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Approaches and techniques used for diagnostic prostate biopsy have undergone considerable evolution over the past few decades: from the original finger-guided techniques to the latest MRI-directed strategies, from aspiration cytology to tissue core sampling, and from transrectal to transperineal approaches. In particular, increased adoption of transperineal biopsy approaches have led to reduced infectious complications and improved antibiotic stewardship. Furthermore, as image fusion has become integral, these novel techniques could be incorporated into prostate biopsy methods in the future, enabling 3D-ultrasonography fusion reconstruction, molecular targeting based on PET imaging and autonomous robotic-assisted biopsy., (© 2023. Springer Nature Limited.)

Objective: To report outcomes within the Rapid Assessment for Prostate Imaging and Diagnosis (RAPID) diagnostic pathway, introduced to reduce patient and healthcare burdens and standardize delivery of pre-biopsy multiparametric magnetic resonance imaging (MRI) and transperineal biopsy., Patients and Methods: A total of 2130 patients from three centres who completed the RAPID pathway (3 April 2017 to 31 March 2020) were consecutively entered as a prospective registry. These patients were also compared to a pre-RAPID cohort of 2435 patients. Patients on the RAPID pathway with an MRI score 4 or 5 and those with PSA density ≥0.12 and an MRI score 3 were advised to undergo a biopsy. Primary outcomes were rates of biopsy and cancer detection. Secondary outcomes included comparison of transperineal biopsy techniques, patient acceptability and changes in time to diagnosis before and after the introduction of RAPID., Results: The median patient age and PSA level were 66 years and 6.6 ng/mL, respectively. Biopsy could be omitted in 43% of patients (920/2130). A further 7.9% of patients (168/2130) declined a recommendation for biopsy. The percentage of biopsies avoided among sites varied (45% vs 36% vs 51%; P < 0.001). In all, 30% (221/742) had a local anaesthetic (grid and stepper) transperineal biopsy. Clinically significant cancer detection (any Gleason score ≥3 + 4) was 26% (560/2130) and detection of Gleason score 3 + 3 alone constituted 5.8% (124/2130); detection of Gleason score 3 + 3 did not significantly vary among sites (P = 0.7). Among participants who received a transperineal targeted biopsy, there was no difference in cancer detection rates among local anaesthetic, sedation and general anaesthetic groups. In the 2435 patients from the pre-RAPID cohor, time to diagnosis was 32.1 days (95% confidence interval [CI] 29.3-34.9) compared to 15.9 days (95% CI 12.9-34.9) in the RAPID group. A total of 141 consecutive patient satisfaction surveys indicated a high satisfaction rate with the pathway; 50% indicated a preference for having all tests on a single day., Conclusions: The RAPID prostate cancer diagnostic pathway allows 43% of men to avoid a biopsy while preserving good detection of clinically significant cancers and low detection of insignificant cancers, although there were some centre-level variations., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy., Objective: To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa)., Design, Setting, and Participants: The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019., Intervention: Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml., Outcome Measurements and Statistical Analysis: Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts., Results and Limitations: The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively)., Conclusions: The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy., Patient Summary: In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Liquid biomarkers have not yet reached the level of evidence to replace magnetic resonance imaging in the prebiopsy pathway for prostate cancer., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Introduction: The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic)., Methods: ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes., Results: Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers., Conclusion: The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Hashim U Ahmed receives grant funding from Sonacare Inc., Sophiris Biocorp and Boston commercial entities. Hashim U Ahmed is awarded academic funds from the MRC, CRUK, The Wellcome Trust, The British Medical Association (BMA), The Urology Foundaiton (TUF), Prostate Cancer U.K. (PCUK) and Imperial Health. Mark Emberton serves as a consultant/educator/trainer to Sonacare Inc., Exact Imaging, Angiodynamics Inc and Profound Medical. Acknowledgements - Mark Emberton receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. Caroline M Moore receives funding from the Prostate Cancer UK, Movember, the Medical Research Council, Cancer Research UK and the NIHR. She receives fees for HIFU proctoring from SonaCare. She has received speaker fees from Astellas, and Jannsen. She carries out research into photodyanamic therapy supported by Spectracure. Shonit Punwani receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre Ton Coolen receives funding from Cancer Research UK and is Director of Saddle Point Science Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

To determine the effect of prostate biopsy on erectile function we conducted a systematic review and meta-analysis up to August 2020. Mean difference of International Index of Erectile Function-5 compared to baseline scores were pooled at 1, 3 and 6-months using a random effect model. Of 47 full text articles identified, 7 were included in the meta-analysis. A significant reduction in mean IIEF5 of 4.61 (0.32-8.91, P= .04) was found at 1-month post biopsy. This resolved with non-significant differences at 3- and 6-months post procedure. Patients should be counselled regarding the transient effect on erectile function post biopsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gleason score 7 prostate cancer with a higher proportion of pattern 4 (G4) has been linked to genomic heterogeneity and poorer patient outcome. The current assessment of G4 proportion uses estimation by a pathologist, with a higher proportion of G4 more likely to trigger additional imaging and treatment over active surveillance. This estimation method has been shown to have inter-observer variability. Fifteen patients with Prostate Grade Group (GG) 2 (Gleason 3 + 4) and fifteen patients with GG3 (Gleason 4 + 3) disease were selected from the PROMIS study with 192 haematoxylin and eosin-stained slides scanned. Two experienced uropathologists assessed the maximum cancer core length (MCCL) and G4 proportion using the current standard method (visual estimation) followed by detailed digital manual annotation of each G4 area and measurement of MCCL (planimetric estimation) using freely available software by the same two experts. We aimed to compare visual estimation of G4 and MCCL to a pathologist-driven digital measurement. We show that the visual and digital MCCL measurement differs up to 2 mm in 76.6% (23/30) with a high degree of agreement between the two measurements; Visual gave a median MCCL of 10 ± 2.70 mm (IQR 4, range 5-15 mm) compared to digital of 9.88 ± 3.09 mm (IQR 3.82, range 5.01-15.7 mm) (p = 0.64) The visual method for assessing G4 proportion over-estimates in all patients, compared to digital measurements [median 11.2% (IQR 38.75, range 4.7-17.9%) vs 30.4% (IQR 18.37, range 12.9-50.76%)]. The discordance was higher as the amount of G4 increased (Bias 18.71, CI 33.87-48.75, r 0.7, p < 0.0001). Further work on assessing actual G4 burden calibrated to clinical outcomes might lead to the use of differing G4 thresholds of significance if the visual estimation is used or by incorporating semi-automated methods for G4 burden measurement.

Background: Prostate biopsy guided by magnetic resonance imaging (MRI) is increasingly used to obtain tissue from men with suspected prostate cancer (PC)., Objective: To report a multicentre series of image-fusion transperineal prostate biopsies and compare the diagnostic yield of clinically significant PC (csPC) between targeted and nontargeted biopsies., Design, Setting, and Participants: The study included 640 consecutive patients with elevated prostate specific antigen (PSA) presenting for first biopsy or following a previous negative transrectal biopsy under the care of 13 urologists in 11 centres in the UK (April 2014-June 2017)., Intervention: Multiparametric MRI was carried out in 61 approved prostate MRI centres with transperineal targeted alone (n=283) or targeted plus nontargeted (n=357) transperineal rigid image-fusion targeted biopsy (MIM-Symphony-DX)., Outcome Measurements and Statistical Analysis: Rates of csPC and insignificant cancer detection in targeted and nontargeted biopsies were measured using a number of thresholds to define clinical significance. The primary definition was Gleason≥4+3 or any grade ≥6mm., Results and Limitations: The mean age, median PSA, and median prostate volume for the cohort were 63.8yr (standard deviation [SD] 8.4), 6.3 ng/ml (SD 5.8), and 42.0cm 3 (SD 24.7), respectively. Overall, 276/640 men (43.1%) were diagnosed with csPC. csPC was detected from targeted biopsies alone in 263/640 cases (41.1%). Of the 357 men who underwent nontargeted biopsies, three (0.8%) had csPC exclusively in nontargeted cores, with no evidence of cancer in targeted cores. Overall, 32/357 (9.0%) had csPC in nontargeted biopsies regardless of the targeted biopsy findings. Clinically insignificant disease in nontargeted biopsies was detected in 93/357 men (26.1%). Our findings were consistent across all other thresholds of clinical significance. Limitations include the lack of nontargeted biopsies in all men., Conclusions: In this large multicentre series, nontargeted prostate biopsy cores had a low yield of csPC and a high yield of clinically insignificant PC. An image-fusion targeted-biopsy-only approach maintains high detection for csPC and low detection of clinically insignificant cancers., Patient Summary: In this report, we found that following prostate multiparametric magnetic resonance imaging and targeted transperineal biopsies of suspicious areas, the clinical value of performing additional extensive unguided biopsies of nonsuspicious areas is limited and can often find insignificant cancers that do not need treatment., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Robotic prostate biopsy is an emerging technology. Recent development of this tool has allowed the performance of a transperineal prostate biopsy allowing pre-programmed standardized biopsy schemes. Prospective data collection was undertaken in 86 consecutive men who underwent robotically assisted transperineal prostate biopsy. All underwent a multi-parametric MRI pre-biopsy with centroid targeting followed by systematic template prostate biopsy. For the purposes of this study, our definition of clinically significant prostate cancer (csPCa) is any Gleason score > 6. Mean (SD) age, median (IQR) PSA, and median (IQR) prostate volume were 64.24 (6.97) years, of 7.79 ng/ml (6.5) and 45.06 cc (28), respectively. Overall, 44 (51.2%) men were diagnosed with csPCa. csPCa was detected in the targeted biopsies alone in 35 (40.1%) men. The addition of the 12-zone template biopsy increased the yield of csPCa for another 9 (10.5%) men. Of these 9 men, the majority (7) harbored primary pattern 3 disease and only 1 was identified to have high-grade disease. Out of these 9 men, 7 of them had the identification of csPCa in the sector, where a target was contained within that zone. Robotic-assisted prostate biopsy in our study has demonstrated a high detection of csPCa when combined with limited near-field sampling. Our study suggests the use of more accurate biopsy schemes such as ring-targeting of lesions to mitigate against systematic and random mathematical errors. Adoption of this tool and biopsy strategy would potentially avoid the increased morbidity associated with whole gland systematic unguided biopsies.

Background Biologic specificity of diffusion MRI in relation to prostate cancer aggressiveness may improve by examining separate components of the diffusion MRI signal. The Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT) model estimates three distinct signal components and associates them to (a) intracellular water, (b) water in the extracellular extravascular space, and (c) water in the microvasculature. Purpose To evaluate the repeatability, image quality, and diagnostic utility of intracellular volume fraction (FIC) maps obtained with VERDICT prostate MRI and to compare those maps with apparent diffusion coefficient (ADC) maps for Gleason grade differentiation. Materials and Methods Seventy men (median age, 62.2 years; range, 49.5-82.0 years) suspected of having prostate cancer or undergoing active surveillance were recruited to a prospective study between April 2016 and October 2017. All men underwent multiparametric prostate and VERDICT MRI. Forty-two of the 70 men (median age, 67.7 years; range, 50.0-82.0 years) underwent two VERDICT MRI acquisitions to assess repeatability of FIC measurements obtained with VERDICT MRI. Repeatability was measured with use of intraclass correlation coefficients (ICCs). The image quality of FIC and ADC maps was independently evaluated by two board-certified radiologists. Forty-two men (median age, 64.8 years; range, 49.5-79.6 years) underwent targeted biopsy, which enabled comparison of FIC and ADC metrics in the differentiation between Gleason grades. Results VERDICT MRI FIC demonstrated ICCs of 0.87-0.95. There was no significant difference between image quality of ADC and FIC maps (score, 3.1 vs 3.3, respectively; P = .90). FIC was higher in lesions with a Gleason grade of at least 3+4 compared with benign and/or Gleason grade 3+3 lesions (mean, 0.49 ± 0.17 vs 0.31 ± 0.12, respectively; P = .002). The difference in ADC between these groups did not reach statistical significance (mean, 1.42 vs 1.16 × 10 -3 mm 2 /sec; P = .26). Conclusion Fractional intracellular volume demonstrates high repeatability and image quality and enables better differentiation of a Gleason 4 component cancer from benign and/or Gleason 3+3 histology than apparent diffusion coefficient. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sigmund and Rosenkrantz in this issue.

Introduction: Diagnosing prostate cancer routinely involves tissue biopsy and increasingly image guided biopsy using multiparametric MRI (mpMRI). Excess tissue after diagnosis can be used for research to improve the diagnostic pathway and the vertical assembly of prostate needle biopsy cores into tissue microarrays (TMAs) allows the parallel immunohistochemical (IHC) validation of cancer biomarkers in routine diagnostic specimens. However, tissue within a biopsy core is often heterogeneous and cancer is not uniformly present, resulting in needle biopsy TMAs that suffer from highly variable cancer detection rates that complicate parallel biomarker validation., Materials and Methods: The prostate cores with the highest tumor burden (in terms of Gleason score and/or maximum cancer core length) were obtained from 249 patients in the PICTURE trial who underwent transperineal template prostate mapping (TPM) biopsy at 5 mm intervals preceded by mpMRI. From each core, 2 mm segments containing tumor or benign tissue (as assessed on H&E pathology) were selected, excised and embedded vertically into a new TMA block. TMA sections were then IHC-stained for the routinely used prostate cancer biomarkers PSA, PSMA, AMACR, p63, and MSMB and assessed using the h-score method. H-scores in patient matched malignant and benign tissue were correlated with the Gleason grade of the original core and the MRI Likert score for the sampled prostate area., Results: A total of 2240 TMA cores were stained and IHC h-scores were assigned to 1790. There was a statistically significant difference in h-scores between patient matched malignant and adjacent benign tissue that is independent of Likert score. There was no association between the h-scores and Gleason grade or Likert score within each of the benign or malignant groups., Conclusion: The construction of highly selective TMAs from prostate needle biopsy cores is possible. IHC data obtained through this method are highly reliable and can be correlated with imaging. IHC expression patterns for PSA, PSMA, AMACR, p63, and MSMB are distinct in malignant and adjacent benign tissue but did not correlate with mpMRI Likert score., (© 2018 Wiley Periodicals, Inc.)

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., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Transperineal template prostate mapping biopsy is an increasingly used method of procuring tissue from men with suspected prostate cancer. We report patient related outcome measures and adverse events in men in the PICTURE trial (ClinicalTrials.gov NCT01492270) who underwent this diagnostic test., Materials and Methods: A total of 249 men underwent multiparametric magnetic resonance imaging followed by transperineal template prostate mapping biopsy as a validation study. Functional outcomes before and after transperineal template prostate mapping were prospectively collected and recorded with questionnaires, including the I-PSS (International Prostate Symptom Score), the I-PSS-QoL (Quality of Life), the IIEF-15 (International Index of Erectile Function-15) and the EPIC (Expanded Prostate Cancer Index Composite) urinary function., Results: Mean age was 62 years, median prostate specific antigen was 6.8 ng/ml and median gland size was 37 ml. At transperineal template prostate mapping biopsy a median of 49 cores (IQR 40-55) were taken. Mean time to complete the post-procedure patient related outcome measure questionnaires was 46 days. Adverse events included post-procedure acute urinary retention in 24% of patients, rectal pain in 26% and perineal pain in 41%. Transperineal template prostate mapping biopsy resulted in a statistically significant increase in scores on the I-PSS from 10.9 to 11.8 (p = 0.024) and the I-PSS-QoL from 1.57 to 1.76 (p = 0.03). The IIEF-15 erectile function score decreased by 23.2% from 47.7 to 38.7 (p <0.001). Significant deterioration was noted in all 5 of IIEF-15 functional domains, including erectile and orgasmic function, sexual desire, and intercourse and overall satisfaction (p <0.001). EPIC urinary scores showed no overall change from baseline., Conclusions: Transperineal template prostate mapping biopsy causes a high urinary retention rate and a detrimental impact on genitourinary functional outcomes, including deterioration in urinary flow and sexual function. Our findings can be used to ensure adequate counseling about transperineal template prostate mapping biopsies. The results point to a need for strategies such as multiparametric magnetic resonance imaging and targeted biopsies to minimize the harms of transperineal template prostate mapping biopsy., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects., Objective: To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate., Design, Setting, and Participants: This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%)., Intervention: Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies., Outcome Measurements and Statistical Analysis: The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality., Results and Limitations: The median follow-up was 56 mo (interquartile range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98-100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up., Conclusions: Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects., Patient Summary: In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Image-guided systems that fuse magnetic resonance imaging (MRI) with three-dimensional (3D) ultrasound (US) images for performing targeted prostate needle biopsy and minimally invasive treatments for prostate cancer are of increasing clinical interest. To date, a wide range of different accuracy estimation procedures and error metrics have been reported, which makes comparing the performance of different systems difficult., Methods: A set of nine measures are presented to assess the accuracy of MRI-US image registration, needle positioning, needle guidance, and overall system error, with the aim of providing a methodology for estimating the accuracy of instrument placement using a MR/US-guided transperineal approach., Results: Using the SmartTarget fusion system, an MRI-US image alignment error was determined to be 2.0 ± 1.0 mm (mean ± SD), and an overall system instrument targeting error of 3.0 ± 1.2 mm. Three needle deployments for each target phantom lesion was found to result in a 100% lesion hit rate and a median predicted cancer core length of 5.2 mm., Conclusions: The application of a comprehensive, unbiased validation assessment for MR/US guided systems can provide useful information on system performance for quality assurance and system comparison. Furthermore, such an analysis can be helpful in identifying relationships between these errors, providing insight into the technical behavior of these systems., (© 2018 American Association of Physicists in Medicine.)

Objectives: To systematically review erectile function (EF) outcomes following primary whole gland (WG) and focal ablative therapies for localized prostate cancer to ascertain whether the treatment modality or intended treatment volume affects the time taken to recover baseline EF., Method and Materials: A systematic review was performed according to the preferred reporting items for systematic review and meta-analysis statement. Inclusion criteria were men with localized prostate cancer treated with primary, ablative therapy. Primary outcome was the return to baseline EF measured with objective, validated symptoms scores. Secondary outcome was use of phosphodiesterase inhibitors or erectile aids. Meta-analysis was not performed owing to heterogenous outcome measures., Results: Of 222 articles identified in February 2017, 55 studies which reported EF after ablative therapy were identified but only 17 used validated outcome measures and met inclusion criteria. WG cryotherapy was used in 2 studies, WG high-intensity focused ultrasound (HIFU) in 5, focal cryotherapy in 2, focal HIFU in 3, focal phototherapy or laser therapy in 4, vascular-targeted photodynamic therapy in 3, and irreversible electroporation in 2. WG cryotherapy was associated with a significant decline in EF at 6 months with minimal improvement at 36 months. Baseline IIEF-15 of patients undergoing focal HIFU fell 30 points at 1 month but returned to baseline by 6 months. The remaining focal therapies demonstrated minimal or no effect on EF, but the men in these studies had small foci of disease. The review is limited by lack of randomized studies and heterogenous outcome measures., Conclusions: Most studies assessing the outcomes of focal therapy on sexual function were not of high quality, used heterogenous outcomes, and had relatively short follow up, highlighting the need for more robustly designed studies using validated patient reported outcome measures  for comparison. However, FT in general resulted in less effect on EF than WG ablation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour., Methods: Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis., Results: ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83)., Conclusion: Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion., Key Points: • MR textural features of prostate transition zone may discriminate significant prostatic cancer. • Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram. • TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity. • The utility of MR texture analysis in prostate cancer merits further investigation.

Objectives: To determine whether modified transperineal template prostate-mapping (TTPM) biopsy protocols, altering the template or the biopsy density, have sensitivity and negative predictive value (NPV) equal to full 5-mm TTPM., Patients and Methods: Retrospective analysis of an institutional registry including treatment-naïve men undergoing 5-mm TTPM biopsy analysed in a 20-zone fashion. The value of three modified strategies was assessed by comparing the information provided by selected zones against full 5-mm TTPM. Strategy 1, did not consider the findings of anterior areas; strategies 2 and 3 simulated a reduced biopsy density by excluding intervening zones. A bootstrapping technique was used to calculate reliable estimates of sensitivity and NPV of these three strategies for the detection of clinically significant disease (maximum cancer core length ≥4 mm and/or Gleason score ≥3 + 4)., Results: In all, 391 men with a median (interquartile range, IQR) age of 62 (58-67) years were included. The median (IQR) PSA level and PSA density were 6.9 (4.8-10) ng/mL and 0.17 (IQR 0.12-0.25) ng/mL/mL, respectively. A median (IQR) of 6 (2-9) cores out of 48 (33-63) taken per man were positive for prostate cancer. No cancer was detected in 67 men (17%), whilst low-, intermediate- and high-risk disease was identified in 78 (20%), 80 (21%), and 166 (42%), respectively. Strategy 1, 2 and 3 had sensitivities of 78% [95% confidence interval (CI) 73-84%], 85% (95% CI 80-90%) and 84% (95% CI 79-89%), respectively. The NPVs of the three strategies were 73% (95% CI 67-80%), 80% (95% CI 74-86%) and 79% (95% CI 72-84%), respectively., Conclusion: Altering the template or decreasing sampling density has a substantial negative impact on the ability of TTPM biopsy to exclude clinically significant disease. This should be considered when modified TTPM biopsy strategies are used to select men for tissue-preserving approaches, and when modified TTPM are used to validate new diagnostic tests., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate the minimum disease burden of prostate cancer at which multiparametric magnetic resonance imaging (MRI) optimally performs., Methods: Between 2006 and 2008, 64 men underwent multiparametric MRI imaging (index test) followed by template prostate mapping biopsy (reference test). Three radiologists independently reported each quadrant of every prostate on a scale of 1 to 5: highly likely benign, likely benign, equivocal, likely malignant, highly likely malignant (≥3 or ≥4 was considered positive). There were 256 prostate sectors; bootstrapping adjustment was used to account for nonindependence. The target condition indicating cancer on biopsies was varied by changing the maximum cancer core length (MCCL) and total cancer core length (TCCL) within each sector from 1 mm to 10 mm. The sensitivity, specificity, and positive (PPVs) and negative predictive values (PPVs) were calculated for each MCCL and TCCL. Gleason ≤3+3 and Gleason ≥3+4 cancers were analyzed separately., Results: Mean age was 62 years (range, 40-76 years), and mean prostate-specific antigen level was 8.2 μg/L (range, 2.1-43 μg/L). Fifty percent of quadrants (127 of 256) had prostate cancer, of which 65% (83 of 127) were Gleason ≤3+3. For Gleason ≤3+3, multiparametric MRI had an NPV of ≥95% at an MCCL of ≥5 mm and at a TCCL of ≥7 mm (MRI score ≥3). For Gleason ≥3+4, an NPV of ≥95% was seen at an MCCL of ≥5 mm (MRI score ≥3) and TCCL ≥6 mm., Conclusion: Multiparametric MRI may allow areas of the prostate which test negative to avoid biopsy. Whether multiparametric MRI can be used as a "triage" test before the first biopsy requires results from ongoing prospective validating cohort studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA)., Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations., Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm(3) was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types., Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)-guided biopsy., Materials and Methods: Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI-guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection., Results: The mean age was 61.6 ± 6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients., Conclusion: Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI-guided biopsy. Most of the cancers detected were predominantly anterior tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed., Objective: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared., Evidence Acquisition: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool., Evidence Synthesis: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%)., Conclusions: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies., Patient Summary: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to demonstrate the feasibility of the recently introduced Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT) framework for imaging prostate cancer with diffusion-weighted magnetic resonance imaging (DW-MRI) within a clinical setting., Materials and Methods: The VERDICT framework is a noninvasive microstructure imaging technique that combines an in-depth diffusion MRI acquisition with a mathematical model to estimate and map microstructural tissue parameters such as cell size and density and vascular perfusion. In total, 8 patients underwent 3-T MRI using 9 different b values (100-3000 s/mm). All patients were imaged before undergoing biopsy. Experiments with VERDICT analyzed DW-MRI data from patients with histologically confirmed prostate cancer in areas of cancerous and benign peripheral zone tissue. For comparison, we also fitted commonly used diffusion models such as the apparent diffusion coefficient (ADC), the intravoxel incoherent motion (IVIM), and the kurtosis model. We also investigated correlations of ADC and kurtosis with VERDICT parameters to gain some biophysical insight into the various parameter values., Results: Eight patients had prostate cancer in the peripheral zone, with Gleason score 3 + 3 (n = 1), 3 + 4 (n = 6), and 4 + 3 (n = 1). The VERDICT model identified a significant increase in the intracellular and vascular volume fraction estimates in cancerous compared with benign peripheral zone, as well as a significant decrease in the volume of the extracellular-extravascular space (EES) (P = 0.05). This is in agreement with manual segmentation of the biopsies for prostate tissue component analysis, which found proliferation of epithelium, loss of surrounding stroma, and an increase in vasculature. The standard ADC and kurtosis parameters were also significantly different (P = 0.05) between tissue types. There was no significant difference in any of the IVIM parameters (P = 0.11 to 0.29). The VERDICT parametric maps from voxel-by-voxel fitting clearly differentiated cancer from benign regions. Kurtosis and ADC parameters correlated most strongly with VERDICT's intracellular volume fraction but also moderately with the EES and vascular fractions., Conclusions: The VERDICT model distinguished tumor from benign areas, while revealing differences in microstructure descriptors such as cellular, vascular, and EES fractions. The parameters of ADC and kurtosis models also discriminated between cancer and benign regions. However, VERDICT provides more specific information that disentangles the various microstructural features underlying the changes in ADC and kurtosis. These results highlight the clinical potential of the VERDICT framework and motivate the construction of a shorter, clinically viable imaging protocol to enable larger trials leading to widespread translation of the method.

Background: Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field., Objective: To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design., Design, Setting, and Participants: Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health., Outcome Measurements and Statistical Analysis: Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level., Results and Limitations: Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging-targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3+3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus., Conclusions: The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy., Patient Summary: In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The natural history of prostate cancer might be driven by the index lesion. We determined the percent of men in whom the index lesion could be defined using transperineal template prostate mapping biopsies., Materials and Methods: Included in study were consecutive men undergoing transperineal template prostate mapping biopsies with biopsies grouped into 20 zones. Men with clinically significant disease in only 1 prostate area were considered to have an identifiable index lesion. We evaluated the impact of using 2 definitions of clinically significant disease (Gleason grade pattern 4 and/or lesion volume 0.5 cc or greater) and 2 clustering rules (stringent and tolerant) to define the index lesion., Results: Included in study were 391 men with a median age of 62 years (IQR 58-67) and a median prostate specific antigen of 6.9 ng/ml (IQR 4.8-10.0). Of the men 269 (69%) were previously diagnosed with prostate cancer. By deploying a median of 1.2 cores per ml (IQR 0.9-1.7) cancer was diagnosed in 82.9% of the men (324 of 391) with a median of 6 positive cores (IQR 2-9), a median maximum cancer core length of 5 mm (IQR 3-8) and a total cancer core length per zone of 7 mm (IQR 3-13). Insignificant disease was found in 26.3% to 42.9% of cases. When a stringent spatial relationship was used to define individual lesions, 44.4% to 54.6% of patients had 1 index lesion and 12.7% to 19.1% had more than 1 area with clinically significant disease. These proportions changed to 46.6% to 59.2% and 10.5% to 14.5%, respectively, when less stringent spatial clustering was applied., Conclusions: Transperineal template prostate mapping biopsies enable the index lesion to be localized in most men with clinically significant disease. This information may be important to select appropriate candidates for targeted therapy and to plan a tailored treatment strategy in men undergoing radical therapy., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The current diagnostic and therapeutic strategy for localized prostate cancer is not working. In fact, it is severely flawed and, as such, fraught with controversy. Our current strategy has arisen from the imprecision of our diagnostic pathway. We do not know where the cancer is, so we subject the prostate to randomly placed needles in the hope of hitting the tumor. This leads to overdiagnosis, underdiagnosis, missclassification of risk and overtreatment and undertreatment. If we do find cancer, we usually subject the entire prostate to radiotherapy or surgery, which damages the surrounding structures--neurovascular bundles, external urinary sphincter, rectum, and bladder neck. Multiparametric magnetic resonance imaging, coupled with an intensive sampling strategy (targeted biopsies), might be able to rule out clinically significant lesions with a negative predictive value in the order of 90% to 95%. Focal therapy certainly leads to less genitourinary and rectal side effects. Current data from more than 3,000 men treated internationally show that incontinence after focal therapy is 0% to 5% (radical therapy can lead to incontinence in 15%-20%) whereas erectile dysfunction occurs in 5% to 10% of men with good baseline function (radical therapy rates vary between 30% and 60%). Early to medium cancer control using biopsies after treatment shows between 80% and 90% of patients have a successful treatment, with 10% to 15% of men requiring redo-treatment with minimal additional morbidity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes., (© 2013 Published by Elsevier Inc.)

Objective: To determine whether multiparametric magnetic resonance imaging (mp-MRI) has a role in reducing the uncertainty in risk stratification by transrectal ultrasound (TRUS) biopsy, using histology at transperineal template-guided prostate mapping (TPM) biopsy as the reference test., Materials and Methods: Overall, 194 patients underwent TRUS biopsy, who were followed up in less than 18 months by means of (a) mp-MRI with pelvic phased array using T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences and (b) TPM biopsy. Of those patients, low risk on TRUS biopsy was defined in 4 different ways--(a) definition 1: Gleason 3+3 (any cancer core length) (n = 137), (b) definition 2: maximum cancer core length (MCCL)<50% (any Gleason score) (n = 62), (c) definition 3: Gleason 3+3 and MCCL<50% (n = 52), and (d) definition 4: Gleason 3+3, MCCL<50%, prostate-specific antigen level<10 ng/ml, and<50% positive cores (n = 28). Mp-MRI was scored for the likelihood of cancer from 1 (cancer very unlikely) to 5 (cancer very likely). Binary logistic regression analysis was performed to evaluate the association between MRI scores and TPM histology., Results: Median prostate-specific antigen level was 7 ng/ml (range: 0.9-29), median time between TRUS biopsy and mp-MRI was 120 days (range: 41-480), and median time between mp-MRI and TPM biopsy was 60 days (range: 1-420). A median of 48 cores (range: 20-118) were taken at TPM biopsy. Gleason score was upgraded in 62 of 137 (45%) patients at TPM biopsy. The negative predictive values of mp-MRI score 1 to 2 for predicting that cancer remained low risk (according to each definition) were 75%, 100%, 83%, and 100% for definitions 1, 2, 3, and 4, respectively. An mp-MRI score of 4 to 5 had positive predictive values for upgrade or upsize of 59%, 67%, 75%, and 69% for definitions 1, 2, 3, and 4, respectively., Conclusion: The presence of an mp-MRI lesion in men with low-risk prostate cancer on TRUS biopsy confers, in most patients, a high likelihood that higher-risk disease will be present (either Gleason pattern 4 or a significant cancer burden). Conversely, if a lesion is not seen on mp-MRI, the attribution of low-risk grade or cancer burden is much more likely to be correct. Mp-MRI might therefore be used to triage men for resampling biopsies before entering active surveillance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Focal therapy is being offered as a viable alternative for men with localised prostate cancer (PCa), but it is unclear which men may be suitable., Objective: To determine the proportion of men with localised PCa who are potentially suitable for focal therapy., Design, Setting, and Participants: Our institutional transperineal template prostate-mapping (TTPM) biopsy registry of 377 men from 2006 to 2010 identified 291 consecutive men with no prior treatment., Intervention: TTPM biopsies using a 5-mm sampling frame., Outcome Measurements and Statistical Analysis: Suitability for focal therapy required the cancer to be (1) unifocal, (2) unilateral, (3) bilateral/bifocal with at least one neurovascular bundle avoided, or (4) bilateral/multifocal with one dominant index lesion and secondary lesions with Gleason ≤3 + 3 and cancer core involvement ≤3 mm. Binary logistic regression modelling was used to determine variables predictive for focal therapy suitability., Results and Limitations: The median age was 61 yr, and the median prostate-specific antigen was 6.8 ng/ml. The median total was 29 cores, with a median of 8 positive cores. Of 239 of 291 men with cancer, 29% (70 men), 60% (144 men), and 8% (20 men) had low-, intermediate-, and high-risk PCa, respectively. Ninety-two percent (220 men) were suitable for one form of focal therapy: hemiablation (22%, 53 men), unifocal ablation (31%, 73 men), bilateral/bifocal ablation (14%, 33 men), and index lesion ablation (26%, 61 men). Binary logistic regression modelling incorporating transrectal biopsy parameters showed no statistically significant predictive variable. When incorporating TTPM parameters, only T stage was a significant negative predictor for suitability (p=0.001) (odds ratio: 0.001 [95% confidence interval, 0.000-0.048]). Limitations of the study include potential selection bias caused by tertiary referral practise and lack of long-term results on focal therapy efficacy., Conclusions: Focal therapy requires an accurate tool to localise individual cancer lesions. When such a test, TTPM biopsy, was applied to men with low- and intermediate-risk PCa, most of the men were suitable for a tissue preservation strategy., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive., Design: Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making., Population: A hypothetical cohort of 1000 men with suspected prostate cancer., Interventions: mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men., Outcome Measures: We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters., Results: In 1000 men, mpMRI followed by MRI-targeted biopsy 'clinically dominates' TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis., Conclusions: Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Magnetic resonance imaging (MRI) has become increasingly used worldwide in the diagnosis and management of prostate cancer. With advances in multiparametric MRI (mpMRI) technology, such as the use of dynamic contrast-enhanced and diffusion-weighted imaging sequences, observational studies have evaluated the utility for mpMRI in the continuum of prostate cancer management, from improving the detection of clinically significant prostate cancer, to planning radical prostatectomy and radiation therapy and the early detection of local recurrence. Furthermore, the potential for advanced imaging to reduce the burden of routine serial prostate needle biopsies for men on active surveillance is a promising area of research. MRI technology continues to evolve, and the potential applications in the management of prostate cancer care will require well-designed multi-institutional prospective clinical trials and rigorous efforts to standardize reporting and improve dissemination of expertise across institutions.

Background: Prostate biopsy parameters are commonly used to attribute cancer risk. A targeted approach to lesions found on imaging may have an impact on the risk attribution given to a man., Objective: To evaluate whether, based on computer simulation, targeting of lesions during biopsy results in reclassification of cancer risk when compared with transrectal ultrasound (TRUS) guided biopsy., Design, Setting, and Participants: A total of 107 reconstructed three-dimensional models of whole-mount radical prostatectomy specimens were used for computer simulations. Systematic 12-core TRUS biopsy was compared with transperineal targeted biopsies using between one and five cores. All biopsy strategies incorporated operator and needle deflection error. A target was defined as any lesion ≥ 0.2 ml. A false-positive magnetic resonance imaging identification rate of 34% was applied., Outcome Measurements and Statistical Analysis: Sensitivity was calculated for the detection of all cancer and clinically significant disease. Cases were designated as high risk based on achieving ≥ 6 mm cancer length and/or ≥ 50% positive cores. Statistical significance (p values) was calculated using both a paired Kolmogorov-Smirnov test and the t test., Results and Limitations: When applying a widely used biopsy criteria to designate risk, 12-core TRUS biopsy classified only 24% (20 of 85) of clinically significant cases as high risk, compared with 74% (63 of 85) of cases using 4 targeted cores. The targeted strategy reported a significantly higher proportion of positive cores (44% vs 11%; p<0.0001) and a significantly greater mean maximum cancer core length (7.8mm vs 4.3mm; p<0.0001) when compared with 12-core TRUS biopsy. Computer simulations may not reflect the sources of errors encountered in clinical practice. To mitigate this we incorporated all known major sources of error to maximise clinical relevance., Conclusions: Image-targeted biopsy results in an increase in risk attribution if traditional criteria, based on cancer core length and the proportion of positive cores, are applied. Targeted biopsy strategies will require new risk stratification models that account for the increased likelihood of sampling the tumour., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the performance of multiparametric magnetic resonance imaging (mp-MRI) in patients with previous negative transrectal ultrasound (TRUS) guided prostate biopsy., Materials and Methods: Fifty-four patients with at least 1 previous negative TRUS prostate biopsy underwent mp-MRI in the form of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. This was followed by transperineal template systematic prostate biopsies. Analysis was done based on 2 sectors per prostate, right and left (108 sectors out of 54 prostates). mp-MRI was scored using an ordinal scale 1 to 5 based on the suspicion of the presence of clinically significant disease. We used 6 different definitions for clinically significant disease and tested the performance of mp-MRI at each single definition., Results: Median age was 64 (range, 39-75), median PSA level was 10 (range, 2-23), and median number of biopsies was 45 (range, 21-137). Cancer of any volume and any grade was detected in 34 of 54 (63%) patients. mp-MRI accuracy at detection of clinically significant cancer using University College London (UCL) definition 2 (any Gleason score of 4 or maximum cancer core length of ≥ 4 mm or both) showed sensitivity of 76%, specificity of 42%, positive predictive value of 38%, and negative predictive value of 79%. For a different definition of significant tumor (UCL definition 1; dominant Gleason score 4 or maximum cancer core length ≥ 6 mm or both), the sensitivity was 90%, specificity 42%, positive predictive value 26%, and negative predictive value 95%., Conclusions: mp-MRI showed good performance at both detection and ruling out clinically significant disease, according to the definition used. mp-MRI can then be used as a triage test in the population with persistently elevated or rising PSA levels to select patients that can avoid unnecessary prostate biopsy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening and treatment., Objective: To perform a systematic review of complications from prostate biopsy., Evidence Acquisition: A literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality., Evidence Synthesis: After biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and <2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare., Conclusions: Preparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies., (Published by Elsevier B.V.)

Objective: To evaluate the feasibility of using computer-assisted, deformable image registration software to enable three-dimensional (3D), multi-parametric (mp) magnetic resonance imaging (MRI)-derived information on tumour location and extent, to inform the planning and conduct of focal high-intensity focused ultrasound (HIFU) therapy., Patients and Methods: A nested pilot study of 26 consecutive men with a visible discrete focus on mpMRI, correlating with positive histology on transperineal template mapping biopsy, who underwent focal HIFU (Sonablate 500®) within a prospective, Ethics Committee-approved multicentre trial ('INDEX'). Non-rigid image registration software developed in our institution was used to transfer data on the location and limits of the index lesion as defined by mpMRI. Manual contouring of the prostate capsule and histologically confirmed MR-visible lesion was performed preoperatively by a urologist and uro-radiologist. A deformable patient-specific computer model, which captures the location of the target lesion, was automatically generated for each patient and registered to a 3D transrectal ultrasonography (US) volume using a small number (10-20) of manually defined capsule points. During the focal HIFU, the urologist could add additional sonications after image-registration if it was felt that the original treatment plan did not cover the lesion sufficiently with a margin., Results: Prostate capsule and lesion contouring was achieved in <5 min preoperatively. The mean (range) time taken to register images was 6 (3-16) min. Additional treatment sonications were added in 13 of 26 cases leading to a mean (range) additional treatment time of 45 (9-90) s., Conclusion: Non-rigid MR-US registration is feasible, efficient and can locate lesions on US. The process has potential for improved accuracy of focal treatments, and improved diagnostic sampling strategies for prostate cancer. Further work on whether deformable MR-US registration impacts on efficacy is required., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: Multiparametric magnetic resonance imaging can be used to guide prostate biopsy by targeting biopsies to areas in the prostate at high risk for cancer. We compared the detection of clinically significant and insignificant cancer by transperineal magnetic resonance imaging targeted biopsy and transperineal template guided prostate biopsy., Materials and Methods: A total of 182 men with a lesion suspicious for cancer on multiparametric magnetic resonance imaging underwent transperineal magnetic resonance imaging targeted biopsy using a cognitive registration technique, followed by systematic transperineal template guided prostate biopsy. The primary outcome was the detection rate of clinically significant prostate cancer. Clinical significance was defined using maximum cancer core length 4 mm or greater and/or Gleason grade 3 + 4 or greater (University College London definition 2). We secondarily evaluated other commonly used thresholds of clinically significant disease, including maximum cancer core length 6 mm or greater and/or Gleason grade 4 + 3 or greater, maximum cancer core length 3 mm or greater and/or Gleason grade 3 + 4 or greater, and maximum cancer core length 2 or greater mm and/or Gleason grade 3 + 4 or greater. Strategies were statistically compared with the McNemar test., Results: Mean ± SD patient age was 63.3 ± 7.2 years. Median prostate specific antigen was 6.7 ng/ml (IQR 4.7-10.0). Clinically significant cancer was detected by magnetic resonance imaging targeted biopsy and template guided prostate biopsy in 103 (57%) and 113 of the 182 men (62%) (p = 0.174), and clinically insignificant cancer was detected in 17 (9.3%) and 31 (17.0%), respectively (p = 0.024)., Conclusions: Prostate biopsy targeted to suspicious lesions on multiparametric magnetic resonance imaging has encouraging rates of detection of clinically significant cancer while also decreasing the detection rate of clinically insignificant cancer. This is achieved with fewer biopsy cores than for systematic template guided biopsy. Further prospective, multicenter, comparative trials of the performance of targeting strategies are needed to consider magnetic resonance imaging targeted biopsy an alternative to conventional systematic biopsy., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Active surveillance is increasingly recommended to reduce overtreatment in men with favorable risk prostate cancer. A repeat confirmatory biopsy has become the standard recommendation for these men to increase the precision of this risk attribution. We investigate the usefulness of this approach by comparing the current practice standard, repeat transrectal ultrasound biopsy, with template prostate mapping., Materials and Methods: A total of 124 men who were attributed a favorable risk prostate cancer status based on transrectal ultrasound guided biopsy and who were considering a policy of active surveillance underwent combined transrectal ultrasound biopsy and template prostate mapping as a confirmatory strategy. Maximum Gleason grade and disease burden were compared between the 2 confirmatory tests., Results: Depending on the definition used between 8% and 22% of men had prostate cancer reclassified as clinically important by repeat transrectal ultrasound biopsy whereas template guided prostate mapping reclassified the disease in 41% to 85% of the men. Repeat transrectal ultrasound biopsy failed to detect up to 80% of clinically important cancers detected by the reference standard. The sensitivity of repeat transrectal ultrasound biopsy to identify clinically important disease varied from 9% to 24% with the negative predictive value ranging from 23% to 60%., Conclusions: When applied to a population of men initially deemed to have favorable risk prostate cancer, transrectal ultrasound biopsy will miss a large proportion of clinically important cancers compared to template guided prostate mapping. The usefulness of repeat transrectal ultrasound biopsy in ruling out clinically important prostate cancer needs to be reconsidered., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: What's known on the subject? and What does the study add? Transrectal ultrasonography (TRUS)-guided biopsies can miss prostate cancer and misclassify risk in a diagnostic setting; the exact extent to which it does so in a repeat biopsy strategy in men with low-intermediate risk prostate cancer is unknown. A simulation study of different biopsy strategies showed that repeat 12-core TRUS biopsy performs poorly. Adding anterior sampling improves on this but the highest accuracy is achieved using transperineal template prostate mapping using a 5 mm sampling frame., Objective: To determine the effectiveness of two sampling strategies; repeat transrectal ultrasonography (TRUS)-biopsy and transperineal template prostate mapping (TPM) to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL using computer simulation on reconstructed three-dimensional (3-D) computer models of radical whole-mount specimens., Patients and Methods: Computer simulation on reconstructed 3-D computer models of radical whole-mount specimens was used to evaluate the performance characteristics of repeat TRUS-biopsy and TPM to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL. In all, 107 consecutive cases were analysed (1999-2001) with simulations repeated 500 times for each biopsy strategy. TPM and five different TRUS-biopsy strategies were simulated; the latter involved a standard 12-core sampling and incorporated variable amounts of error, as well as the addition of anterior cores. Sensitivity, specificity, negative and positive predictive values for detection of lesions with a volume of ≥0.2 mL or ≥0.5 mL were calculated., Results: The mean (SD) age and PSA concentration were 61 (6.4) years and 8.5 (5.9) ng/mL, respectively.In all, 53% (57/107) had low-intermediate risk disease. In all, 665 foci were reconstructed; there were 149 foci ≥0.2 mL and 97 ≥ 0.5 mL in the full cohort and 68 ≥ 0.2 mL and 43 ≥ 0.5 mL in the low-intermediate risk group. Overall, TPM accuracy (area under the receiver operating curve, AUC) was ≈0.90 compared with AUC 0.70-0.80 for TRUS-biopsy. In addition, at best, TRUS-biopsy missed 30-40% of lesions of ≥0.2 mL and ≥0.5 mL whilst TPM missed 5% of such lesions., Conclusion: TPM under simulation conditions appears the most effective re-classification strategy, although augmented TRUS-biopsy techniques are better than standard TRUS-biopsy., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Unlabelled: What's known on the subject? and What does the study add? Much of our understanding of the pathological basis of prostate cancer comes from our analysis of radical prostatectomy specimens. Prostate cancer diagnosed by transrectal ultrasonography-guided biopsy is more likely to be posterior and basal in orientation rather than anterior or apical. Quantitative tissue analyses have not been undertaken both with details and in an unselected population, e.g. prostate specimens from autopsy cystoprostatectomy series from bladder cancer. Quantitative tissue analysis of incidentally detected prostate cancer such as largest cancer surface area, volume, site of origin, multifocality and laterality could be of paramount importance when trying to understand the findings of screen-detected programmes and focal therapy. Cancers were found in 30% of prostates. In the 96 prostates, 215 cancer foci were identified (mean 2.24). Prostate cancer was multifocal in 60% and bilateral in 80% of cases. The site of origin was in the peripheral and transition zone (TZ) in 75% and 25%, respectively. Overall, 90% of cancer foci were clinically insignificant with volume of <0.5 mL and no grades 4-5. In all, 75% of the cancer foci were in the peripheral zone, the remainder were within the TZ. One third of cancer foci were anteriorly located beyond the area sampled by posterior biopsies. One fifth of cancer foci were ≤ 6 mm of the apex., Objective: • To describe multifocality, volume and location of prostate cancers incidentally found in cystoprostatectomy specimens. Quantitative tissue analysis of prostate cancer in a population free of the evaluation bias associated with prostate-specific antigen level and biopsy is important as some men are likely to be offered tissue-preserving therapeutic strategies in the future., Patients and Methods: • Cystoprostatectomy specimens for bladder cancer from 345 consecutive patients without clinically manifest prostate cancer were included. • Cancers were found in 104/345 (30%) of prostates. Cases with largest cancer >2 mL (eight patients) were excluded from morphometric study. Quantitative tissue analysis of 3-mm step-sectioned glands included largest cancer surface area, volume, site of origin, multifocality and laterality., Results: • In the 96 prostates, 215 cancer foci were identified (mean 2.24). Prostate cancer was multifocal in 58% and bilateral in 79% of cases. • Of the 215 cancers, 90% were <0.5 mL and 79% <0.2 mL. Overall, 88% of cancer foci were clinically insignificant with a volume of <0.5 mL and no grades 4-5. • In all, 75% of the cancer foci were in the peripheral zone, the remainder were within the transition zone. • One third of cancer foci were anteriorly located beyond the area sampled by posterior biopsies. One fifth of cancer foci were ≤ 6 mm of the apex. • Limitations include the fact that cystoprostatectomy cancer foci are at an earlier stage than screened-detected cancers., Conclusion: • This detailed morphometric analysis of prostate cancer foci in a population that is free from the selection bias associated with screening can help inform our diagnostic and treatment strategies., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Purpose: The objective of this study was to evaluate the impact of tumor focality on positive surgical margins (PSM) after laparoscopic radical prostatectomy., Patients and Methods: Ninety-five consecutive whole-mount laparoscopic radical prostatectomy samples (January 2007 to November 2009) were evaluated for tumor focality, laterality, Gleason score, and volume of individual foci, total tumor volume, pathologic stage, and surgical margin status., Results: Thirty-nine percent, 36%, and 25% were in low, intermediate, and high D'Amico risk categories. Thirty-three percent (31/95) had PSM. Overall, 269 tumor foci were identified. The incidence of PSM within lesions ≤ 0.5 cc and ≤ 0.2 cc was 1.2% (2/160) and 0% (0/132), respectively. Among the 71 multifocal cases, 19 (27%) exhibited PSM. In 13 of these, the index lesion appeared at the inked surface (mean volume 5.4 cc, range 0.63-26.9 cc) compared with 6 in which both index and satellite foci appeared at the inked margins. Mean volume of these satellite foci was 1.06 cc (range 0.22-2 cc); three had Gleason score 6 and three had Gleason score 7 (3+4)., Conclusions: PSM is usually attributed to the index lesion and lesions larger than commonly used thresholds for clinically significant lesion volumes. Because such lesions might be detected by multiparametric magnetic resonance imaging (MRI) or template mapping biopsies, the information from these staging modalities could be used intraoperatively to reduce PSM.

In recent years, there has been a growing interest in focal treatment for prostate cancer. Although widely used for the treatment of tumors of the breast and kidney, focal treatment for prostate cancer remains a controversial area. Criticism of focal prostate therapy has been based on the fact that prostate cancer is a multifocal disease. Until now, little attention has been paid to distinguishing between men with unifocal and those with multifocal disease because such information has little clinical relevance when treatment is aimed at the whole gland irrespective of the volume or number of cancers in the prostate. In this Review, we summarize existing knowledge and examine the issue of prostate cancer focality in the context of focal treatment.

Objectives: Overdiagnosis is arguably the greatest challenge in the management of men with prostate cancer. Multi-parametric (mp)-MRI prior to prostate biopsy may have a role in ruling-in and ruling-out clinically significant disease., Patients and Methods: 114 consecutive men at risk of prostate cancer with previous biopsy underwent mp-MRI prior to transrectal ultrasound (TRUS)-guided biopsies. Standard systematic biopsies were carried out with targeting to suspicious areas., Results: 59.6% had cancer detected by TRUS-guided biopsy. Mean age was 63.6 years (SD 9.0). If men had not been biopsied because of a negative mp-MRI, 21% (24/114) with no cancer and 5% (6/114) with clinically insignificant cancer could have avoided a biopsy. However, 4% (4/114) would have been advised to defer a biopsy that demonstrated the presence of clinically significant cancer., Conclusion: mp-MRI may have a role in ruling-in and ruling-out clinically significant prostate cancer in men at risk prior to biopsy., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To determine the pathological characteristics of radical prostatectomy specimens with respect to index and secondary lesions., Methods: A total of 100 consecutive radical prostatectomy specimens examined at a single hospital were assessed. Patients undergoing salvage prostatectomy or those who had received neoadjuvant hormonal manipulation were excluded. Preoperative data and the number, volume and Gleason grade of each tumour focus were recorded. Criteria used to define a clinically significant lesion were tumour volume ≥0.5 mL and/or Gleason pattern 4 or 5 and/or extra-capsular disease., Results: Overall, 374 foci were examined. The median number of tumours per patient was 3.5 (range 1-15). The overall median tumour volume was 1.4 mL (range 0.1-18.2), the median volume of the largest (index) tumour was 0.95 mL (range 0.1-18.2) and the median volume of the largest secondary tumour was 0.2 mL (range 0.05-1.7). There were no patients in whom the index lesion was insignificant and secondary tumours were significant (by grade or extra-capsular disease). Seventy-seven fulfilled the clinical parameters of low-to-intermediate-risk disease. If focal therapy can be delivered with the aim of ablating all clinically significant disease, with untreated areas harbouring no cancer or clinically insignificant disease, between 58.5 and 67.5% might have been suitable for such a strategy., Conclusions: The proportion of men with low-to-intermediate-risk prostate cancer who may potentially be suitable for a focal therapy approach is unknown. The key question is whether the volume of individual lesions points to clinically significant cancer and whether ablation of these lesions alone would lead to cancer control. This research question is currently undergoing evaluation within a prospective clinical trial., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: To assess the role of multiparametric magnetic resonance imaging (mp-MRI) of the prostate in evaluating local recurrence of prostate cancer, using transperineal template-guided 5 mm-spaced biopsies as a reference standard, in men treated with external beam radiotherapy (EBRT) for prostate cancer., Patients and Methods: The study included 13 patients with evidence of biochemical recurrence after EBRT who had undergone mp-MRI and prostate mapping. Each MRI scan (consisting of T1/T2 weighting, dynamic contrast enhancement and diffusion weighting) was reported by two expert uro-radiologists. Each prostate was divided into four regions of interest (ROI), generating 52 paired datasets for analysis., Results: The mean (range) age of the men was 65.5 (55-70) years, the mean prostate-specific antigen (PSA) level before EBRT was 36.6 (4.5-150) ng/mL, the mean time from EBRT to biochemical recurrence was 5.7 (3-10) years and the mean PSA level at the time of recurrence was 7.1 (0.83-27.9) ng/mL. Eleven men had histological evidence of recurrence, with 23 of 52 ROIs involved with cancer. Overall accuracy, as expressed by the area under a receiver-operator curve, was 0.77 and 0.89 for all cancer, with accuracies of 0.86 and 0.93 for those cancers with ≥3 mm biopsy core length. Inter-observer variability was measured by calculating κ coefficients, which showed fair and moderate agreement between radiologists., Conclusions: Interpretation of mpMRI of the prostate after previous EBRT is challenging. Our results show that the accuracy is good using an accurate reference standard. These results need verification in more patients, but have implications for determining presence or absence of local recurrence and subsequent local salvage therapy., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)