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Purpose: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men.Experimental Design: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102).Results: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center.Conclusions: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified. Clin Cancer Res; 17(5); 1090–8. ©2011 AACR.

Supplementary Figures S1-S3.

Introduction: The coronavirus (COVID-19) pandemic of 2020 had a major impact on NHS services. From the 23rd of March 2020, the Urology Department in Basingstoke initiated telephone-led consultation clinicsinstead of face-to-face outpatient appointments, in accordance with U.K. guidance.Objectives: To evaluate patient experience and satisfaction following the introduction of remote (telephone) consultations during the COVID-19 pandemic.Patients and methods: The first 200 remote patient appointments between the 30th of March 2020 and the 16th of April 2020 were sent a postal questionnaire (19 questions relating to their experience and level of satisfaction with the interaction). Telephone consultations were conducted by 6 consultants, 3 registrars, and 2 specialist nurses. The patients were not prewarned to expect a questionnaire after the remote ap-pointment. The associated cost saving resulting from a switch from face-to-face appointments to remote telephone appointments was also calculated.Results: 100 out of the 200 patients responded within 1 month (response rate 50%). A total of 44% of the patients were new referrals, while 56% were follow-ups. Overall, the feedback was positive regarding the telephone consultation, with 88% rating the care received as excellent or very good. In addition, 90% would recommend a telephone consultation to family and friends. However, 35% would prefer in the future to have another telephone consultation rather than face-to-face consultation, with 46% preferring a face-to-face appointment in the future and 19% unsure. For new patients, the proportion wishing to have a face-to-face appointment, in the end, was unsurprisingly higher than it was for those undergoing a follow-up (39% vs. 7 %). In these 2 weeks, the cost reduction to the NHS from shifting from face-to-face consultation to telephone consultation was estimated to be £6500.Conclusions: Telephone urology clinics are a satisfactory alternative to face-to-face appointments for many of our patients now and beyond the COVID-19 pandemic. They are efficient, cost-effective, and feasible to undertake urological consultation and can be implemented successfully in selected patients. The feedback from this questionnaire would suggest that priority should be given to face-to-face appointments for new patients and for complex follow-up appointments. Telephone follow-up appointments, however, are a good approach for the majority of patients.

Benign prostatic hyperplasia (BPH) is a common condition amongst older men and is associated with lower urinary tract symptoms and erectile dysfunction; these symptoms can be burdensome and negatively affect quality of life. Various surgical and pharmaceutical treatment options exist but there is a paucity of qualitative research exploring men’s decision-making when seeking BPH treatment. This study qualitatively explored men’s experience of living with BPH and seeking treatment for BPH. Twenty men (aged 52–75) were recruited from outpatient urology clinics at a hospital trust in Southern England. Data were collected using semi-structured interviews (via video or telephone call) and were audio-recorded; transcripts were analysed using thematic analysis. Four themes were generated: ‘Impacts are about more than just physical symptoms’, ‘The path towards treatment’, ‘The process of information gathering’ and ‘Navigating hopes, fears and uncertainty’. Results indicate most men appear to seek treatment for BPH following a gradual, and sometimes lengthy, period of deterioration in symptoms; for some men, however, treatment seeking follows an acute episode of sudden or severe symptoms. The decision to proceed with surgical or minimally invasive treatment options appears to be dependent on men reaching a tipping point; they no longer perceive their symptoms as tolerable and feel their ability to cope with symptoms is reduced. Men each bring their own set of concerns and preferences about side effects and risk-benefit profiles of different treatments. Clinicians need to be sensitive to these individual differences and incorporate them into shared decision-making for choosing between treatment options for BPH.

Clinicians and patients must weigh the risk of treatment of prostate cancer during a global pandemic with the risk of cancer treatment delays. With the possibility of another peak, public confidence in cancer treatments requiring general anaesthetic will be critical. We report on the safety of performing focal therapy in the UK during the initial Covid-19 peak. Patients and Methods: Consecutive patients treated in 8 centres (23/3/20-23/7/20) were contacted at least 2 weeks after receiving focal ablative therapy. Treatment modalities included high intensity focused ultrasound (HIFU, n=90), cryotherapy (n=32) or irreversible electroporation (IRE, n=6). Results: 128/129 patients treated during the study period were successfully contacted. 107/ 128 (83.5%) underwent primary focal treatment, all had D'Amico intermediate or high-risk disease. National guidelines varied throughout the period. Treating sites requested formal shielding from May 2020 and done in 48/128 (37.5%). 20/128 (15.6%) underwent pre-operative swab tests and 5/128 (3.9%) pre-operative chest imaging. Two (1.6%) had intra-operative complications secondary to catheterisation, but none required overnight admission. No COVID-19 related post-treatment admissions were reported;2 (1.6%) had Covid-19 related symptoms but were not tested as symptoms spontaneously resolved. 3 were admitted for non- COVID-19 issues and one was directly due to treatment related clot retention resulting in the only reported Clavien-Dindo score >2 complication [Table 1]. Conclusions: Focal therapy for non-metastatic prostate cancer was a safe treatment option during a COVID-19 pandemic when appropriate precautions are taken and should be discussed with eligible patients.

Level of evidence: 5

OBJECTIVES To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. PATIENTS AND METHODS Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. RESULTS Twenty-four men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 vs 100) but there was no statistically significant difference from baseline at 12 months (100 vs 100, P = 0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 vs 87.5, P = 0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 vs 58.3, P < 0.001). Utilising a minimally important difference of nine points, at 12 months after surgery 17/23 (74%) reported urinary continence to be 'better' or 'not different' to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1-93.1%) while 4/23 (17%) received salvage radiation. CONCLUSIONS The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable.

Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA

Background False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. Objective To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). Design, setting, and participants PROMIS participants (n = 235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3 + 4 of any length and/or maximum cancer core length ≥4 mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4 + 3 of any length and/or maximum cancer core length ≥6 mm of any grade). Outcome measurements and statistical analysis Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. Results and limitations Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p, Take Home Message Significant cancer-associated magnetic resonance imaging lesions in biopsy-naïve men with suspected prostate cancer are larger, more conspicuous, and more diffusion restricted than false positives. Prostate-specific antigen density and apparent diffusion coefficient are predictors of significant disease, and could help guide decisions to biopsy men with indeterminate phenotypes.

Background Multiparametric magnetic resonance imaging (MP-MRI) is established in the diagnosis of prostate cancer, but the need for enhanced sequences has recently been questioned. Objective To assess whether dynamic contrast-enhanced imaging (DCE) improves accuracy over T2 and diffusion sequences. Design, setting, and participants PROMIS was a multicentre, multireader trial, with, in this part, 497 biopsy-naive 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. Outcome measurements and statistical analysis 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. Results and limitations 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. Conclusions Contrast adds little when MP-MRI is used to exclude significant prostate cancer. Patient summary 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.

Objectives To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. Patients and methods In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. Results Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. Conclusion A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

Purpose of review This review aims to give a brief description of the latest minimally invasive surgical techniques (MISTs) for the treatment of benign prostatic obstruction (BPO). Recent findings In recent years technological advances have made the implementation of MISTs in the armamentarium of BPO surgery possible and in many cases could replace standard procedures.These techniques offer many advantages -short recovery time, rapid symptomatic relief, few adverse effects, lower risk of sexual/ejaculatory dysfunction, acceptable durability and most can be performed as an outpatient procedure.Many of the newer MISTs can be performed outside the operating room under local anesthesia, hence the term office-based MIST. Summary A tailored BPO surgical treatment should not only take into account the prostate volume, but also many other factors including possible adverse events and the patient's expectations.Further studies and long-term data are necessary to standardize methods for evaluating the outcomes of these new procedures and to see which will pass the test of time and end-up replacing the gold standard procedures.

Background Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. Objective Early-medium-term cancer control and functional outcomes. Design, setting, and participants A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8mo [interquartile range (IQR) 19.5–36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies. Intervention Focal cryoablation of MR-visible tumours. Outcome measurements and statistical analysis Follow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes. Results and limitations A total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7yr (IQR 64.9–73.8) and preoperative PSA 10.8ng/ml (IQR 7.8–15.6). Overall FFS at 3yr was 90.5% [95% confidence interval (CI) 84.2–97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4–100) in high risk and 93.3% (95% CI 86.8–100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes. Conclusions Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. Patient summary In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems.

This review seeks to review up to date literature surrounding the chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to provide an overview of the subject. The review includes current understandings of the syndrome, the use of UPOINT, novel treatment strategies and future targets for management. Using the US National Institute of Health Chronic Prostatitis Symptom Index helps clinicians to monitor prostatitis symptoms, whilst using UPOINT as guidance of therapies based on patient phenotype(s) has advanced our ability to treat patients suffering with CP/CPPS. Furthermore, novel treatments look beyond traditional prostatic targets to treat CP/CPPS. Whilst the use of UPOINT has opened up new targets for the treatment of CP/CPPS, more work is needed to both improve the quality of trials assessing them, as well as further elucidate the underlying pathophysiology behind this troublesome syndrome.

Introduction: Basingstoke was a participating centre in the MRC funded PROMIS trial between 2013 and 2015 recruiting 130 patients. In response to a perceived change in prostate biopsy histological grading following the introduction of pre-biopsy magnetic resonance imaging at our centre, we decided to undertake a retrospective analysis of prostate histology before and after participation in the study. Methods: We identified 206 patients in both 2012 and 2016 who had undergone prostate biopsy. We reviewed the type of biopsy performed (transrectal or transperineal), the number of cores sampled, the number of positive cores and the cancer grade. The proportion of men who had pre-biopsy multiparametric magnetic resonance imaging was also recorded. Results: Although the total numbers undergoing biopsy were equivalent in 2012 and 2016, 37% of all patients undergoing biopsy underwent a transperineal template biopsy in 2012, increasing to 54% in 2016. The overall percentage of positive biopsy results (Gleason score ⩾3+3) increased from 70% to 83.0% (χ2=9.83, P=0.002). While the number of grade group 1 cancers significantly decreased from 63.9% (2012) to 22% (2016), there was a corresponding increase in the number of grade group 3 or higher cancers detected from 11% to 51%. In 2012, 33% of patients had multiparametric magnetic resonance imaging prior to biopsy compared with 90% in 2016. The pre-biopsy magnetic resonance imaging improved the cancer detection rates for both methods of biopsy sampling. Conclusion: Our study has confirmed that the introduction of pre-biopsy multiparametric magnetic resonance imaging can improve diagnostic accuracy and reduce the number of insignificant cancers detected. This overall upgrading of the biopsied population, and the resulting shift towards detecting an increased number of significant cancers, is likely to have a positive impact on treatment allocation and longer-term outcomes for our patients. This effect should be reproducible in other centres. Level of evidence: Not applicable for this multicentre audit.

Objective To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. Materials and methods In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007–November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6–12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. Results 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). Conclusion Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours.

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

Since first reported in December 2019, the novel RNA betacoronavirus disease (COVID‐19) has spread rapidly across the world with, as of the 3rd May 2020, 3.3 million confirmed cases with more than 230,000 deaths worldwide and more than 200 countries affected. The most common symptoms reported include dry cough, fever and fatigue with ground‐glass opacification bilaterally in the lungs on imaging and lymphopenia on haematological analysis. In severe cases the patients can develop acute respiratory distress syndrome (ARDS) or multi organ failure which can lead to death. Transmission of the virus (SARS‐CoV‐2) is via direct contact or via droplets spread by a cough or sneeze from an infected individual. The difficulty in disease detection and containment has been the long course of COVID‐19. Current evidence shows an incubation period of up to 14 days post exposure to the virus, and on average most patients first display symptoms on day five after initial exposure. More importantly, carriers are contagious even during this preceding asymptomatic incubation phase of the disease.

INTRODUCTION AND OBJECTIVE:All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore prostate can...

PURPOSE: We determined whether prostate specific antigen criteria after focal high intensity focused ultrasound to treat prostate cancer could diagnose treatment failure. MATERIALS AND METHODS: A total of 598 patients in a prospectively maintained national database underwent focal high intensity focused ultrasound with a Sonablate® 500 device from March 2007 to November 2016. Followup consisted of 3-month clinic visits and prostate specific antigen testing in year 1 with prostate specific antigen measurement every 6 to 12 months and multiparametric magnetic resonance imaging with biopsy for magnetic resonance imaging suspicious for recurrence. Treatment failure was considered any secondary treatment, tumor recurrence with Gleason 3 + 4 or greater disease on prostate biopsy without further treatment or metastasis and/or prostate cancer related mortality. To diagnose failure we evaluated a series of nadir + x thresholds with x values of 0.1 to 2.0 ng/ml. RESULTS: Median patient age was 65 years (IQR 60-71) and the median Gleason score was 7 (range 6-9). Gleason 3 + 4 or greater disease was present in 80% of cases. Tumors were radiologically staged as T1c-T2c in 522 of the 596 patients (88%) and as and T3a/b in 74 (12.4%). Baseline median prostate specific antigen was 7.80 ng/ml (IQR 5.96-10.45) in failed cases and 6.77 ng/ml (IQR 2.65-9.71) in cases without failure. Optimal performance according to the Youden index to indicate the most appropriate nadir + x at all analyzed time points at 3-month intervals showed that nadir + 1.0 ng/ml would have 27.3% to 100% sensitivity and 39.4% to 85.6% specificity depending on the time of evaluation in the first 3 years. Nadir + 1.5 ng/ml showed 18.2% to 100% sensitivity and 60.6% to 91.8% specificity with nadir + 2.0 ng/ml leading to similar sensitivity and specificity ranges. Nadir + 1.0 ng/ml at 12 months and nadir + 1.5 ng/ml at 24 and 36 months had 100% sensitivity and 96.1% to 100% negative predictive value. CONCLUSIONS: Following focal high intensity focused ultrasound a prostate specific antigen nadir of 1.0 ng/ml at 12 months and 1.5 ng/ml at 24 to 36 months might be used to triage men requiring magnetic resonance imaging and biopsy. These data need prospective validation.

The aim of this paper is to provide an update on the classification of urethral syndrome and explore some of the current hypotheses and management options for patients suffering from this common condition. Ever since urethral syndrome was first reported in the mid-twentieth century, there has been much mystery and confusion around this condition. This was primarily due to lack of clear definitions and limited understanding of its aetiology and pathogenesis. Recent advances have led to a paradigm shift, resulting in urethral syndrome no longer being seen as a condition in itself but as part of the spectrum of chronic pelvic pain syndromes.

The ability of free to total prostate-specific antigen and prostate-specific antigen density to detect clinically significant prostate cancer in men undergoing transperineal template biopsy Show all authors Surayne V Segaran, Amr M Emara, Tharani Mahesan, ... First Published September 12, 2017 Research Article Download PDFPDF download for The ability of free to total prostate-specific antigen and prostate-specific antigen density to detect clinically significant prostate cancer in men undergoing transperineal template biopsy Article information Full Access Article Information Volume: 10 issue: 6, page(s): 529-534 Article first published online: September 12, 2017; Issue published: November 1, 2017 Received: May 04, 2017; Accepted: August 08, 2017 https://doi.org/10.1177/2051415817730494 Surayne V Segaran1, Amr M Emara1, 2, Tharani Mahesan3, Joshua Silverman1, Hashim U Ahmed4, Simon RJ Bott3, Richard G Hindley1 1Urology Department, North Hampshire Hospitals NHS Trust, UK 2Urology Department, Ain Shams University, Egypt 3Urology Department, Frimley Park Hospital, UK 4Imperial College London, UK Corresponding Author: Surayne V Segaran, Urology Department, North Hampshire Hospitals NHS Trust, Aldermaston Road, Basingstoke, RG24 9NA, UK. Email: surayne.segaran@fhft.nhs.uk Abstract Objective: The purpose of this study was to determine the ability of the ratio of free to total prostate-specific antigen and prostate-specific antigen density to predict the presence of clinically significant prostate cancer on template biopsies. The value of these tests may be underestimated as they were previously validated against sextant transrectal biopsy of the prostate, which has been proved to miss a large proportion of significant prostate cancers. The ability of these tests to specifically detect clinically significant cancers has not previously been studied. Patients and methods: A retrospective analysis was performed of patients undergoing transperineal template biopsy who also had free to total prostate-specific antigen and prostate-specific antigen density. Receiver-operating characteristic analysis was performed to determine the comparative utility of each test in the detection of all cancers as well as clinically significant cancers, by means of the area under the curve. Results: Data from 293 patients were analysed. Prostate cancer was detected in 72% of patients, of which 62% of this group had clinically significant disease. Receiver-operating characteristic analysis demonstrated the superiority of prostate-specific antigen density and free to total prostate-specific antigen over standard prostate-specific antigen in the overall detection of cancer (area under the curve 0.662 and 0.674 vs 0.534, p=0.003 and 0.02 respectively). Both tests were even more effective in the detection of clinically significant cancers (area under the curve 0.755 and 0.715 vs 0.572, p

BACKGROUND: Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy. METHODS: We did this multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (template prostate mapping biopsy [TPM-biopsy]). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer. This study is registered on ClinicalTrials.gov, NCT01292291. FINDINGS: Between May 17, 2012, and November 9, 2015, we enrolled 740 men, 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88-96%) than TRUS-biopsy (48%, 42-55%; p

Purpose To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. Methods A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. Results Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. Conclusion Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified. Electronic supplementary material The online version of this article (10.1007/s00345-019-02636-7) contains supplementary material, which is available to authorized users.

ObjectiveTo describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation vs Radical prosTatectomy in intermediate‐risk unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment.Subjects and MethodsPART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included: scrutinising recruitment data, interviewing the trial management group and recruiters (n = 13), and audio‐recording recruitment consultations (n = 64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered. ResultsInitially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information, and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from a mean [range] of 1.4 [0–4] to 4.5 [0–12] patients/month) and the feasibility study reached its recruitment target.ConclusionAlthough clinicians find it challenging to recruit patients to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients.

INTRODUCTION AND OBJECTIVES:PROMIS provided level 1 evidence for pre-biopsy MP-MRI triage in diagnosing clinically significant prostate cancer (csPCa). We evaluated the performance of transrectal u...

INTRODUCTION AND OBJECTIVES:Focal therapy (FT) has a low side-effect profile but there is uncertainty about its medium-long term cancer control compared to radical approaches. Both focal HIFU and f...

INTRODUCTION AND OBJECTIVES:The Rezūm System is a minimally invasive thermal therapy for the treatment of symptomatic BPH. It can be safely performed under local anaesthetic and sedation with minim...

Objective To report our intermediate outcomes of the use of focal ablation for treating significant unilateral prostate cancer. This technique was adopted in our center 10 years ago. With improving diagnostic accuracy of index prostate cancer lesions and a low side-effect profile, use of focal high intensity focused ultrasound (HIFU) ablation is increasing. Methods Patients were diagnosed using prostate specific antigen (PSA), multiparametric magnetic resonance imaging, and template transperineal biopsies. Focal ablation of significant cancer was performed with the Sonablate device. Follow-up consisted of magnetic resonance imaging scanning, PSA, validated questionnaires, biopsy for cause, and redo HIFU if required as part of the treatment strategy. Results A total of 107 men underwent focal HIFU. In total, 88% had intermediate/high risk disease, and the mean pre-HIFU PSA was 7.7. A total of 31% had high volume Gleason 6 disease, 55% had Gleason 3+4 disease, and 13% had Gleason ≥ 4+3 disease. In total, 54 men received a hemiablation, 10 a focal ablation, and 43 a quadrant ablation. Median follow-up was 30 months, subjects’ PSA dropped to an average 71% nadir. A total of 8% had biochemical recurrence and 11% required adjuvant treatment. Freedom from additional procedures for clinically significant recurrent disease, including redo-HIFU, was 85.5%. Postoperative complications included 1% new use of pads, 1.9% urethral stricture, 2.8% post-HIFU TURP, and new onset ED of 14%. Conclusion In a carefully chosen cohort of patients for focal HIFU our results suggest acceptable oncological control with minimal postoperative morbidity. Further studies are required to establish this technique as a less morbid alternative to radical therapy.

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 ≥6 mm. Results and limitations The mean age, median PSA, and median prostate volume for the cohort were 63.8 yr (standard deviation [SD] 8.4), 6.3 ng/ml (SD 5.8), and 42.0 cm3 (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.

5009 Background: Radiotherapy is a common and effective treatment for localised prostate cancer. However, recurrence of cancer can occur in 10-15% of men in the following 5 years. Most patients with recurrence are managed using hormonal therapy with associated systemic side-effects and subsequent development of castrate resistance. Salvage prostatectomy confers a high risk of urine incontinence and rectal injury. Accurately localising and ablating only areas of recurrence within the prostate might be effective with fewer side-effects. The FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial assessed this diagnostic and treatment pathway for men with radiorecurrent cancer (NCT01883128). Methods: We first compared the accuracy of multi-parametric MRI (mp-MRI) and MRI-targeted biopsy in identifying areas of recurrent cancer to a transperineal template prostate mapping (TTPM) biopsy (Apr/2014-Jan/2018) in 181 patients from 6 UK centres. We then assessed the functional and cancer control outcomes of focally ablating areas of intraprostatic recurrence in 93 patients with localised or metastatic cancer (using cryotherapy or HIFU). Primary outcomes were sensitivity of mpMRI and MRI-targeted biopsies and urinary continence after focal ablation. A key secondary outcome was progression free survival (PFS) defined as no new metastases or hormone use (localised group only), or chemotherapy or further local treatment. Results: Of 181 men with suspicion of recurrence following radiotherapy, re-staging whole-body imaging (Choline PET and Bone Scan) showed localised disease in 128 (71%), nodal disease only in 13 (7%) and 38 (21%) metastatic. The sensitivity of MRI-targeted biopsy was 92% (95%CI 83-97%). Specificity, and positive and negative predictive values, were 75% (95%CI 45-92%), 94% (95%CI 86-98%) and 65% (95%CI 38-86%). 4/72 (6%) cancers were missed on TTPM biopsies alone and 6/72 (8%) were missed on MRI-targeted biopsies alone. Overall sensitivity of mpMRI was 81% (95%CI 73-88%) using Likert score 4-5 to denote a positive test. Specificity, and positive and negative predictive values, were 88% (95%CI 73-98%), 96% (95%CI 90-99%) and 57% (95%CI 42-70%). In the 93 men undergoing focal ablation, urinary continence was preserved in 78/93 (84%); 5/93 (5%) had a CTCAE grade 3+ adverse events. There were no rectal injuries. With a median follow-up of 27.8 [SD 1.3] months, PFS was 66% [54-75] at 24-months. Metastases-free survival in the 73 men with localised disease was 80% [95%CI 68–88] at 24-months. There were no cancer specific deaths. Conclusions: Prostate mpMRI and MRI-targeted biopsies can accurately detect and localise recurrent prostate cancer following radiotherapy. Focal ablation to areas of intra-prostatic recurrence preserves continence in the majority of men with good cancer control. Clinical trial information: NCT01883128.

Background High-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer. Objective To report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort. Design, setting, and participants Five-hundred and sixty-nine patients at eight hospitals were entered into an academic registry. Intervention Whole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention. Outcome measurements and statistical analysis Our primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function. Results and limitations Mean age was 65 yr (47–87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4–10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23–61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64–74). This was 87% (95% CI: 78–93), 63% (95% CI: 56–70), and 58% (95% CI: 32–77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data. Conclusions Whole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments. Patient summary In this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy.

Objective: The purpose of this study was to investigate the short-term results of extended pelvic lymphadenectomy (ePLND) during laparoscopic radical prostatectomy (LRP). Patients and methods: Of 1330 consecutive patients undergoing LRP during a 90-month period 1000 (75%) had an ePLND for d’Amico intermediate- or high-risk prostate cancer. Results: Operating time, blood loss, conversion and transfusion rates and hospital stay were similar in patients having standard pelvic lymphadenectomy (sPLND) and ePLND. Median lymph node count was significantly greater following ePLND vs sPLND (17 vs 6; p⩽0.0001). Complication rates were also similar but trended ( p=0.06) towards a greater rate after ePLND vs sPLND: 9.0% and 5.5%. Lymph node involvement (LNI) was detected more frequently following ePLND in patients with: prostate specific antigen (PSA)=0–9.9 ( p=0.01) and PSA=10–19.9 ( p⩽0.0001); biopsy Gleason sum ⩽8 ( p⩽0.0001 to 0.03); intermediate- ( p⩽0.0001) and high-risk ( p⩽0.0001) cancer; pathological Gleason grade 7 ( p⩽0.0001) and pathological stage T3 ( p=0.0009 for pT3a and p⩽0.0001 for pT3b). Conclusion: ePLND is a more effective tool than sPLND in detecting LNI for patients in all prognostic clinical groups. This can be achieved without significant penalty with respect to operating time or complication rates.

Background Tissue preservation by means of focal therapy offers some men with clinically significant prostate cancer an alternative to standard care that appears to confer favourable genito-urinary outcomes. The precise estimates of these outcomes have so far been based on small series. Objective This analysis pools the sexual domain related patient reported outcomes from three prospective, registered studies that represent a range of inclusion criteria. Design, setting, and participants One-hundred and eighteen men with localised prostate cancer (prostate specific antigen ≤ 15ng/ml, Gleason ≤ 4+3, stage ≤ T3aN0M0) treated in a tissue-preserving manner using high intensity focused ultrasound from three registered studies were included. Data on International Index of Erectile Function (IIEF-5) scores and use of phosphodiesterase-5-inhibitors were collected at baseline, and 1 mo, 3 mo, 6 mo, 9 mo, and 12 mo postoperatively. The IIEF-15 total and individual domain scores were used to assess overall sexual function. Urinary function was assessed with the International Prostate Symptom Score (IPSS), IPSS quality-of-life, and UCLA-Expanded Prostate Cancer Index Composite continence questionnaires. General health status was derived by means of the Charlson score. Multiple linear regression was used to assess whether age, grade, stage, qualitative scores (IIEF, IPSS, Expanded Prostate Cancer Index Composite, Charlson), or focal therapy type duration were associated with IIEF-5 and IIEF-15 scores at 12 mo. Results and limitations Median age was 63 yr (interquartile range [IQR] 52–70 yr). Median IIEF-erectile score at baseline was 23 (IQR 11–28). This declined significantly to 9 (IQR 3–22, p p =0.30) at 1 yr posttreatment. Changes in total IIEF and other IIEF domains were only significantly different from preoperative values at 1 mo and 3 mo postoperatively. In the same period, the proportion of men using phosphodiesterase-5-inhibitors was 10% preoperatively, reaching 43% and 42% at 6 mo and 9 months before declining to 37% at 1 yr. The only baseline determinants of postoperative erectile function were total IIEF and IIEF-erectile function scores ( p =0.002). The primary limitation of our study is the relatively short follow-up of 1 yr. Conclusion Men who received a range of tissue preserving therapies from the three pertinent studies experienced small decreases in total IIEF, erectile, and individual sexual domain scores that are not significantly different to those recorded at baseline. The only determinant of erectile dysfunction after tissue preserving therapy was preoperative erectile dysfunction status. Tissue preservation confers a high probability of maintaining erectile function that appears independent of all perioperative factors with the exception of baseline status. Patient summary In this report, the largest prospectively collected and published set of patients with erectile dysfunction outcomes post–focal therapy for prostate cancer, we have found a return to baseline International Index of Erectile Function–erectile and total International Index of Erectile Function scores by 6 mo post–focal therapy which was maintained at 1 yr, with the majority of patients not on any form of medical treatment for their erectile dysfunction at that point. Focal therapy may represent a suitable alternative for men of any age or comorbidity wishing to maintain erectile function.

5582 Background: Patients that have previously failed radiotherapy for prostate cancer is usually limited to systemic therapy due to morbidity from salvage prostatectomy. We reviewed the outcomes following focal salvage ablative therapy with HIFU or cryotherapy within the UK’s HEAT and ICE registries. Methods: 356 consecutive patients underwent focal ablative treatment after initial radiation treatment failure (28/1/2004-1/10/2019, 194 (54.5%) underwent HIFU (posterior recurrence) and 162 (45.5%) underwent cryotherapy (mostly anterior or T3b). Primary outcome was failure-free survival (FFS) defined as no systemic therapy, whole-gland treatment, metastases or prostate cancer-specific death. Secondary outcomes were adverse events and overall survival. Results: Median (IQR) age was 69years (65-73) and PSA (IQR) was 4.0ng/ml (1-7-7.2). Overall median (IQR) follow-up was 41.3 months (21.4-58.5). Quadrant ablation was performed in 128 (36.0%), hemi-ablation performed in 64 (18.0%), hockey-stick in 5 (1.4%) and 159 (43.8%) had unknown ablative patterns. Due to histological or MRI proven recurrence/residual disease, 31 (8.7%) underwent further focal salvage re-treatment. FFS (95%CI) at 3 and 6 years were 81% (76-87%) and 75% (68-83%) respectively. Median (IQR) time to failure was 15.5 months (19.7). Overall survival (95%CI) at 3 and 6 years were 97% (95-100%) and 88% (81-96%) respectively. Prostate-specific mortality was 2.8%. Overall 3 (0.8%) patients were managed for fistula formation, 16 (4.5%) were treated for UTIs. Conclusions: Salvage focal ablative therapy for radio-recurrent prostate cancer is safe and provides good short to medium-term oncological control. The FORECAST study is awaited to further determine oncological outcomes in this cohort.

INTRODUCTION AND OBJECTIVE:Although the association between PSA density and the presence of clinically significant cancer in men without a prior biopsy has been thoroughly discussed, a precise rela...

Background Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy. Objectives To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway. Design A validating paired-cohort study and an economic evaluation using a decision-analytic model. Setting Eleven NHS hospitals in England. Participants Men at risk of prostate cancer undergoing a first prostate biopsy. Interventions Participants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test). Main outcome measures Diagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy. Results Diagnostic study – a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation – the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected. This strategy is cost-effective at the TRUS-guided biopsy definition 2 (any Gleason pattern of ≥ 4 and/or cancer core length of ≥ 4 mm), mpMRI definition 2 (lesion volume of ≥ 0.2 ml and/or Gleason score of ≥ 3 + 4) and cut-off point 2 (likely to be benign) and detects 95% (95% CI 92% to 98%) of CS cancers. The main drivers of cost-effectiveness were the unit costs of tests, the improvement in sensitivity of MRI-guided TRUS-guided biopsy compared with blind TRUS-guided biopsy and the longer-term costs and outcomes of men with cancer. Limitations The PROstate Magnetic resonance Imaging Study (PROMIS) was carried out in a selected group and excluded men with a prostate volume of > 100 ml, who are less likely to have cancer. The limitations in the economic modelling arise from the limited evidence on the long-term outcomes of men with prostate cancer and on the sensitivity of MRI-targeted repeat biopsy. Conclusions Incorporating mpMRI into the diagnostic pathway as an initial test prior to prostate biopsy may (1) reduce the proportion of men having unnecessary biopsies, (2) improve the detection of CS prostate cancer and (3) increase the cost-effectiveness of the prostate cancer diagnostic and therapeutic pathway. The PROMIS data set will be used for future research; this is likely to include modelling prognostic factors for CS cancer, optimising MRI scan sequencing and biomarker or translational research analyses using the blood and urine samples collected. Better-quality evidence on long-term outcomes in prostate cancer under the various management strategies is required to better assess cost-effectiveness. The value-of-information analysis should be developed further to assess new research to commission. Trial registration Current Controlled Trials ISRCTN16082556 and NCT01292291. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 39. See the NIHR Journals Library website for further project information. This project was also supported and partially funded by the NIHR Biomedical Research Centre at University College London (UCL) Hospitals NHS Foundation Trust and UCL and by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre and was co-ordinated by the Medical Research Council’s Clinical Trials Unit at UCL (grant code MC_UU_12023/28). It was sponsored by UCL. Funding for the additional collection of blood and urine samples for translational research was provided by Prostate Cancer UK.