Prostagram magnetic resonance imaging in a screening population: Prostate Imaging-Reporting and Data System or Likert?

OBJECTIVE: To compare biopsy recommendation rates and accuracy of the Prostate Imaging-Reporting and Data System, version 2 (PI-RADSv2) with the Likert scale for detection of clinically significant and insignificant prostate cancer in men screened within the Imperial Prostate 1 Prostate Cancer Screening Trial Using Imaging (IP1-PROSTAGRAM). PATIENTS AND METHODS: Men aged 50-69 years were screened with Prostagram MRI. Scans were prospectively reported using both PI-RADSv2 (excluding dynamic contrast-enhanced sequence score) and 5-point Likert scores by expert uro-radiologists. Systematic and targeted transperineal biopsy was recommended if the scan was scored ≥ 3, based on either reporting system. The proportion of patients recommended for biopsy and detection rates for Grade Groups (GGs) 1 and ≥ 2 were compared. Receiver operating characteristic (ROC) analysis was performed to compare performance. RESULTS: A total of 406 men underwent Prostagram MRI. The median (interquartile range) age and prostate-specific antigen level were 57 (53-61) years and 0.91 (0.56-1.74) ng/mL, respectively. At MRI score ≥ 3, more patients were recommended for biopsy based on Likert criteria (94/406; 23%, 95% confidence interval [CI] 19.2%-27.6%) compared to PI-RADSv2 (72/406; 18%, 95% CI 14.2%-21.9%; P = 0.03). For MRI scores ≥ 4, PI-RADSv2 and Likert scales led to 43/406 (11%, 95% CI 7.9%-14.1%) and 35/406 (9%, 95% CI 6.2%-11.9%) men recommended for biopsy (P = 0.40). For GG ≥ 2 detection, PIRADSv2 and Likert detected 22% (95% CI 11.4%-30.8%, 14/72) and 16% (95% CI 9.5%-25.3%, 15/94), respectively (P = 0.56). For GG1 cancers detection these were 11% (95% CI 4.3%-19.6%, seven of 72) vs 11% (95% CI 4.7%-17.8%, nine of 94; P = 1.00). The accuracy of PI-RADSv2 and Likert scale was similar (area under the ROC curve 0.64 vs 0.65, P = 0.95). CONCLUSIONS: In reporting non-contrast-enhanced Prostagram MRI in a screening population, the PI-RADSv2 and Likert scoring systems were equally accurate; however, Likert scale use led to more men undergoing biopsy without a subsequent increase in significant cancer detection rates. To improve reporting of Prostagram MRI, either the PI-RADSv2 or a modified Likert scale or a standalone scoring system should be developed.

The rapid assessment for prostate imaging and diagnosis (RAPID) prostate cancer diagnostic pathway.

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

A Comparison of Prostate Cancer Detection between Visual Estimation (Cognitive Registration) and Image Fusion (Software Registration) Targeted Transperineal Prostate Biopsy.

PURPOSE: We compared clinically significant prostate cancer detection by visual estimation and image fusion targeted transperineal prostate biopsy. MATERIALS AND METHODS: This multicenter study included patients with multiparametric magnetic resonance imaging lesions undergoing visual estimation or image fusion targeted transperineal biopsy (April 2017-March 2020). Propensity score matching was performed using demographics (age and ethnicity), clinical features (prostate specific antigen, prostate volume, prostate specific antigen density and digital rectal examination), multiparametric magnetic resonance imaging variables (number of lesions, PI-RADS® score, index lesion diameter, whether the lesion was diffuse and radiological T stage) and biopsy factors (number of cores, operator experience and anesthetic type). Matched groups were compared overall and by operator grade, PI-RADS score, lesion multiplicity, prostate volume and anesthetic type using targeted-only and targeted plus systematic histology. Multiple clinically significant prostate cancer thresholds were evaluated (primary: Gleason ≥3+4). RESULTS: A total of 1,071 patients with a median age of 67.3 years (IQR 61.3-72.4), median prostate specific antigen of 7.5 ng/ml (IQR 5.3-11.2) and 1,430 total lesions underwent targeted-only biopsies (visual estimation: 372 patients, 494 lesions; image fusion: 699 patients, 936 lesions). A total of 770 patients with a median age of 67.4 years (IQR 61-72.1), median prostate specific antigen of 7.1 ng/ml (IQR 5.2-10.6) and 919 total lesions underwent targeted plus systematic biopsies (visual estimation: 271 patients, 322 lesions; image fusion: 499 patients, 597 lesions). Matched comparisons demonstrated no overall difference in clinically significant prostate cancer detection between visual estimation and image fusion (primary: targeted-only 54% vs 57.4%, p=0.302; targeted plus systematic 51.2% vs 58.2%, p=0.123). Senior urologists had significantly higher detection rates using image fusion (primary: targeted-only 45.4% vs 63.7%, p=0.001; targeted plus systematic 39.4% vs 64.5%, p <0.001). CONCLUSIONS: We found no overall difference in clinically significant prostate cancer detection, although image fusion may be superior in experienced hands.

Likert vs PI-RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer.

OBJECTIVE: To compare the clinical validity and utility of Likert assessment and the Prostate Imaging Reporting and Data System (PI-RADS) v2 in the detection of clinically significant and insignificant prostate cancer. PATIENTS AND METHODS: A total of 489 pre-biopsy multiparametric magnetic resonance imaging (mpMRI) scans in consecutive patients were subject to prospective paired reporting using both Likert and PI-RADS v2 by expert uro-radiologists. Patients were offered biopsy for any Likert or PI-RADS score ≥4 or a score of 3 with PSA density ≥0.12 ng/mL/mL. Utility was evaluated in terms of proportion biopsied, and proportion of clinically significant and insignificant cancer detected (both overall and on a 'per score' basis). In those patients biopsied, the overall accuracy of each system was assessed by calculating total and partial area under the receiver-operating characteristic (ROC) curves. The primary threshold of significance was Gleason ≥3 + 4. Secondary thresholds of Gleason ≥4 + 3, Ahmed/UCL1 (Gleason ≥4 + 3 or maximum cancer core length [CCL] ≥6 or total CCL≥6) and Ahmed/UCL2 (Gleason ≥3 + 4 or maximum CCL ≥4 or total CCL ≥6) were also used. RESULTS: The median (interquartile range [IQR]) age was 66 (60-72) years and the median (IQR) prostate-specific antigen level was 7 (5-10) ng/mL. A similar proportion of men met the biopsy threshold and underwent biopsy in both groups (83.8% [Likert] vs 84.8% [PI-RADS v2]; P = 0.704). The Likert system predicted more clinically significant cancers than PI-RADS across all disease thresholds. Rates of insignificant cancers were comparable in each group. ROC analysis of biopsied patients showed that, although both scoring systems performed well as predictors of significant cancer, Likert scoring was superior to PI-RADS v2, exhibiting higher total and partial areas under the ROC curve. CONCLUSIONS: Both scoring systems demonstrated good diagnostic performance, with similar rates of decision to biopsy. Overall, Likert was superior by all definitions of clinically significant prostate cancer. It has the advantages of being flexible, intuitive and allowing inclusion of clinical data. However, its use should only be considered once radiologists have developed sufficient experience in reporting prostate mpMRI.

Clinical, fiscal and environmental benefits of a specialist-led virtual ureteric colic clinic: a prospective study.

OBJECTIVES: To evaluate the clinical, fiscal and environmental impact of a specialist-led acute ureteric colic virtual clinic (VC) pathway. PATIENTS AND METHODS: All patients with uncomplicated acute ureteric colic, referred to a single tertiary centre, were prospectively entered into the study over a 4-year period (January 2015-December 2018). Inclusion criteria were: low-dose non-contrast computed tomography of kidneys, ureters and bladder; white blood cell count <16 × 109/L; pain controlled; normal renal function; and no clinical concern. Primary outcomes were: time (days) from referral to VC outcome; VC outcome (discharge, further VC, face-to-face [FTF] clinic, extracorporeal shockwave lithotripsy [ESWL], ureterorenoscopy [URS], percutaneous nephrolithotomy [PCNL]); and adverse events (sepsis or obstruction). Secondary outcomes were patient and stone demographics, cost and environmental analysis. The minimum follow-up was 3 months. RESULTS: A total of 1008 patients entered the study, of whom 91.5% (n = 922) were of working age. The median (interquartile range) time from presentation to VC outcome was 2 (4) days. VC outcomes were as follows: 16.3% of patients (n = 164) were discharged; 18.2% (n = 183) were discharged after further VC; 17.2% (n = 173) underwent an intervention; and 48.4% (n = 488) were referred to an FTF clinic. Interventions comprised: PCNL 0.5% (n = 5); ESWL 7.7% (n = 78); and URS 8.9% (n = 90). Stone demographics were as follows: 570 patients (56.5%) had lower, 157 (15.6%) had upper, 96 (9.5%) had mid-ureteric and 163 (16.2%) had renal calculi, and in 22 patients (2.2%) the stones had recently passed. The mean (sd) stone size was 3.5  (2.3) mm. Two adverse events (0.2%) were reported. Introducing a VC saved £145,152 for Clinical Commissioning Groups, the equivalent NHS tariff payment of performing 106 URS procedures or 211 ureteric stent insertions. Overall, 15,085 patient journey kilometres were avoided, equal to 0.70-2.93 metric tonnes of carbon dioxide equivalent production and the need to plant 14.7 trees to achieve carbon balance. CONCLUSION: A specialist-led acute ureteric colic VC reduced time to treatment decision to a median of 2 days. This creates additional clinic capacity and reduces the fiscal burden of traditional clinics and their associated carbon footprint.

CEDAR OnDemand: a browser extension to generate ontology-based scientific metadata.

BACKGROUND: Public biomedical data repositories often provide web-based interfaces to collect experimental metadata. However, these interfaces typically reflect the ad hoc metadata specification practices of the associated repositories, leading to a lack of standardization in the collected metadata. This lack of standardization limits the ability of the source datasets to be broadly discovered, reused, and integrated with other datasets. To increase reuse, discoverability, and reproducibility of the described experiments, datasets should be appropriately annotated by using agreed-upon terms, ideally from ontologies or other controlled term sources. RESULTS: This work presents "CEDAR OnDemand", a browser extension powered by the NCBO (National Center for Biomedical Ontology) BioPortal that enables users to seamlessly enter ontology-based metadata through existing web forms native to individual repositories. CEDAR OnDemand analyzes the web page contents to identify the text input fields and associate them with relevant ontologies which are recommended automatically based upon input fields' labels (using the NCBO ontology recommender) and a pre-defined list of ontologies. These field-specific ontologies are used for controlling metadata entry. CEDAR OnDemand works for any web form designed in the HTML format. We demonstrate how CEDAR OnDemand works through the NCBI (National Center for Biotechnology Information) BioSample web-based metadata entry. CONCLUSION: CEDAR OnDemand helps lower the barrier of incorporating ontologies into standardized metadata entry for public data repositories. CEDAR OnDemand is available freely on the Google Chrome store https://chrome.google.com/webstore/search/CEDAROnDemand.

Prevalence of Active Long-term Problems in Patients With Anorectal Malformations: A Systematic Review.

BACKGROUND: Anorectal malformations are a spectrum of congenital anomalies of the rectum with high infantile survival rates and variable outcomes. Long-term (>10 years old) active problems associated with this condition have been poorly investigated. OBJECTIVE: The purpose of this review was to systematically define the prevalence of the most common active long-term problems in patients with a history of anorectal malformation repair. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Library were searched electronically using the OVID search platform. STUDY SELECTION: Original articles from August 1, 1994, to October 20, 2015, that included outcome data for patients aged ≥10 years with anorectal malformation. Cloaca was excluded from the study. INTERVENTIONS: Prevalence estimates of anorectal malformations were obtained from published articles. CIs were ascertained in the logit scale after transforming prevalence into log odds and were then transformed into the original scale. The same method was used for subgroup analysis investigating high and low anorectal malformations. MAIN OUTCOME MEASURES: The overall prevalences of fecal, urinary, and sexual dysfunction were analyzed. RESULTS: Twelve studies including 455 patients with a history of anorectal malformation repair were included for analysis. The range of reported prevalence of long-term active problems was as follows: fecal incontinence, 16.7% to 76.7%; chronic constipation, 22.2% to 86.7%; urinary incontinence, 1.7% to 30.5%; ejaculatory dysfunction, 15.6% to 41.2%; and erectile dysfunction, 5.6% to 11.8%. LIMITATIONS: The study was limited by its retrospective, small size; multiple complex associated anomalies often not reported; and heterogeneous composition of patients with limited stratification analysis. CONCLUSIONS: There is an overall high prevalence of active long-term issues in adolescents and young adults with anorectal malformations. Additional multicenter research is needed to define characteristics and predictors of long-term outcome, to implement effective follow-up, and to transition to adult health care.

Diagnostic Performance of 68Ga-PSMA-11 PET/CT Versus Multiparametric MRI for Detection of Intraprostatic Radiorecurrent Prostate Cancer.

For men with prostate cancer who develop biochemical failure after radiotherapy, European guidelines recommend reimaging with 68Ga-PSMA-11 PET/CT and multiparametric MRI (mpMRI). However, the accuracy of 68Ga-PSMA-11 PET/CT for detecting intraprostatic recurrences is unclear, both with and without mpMRI. Methods: A single-center retrospective study of a series of patients investigated for radiorecurrence between 2016 and 2022 is described. All patients underwent 68Ga-PSMA-11 PET/CT, mpMRI, and prostate biopsy. PET/CT images were interpreted independently by 2 expert readers masked to other imaging and clinical data. The primary outcome was the diagnostic accuracy of PET/CT versus mpMRI and of PET/CT with mpMRI together versus mpMRI alone. The secondary outcome was the proportion of cancers missed by mpMRI but detected by PET/CT. Diagnostic accuracy analysis was performed at the prostate hemigland level using cluster bootstrapping. Results: Thirty-five men (70 hemiglands) were included. Cancer was confirmed by biopsy in 43 of 70 hemiglands (61%). PET/CT sensitivity and negative predictive values (NPVs) were 0.89 (95% CI, 0.78-0.98) and 0.79 (95% CI, 0.62-0.95), respectively, which were not significantly different from results by MRI (sensitivity of 0.72; 95% CI, 0.61-0.83; P = 0.1) (NPV of 0.59; 95% CI, 0.41-0.75; P = 0.07). Specificity and positive predictive values were not significantly different. When PET/CT and MRI were used together, the sensitivity was 0.98 (95% CI, 0.92-1.00) and NPV was 0.93 (95% CI, 0.75-1.00), both significantly higher than MRI alone (P = 0.003 and P < 0.001, respectively). Specificity and positive predictive values remained not significantly different. MRI missed 12 of 43 cancers (28%; 95% CI, 17%-43%), of which 11 of 12 (92%; 95% CI, 62%-100%) were detected by PET/CT. Conclusion: For detecting intraprostatic radiorecurrence, 68Ga-PSMA-11 PET/CT has high sensitivity that is not significantly different from mpMRI. When 68Ga-PSMA-11 PET/CT and mpMRI were used together, the results conferred a significantly greater sensitivity and NPV than with mpMRI alone. 68Ga-PSMA-11 PET/CT may therefore be a useful tool in the diagnosis of localized radiorecurrence.

Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study.

BACKGROUND AND OBJECTIVE: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. METHODS: A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. KEY FINDINGS AND LIMITATIONS: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. PATIENT SUMMARY: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

Landmarks in the evolution of prostate biopsy.

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

Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection.

BACKGROUND: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch® PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. METHODS: n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. RESULTS: PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.92 and NPV of 0.94 when tested on the independent prospective cohort. CONCLUSIONS: Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing. Further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence would be the recommended step for PSE adoption in PCa screening.

Perceived patient burden and acceptability of MRI in comparison to PSA and ultrasound: results from the IP1-PROSTAGRAM study.

BACKGROUND: The IP1-PROSTAGRAM study showed that a short, non-contrast MRI detected more significant cancers with similar rates of biopsy compared to PSA. Herein, we compare the expected and perceived burden of PSA, MRI and ultrasound as screening tests. METHODS: IP1-PROSTAGRAM was a prospective, population-based, paired screening study of 408 men conducted at seven UK primary care practices and two imaging centres. The screening tests were serum PSA, non-contrast MRI and ultrasound. If any test was screen-positive, a prostate biopsy was performed. Participants completed an Expected Burden Questionnaire (EBQ) and Perceived Burden Questionnaire (PBQ) before and after each screening test. RESULTS: The overall level of burden for MRI and PSA was minimal. Few men reported high levels of anxiety, burden, embarrassment or pain following either MRI or PSA. Participants indicated an overall preference for MRI after completing all screening tests. Of 408 participants, 194 (47.5%) had no preference, 106 (26.0%) preferred MRI and 79 (19.4%) preferred PSA. This indicates that prior to screening, participants preferred MRI compared to PSA (+6.6%, 95% CI 4.4-8.4, p = 0.02) and after completing screening, the preference for MRI was higher (+21.1%, 95% CI 14.9-27.1, p < 0.001). The proportion of participants who strongly agreed with repeating the test was 50.5% for ultrasound, 65% for MRI and 68% for PSA. A larger proportion of participants found ultrasound anxiety-inducing, burdensome, embarrassing and painful compared to both MRI and PSA. CONCLUSIONS: Prostagram MRI and PSA are both acceptable as screening tests among men aged 50-69 years. Both tests were associated with minimal amounts of anxiety, burden, embarrassment and pain. The majority of participants preferred MRI over PSA and ultrasound. REGISTRATION: This study was registered on clinicaltrials.gov at https://clinicaltrials.gov/ct2/show/NCT03702439 .

Modeling community standards for metadata as templates makes data FAIR.

It is challenging to determine whether datasets are findable, accessible, interoperable, and reusable (FAIR) because the FAIR Guiding Principles refer to highly idiosyncratic criteria regarding the metadata used to annotate datasets. Specifically, the FAIR principles require metadata to be "rich" and to adhere to "domain-relevant" community standards. Scientific communities should be able to define their own machine-actionable templates for metadata that encode these "rich," discipline-specific elements. We have explored this template-based approach in the context of two software systems. One system is the CEDAR Workbench, which investigators use to author new metadata. The other is the FAIRware Workbench, which evaluates the metadata of archived datasets for their adherence to community standards. Benefits accrue when templates for metadata become central elements in an ecosystem of tools to manage online datasets-both because the templates serve as a community reference for what constitutes FAIR data, and because they embody that perspective in a form that can be distributed among a variety of software applications to assist with data stewardship and data sharing.

A Systematic Review of Patients' Values, Preferences, and Expectations for the Treatment of Metastatic Prostate Cancer.

CONTEXT: Advances in systemic agents have increased overall survival for men diagnosed with metastatic prostate cancer. Additional cytoreductive prostate treatments and metastasis-directed therapies are under evaluation. These confer toxicity but may offer incremental survival benefits. Thus, an understanding of patients' values and treatment preferences is important for counselling, decision-making, and guideline development. OBJECTIVE: To perform a systematic review of patients' values, preferences, and expectations regarding treatment of metastatic prostate cancer. EVIDENCE ACQUISITION: The MEDLINE, Embase, and CINAHL databases were systematically searched for qualitative and preference elucidation studies reporting on patients' preferences for treatment of metastatic prostate cancer. Certainty of evidence was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE) or GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual). The protocol was registered on PROSPERO as CRD42020201420. EVIDENCE SYNTHESIS: A total of 1491 participants from 15 studies met the prespecified eligibility for inclusion. The study designs included were discrete choice experiments (n = 5), mixed methods (n = 3), and qualitative methods (n = 7). Disease states reported per study were: metastatic castration-resistant prostate cancer in nine studies (60.0%), metastatic hormone-sensitive prostate cancer in two studies (13.3%), and a mixed cohort in four studies (26.6%). In quantitative preference elicitation studies, patients consistently valued treatment effectiveness and delay in time to symptoms as the two top-ranked treatment attributes (low or very low certainty). Patients were willing to trade off treatment-related toxicity for potential oncological benefits (low certainty). In qualitative studies, thematic analysis revealed cancer progression and/or survival, pain, and fatigue as key components in treatment decisions (low or very low certainty). Patients continue to value oncological benefits in making decisions on treatments under qualitative assessment. CONCLUSIONS: There is limited understanding of how patients make treatment and trade-off decisions following a diagnosis of metastatic prostate cancer. For appropriate investment in emerging cytoreductive local tumour and metastasis-directed therapies, we should seek to better understand how this cohort weighs the oncological benefits against the risks. PATIENT SUMMARY: We looked at how men with advanced (metastatic) prostate cancer make treatment decisions. We found that little is known about patients' preferences for current and proposed new treatments. Further studies are required to understand how patients make decisions to help guide the integration of new treatments into the standard of care.

Predicting the Need for Biopsy to Detect Clinically Significant Prostate Cancer in Patients with a Magnetic Resonance Imaging-detected Prostate Imaging Reporting and Data System/Likert ≥3 Lesion: Development and Multinational External Validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis Risk Score.

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

Retrograde migration of a vesicoureteric junction calculus: A potential pitfall of the noncontrast limited pelvic computerized tomography.

Retrograde ureteric calculus migration is a rare phenomenon. Herein, we report two such cases where each patient presented with a calculus, measured at 5 mm and 6 mm, respectively, at the vesicoureteric junction (VUJ) on noncontrast computerized tomography kidneys, ureters, and bladder (CTKUB). Following acute presentation with renal colic, each patient opted for conservative management of their ureteric stone and became asymptomatic when undergoing their follow-up imaging. The first patient underwent a follow-up noncontrast limited pelvic computerized tomography (CT) where it had appeared that the radiolucent VUJ calculus had passed. This stone was then discovered incidentally 3 months later in the upper ureter when the patient had undergone a CT colonography. The other patient underwent a follow-up X-ray KUB where the stone was shown to have migrated to the lower renal pole calyx which was confirmed with noncontrast CTKUB imaging. In all reported cases of retrograde VUJ calculus migration, the use of a noncontrast limited pelvic CT scan either missed or would have missed this phenomenon. This potential pitfall of the noncontrast limited pelvic CT scan should be appreciated and the use of full upper renal tract imaging should be considered for the follow-up of radiolucent VUJ calculus cases whereby there is no clear history of calculus passage.

Clinical Translation of Positive Metastases Identified on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging in the Management of De Novo Synchronous Oligometastatic Prostate Cancer.

Recent evidence from randomised trials supports the diagnostic superiority of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) over conventional imaging in the detection of distant occult metastasis in men with newly diagnosed high-risk prostate cancer. This may result in a rise in the detection of de novo synchronous hormone-sensitive "oligometastatic" prostate cancer. We outline the evidence supporting PSMA PET/CT imaging in primary staging. We also discuss the translation of positive areas with a high probability of distant metastasis into clinical therapeutic targets for metastasis-directed interventions. Finally, we highlight the role of PSMA PET/CT as an imaging biomarker. This may have future utility in disease monitoring and prediction of response to systemic, local cytoreductive and metastasis-directed interventions. PATIENT SUMMARY: A new whole-body scan can accurately detect cancer deposits in men in whom distant prostate cancer spread is suspected. This may be useful for monitoring and predicting response to drug therapy, treatments to the prostate, and cancer deposits.

Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography: The IP1-PROSTAGRAM Study.

IMPORTANCE: Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations. OBJECTIVE: To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019. INTERVENTIONS: All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion-targeted biopsies were performed if the MRI or ultrasonography results were positive. MAIN OUTCOMES AND MEASURES: The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 µg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher. RESULTS: A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases. CONCLUSIONS AND RELEVANCE: In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.