within lesions at baseline (83.5 and 80.5 msec) and 6 months (81.5 and 81.9 msec) in the placebo and dutasteride arm, respectively. No significant differences for T2 W contrast at baseline and after 6 months were observed, both in the placebo (0.40 [0.29-0.49] vs. 0.43 [0.25-0.49]; P = 0.881) and dutasteride arm (0.35 [0.24-0.47] vs. 0.37 [0.22-0.44]; P = 0.668). There was a significant, positive correlation between the T2 Q contrast and the T2 W contrast values (r = 0.786; P < 0.001).Data Conclusion: The exposure to antiandrogen therapy did not significantly influence the T2 contrast or the T2 relaxation values in men on active surveillance for prostate cancer.Level Of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1646-1653. [ABSTRACT FROM AUTHOR]

Objectives: To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo.Methods: We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magnetic Resonance Imaging (mpMRI) scans at baseline and 6 months. Images were reviewed blind to treatment allocation and clinical information. Mean ADC of peripheral (PZ) and transition (TZ) zones, and MR-suspicious lesions were compared between groups over 6 months. Conspicuity was defined as the PZ divided by tumour ADC, and its change over 6 months was assessed.Results: A decrease in mean conspicuity in the dutasteride group (but not the controls) was seen over 6 months (1.54 vs 1.38; p = 0.025). Absolute changes in ADC and conspicuity were significantly different between placebo and dutasteride groups at 6 months: (-0.03 vs 0.08, p = 0.033) and (0.11 vs -0.16, p = 0.012), as were percentage changes in the same parameters: (-2.27% vs 8.56% p = 0.048) and (9.25% vs -9.89% p = 0.013).Conclusions: Dutasteride was associated with increased tumour ADC and reduced conspicuity. A lower threshold for triggering biopsy might be considered in men on dutasteride undergoing mpMRI for prostate cancer.Key Points: • Dutasteride increases ADC and reduces conspicuity in small mpMRI-visible prostate cancers. • Knowledge of dutasteride exposure is important in the interpretation of prostate mpMRI. • A lower threshold for triggering biopsy may be appropriate on dutasteride. [ABSTRACT FROM AUTHOR]

Multiparametric magnetic resonance imaging (MP-MRI) is established in the diagnosis of prostate cancer, but the need for enhanced sequences has recently been questioned. To assess whether dynamic contrast-enhanced imaging (DCE) improves accuracy over T2 and diffusion sequences. PROMIS was a multicentre, multireader trial, with, in this part, 497 biopsy-naïve men undergoing standardised 1.5T MP-MRI using T2, diffusion, and DCE, followed by a detailed transperineal prostate mapping (TPM) biopsy at 5 mm intervals. Likert scores of 1–5 for the presence of a significant tumour were assigned in strict sequence, for (1) T2 + diffusion and then (2) T2 + diffusion + dynamic contrast-enhanced images. For the primary analysis, the primary PROMIS outcome measure (Gleason score ≥4 + 3 or ≥6 mm maximum cancer length) on TPM was used, and an MRI score of ≥3 was considered positive. Sensitivity without and with DCE was 94% and 95%, specificity 37% and 38%, positive predictive value 51% and 51%, and negative predictive value 90% and 91%, respectively (p > 0.05 in each case). The number of patients avoiding biopsy (scoring 1–2) was similar (123/497 vs 121/497, p = 0.8). The number of equivocal scores (3/5) was slightly higher without DCE (32% vs 28% p = 0.031). The proportion of MRI equivocal (3/5) and positive (4–5) cases showing significant tumours were similar (23% and 71% vs 20% and 69%). No cases of dominant Gleason 4 or higher were missed with DCE, compared with a single case with T2 + diffusion-weighted imaging. No attempt was made to correlate lesion location on MRI and histology, which may be considered a limitation. Radiologists were aware of the patient's prostate-specific antigen. Contrast adds little when MP-MRI is used to exclude significant prostate cancer. An intravenous injection of contrast may not be necessary when magnetic resonance imaging is used as a test to rule out significant tumours in the prostate. The addition of dynamic contrast-enhanced imaging did not offer a statistically significant improvement in diagnostic accuracy compared with T2 + diffusion sequences alone, although there was a marginal reduction of equivocal (3/5) magnetic resonance imaging results. [ABSTRACT FROM AUTHOR]

Objective To compare the proportion of clinically significant prostate cancers (PCa) found in lesions detected by multiparametric MRI (mpMRI) with that found in lesions detected by multiparametric ultrasound (mpUSS), in men at risk. Patients and methods CADMUS (Cancer Detection by Multiparametric Ultrasound of the prostate) is a prospective, multi-centre paired cohort diagnostic utility study with built-in randomisation of order of biopsies. The trial is registered ISRCTN38541912. All patients will undergo the index test under evaluation (mpUSS ± biopsies), as well as the standard test (mpMRI ± biopsies). Eligible men will be those at risk of harbouring prostate cancer usually recommended for prostate biopsy, either for the first time or as a repeat, who have not had any prior treatment for prostate cancer. Men in need of repeat biopsy will include those with prior negative results but ongoing suspicion, and those with an existing prostate cancer diagnosis but a need for accurate risk stratification. Both scans will be reported blind to the results of the other and the order in which the targeted biopsies derived from the two different imaging modalities are taken will be randomised. Comparison will be drawn between biopsy results of lesions detected by mpUSS with those lesions detected by mpMRI. Agreement over position between the two imaging modalities will be studied. Discussion CADMUS will provide level one evidence on the performance of mpUSS derived targeted biopsies in the identification of clinically significant prostate cancer in comparison to mpMRI targeted biopsies. Recruitment is underway and expected to complete in 2018. [ABSTRACT FROM AUTHOR]