Accuracy of Ex-vivo Fluorescence Confocal Microscopy in Margin Assessment of Solid Tumors: A Systematic Review.

Fluorescence confocal microscopy (FCM) is a novel technology that enables rapid high-resolution digital imaging of non-formalin-fixed tissue specimens and offers real-time positive surgical margin identification. In this systematic review, we evaluated the accuracy metrics of ex vivo FCM for intraoperative margin assessment of different tumor types. A systematic search of MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus was performed for relevant papers (PROSPERO ID: CRD42022372558). We included 14 studies evaluating four types of microscopes in six different tumor types, including breast, prostate, central nervous system, kidney, bladder, and conjunctival tumors. Using the Quality Assessment of Diagnostic Accuracy Studies tool, we identified a high risk of bias in patient selection (21%) and index test (36%) of the included studies. Overall, we found that FCM has good accuracy metrics in all tumor types, with high sensitivity and specificity (>80%) and almost perfect concordance (>90%) against final pathology results. Despite these promising findings, the quality of the available evidence and bias concerns highlight the need for adequately designed studies to further define the role of ex vivo FCM in replacing the frozen section as the tool of choice for intraoperative margin assessment.

Protocol for a prospective study evaluating circulating tumour cells status to predict radical prostatectomy treatment failure in localised prostate cancer patients (C-ProMeta-1).

BACKGROUND: Treatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence. METHODS: We plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood samples (20 ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time. DISCUSSION: CTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment. TRIAL REGISTRATION: ISRCTN17332543.

Insights into the Effect of Metal Ratio on Cooperative Redox Enhancement Effects over Au- and Pd-Mediated Alcohol Oxidation.

The aerobic oxidation of alcohols and aldehydes over supported heterogeneous catalysts can be considered as comprising two complementary and linked processes: dehydrogenation and oxygen reduction. Significant rate enhancements can be observed when these processes are catalyzed by independent active sites, coupled by electron transport between the two catalysts. This effect, termed cooperative redox enhancement (CORE), could significantly influence how researchers approach catalyst design, but a greater understanding of the factors which influence it is required. Herein, we demonstrate that the Au/Pd ratio used in physical mixtures of monometallic catalysts and phase-separated Au and Pd bimetallic catalysts dramatically influences the degree to which CORE effects can promote alcohol oxidation. Perhaps more interestingly, the roles of Au and Pd in this coupled system are determined to be interchangeable. Preliminarily, we hypothesize that this is attributed to the relative rates of the coupled reactions and demonstrate how physical properties can influence this. This deeper understanding of the factors which influence CORE is an important development in bimetallic catalysis.

Avoiding Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The INNOVATE Study.

Background In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert score of 3 or higher) have no clinically significant (Gleason score ≤3+3, benign) biopsy findings. Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis could improve the stratification of positive mpMRI findings. Purpose To evaluate VERDICT MRI, mpMRI-derived apparent diffusion coefficient (ADC), and prostate-specific antigen density (PSAD) as determinants of clinically significant PCa (csPCa). Materials and Methods Between April 2016 and December 2019, men suspected of having PCa were prospectively recruited from two centers and underwent VERDICT MRI and mpMRI at one center before undergoing targeted biopsy. Biopsied lesion ADC, lesion-derived fractional intracellular volume (FIC), and PSAD were compared between men with csPCa and those without csPCa, using nonparametric tests subdivided by Likert scores. Area under the receiver operating characteristic curve (AUC) was calculated to test diagnostic performance. Results Among 303 biopsy-naive men, 165 study participants (mean age, 65 years ± 7 [SD]) underwent targeted biopsy; of these, 73 had csPCa. Median lesion FIC was higher in men with csPCa (FIC, 0.53) than in those without csPCa (FIC, 0.18) for Likert 3 (P = .002) and Likert 4 (0.60 vs 0.28, P < .001) lesions. Median lesion ADC was lower for Likert 4 lesions with csPCa (0.86 × 10-3 mm2/sec) compared with lesions without csPCa (1.12 × 10-3 mm2/sec, P = .03), but there was no evidence of a difference for Likert 3 lesions (0.97 × 10-3 mm2/sec vs 1.20 × 10-3 mm2/sec, P = .09). PSAD also showed no difference for Likert 3 (0.17 ng/mL2 vs 0.12 ng/mL2, P = .07) or Likert 4 (0.14 ng/mL2 vs 0.12 ng/mL2, P = .47) lesions. The diagnostic performance of FIC (AUC, 0.96; 95% CI: 0.93, 1.00) was higher (P = .02) than that of ADC (AUC, 0.85; 95% CI: 0.79, 0.91) and PSAD (AUC, 0.74; 95% CI: 0.66, 0.82) for the presence of csPCa in biopsied lesions. Conclusion Lesion fractional intracellular volume enabled better classification of clinically significant prostate cancer than did apparent diffusion coefficient and prostate-specific antigen density. Clinical trial registration no. NCT02689271 © RSNA, 2022 Online supplemental material is available for this article.

NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

E-Consent-a guide to maintain recruitment in clinical trials during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has posed daunting challenges when conducting clinical research. Adopting new technologies such as remote electronic consent (e-Consent) can help overcome them. However, guidelines for e-Consent implementation in ongoing clinical trials are currently lacking. The NeuroSAFE PROOF trial is a randomized clinical trial evaluating the role of frozen section analysis during RARP for prostate cancer. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this paper is to describe the process of implementation, impact on recruitment rate, and patients' experience using e-Consent. METHODS: A substantial amendment of the protocol granted the creation of a remote e-Consent framework based on the REDCap environment, following the structure and content of the already approved paper consent form. Although e-Consent obviated the need for in-person meeting, there was nonetheless counselling sessions performed interactively online. This new pathway offered continuous support to patients through remote consultations. The whole process was judged to be compliant with regulatory requirements before implementation. RESULTS: Before the first recruitment suspension, NeuroSAFE PROOF was recruiting an average of 9 patients per month. After e-Consent implementation, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. Limited troubleshooting has been required after implementation. CONCLUSION: Remote e-Consent-based recruitment was critical for the continuation of the NeuroSAFE PROOF trial during the COVID-19 pandemic. The described pathway complies with ethical and regulatory guidelines for informed consent, while minimizing face-to-face interactions that increase the risk of COVID-19 transmission. This guide will help researchers integrate e-Consent to ongoing or planned clinical trials while uncertainty about the course of the pandemic continues. TRIAL REGISTRATION: NeuroSAFE PROOF trial NCT03317990 . Registered on 23 October 2017. Regional Ethics Committee reference 17/LO/1978.

Negative mpMRI Rules Out Extra-Prostatic Extension in Prostate Cancer before Robot-Assisted Radical Prostatectomy.

Background: The accuracy of multi-parametric MRI (mpMRI) in the pre-operative staging of prostate cancer (PCa) remains controversial. Objective: The purpose of this study was to evaluate the ability of mpMRI to accurately predict PCa extra-prostatic extension (EPE) on a side-specific basis using a risk-stratified 5-point Likert scale. This study also aimed to assess the influence of mpMRI scan quality on diagnostic accuracy. Patients and Methods: We included 124 men who underwent robot-assisted RP (RARP) as part of the NeuroSAFE PROOF study at our centre. Three radiologists retrospectively reviewed mpMRI blinded to RP pathology and assigned a Likert score (1-5) for EPE on each side of the prostate. Each scan was also ascribed a Prostate Imaging Quality (PI-QUAL) score for assessing the quality of the mpMRI scan, where 1 represents the poorest and 5 represents the best diagnostic quality. Outcome measurements and statistical analyses: Diagnostic performance is presented for the binary classification of EPE, including 95% confidence intervals and the area under the receiver operating characteristic curve (AUC). Results: A total of 231 lobes from 121 men (mean age 56.9 years) were evaluated. Of these, 39 men (32.2%), or 43 lobes (18.6%), had EPE. A Likert score ≥3 had a sensitivity (SE), specificity (SP), NPV, and PPV of 90.4%, 52.3%, 96%, and 29.9%, respectively, and the AUC was 0.82 (95% CI: 0.77-0.86). The AUC was 0.76 (95% CI: 0.64-0.88), 0.78 (0.72-0.84), and 0.92 (0.88-0.96) for biparametric scans, PI-QUAL 1-3, and PI-QUAL 4-5 scans, respectively. Conclusions: MRI can be used effectively by genitourinary radiologists to rule out EPE and help inform surgical planning for men undergoing RARP. EPE prediction was more reliable when the MRI scan was (a) multi-parametric and (b) of a higher image quality according to the PI-QUAL scoring system.

Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer.

INTRODUCTION: Multiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required. METHODS AND ANALYSIS: This study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer. ETHICS AND DISSEMINATION: Ethical approval was granted by the London-Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04792138.

Au-Pd separation enhances bimetallic catalysis of alcohol oxidation.

In oxidation reactions catalysed by supported metal nanoparticles with oxygen as the terminal oxidant, the rate of the oxygen reduction can be a limiting factor. This is exemplified by the oxidative dehydrogenation of alcohols, an important class of reactions with modern commercial applications1-3. Supported gold nanoparticles are highly active for the dehydrogenation of the alcohol to an aldehyde4 but are less effective for oxygen reduction5,6. By contrast, supported palladium nanoparticles offer high efficacy for oxygen reduction5,6. This imbalance can be overcome by alloying gold with palladium, which gives enhanced activity to both reactions7,8,9; however, the electrochemical potential of the alloy is a compromise between that of the two metals, meaning that although the oxygen reduction can be improved in the alloy, the dehydrogenation activity is often limited. Here we show that by separating the gold and palladium components in bimetallic carbon-supported catalysts, we can almost double the reaction rate compared with that achieved with the corresponding alloy catalyst. We demonstrate this using physical mixtures of carbon-supported monometallic gold and palladium catalysts and a bimetallic catalyst comprising separated gold and palladium regions. Furthermore, we demonstrate electrochemically that this enhancement is attributable to the coupling of separate redox processes occurring at isolated gold and palladium sites. The discovery of this catalytic effect-a cooperative redox enhancement-offers an approach to the design of multicomponent heterogeneous catalysts.

Inter-reader agreement of the PI-QUAL score for prostate MRI quality in the NeuroSAFE PROOF trial.

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.

The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer.

Background: Docetaxel improves overall survival (OS) in castration-resistant prostate cancer (PCa) (CRPC) and metastatic hormone-sensitive PCa (mHSPC). However, not all patients respond due to inherent and/or acquired resistance. There remains an unmet clinical need for a robust predictive test to stratify patients for treatment. Liquid biopsy of circulating tumour cell (CTCs) is minimally invasive, can provide real-time information of the heterogeneous tumour and therefore may be a potentially ideal docetaxel response prediction biomarker. Objective: In this study we investigate the potential of using CTCs and their gene expression to predict post-docetaxel tumour response, OS and progression free survival (PFS). Methods: Peripheral blood was sampled from 18 mCRPC and 43 mHSPC patients, pre-docetaxel treatment, for CTC investigation. CTCs were isolated using the epitope independent Parsortix® system and gene expression was determined by multiplex RT-qPCR. We evaluated CTC measurements for post-docetaxel outcome prediction using receiver operating characteristics and Kaplan Meier analysis. Results: Detection of CTCs pre-docetaxel was associated with poor patient outcome post-docetaxel treatment. Combining total-CTC number with PSA and ALP predicted lack of partial response (PR) with an AUC of 0.90, p= 0.037 in mCRPC. A significantly shorter median OS was seen in mCRPC patients with positive CTC-score (12.80 vs. 37.33 months, HR= 5.08, p= 0.0005), ≥3 total-CTCs/7.5mL (12.80 vs. 37.33 months, HR= 3.84, p= 0.0053), ≥1 epithelial-CTCs/7.5mL (14.30 vs. 37.33 months, HR= 3.89, p= 0.0041) or epithelial to mesenchymal transitioning (EMTing)-CTCs/7.5mL (11.32 vs. 32.37 months, HR= 6.73, p= 0.0001). Significantly shorter PFS was observed in patients with ≥2 epithelial-CTCs/7.5mL (7.52 vs. 18.83 months, HR= 3.93, p= 0.0058). mHSPC patients with ≥5 CTCs/7.5mL had significantly shorter median OS (24.57 vs undefined months, HR= 4.14, p= 0.0097). In mHSPC patients, expression of KLK2, KLK4, ADAMTS1, ZEB1 and SNAI1 was significantly associated with shorter OS and/or PFS. Importantly, combining CTC measurements with clinical biomarkers increased sensitivity and specificity for prediction of patient outcome. Conclusion: While it is clear that CTC numbers and gene expression were prognostic for PCa post-docetaxel treatment, and CTC subtype analysis may have additional value, their potential predictive value for docetaxel chemotherapy response needs to be further investigated in large patient cohorts.

Salvage Versus Primary Robot-assisted Radical Prostatectomy: A Propensity-matched Comparative Effectiveness Study from a High-volume Tertiary Centre.

BACKGROUND: Salvage robot-assisted radical prostatectomy (sRARP) is a potential treatment option for locally recurrent prostate cancer (PCa) after nonsurgical primary treatment. There are minimal data comparing outcomes between propensity-matched sRARP and primary robot-assisted radical prostatectomy (RARP). OBJECTIVE: The primary objective is to compare perioperative, oncological, and functional outcomes of sRARP with primary RARP, and the secondary is to compare outcomes between sRARP after whole and focal gland therapy. DESIGN SETTING AND PARTICIPANTS: A 1:1 propensity-matched comparison was carried out of 135 sRARP cases with primary RARP cases from a cohort of 3852 consecutive patients from a high-volume tertiary centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative, oncological, and functional outcomes including complication rates, positive surgical margins, biochemical recurrence (BCR), continence, and erectile dysfunction (ED) were retrospectively collected. RESULTS AND LIMITATIONS: There were no significant differences in patient characteristics between sRARP and primary RARP groups. In the salvage and primary groups, median (interquartile range) follow-up periods were 521 (304-951) and 638 (394-951) d, grade III-V Clavien-Dindo complication rates were 1.5% and 0% (p = 0.310), BCR rates were 31.9% and 14.1% (p < 0.001) at the last follow-up, pad-free continence rates were 78.8% and 84.3% at 2 yr (p = 0.337), and ED rates were 94.8% and 76.3% (p < 0.001), respectively. Comparing the whole and focal gland groups, BCR rates were 36.7% and 29.1% (p = 0.687) at follow-up, pad-free continence rates were 53.1% and 89.3% at 2 yr (p < 0.001), and ED rates were 98% and 93% (p = 0.214), respectively. CONCLUSIONS: Salvage RARP has similar perioperative outcomes to primary RARP with inferior potency rates. Post-focal therapy sRARP has similar recurrence and continence rates to primary RARP. Post-whole gland therapy, complication, and recurrence rates are higher, and there is a higher risk of urinary incontinence. PATIENT SUMMARY: We report the largest propensity-matched comparison of salvage robot-assisted radical prostatectomy (RARP) after focal and whole gland therapy. Salvage RARP is a feasible procedure for the treatment of locally recurrent prostate cancer in high-volume centres; however, patients should be counselled appropriately as to the different outcomes.

Proceedings from an International Virtual Townhall: Reflecting on the COVID-19 Pandemic: Themes from Long-Term Care.

Residents of long-term care (LTC) homes have suffered disproportionately during the COVID-19 pandemic, from the virus itself and often from the imposition of lockdown measures. Provincial Geriatrics Leadership Ontario, in collaboration with interRAI and the International Federation on Aging, hosted a virtual Town Hall on September 25, 2020. The purpose of this event was to bring together international perspectives from researchers, clinicians, and policy experts to address important themes potentially amenable to timely policy interventions. This article summarizes these themes and the ensuing discussions among 130 attendees from 5 continents. The disproportionate impact of the COVID-19 pandemic on frail residents of LTC homes reflects a systematic lack of equitable prioritization by health system decision makers around the world. The primary risk factors for an outbreak in an LTC home were outbreaks in the surrounding community, high staff and visitor traffic in large facilities, and crowding of residents in ageing buildings. Infection control measures must be prioritized in LTC homes, though care must be taken to protect frail and vulnerable residents from their overly blunt application that deprives residents from appropriate physical and psychosocial support. Staffing, in terms of overall numbers, training, and leadership skills, was inadequate. The built environment of LTC homes can be configured for both optimal resident well-being and infection control. Infection control and resident wellness need not be mutually exclusive. Improving outcomes for LTC residents requires more staffing with proper training and interprofessional leadership. All these initiatives must be underpinned by an effective quality assurance system based on standardized, comprehensive, accessible, and clinically relevant data, and which can support broad communities of practice capable of effecting real and meaningful change for frail older persons, wherever they chose to reside.

Evaluation of PSA and PSA Density in a Multiparametric Magnetic Resonance Imaging-Directed Diagnostic Pathway for Suspected Prostate Cancer: The INNOVATE Trial.

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 <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.

Current process and outcomes of the surgical management of LUTS due to benign prostatic enlargement: how consistent are we? - results from the multi-institutional audit of surgical management of BPE (AuSuM BPE) in the United Kingdom.

OBJECTIVE: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK. MATERIALS AND METHOD: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data. RESULTS: 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs. CONCLUSION: Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies.