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Introduction: RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes., Methods: RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%., Results: Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis., Conclusion: We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: 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. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Marsden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear., Objective: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation., Design, Setting, and Participants: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here., Intervention: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious., Outcome Measurements and Statistical Analysis: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease., Results and Limitations: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation., Conclusions: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease., Patient Summary: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

At present there is no standardised system for scoring the appearance of the prostate on multiparametric magnetic resonance imaging (MRI) after focal ablation for localised prostate cancer. We propose a novel scoring system, the Prostate Imaging after Focal Ablation (PI-FAB) score, to fill this gap. PI-FAB involves a 3-point scale for rating MRI sequences in sequential order: (1) dynamic contrast-enhanced sequences; (2) diffusion-weighted imaging, split into assessment of the high-b-value sequence first and then the apparent diffusion coefficient map; and (3) T2-weighted imaging. It is essential that the pretreatment scan is also available to help with this assessment. We designed PI-FAB using our experience of reading postablation scans over the past 15 years and include details for four representative patients initially treated with high-intensity focus ultrasound at our institution to demonstrate the scoring system. We propose PI-FAB as a standardised method for evaluating prostate MRI scans after treatment with focal ablation. The next step is to evaluate its performance across multiple experienced readers of MRI after focal therapy in a clinical data set. PATIENT SUMMARY: We propose a scoring system called PI-FAB for assessing the appearance of magnetic resonance imaging scans of the prostate after focal treatment for localised prostate cancer. This will help clinicians in deciding on further follow-up., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset., Patients and Methods: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments., Results: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range., Conclusion: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: The optimal radiological follow-up of prostate lesions negative on magnetic resonance imaging (MRI)-targeted biopsy (MRI-TB) is yet to be optimised., Objective: To present medium-term radiological and clinical follow-up of biopsy-negative lesions., Design, Setting, and Participants: The records for men who underwent multiparametric MRI at the UCLH one-stop clinic for suspected prostate cancer between September 2017 and March 2020 were reviewed (n = 1199). Patients with Likert 4 or 5 lesions were considered (n = 495), and those with a subsequent negative MRI-TB comprised the final study population (n = 91)., Outcome Measurements and Statistical Analysis: Baseline and follow-up MRI and biopsy data (including prostate-specific antigen [PSA], prostate volume, radiological scores, and presence of any noncancerous pathology) were extracted from reports. The last follow-up date was the date of the last test or review in clinic., Results and Limitations: Median follow-up was 1.8 yr (656 d, interquartile range [IQR] 359-1008). At baseline, the median age was 65.4 yr (IQR 60.7-70.0), median PSA was 7.1 ng/ml (IQR 4.7-10.0), median prostate volume was 54 ml (IQR 39.5-75.0), and median PSA density (PSAD) was 0.13 ng/ml 2 (IQR 0.09-0.18). Eighty-six men (95%) had Likert 4 lesions, while the remaining five (5%) had Likert 5 lesions. Only 21 men (23%) had a single lesion; most had at least two. Atrophy was the most prevalent pathology on MRI-TB, present in 64 men (74%), and followed by acute inflammation in 42 (46%), prostatic intraepithelial neoplasia in 33 (36%), chronic inflammation in 18 (20%), atypia in 13 (14%), and granulomatous inflammation in three (3%). Fifty-eight men had a second MRI study (median 376 d, IQR 361-412). At the second MRI, median PSAD decreased to 0.11 ng/ml 2 (IQR 0.08-0.18). A Likert 4 or 5 score persisted only in five men (9%); 40 men (69%) were scored Likert 3, while the remaining 13 (22%) were scored Likert 2 (no lesion). Of 45 men with a Likert ≥3 score, most only had one lesion at the second MRI (28 men; 62%). Of six men with repeat MRI-TB during the study period, two were subsequently diagnosed with prostate cancer and both had persistent Likert 4 scores (at baseline and at least one follow-up MRI)., Conclusions: Most biopsy-negative MRI lesions in the prostate resolve over time, but any persistent lesions should be closely monitored., Patient Summary: Lesions in the prostate detected via magnetic resonance imaging (MRI) scans that are negative for cancer on biopsy usually resolve. Repeat MRI can indicate persistent lesions that might need a second biopsy., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality., Materials and Methods: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis., Results: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively ( P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen., Conclusions: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.

Purpose: To investigate the utility of a prostate magnetic resonance imaging (MRI) second read using a semi-automated software program in the one-stop clinic, where patients undergo multiparametric MRI, review and biopsy planning in one visit. We looked at concordance between readers for patients with equivocal scans and the possibility for biopsy deferral in this group., Methods: We present data from 664 consecutive patients. Scans were reported by seven different expert genitourinary radiologists using dedicated software (MIM®) and a Likert scale. All scans were rescored by another expert genitourinary radiologist using a customised workflow for second reads that includes annotated biopsy contours for accurate visual targeting. The number of scans in which a biopsy could have been deferred using biopsy results and prostate specific antigen density was assessed. Gleason score ≥ 3 + 4 was considered clinically significant disease. Concordance between first and second reads for equivocal scans (Likert 3) was evaluated., Results: A total of 209/664 (31%) patients scored Likert 3 on first read, 128 of which (61%) were concordant after second read. 103/209 (49%) of patients with Likert 3 scans were biopsied, with clinically significant disease in 31 (30%) cases. Considering Likert 3 scans that were both downgraded and biopsied using the workflow-generated biopsy contours, 25/103 (24%) biopsies could have been deferred., Conclusions: Implementing a semi-automated workflow for accurate lesion contouring and targeting biopsies is helpful during the one-stop clinic. We observed a reduction of indeterminate scans after second reading and almost a quarter of biopsies could have been deferred, reducing the potential biopsy-related side effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Focal therapy treats individual areas of tumour in non-metastatic prostate cancer in patients unsuitable for active surveillance. The aim of this work was to evaluate the cost-effectiveness of focal therapy versus prostatectomy and external beam radiotherapy (EBRT)., Materials and Methods: A Markov cohort health state transition model with four health states (stable disease, local recurrence, metastatic disease and death) was created, evaluating costs and utilities over a 10-year time horizon for patients diagnosed with non-metastatic prostate cancer. National Health Service (NHS) for England perspective was used, based on direct healthcare costs. Clinical transition probabilities were derived from prostate cancer registries in patients undergoing radical prostatectomy, EBRT and focal therapy using cryotherapy (Boston Scientific) or high-intensity focused ultrasound (HIFU) (Sonablate). Propensity score matching was used to ensure that at-risk populations were comparable. Variables included age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, maximum cancer core length (mm), T-stage and year of treatment., Results: Focal therapy was associated with a lower overall cost and higher quality-adjusted life year (QALY) gains than either prostatectomy or EBRT, dominating both treatment strategies. Positive incremental net monetary benefit (NMB) values confirm focal therapy as cost-effective versus the alternatives at a willingness to pay (WTP) threshold of £30,000/QALY. One-way deterministic sensitivity analyses revealed consistent results., Limitations: Data used to calculate the transition probabilities were derived from a limited number of hospitals meaning that other potential treatment options were excluded. Limited data were available on later outcomes and none on quality of life data, therefore, literature-based estimates were used., Conclusions: Cost-effectiveness modelling demonstrates use of focal therapy (cryotherapy or HIFU) is associated with greater QALY gains at a lower overall cost than either radical prostatectomy or EBRT, representing good value for money in the NHS.

Background: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed., Objective: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease., Design, Setting, and Participants: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis., Intervention: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases., Outcome Measurements and Statistical Analysis: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS)., Results and Limitations: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The specificity and positive and negative predictive values were 75% (95% CI 45-92%), 94% (95% CI 86-98%), and 65% (95% CI 38-86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo., Conclusions: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control., Patient Summary: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment., Objective: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer., Design, Setting, and Participants: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA)., Outcome Measurements and Statistical Analysis: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification., Results and Limitations: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking., Conclusions: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term., Patient Summary: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Multiparametric magnetic resonance imaging (mpMRI) has improved the triage of men with suspected prostate cancer, through precision prebiopsy identification of clinically significant disease. While multiple important characteristics, including tumour grade and size have been shown to affect conspicuity on mpMRI, tumour location and association with mpMRI visibility is an underexplored facet of this field. Therefore, the objective of this systematic review and meta-analysis is to collate the extant evidence comparing MRI performance between different locations within the prostate in men with existing or suspected prostate cancer. This review will help clarify mechanisms that underpin whether a tumour is visible, and the prognostic implications of our findings., Methods and Analysis: The databases MEDLINE, PubMed, Embase and Cochrane will be systematically searched for relevant studies. Eligible studies will be full-text English-language articles that examine the effect of zonal location on mpMRI conspicuity. Two reviewers will perform study selection, data extraction and quality assessment. A third reviewer will be involved if consensus is not achieved. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will inform the methodology and reporting of the review. Study bias will be assessed using a modified Newcastle-Ottawa scale. A thematic approach will be used to synthesise key location-based factors associated with mpMRI conspicuity. A meta-analysis will be conducted to form a pooled value of the sensitivity and specificity of mpMRI at different tumour locations., Ethics and Dissemination: Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations., Prospero Registration Number: CRD42021228087., Competing Interests: Competing interests: JMN received funding from the MRC. BSSS received funding from the Rosetrees Trust. HCW received funding from PCUK, the Urology Foundation and the Rosetrees Trust. AK, AF and ME have stock interest in Nuada Medical. ME received funding from NIHR-i4i, MRC, Sonacare, Trod Medical, Cancer Vaccine Institute and Sophiris Biocorp for trials in prostate cancer. ME is a medical consultant to Sonacare, Sophiris Biocorp, Steba Biotech, GSK, Exact Imaging and Profound Medical. Travel allowance was previously provided from Sanofi Aventis, Astellas, GSK and Sonacare. ME is a proctor for HIFU with Sonacare Inc and paid for training other surgeons in this procedure., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies., Methods: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28-83) and 62 (42-83) months, respectively., Results: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9-87.3) than after focal therapy (72.8%, 95% CI 66.8-79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1-95.2 versus 97.5%, 95% CI 94-99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008)., Conclusions: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2021 The Authors. BJU International © 2021 BJU International.)

Active surveillance for low-to-intermediate risk prostate cancer is a conservative management approach that aims to avoid or delay active treatment until there is evidence of disease progression. In recent years, multiparametric MRI (mpMRI) has been increasingly used in active surveillance and has shown great promise in patient selection and monitoring. This has been corroborated by publication of the Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation (PRECISE) recommendations, which define the ideal reporting standards for mpMRI during active surveillance. The PRECISE recommendations include a system that assigns a score from 1 to 5 (the PRECISE score) for the assessment of radiologic change on serial mpMRI scans. PRECISE scores are defined as follows: a score of 3 indicates radiologic stability, a score of 1 or 2 denotes radiologic regression, and a score of 4 or 5 indicates radiologic progression. In the present study, we discuss current and future trends in the use of mpMRI during active surveillance and illustrate the natural history of prostate cancer on serial scans according to the PRECISE recommendations. We highlight how the ability to classify radiologic change on mpMRI with use of the PRECISE recommendations helps clinical decision making.

Purpose: We determined the early efficacy of bipolar radiofrequency ablation with a coil design for focal ablation of clinically significant localized prostate cancer visible at multiparametric magnetic resonance imaging., Materials and Methods: A prospective IDEAL phase 2 development study (Focal Prostate Radiofrequency Ablation, NCT02294903) recruited treatment-naïve patients with a single focus of significant localized prostate cancer (Gleason 7 or 4 mm or more of Gleason 6) concordant with a lesion visible on multiparametric magnetic resonance imaging. Intervention was a focal ablation with a bipolar radiofrequency system (Encage™) encompassing the lesion and a predefined margin using nonrigid magnetic resonance imaging-ultrasound fusion. Primary outcome was the proportion of men with absence of significant localized disease on biopsy at 6 months. Trial followup consisted of serum prostate specific antigen, multiparametric magnetic resonance imaging at 1 week, and 6 and 12 months post-ablation. Validated patient reported outcome measures for urinary, erectile and bowel functions, and adverse events monitoring system were used. Analyses were done on a per-protocol basis., Results: Of 21 patients recruited 20 received the intervention. Baseline characteristics were median age 66 years (IQR 63-69) and preoperative median prostate specific antigen 7.9 ng/ml (5.3-9.6). A total of 18 patients (90%) had Gleason 7 disease with median maximum cancer 7 mm (IQR 5-10), for a median of 2.8 cc multiparametric magnetic resonance imaging lesions (IQR 1.4-4.8). Targeted biopsy of the treated area (median number of cores 6, IQR 5-8) showed absence of significant localized prostate cancer in 16/20 men (80%), concordant with multiparametric magnetic resonance imaging. There was a low profile of side effects at patient reported outcome measures analysis and there were no serious adverse events., Conclusions: Focal therapy of significant localized prostate cancer associated with a magnetic resonance imaging lesion using bipolar radiofrequency showed early efficacy to ablate cancer with low rates of genitourinary and rectal side effects.

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68 Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68 Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68 Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68 Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68 Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68 Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68 Ga-THP PSMA in patients with prostate cancer., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objectives: The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol., Methods: A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves., Results: Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53-98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1-3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4-5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density., Conclusions: Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy., Key Points: • Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4-5) during AS. • Patients with radiological progression on MRI (PRECISE 4-5) during AS showed a trend to an increase in PSA density.

Objective: The PRECISE criteria for reporting multiparametric MRI in patients on active surveillance (AS) for prostate cancer (PCa) score the likelihood of clinically significant change over time using a 1-5 scale, where 4 or 5 indicates radiological progression. According to the PRECISE recommendations, the index lesion size can be reported using different definitions of volume (planimetry or ellipsoid formula) or by measuring one or two diameters. We compared different measurements using planimetry as the reference standard and stratified changes according to the PRECISE scores., Methods: We retrospectively analysed 196 patients on AS with PCa confirmed by targeted biopsy who had two MR scans (baseline and follow-up). Lesions were measured on T 2 weighted imaging ( T 2 WI) according to all definitions. A PRECISE score was assessed for each patient., Results: The ellipsoid formula exhibited the highest correlation with planimetry at baseline (ρ = 0.97) and follow-up (ρ = 0.98) imaging, compared to the biaxial measurement and single maximum diameter. There was a significant difference ( p < 0.001) in the yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) for planimetry (39.64%) and for the ellipsoid formula (46.78%)., Conclusion: The ellipsoid formula could be used to monitor tumour growth during AS. Evidence of a significant yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) has been also observed., Advances in Knowledge: The ellipsoid formula is a reasonable surrogate for planimetry in capturing tumour volume changes on T 2 WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations.

Background: Although the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts., Objective: We describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring., Design, Setting, and Participants: Data on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen <20 ng/ml, and baseline mpMRI) were collected from the University College London Hospital (UCLH) database., Outcome Measurements and Statistical Analysis: Primary outcomes were event-free survival (EFS; event defined as prostate cancer treatment, transition to watchful waiting, or death) and treatment-free survival (TFS). Secondary outcomes included rates of all-cause or prostate cancer-related mortality, metastasis, and upgrading to Gleason ≥4 + 3. Data on radiological and histological progression were also collected., Results and Limitations: More than 3800 person-years (py) of follow-up were accrued (median: 58 mo; interquartile range 37-82 mo). Approximately 84.7% (95% confidence interval [CI]: 82.0-87.6) and 71.8% (95% CI: 68.2-75.6) of patients remained on AS at 3 and 5 yr, respectively. EFS and TFS were lower in those with MRI-visible (Likert 4-5) disease or secondary Gleason pattern 4 at baseline (log-rank test; p <  0.001). In total, 216 men were treated. There were 24 deaths, none of which was prostate cancer related (6.3/1000 py; 95% CI: 4.1-9.5). Metastases developed in eight men (2.1 events/1000 py; 95% CI: 1.0-4.3), whereas 27 men upgraded to Gleason ≥4 + 3 on follow-up biopsy (7.7 events/1000 py; 95% CI: 5.2-11.3)., Conclusions: The rates of discontinuation, mortality, and metastasis in MRI-led surveillance are comparable with those of standard AS. MRI-visible disease and/or secondary Gleason grade 4 at baseline are associated with a greater likelihood of moving to active treatment at 5 yr. Further research will concentrate on optimising imaging intervals according to baseline risk., Patient Summary: In this report, we looked at the outcomes of magnetic resonance imaging (MRI)-based surveillance for prostate cancer in a UK cohort. We found that this strategy could allow routine biopsies to be avoided. Secondary Gleason pattern 4 and MRI visibility are associated with increased rates of treatment. We conclude that MRI-based surveillance should be considered for the monitoring of small prostate tumours., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p < 0.001) and radical treatment (HR: 0.97; p < 0.001) after FT. For %PSA reduction of>90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of <10%, the probability of receiving any additional treatment within 5 yr was roughly 70%. This study is the first to assess the role of %PSA reduction in the largest multicentre cohort of men receiving FT for PCa. Given the lack of standardised follow-up strategies in the FT field, the use of the %PSA reduction should be considered. PATIENT SUMMARY: The percentage of prostate-specific antigen reduction is a useful tool to assess men following focal therapy (FT). It can assist the urologist in setting up an appropriate follow-up and during post-FT patient counselling., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To investigate whether patients with Gleason 3 + 4 cancer on transrectal biopsy are upgraded after undergoing transperineal magnetic resonance imaging (MRI)-targeted biopsy and whether this has implications for current clinical practice., Patients and Methods: In this retrospective analysis we examined 107 consecutive patients presenting at a single tertiary referral centre (July 2012 to July 2016) with prostate cancer of Gleason score 3 + 4 on transrectal ultrasonography (TRUS)-guided systematic non-targeted biopsy who then underwent a multiparametric MRI followed by MRI-targeted transperineal prostate biopsy for accurate risk stratification and localization., Results: The patients' mean (sd) age was 67.0 (8.0) years, and they had a median (interquartile range) PSA concentration of 6.2 (4.7-9.6) ng/mL. Of the 107 patients, 84 (78.5%) had Gleason 3 + 4 on both transrectal systematic biopsy and transperineal MRI-targeted biopsy. Nineteen patients (17.8%) were upgraded to Gleason 4 + 3, three patients (3.0%) to Gleason 4 + 4 and one patient (1.0%) to Gleason 4 + 5. These differences were significant (P = 0.0006). Likewise, 23/107 patients (22%) had higher-risk disease based on their targeted biopsies., Conclusion: The use of targeted biopsy in men with impalpable cancer, ultimately upgraded one in five patients from favourable-intermediate- to unfavourable-intermediate-risk disease or worse. This has significant clinical implications for men considering active surveillance or radical treatment. Our risk calculators must now be validated using these data from targeted biopsy as the technique becomes widely adopted., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Objective: To report medium-term oncological outcomes in men receiving primary focal treatment with high-intensity focused ultrasonography ( HIFU) for prostate cancer (PCa)., Patients and Methods: Consecutive patients with PCa treated with primary focal HIFU at two centres by six treating clinicians were assessed. Patients were submitted to either focal ablation or hemi-ablation using HIFU (Sonablate 500). The primary objective of the study was to assess medium-term oncological outcomes, defined as overall survival, freedom from biopsy failure, freedom from any further treatment and freedom from radical treatment after focal HIFU. The secondary objective was to evaluate the changes in pathological features among patients treated with focal HIFU over time. We also assessed the relationship between year of surgery and 5-year retreatment probability., Results: A total of 1032 men treated between November 2005 and October 2017 were assessed. The median age was 65 years and median prostate-specific antigen level was 7 ng/mL. The majority of patients had a Gleason score of 3 + 4 or above (80.3%). The median (interquartile range) follow-up was 36 (14-64) months. The overall survival rates at 24, 60 and 96 months were 99%, 97% and 97%, respectively. Freedom from biopsy failure, defined as absence of Gleason 3 + 4 disease, was 84%, 64% and 54% at 24, 60 and 96 months. Freedom from any further treatment was 85%, 59% and 46% at 24, 60 and 96 months, respectively. Approximately 70% of patients who were retreated received a second focal treatment. Freedom from radical treatment was 98%, 91% and 81% at 24, 60 and 96 months. During the study period, we observed an increase in the proportion of patients undergoing focal HIFU with Gleason 3 + 4 disease and with T2 stage disease as defined by multiparametric magnetic resonance imaging. Finally, there was a reduction over time in the proportion of patients undergoing re-treatment within 5 years of first treatment., Conclusions: Focal HIFU for PCa is a feasible therapeutic strategy, with acceptable survival and oncological results and a reduction in the 5-year retreatment rates over the last decade. Re-do focal treatment is a feasible technique whose functional and oncological outcomes have still to be evaluated., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Background: Risk models (RM) need external validation to assess their value beyond the setting in which they were developed. We validated a RM combining mpMRI and clinical parameters for the probability of harboring significant prostate cancer (sPC, Gleason Score ≥ 3+4) for biopsy-naïve men., Material and Methods: The original RM was based on data of 670 biopsy-naïve men from Heidelberg University Hospital who underwent mpMRI with PI-RADS scoring prior to MRI/TRUS-fusion biopsy 2012-2015. Validity was tested by a consecutive cohort of biopsy-naïve men from Heidelberg (n = 160) and externally by a cohort of 133 men from University College London Hospital (UCLH). Assessment of validity was performed at fusion-biopsy by calibration plots, receiver operating characteristics curve and decision curve analyses. The RM`s performance was compared to ERSPC-RC3, ERSPC-RC3+PI-RADSv1.0 and PI-RADSv1.0 alone., Results: SPC was detected in 76 men (48%) at Heidelberg and 38 men (29%) at UCLH. The areas under the curve (AUC) were 0.86 for the RM in both cohorts. For ERSPC-RC3+PI-RADSv1.0 the AUC was 0.84 in Heidelberg and 0.82 at UCLH, for ERSPC-RC3 0.76 at Heidelberg and 0.77 at UCLH and for PI-RADSv1.0 0.79 in Heidelberg and 0.82 at UCLH. Calibration curves suggest that prevalence of sPC needs to be adjusted to local circumstances, as the RM overestimated the risk of harboring sPC in the UCLH cohort. After prevalence-adjustment with respect to the prevalence underlying ERSPC-RC3 to ensure a generalizable comparison, not only between the Heidelberg and die UCLH subgroup, the RM`s Net benefit was superior over the ERSPC`s and the mpMRI`s for threshold probabilities above 0.1 in both cohorts., Conclusions: The RM discriminated well between men with and without sPC at initial MRI-targeted biopsy but overestimated the sPC-risk at UCLH. Taking prevalence into account, the model demonstrated benefit compared with clinical risk calculators and PI-RADSv1.0 in making the decision to biopsy men at suspicion of PC. However, prevalence differences must be taken into account when using or validating the presented risk model., Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: DB is a speaker for Profound Medical Inc.. JPR is company consultant for Invivo Uronav, Bender Group, Beckelmann and Saegeling Medizintechnik. FG is funded by the UCL Graduate Research Scholarship and the Brahm PhD scholarship in memory of Chris Adams. ME is a United Kingdom National Institute of Health Research (NIHR) Senior Investigator and receives research support from UCL Hospitals–UCL NIHR Biomedical Research Centre. However this funding is not related to this work and does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: The goal of radical prostatectomy is to eradicate oncological disease while achieving the best possible functional outcomes. In this regard, nerve sparing offers a greater chance of recovering potency after surgery. Accurately locating prostate cancer foci is instrumental for identifying good candidates for this approach whilst maintaining safe oncological margins. In addition to this, the length of membranous urethra is an independent predictor of time to, and extent of, continence recovery. The introduction of Mp-MRI allows visualising malignant tissue within the prostate gland, which could lead to image-directed surgery planning as with other solid-organ cancers such as kidney, pancreas, breast or testes., Methods: A narrative review of the available literature was performed., Results: Mp-MRI demonstrated moderate sensitivity and high specificity to detect extra-capsular extension, seminal vesicle involvement or T3 stage. Measurements of membranous urethral length have shown to be useful in predicting probability of achieving continence after surgery. Furthermore, image-guided surgery has shown to be accurate to determine surgical planes to safely preserve neurovascular bundles., Conclusion: The use of Mp-MRI for pre-surgical planning introduces a new scenario where the previously homogeneous radical prostatectomy can be tailored to suit patient and tumour features. This has the potential to improve functional outcomes whilst not compromising on surgical margins. Moreover, the introduction of Mp-MRI increases the ability to predict functional outcomes after surgery and allows for a more accurate local staging. This in turn provides more information to both patients and clinicians in the decision-making process regarding treatment.

Objective: To undertake an early proof-of-concept study on a novel, semi-automated texture-based scoring system in order to enhance the association between magnetic resonance imaging (MRI) lesions and clinically significant prostate cancer (SPCa)., Patients and Methods: With ethics approval, 536 imaging volumes were generated from 20 consecutive patients who underwent multiparametric MRI (mpMRI) at time of biopsy. Volumes of interest (VOIs) included zonal anatomy segmentation and suspicious MRI lesions for cancer (Likert Scale score >2). Entropy (E), measuring heterogeneity, was computed from VOIs and plotted as a multiparametric score defined as the entropy score (ES) = E ADC + E K trans + E Ve + E T2WI. The reference test that was used to define the ground truth comprised systematic saturation biopsies coupled with MRI-targeted sampling. This generated 422 cores in all that were individually labelled and oriented in three-dimensions. Diagnostic accuracy for detection of SPCa, defined as Gleason score ≥3 + 4 or >3 mm of any grade of cancer on a single core, was assessed using receiver operating characteristics, correlation, and descriptive statistics. The proportion of cancerous lesions detected by ES and visual scoring (VS) were statistically compared using the paired McNemar test., Results: Any cancer (Gleason score 6-8) was found in 12 of the 20 (60%) patients, with a median PSA level of 8.22 ng/mL. SPCa (mean [95% confidence interval, CI] ES = 17.96 [0.72] NATural information unit [NAT]) had a significantly higher ES than non-SPCa (mean [95% CI] ES = 15.33 [0.76] NAT). The ES correlated with Gleason score (r s = 0.568, P = 0.033) and maximum cancer core length (ρ = 0.781; P < 0.001). The area under the curve for the ES (0.89) and VS (0.91) were not significantly different (P = 0.75) for the detection of SPCa amongst MRI lesions. Best ES estimated numerical threshold of 16.61 NAT led to a sensitivity of 100% and negative predictive value of 100%. The proportion of MRI lesions that were found to be positive for SPCa using this ES threshold (54%) was significantly higher (P < 0.001) than using the VS (24% of score 3, 4, 5) in a paired analysis using the McNemar test. In all, 53% of MRI lesions would have avoided biopsy sampling without missing significant disease., Conclusion: Capturing heterogeneity of prostate cancer across multiple MRI sequences with the ES yielded high performances for the detection and stratification of SPCa. The ES outperformed the VS in predicting positivity of lesions, holding promise in the selection of targets for biopsy and calling for further understanding of this association., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Purpose: We describe the pathological characteristics of recurrence following high intensity focused ultrasound partial ablation in men treated with salvage robot-assisted radical prostatectomy. We assessed the sensitivity of magnetic resonance imaging before salvage robot-assisted radical prostatectomy in these men., Materials and Methods: A total of 35 men underwent salvage robot-assisted radical prostatectomy after high intensity focused ultrasound partial ablation from 2012 to 2018. We compared clinicopathological characteristics before ultrasound and before salvage prostatectomy after ultrasound to histopathology on salvage prostatectomy. We assessed infield recurrence, out of field disease, positive surgical margins and magnetic resonance imaging sensitivity before salvage robot-assisted radical prostatectomy., Results: Before high intensity focused ultrasound 55.9% of men had multifocal disease and 47.1% had Gleason 3 + 3 disease outside the treatment field. Median time to salvage prostatectomy was 16 months (IQR 11-26). Indications for salvage prostatectomy were infield recurrence in 55.8% of cases, out of field recurrence in 20.6%, and infield and out of field recurrence in 23.5%. On salvage prostatectomy histopathology revealed significant cancer, defined as ISUP (International Society of Urological Pathology) 2 or greater, infield in 97.1% of cases, out of field in 81.3%, and infield and out of field in 79.4%. Of the cases 82.4% were adversely reclassified at salvage prostatectomy compared to 67.6% before ultrasound. The positive surgical margin rate was 40.0%. Of the positive margins 84.6% were in the region of previous ultrasound despite wide excision, including pT2 in 28.6%, pT3 in 47.6% and size 3 mm or greater, pT3 or multifocal (ie significant) in 31.4%. After ultrasound the sensitivity of magnetic resonance imaging for infield and out of field recurrence was 81.8% and 60.7%, respectively., Conclusions: Salvage robot-assisted radical prostatectomy may confer a higher risk of positive surgical margins, upgrading and up-staging than primary robot-assisted radical prostatectomy. High intensity focused ultrasound carries a risk of recurrence inside and outside the ablation zone. This information may inform salvage surgical planning and patient counseling regarding the choice of initial therapy and salvage treatment after high intensity focused ultrasound.

Background: To assess multiparametric magnetic resonance imaging (mpMRI) characteristics in prostate cancer (PCa) before and after irreversible electroporation (IRE) and to investigate their correlation with the presence of post-operative recurrence of PCa., Methods: MpMRI was performed in 30 men with PCa prior to treatment, after 10 days and at 6 months. An additional scan at 1 year was available for 18 men. Two radiologists assessed retrospectively the following parameters by planimetry: tumour volume, necrotic volume (early post-treatment scan) and residual fibrosis. Residual tumour/recurrence were defined as a suspicious area within the treatment field scored ≥ 4 on a 1-to-5 scale. Oncological outcome was also assessed., Results: The median follow-up of the entire study was 16 months. Six men were undertreated and showed mpMRI recurrence after 6 months. At 1-year, three additional men had recurrence. Overall, four of these 9 men (44%) were retreated. The other five men did not receive any further treatment. Median time to re-treatment was 15 months. Median pre-treatment lesion volume was 0.65 cc, 0.66 cc and 0.43 cc on the different mpMRI sequences (T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging). Median necrotic volume was 10.77 cc. Median overall residual fibrosis volumes were 0.84 cc and 0.95 cc at 6-month and 1-year mpMRI. Pre-treatment, necrotic and residual fibrosis volumes were significantly different (p < 0.001). Pre-treatment tumour volumes on diffusion-weighted imaging and necrotic volumes were correlated (r = 0.18; p = 0.02)., Conclusions: MpMRI is able to visualise the IRE ablation effects in men with PCa. MpMRI-derived parameters - such as tumour, necrotic and fibrosis volumes - can be measured and are potentially useful for assessing efficacy in the medium term, as with other ablative techniques., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rationale and Objectives: This study aimed to assess a novel method of three-dimensional (3D) co-registration of prostate magnetic resonance imaging (MRI) examinations performed before and after prostate cancer focal therapy., Materials and Methods: We developed a software platform for automatic 3D deformable co-registration of prostate MRI at different time points and applied this method to 10 patients who underwent focal ablative therapy. MRI examinations were performed preoperatively, as well as 1 week and 6 months post treatment. Rigid registration served as reference for assessing co-registration accuracy and precision., Results: Segmentation of preoperative and postoperative prostate revealed a significant postoperative volume decrease of the gland that averaged 6.49 cc (P = .017). Applying deformable transformation based on mutual information from 120 pairs of MRI slices, we refined by 2.9 mm (max. 6.25 mm) the alignment of the ablation zone, segmented from contrast-enhanced images on the 1-week postoperative examination, to the 6-month postoperative T2-weighted images. This represented a 500% improvement over the rigid approach (P = .001), corrected by volume. The dissimilarity by Dice index of the mapped ablation zone using deformable transformation vs rigid control was significantly (P = .04) higher at the ablation site than in the whole gland., Conclusions: Our findings illustrate our method's ability to correct for deformation at the ablation site. The preliminary analysis suggests that deformable transformation computed from mutual information of preoperative and follow-up MRI is accurate in co-registration of MRI examinations performed before and after focal therapy. The ability to localize the previously ablated tissue in 3D space may improve targeting for image-guided follow-up biopsy within focal therapy protocols., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The widely acknowledged limitations of the standard prostate cancer (PCa) diagnostic paradigm have provided an impetus to explore novel imaging modalities to diagnose, localize, and risk stratify PCa. As the body of literature focused on HistoScanning™(HS) grows, there is need for a comprehensive review of the clinical efficacy of this technology., Recent Findings: Eighteen original, English language articles were found to adequately study the use of HistoScanning™ for prostate cancer diagnosis in the clinical setting. The articles were found by conducting a bibliographic search of PubMed in April 2017 in addition to utilizing references. The studies are divided into four groups based on study design. Study methods and quantitative data are summarized for each of the relevant articles. The results are synthesized to evaluate the utility of HistoScanning™ for the purpose of diagnosing PCa. Despite the promise of early pilot studies, there is a lack of consistent results across a number of further investigations of HistoScanning™. This becomes increasingly evident as study size increases. As various other modern diagnostic modalities continue to develop, the future of HistoScanning™, both alone and in conjunction with these technologies, remains unclear.

Introduction: There is increasing interest in using imaging in the detection and localization of prostate cancer (PCa). Both multiparametric magnetic resonance imaging (mpMRI) and HistoScanning (HS) have been independently evaluated in the detection and localization of PCa. We undertook a prospective, blinded comparison of mpMRI and HS for cancer localization among men undergoing radical prostatectomy., Methods: Following approval by the institutional review board, men scheduled to undergo radical prostatectomy, who had previously undergone mpMRI at our institution, were offered inclusion in the study. Those consenting underwent preoperative HS following induction of anesthesia; mpMRI, HS, and surgical step-section pathology were independently read by a single radiologist, urologist, and pathologist, respectively, in a blinded fashion. Disease maps created by each independent reader were compared and evaluated for concordance by a 5 persons committee consisting of 2 urologists, 2 pathologists, and 1 radiologist. Logistic regression for correlated data was used to assess and compare mpMRI and HS in terms of diagnostic accuracy for cancer detection. Generalized estimating equations based on binary logistic regression were used to model concordance between reader opinion and the reference standard assessment of the same lesion site or region as a function of imaging modality., Results: Data from 31/35 men enrolled in the trial were deemed to be evaluable. On evaluation of cancer localization, HS identified cancer in 36/78 (46.2%) regions of interest, as compared with 41/78 (52.6%) on mpMRI (P = 0.3968). The overall accuracy, positive predictive value, negative predictive value, and specificity for detection of disease within a region of interest were significantly better with mpMRI as compared with HS. HS detected 36/84 (42.9%) cancer foci as compared with 42/84 (50%) detected by mpMRI (P = 0.3678). Among tumors with Gleason score>6, mpMRI detected 19/22 (86.4%) whereas HS detected only 11/22 (50%, P = 0.0078). Similarly, among tumors>10mm in maximal diameter, mpMRI detected 28/34 (82.4%) whereas HS detected only 19/34 (55.9%, P = 0.0352)., Conclusion: In our institution, the diagnostic accuracy of HS was inferior to that of mpMRI in PCa for PCa detection and localization. Although our study warrants validation from larger cohorts, it would suggest that the HS protocol requires further refinement before clinical implementation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation., Materials and Methods: Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin., Results: Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients., Conclusions: Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)