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Non-ischemic priapism (NiP) is painless partial tumescence caused by genital trauma and the formation of intracorporal arterio-venous fistula (AVF). This retrospective study aims to determine the long-term erectile function (EF) after NiP and to correlate this with colour doppler ultrasound (CDUS) parameters in 25 patients. EF was assessed by IIEF domain A questionnaire and CDUS parameters (mean velocity (MV), peak systolic velocity (PSV), end diastolic velocity (EDV) and Resistive Index (RI)) at diagnosis and follow up. At a median follow-up of 24 months: 16 men had normal EF (64%) with median IIEF score 29; nine had erectile dysfunction (ED) (36%) with a median IIEF-EF score 17. Raised MV and EDV on late follow-up CDUS traces demonstrated a statistically significant correlation with developing ED: median MV 5.3cm/sec vs 2.95cm/sec and median EDV 4.0cm/sec vs 0cm/sec in patients with ED compared to those with normal EF p

Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3-5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9

Objectives The Prostate Imaging Quality (PI-QUAL) score assesses the quality of multiparametric MRI (mpMRI). A score of 1 means all sequences are below the minimum standard of diagnostic quality, 3 implies that the scan is of sufficient diagnostic quality, and 5 means that all three sequences are of optimal diagnostic quality. We investigated the inter-reader reproducibility of the PI-QUAL score in patients enrolled in the NeuroSAFE PROOF trial. Methods We analysed the scans of 103 patients on different MR systems and vendors from 12 different hospitals. Two dedicated radiologists highly experienced in prostate mpMRI independently assessed the PI-QUAL score for each scan. Interobserver agreement was assessed using Cohen’s kappa with standard quadratic weighting (κw) and percent agreement. Results The agreement for each single PI-QUAL score was strong (κw = 0.85 and percent agreement = 84%). A similar agreement (κw = 0.82 and percent agreement = 84%) was observed when the scans were clustered into three groups (PI-QUAL 1–2 vs PI-QUAL 3 vs PI-QUAL 4–5). The agreement in terms of diagnostic quality for each single sequence was highest for T2-weighted imaging (92/103 scans; 89%), followed by dynamic contrast-enhanced sequences (91/103; 88%) and diffusion-weighted imaging (80/103; 78%). Conclusion We observed strong reproducibility in the assessment of PI-QUAL between two radiologists with high expertise in prostate mpMRI. At present, PI-QUAL offers clinicians the only available tool for evaluating and reporting the quality of prostate mpMRI in a systematic manner but further refinements of this scoring system are warranted. Key Points • Inter-reader agreement for each single Prostate Imaging Quality (PI-QUAL) score (i.e., PI-QUAL 1 to PI-QUAL 5) was strong, with weighted kappa = 0.85 (95% confidence intervals: 0.51 – 1) and percent agreement = 84%. • Interobserver agreement was strong when the scans were clustered into three groups according to the ability (or not) to rule in and to rule out clinically significant prostate cancer (i.e., PI-QUAL 1-2 vs PI-QUAL 3 vs PI-QUAL 4–5), with weighted kappa = 0.82 (95% confidence intervals: 0.68 – 0.96) and percent agreement = 84%. • T2-weighted acquisitions were the most compliant with the Prostate Imaging Reporting and Data System (PI-RADS) v. 2.0 technical recommendations and were the sequences of highest diagnostic quality for both readers in 95/103 (92%) scans, followed by dynamic contrast enhanced acquisition with 81/103 (79%) scans and lastly by diffusion-weighted imaging with 79/103 (77%) scans.

To report the management outcomes of men with ≤20-mm small testicular masses (STMs) and to identify clinical and histopathological factors associated with malignancy.A retrospective analysis of men managed at a single centre between January 2010 and December 2020 with a STM ≤20 mm in size was performed.Overall, 307 men with a median (interquartile range [IQR]) age of 36 (30-44) years were included. Of these, 161 (52.4%), 82 (26.7%), 62 (20.2%) and 2 men (0.7%) underwent surveillance with interval ultrasonography (USS), primary excisional testicular biopsy (TBx) or primary radical orchidectomy (RO), or were discharged, respectively. The median (IQR) surveillance duration was 6 (3-18) months. The majority of men who underwent surveillance had lesions5 mm (59.0%) and no lesion vascularity (67.1%) on USS. Thirty-three (20.5%) men undergoing surveillance had a TBx based on changes on interval USS or patient choice; seven (21.2%) were found to be malignant. The overall rate of malignancy in the surveillance cohort was 4.3%. The majority of men who underwent primary RO had lesions ≥10 mm (85.5%) and the presence of vascularity (61.7%) on USS. Nineteen men (23.2%) who underwent primary TBx (median lesion size 6 mm) had a malignancy confirmed on biopsy and underwent RO. A total of 88 men (28.7%) underwent RO, and malignancy was confirmed in 73 (83.0%) of them. The overall malignancy rate in the whole STM cohort was 23.8%. Malignant RO specimens had significantly larger lesion sizes (median [IQR] 11 [8-15] mm, vs benign: median [IQR] 8 [5-10] mm; P = 0.04).Small testicular masses can be stratified and managed based on lesion size and USS features. The overall malignancy rate in men with an STM was 23.8% (4.3% in the surveillance group). Surveillance should be considered in lesions10 mm in size, with a TBx or frozen-section examination offered prior to RO in order to preserve testicular function.

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.

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.

Pre‐biopsy multiparametric magnetic resonance imaging (mpMRI) has transformed the risk stratification and diagnostic approach for suspected prostate cancer. The majority of clinically significant prostate cancers are visible on pre‐biopsy mpMRI, however, there are a subset of significant tumors that are not detected by mpMRI. The radiobiological mechanisms underpinning mpMRI‐visibility and invisibility of these cancers remain uncertain. Emerging evidence suggests that mpMRI‐visible tumors are enriched with molecular features associated with increased disease aggressivity and poor clinical prognosis, which is supported by short‐term endpoints, such as biochemical recurrence following surgery. Furthermore, at the histopathological level, mpMRI‐visible tumors appear to exhibit increased architectural and vascular density compared to mpMRI‐invisible disease. It seems probable that the genomic, pathological, radiological, and clinical features of mpMRI‐visible and mpMRI‐invisible prostate cancers are interrelated. Here, we propose a novel cross‐disciplinary theory that links genomic and molecular evidence with cellular and histopathological appearances, elucidating both the mpMRI visibility and clinical status of significant prostate cancer.

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, Take Home Message We report excellent clinical outcomes from one of the largest imaging-based active surveillance cohorts to date. Magnetic resonance imaging (MRI)-visible cancer at baseline, along with 3 + 4 Gleason grade, predicts a greater likelihood of treatment at five years. MRI-visible lesions appear to have a distinct clinical trajectory from less conspicuous ones.

Context Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility., Take Home Message The genomic evidence surrounding multiparametric magnetic resonance imaging (mpMRI) visibility is varied and often discordant; however, the literature suggests that tumour mpMRI visibility correlates with aggressive genomic features.

In prostate Diffusion Weighted MRI, differences in susceptibility values exist at the interface between the prostate and rectal-air. This can result in off-resonance magnetic field leading to geometric distortions including signal stretching and signal pile-up in the reconstructed images. Using a set of EPI data acquired with blip-up and blip-down phase encoding gradient directions, model based reconstruction has recently been proposed that can correct these distortions by using a B0 field estimated from a separate B0 scan. However, change in the size of the rectal air region across time can occur that can result in a mismatch of the B0 field to the EPI scan. Also, the measured B0 field itself can be erroneous in regions of low Signal to Noise ratio around the prostate rectal air interface. In this work, using a set of single shot EPI data acquired with blip-up and blip-down phase encoding gradient directions, a novel joint model based reconstruction is proposed that can account for changes in the off resonance effects between the B0 and EPI scans. For ten prostate patients, using a measured B0 field as an initial B0 estimate, on a 5-point scale (1–5) image quality scores evaluated by an experienced radiologist, the proposed framework achieved scores of 3.50 ± 0.85 and 3.40 ± 0.51 for b-values of 0 and 500 s/mm2, respectively compared to 3.40 ± 0.70 and 3.30 ± 0.67 for model based reconstruction. The proposed framework is also capable of estimating a distortion corrected EPI image even without an initial B0 field estimate in situations where a separate B0 scan cannot be obtained due to time constraint.

Objectives The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant’s ability to apply PI-QUAL. Methods Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. Results There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50–0.66]) to post-teaching (0.96 [0.92–0.98]), an improvement of 0.37 [0.21–0.41] (p < 0.001). Conclusions A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. Key Points • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Objectives We aimed to determine the interobserver reproducibility of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria for magnetic resonance imaging in patients on active surveillance (AS) for prostate cancer (PCa) at two different academic centres. Methods The PRECISE criteria score the likelihood of clinically significant change over time. The system is a 1-to-5 scale, where 1 or 2 implies regression of a previously visible lesion, 3 denotes stability and 4 or 5 indicates radiological progression. A retrospective analysis of 80 patients (40 from each centre) on AS with a biopsy-confirmed low- or intermediate-risk PCa (i.e. ≤ Gleason 3 + 4 and prostate-specific antigen ≤ 20 ng/ml) and ≥ 2 prostate MR scans was performed. Two blinded radiologists reported all scans independently and scored the likelihood of radiological change (PRECISE score) from the second scan onwards. Cohen’s κ coefficients and percent agreement were computed. Results Agreement was substantial both at a per-patient and a per-scan level (κ = 0.71 and 0.61; percent agreement = 79% and 81%, respectively) for each PRECISE score. The agreement was superior (κ = 0.83 and 0.67; percent agreement = 90% and 91%, respectively) when the PRECISE scores were grouped according to the absence/presence of radiological progression (PRECISE 1–3 vs 4–5). Higher inter-reader agreement was observed for the scans performed at University College London (UCL) (κ = 0.81 vs 0.55 on a per-patient level and κ = 0.70 vs 0.48 on a per-scan level, respectively). The discrepancies between institutions were less evident for percent agreement (80% vs 78% and 86% vs 75%, respectively). Conclusions Expert radiologists achieved substantial reproducibility for the PRECISE scoring system, especially when data were pooled together according to the absence/presence of radiological progression (PRECISE 1–3 vs 4–5). Key Points • Inter-reader agreement between two experienced prostate radiologists using the PRECISE criteria was substantial. • The agreement was higher when the PRECISE scores were grouped according to the absence/presence of radiological progression (i.e. PRECISE 1–3 vs PRECISE 4 and 5). • Higher inter-reader agreement was observed for the scans performed at UCL, but the discrepancies between institutions were less evident for percent agreement.

IntroductionThe introduction of multiparametric MRI (mpMRI) has improved almost every aspect of the prostate cancer diagnostic pathway. However, the novel imaging technique, prostate-specific membrane antigen positron emission tomography (PSMA PET) may have demonstrable accuracy in detecting and staging prostate cancer. Here, we describe a protocol for a systematic review and meta-analysis comparing mpMRI to PSMA PET for the diagnosis of suspected prostate cancer.Methods and analysisA systematic search of MEDLINE, EMBASE, PubMed and Cochrane databases will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed for screening, data extraction, statistical analysis and reporting. Included papers will be full-text articles providing original data, written in English articles and comparing the use of PSMA PET with mpMRI in the diagnosis of prostate cancer. All studies published between July 1977 and March 2021 will be eligible for inclusion. Study bias and quality will be assessed using Quadas-2 score. To ensure the quality of the reporting of studies, this protocol is written following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist.Ethics and disseminationEthical approval will not be required for this systematic review. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences.PROSPERO registration numberCRD42021239296.

We commend Veerman et al. for investigating the diagnostic performance of radiological apical tumor involvement (radATI) in preoperative prostate magnetic resonance imaging (MRI) and its impact on clinical outcomes in patients with localized prostate cancer. This retrospective study evaluated the diagnostic accuracy of MRI to detect pathological ATI (pathATI) in robot-assisted radical prostatectomy specimens. They found patients with radATI more likely to develop biochemical recurrence (BCR), p = 0.003, and have apical positive surgical margins (APSM), p = 0.004. We believe that the author’s acknowledgement of the relationship between tumor location and cancer risk is an important step in the classification of prostate cancer. An important question that is under addressed is, what is it about apical tumors that carry additional risk? Higher rates of PSM due to incomplete surgical excision may contribute to increased recurrence risk in the apex. If this is the case, surgical management must be tailored by a tumor location-based risk assessment. The literature suggests that a single APSM may be clinically insignificant for long-term outcomes. Conversely, the authors also recommend radATI be treated with reduced apical nerve sparing to avoid APSM. We believe that this approach may lead to overtreatment in the presence of an otherwise good prognosis. We believe the extent of APSMs upon diagnosis would be an interesting topic for further investigation. The authors may also wish to perform multivariable analysis for the effect of radATI on BCR. We believe that MRI may play a critical role in enhancing diagnosis and prognostication of prostate cancer.

Objectives: The aim of this study was to evaluate the changes in lesion volume on serial multiparametric magnetic resonance (mpMRI) during active surveillance for prostate cancer. Methods: A total of 160 patients with a targeted biopsy-confirmed visible lesion on mpMRI, stratified by low- and intermediate-risk disease (Gleason Grade Group 1 vs Gleason Grade Group 2), were analysed. The % change per year was calculated using the formula: [(final volume/initial volume) exp (1/interval between scans in years)]-1. Results: There was no significant difference in the annual median percentage change between Gleason Grade Group 1 (18%) and Gleason Grade Group 2 (23%) disease (p = 0.16), and between ≤ 10% (23%) and > 10% (22%) of Gleason pattern 4 (p = 0.78). Assuming a spherical lesion, these changes corresponded to annual increases in mean tumour diameter of 6% and 7% for Gleason Grade Group 1 and Gleason Grade Group 2 respectively, which may be less than the interscan variability of serial mpMRI. Conclusion: In an active surveillance cohort, we did not see a significant difference in the annual growth rate of Gleason Grade Group 1 and 2 tumours. Advances in knowledge: In patients on active surveillance, the measured growth rates for visible tumours in Gleason Grade Groups 1 and 2 were similar. The annual growth rate was small in most cases and this may have implications for the MRI follow-up interval in active surveillance.

Multiparametric magnetic resonance imaging (mpMRI) has enhanced the risk stratification for men with suspected prostate cancer 1\ud and inevitable implementation challenges around pathway modification, capacity and quality control are well rehearsed. 2\ud Use of pre-biopsy prostate mpMRI is now well-established following publication of multiple Level 1 evidence trials, 1\ud however, views of men undergoing this pathway have not yet been explored, in-depth.

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.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.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).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.

Multiparametric magnetic-resonance imaging (mpMRI) has proven utility in diagnosing primary prostate cancer. However, the diagnostic potential of prostate-specific membrane antigen positron-emission tomography (PSMA PET) has yet to be established. This study aims to systematically review the current literature comparing the diagnostic performance of mpMRI and PSMA PET imaging to diagnose primary prostate cancer. A systematic literature search was performed up to December 2021. Quality analyses were conducted using the QUADAS-2 tool. The reference standard was whole-mount prostatectomy or prostate biopsy. Statistical analysis involved the pooling of the reported diagnostic performances of each modality, and differences in per-patient and per-lesion analysis were compared using a Fisher’s exact test. Ten articles were included in the meta-analysis. At a per-patient level, the pooled values of sensitivity, specificity, and area under the curve (AUC) for mpMRI and PSMA PET/CT were 0.87 (95% CI: 0.83–0.91) vs. 0.93 (95% CI: 0.90–0.96, p < 0.01); 0.47 (95% CI: 0.23–0.71) vs. 0.54 (95% CI: 0.23–0.84, p > 0.05); and 0.84 vs. 0.91, respectively. At a per-lesion level, the pooled sensitivity, specificity, and AUC value for mpMRI and PSMA PET/CT were lower, at 0.63 (95% CI: 0.52–0.74) vs. 0.79 (95% CI: 0.62–0.92, p < 0.001); 0.88 (95% CI: 0.81–0.95) vs. 0.71 (95% CI: 0.47–0.90, p < 0.05); and 0.83 vs. 0.84, respectively. High heterogeneity was observed between studies. PSMA PET/CT may better confirm the presence of prostate cancer than mpMRI. However, both modalities appear comparable in determining the localisation of the lesions.

IntroductionThere is an increasing body of evidence to suggest that visibility of prostate cancer on magnetic resonance (MRI) may be related to likelihood of adverse pathological outcomes. Biochemical recurrence (BCR) after radical prostatectomy remains a significant clinical challenge and a means of predicting likelihood of this prior to surgery could inform treatment choice. It appears that MRI could be a potential candidate strategy for BCR prediction, and as such, there is a need to review extant literature on the prognostic capability of MRI. Here, we describe a protocol for a systematic review and meta-analysis of the utility of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) in predicting BCR following radical prostatectomy for prostate cancer treatment.Methods and analysisPubMed, MEDLINE, Embase and Cochrane databases will be searched and screening will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In order to meet the inclusion criteria, papers must be English-language articles involving patients who have had bpMRI or mpMRI for suspected prostate cancer and have undergone radical prostatectomy as definitive therapy. Patients must have had prostate-specific antigen monitoring before and after surgery. All relevant papers published from July 1977 to October 2020 will be eligible for inclusion. The Newcastle-Ottawa score will be used to determine the quality and bias of the studies. This protocol is written in-line with the PRISMA protocol 2015 checklist.Ethics and disseminationThere are no relevant ethical concerns. Dissemination of this protocol will be via peer-reviewed journals as well as national and international conferences.PROSPERO registration numberCRD42020206074.

Introduction The implications of tumour location on mpMRI conspicuity are not fully understood. Identifying topographical correlates that influence conspicuity may improve outcomes. Here, we present the first systematic review and meta-analysis describing the effect of tumour location on prostate cancer conspicuity on mpMRI. Methods Medline, PubMed, EMBASE and Cochrane databases were systematically searched and results were assessed as per the PRISMA statement. Differential tumour conspicuity on mpMRI was compared between cancers in the peripheral zone (PZ), transitional zone (TZ), base, apex, anterior and posterior. Meta-analysis was conducted to compare diagnostic odds ratios (DOR) of mpMRI detection for tumours in the PZ and TZ. PROSPERO registration: CRD42021228087. Results Thematic synthesis showed apical and basal tumours had reduced conspicuity compared to mid-gland tumours. Cancer in the TZ demonstrated increased conspicuity on T2-weighted imaging, whilst PZ cancers had higher conspicuity on diffusion-weighted and dynamic contrast enhancement imaging. mpMRI had better diagnostic accuracy for PZ lesions, albeit higher specificity for TZ lesions. Meta-analysis showed an increased DOR for PZ tumours (OR: 7.206 [95% CI: 4.991;10.403], compared to TZ (OR: 5.310 [95% CI: 3.082; 9.151]). However, the test for subgroup differences was not significant (p = 0.2743). Conclusions Cancer in the apex or base of the prostate may be less conspicuous than mid-gland tumours. Similarly, TZ cancer appears to have reduced conspicuity compared to PZ cancer, however, meta-analysis did not show a significant difference between DOR. Future larger studies with prospective datasets are required to clarify the relationship between tumour position and conspicuity.

Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. Methods: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. Results: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged &lt, 50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. Conclusions: The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing.

Cribriform, from the Latin for 'sieve-like,' describes an aggressive prostate cancer pattern associated with poor prognosis, including biochemical recurrence after prostatectomy [1]. Following progressive integration of multiparametric magnetic resonance imaging (mpMRI) into risk stratification for suspected prostate cancer, there has been understandable concern that particular morphologies (including, intraductal, mucinous and cribriform) may have reduced visibility on mpMRI [2]. If undetected, mpMRI-invisible pathology may avoid biopsy interrogation, resulting in delayed presentation, management, and adverse clinical outcome. However, evidence surrounding mpMRI conspicuity of cribriform disease is contradictory, and given the clinical importance of this phenomenon, warrants discussion.

Multi-parametric MRI is increasingly used for prostate cancer detection. Improving information from current sequences, such as T2-weighted and diffusion-weighted (DW) imaging, and additional sequences, such as magnetic resonance spectroscopy (MRS) and chemical exchange saturation transfer (CEST), may enhance the performance of multi-parametric MRI. The majority of these techniques are sensitive to B0-field variations and may result in image distortions including signal pile-up and stretching (echo planar imaging (EPI) based DW-MRI) or unwanted shifts in the frequency spectrum (CEST and MRS). Our aim is to temporally and spatially characterize B0-field changes in the prostate. Ten male patients are imaged using dual-echo gradient echo sequences with varying repetitions on a 3 T scanner to evaluate the temporal B0-field changes within the prostate. A phantom is also imaged to consider no physiological motion. The spatial B0-field variations in the prostate are reported as B0-field values (Hz), their spatial gradients (Hz/mm) and the resultant distortions in EPI based DW-MRI images (b-value = 0 s/mm2 and two oppositely phase encoded directions). Over a period of minutes, temporal changes in B0-field values were ≤19 Hz for minimal bowel motion and ≥30 Hz for large motion. Spatially across the prostate, the B0-field values had an interquartile range of ≤18 Hz (minimal motion) and ≤44 Hz (large motion). The B0-field gradients were between −2 and 5 Hz/mm (minimal motion) and 2 and 12 Hz/mm (large motion). Overall, B0-field variations can affect DW, MRS and CEST imaging of the prostate.

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

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 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.

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...

Download PDFPDF\udUrology\udProtocol\udGenetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis\ud\ud Joseph M Norris1, Benjamin S Simpson1, Marina A Parry2, Clare Allen3, Rhys Ball4, Alex Freeman4, Daniel Kelly5, Alex Kirkham3, Veeru Kasivisvanathan1, Hayley C Whitaker1, Mark Emberton1\ud\udAuthor affiliations\udAbstract\ud\udIntroduction The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%–20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI.\ud\udMethods and analysis A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist.\ud\udEthics and dissemination Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.

Background All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MR Imaging Study (PROMIS) provides a unique opportunity to explore cancers that are overlooked by multiparametric magnetic resonance imaging (mpMRI). Objective To summarise attributes of cancers that are systematically overlooked by mpMRI. Design, setting, and participants PROMIS tested performance of mpMRI and transrectal ultrasonography (TRUS)-guided biopsy, using 5 mm template mapping (TPM) biopsy as the reference standard. Outcome measurements and statistical analysis Outcomes were overall and maximum Gleason scores, maximum cancer core length (MCCL), and prostate-specific antigen density (PSAD). Cancer attributes were compared between cancers that were overlooked and those that were detected. Results and limitations Of men with cancer, 7% (17/230; 95% confidence interval [CI] 4.4–12%) had significant disease overlooked by mpMRI according to definition 1 (Gleason ≥ 4 + 3 of any length or MCCL ≥ 6 mm of any grade) and 13% (44/331; 95% CI 9.8–17%) according to definition 2 (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm). In comparison, TRUS-guided biopsy overlooked 52% (119/230; 95% CI 45–58%) of significant disease by definition 1 and 40% (132/331; 95% CI 35–45%) by definition 2. Prostate cancers undetected by mpMRI had significantly lower overall and maximum Gleason scores (p = 0.0007; p 3 + 4 (Gleason Grade Groups 3–5; 95% CI 0–6.4%) or maximum Gleason score > 4 + 3 (Gleason Grade Groups 4–5; 95% CI 0–8.0%) on TPM biopsy were undetected by mpMRI. Application of a PSAD threshold of 0.15 reduced the proportion of men with undetected cancer to 5% (12/230; 95% CI 2.7–8.9%) for definition 1 and 9% (30/331; 95% CI 6.2–13%) for definition 2. Application of a PSAD threshold of 0.10 reduced the proportion of men with undetected disease to 3% (6/230; 95% CI 1.0–5.6%) for definition 1 cancer and to 3% (11/331; 95% CI 1.7–5.9%) for definition 2 cancer. Limitations were post hoc analysis and uncertain significance of undetected lesions. Conclusions Overall, a small proportion of cancers are overlooked by mpMRI, with estimates ranging from 4.4% (lower boundary of 95% CI for definition 1) to 17% (upper boundary of 95% CI for definition 2). Prostate cancers undetected by mpMRI are of lower grade and shorter length than cancers that are detected. Patient summary Prostate cancers that are undetected by magnetic resonance imaging (MRI) are smaller and less aggressive than those that are detected, and none of the most aggressive cancers are overlooked by MRI.

Purpose The PRECISE score estimates the likelihood of radiological progression in patients on active surveillance (AS) for prostate cancer (PCa) with serial multiparametric magnetic resonance imaging (mpMRI). A PRECISE score of 1 or 2 denotes radiological regression, PRECISE 3 indicates stability and PRECISE 4 or 5 implies progression. We evaluated the inter-reader reproducibility of different apparent diffusion coefficient (ADC) calculations and their relationship to the PRECISE score. Material and methods Baseline and follow-up scans (on the same MR systems) of 30 patients with visible lesions from two different institutions (University College London and Sapienza University of Rome) were analysed by two radiologists (one from each site). The PRECISE score was initially assessed in consensus. At least six weeks later, to reduce the likelihood of being influenced by the consensus PRECISE reading, each radiologist independently calculated ADC for the following: lesion, non-cancerous tissue and urine in the bladder. Normalised ADC ratios were calculated with respect to normal prostatic tissue (npADC) and urine. Spearman's correlation (ρ), intraclass correlation coefficients (ICC), differences in ADC and ROC curves were computed. Results Interobserver reproducibility was very good (ρ > 0.8; ICC > 0.90). Lesion ADC (0.91 vs 0.73 × 10−3 mm2/s; p=0.025) and npADC ratio (0.68 vs 0.53; p=0.012) at follow-up mpMRI were different between patients with radiological regression or stability vs progression. Cut-offs of 0.77 × 10−3 mm2/s (lesion ADC) and 0.59 (npADC ratio) could differentiate the two groups (area under the curve: 0.74 and 0.77, respectively). Conclusion The ADC, npADC ratio and the PRECISE score should be recorded for MRI-based AS.

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 T2 weighted imaging (T2WI) 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 T2WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations.

IntroductionMultiparametric 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 analysisThe 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 disseminationEthical 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 numberCRD42021228087.

BACKGROUND Multiparametric magnetic resonance imaging (mpMRI) is being used increasingly in the setting of active surveillance (AS) for prostate cancer. We investigated changes in the mpMRI appearance of lesions on AS, to show the variability of volume measurements in visible lesions and assess change in lesion size according to grade. METHODS We retrospectively retrieved 86 men on AS (NICE guidelines) with more than one mpMRI (the first before 2013). Two radiologists, in consensus, were blinded to patient demographics and date of scan. The scans were randomly reported to reduce any bias. For visible lesions, we measured volume by planimetry on the sequence best showing the most conspicuous (index) tumour and attributed a 5-point Likert score. RESULTS 43/86 men did not have a visible lesion on the initial mpMRI (≤2/5). Of these, 5/43 had developed a lesion scoring ≥3/5 at a median of 3.6 years of follow up. 40/86 had a lesion scoring ≥3/5 on two or more scans. There was a significant increase in volume over 3.6 years by a median of 10% (p