Validation of an algorithm for sound-based voided volume estimation.

A voiding diary is commonly used in clinical practice to monitor urinary tract health. However, manual recording and use of a measuring cup can cause significant inaccuracy and inconvenience. Recently sound-based voided volume estimation algorithms such as proudP have shown potential to accurately measure the voided volumes of patients urination while overcoming these inconveniences. In order to validate the sound-based voided volume estimation algorithm, we chose bodyweight change after urination as a reference value. Total 508 subjects from the United States and Korea were enrolled. 584 data points that have matching bodyweights change data and urination sound data were collected, and fivefold cross validation was performed in order to evaluate the model on all data in the dataset. The mean voided volume estimated by the algorithm was 202.6 mL (SD: ± 114.8) while the mean bodyweight change after urination was 208.0 g (SD: ± 121.5), and there was a strong linear correlation with high statistical significance (Pearson's correlation coefficient = 0.92, p-value < 0.001). Two paired t-test showed the equivalence with bodyweight change data with 10 mL margin. Additionally, a Bland-Altman plot shows a mean difference of - 5.5 mL with LoA (- 98.0, 87.1). The results support high performance of the algorithm across the large population data from multi-site clinical trials.

Validation of a CE-IVD, urine exosomal RNA expression assay for risk assessment of prostate cancer prior to biopsy.

Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) "EPI" is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2-10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56-0.77) versus PCPT 0.59 (95% CI 0.47-0.71) and ERSPC 0.60 (95% CI 0.49-0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.

A Prospective Adaptive Utility Trial to Validate Performance of a Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer in Patients with Prostate-specific Antigen 2-10ng/ml at Initial Biopsy.

BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption. OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI performance assessment during phase I, a clinical implementation document (ie, CarePath) was developed for utilizing the EPI test in phase II, where the biopsy decision is uncertain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance evaluation of the EPI test in patients enrolled in phase I and publication of a consensus CarePath for phase II. RESULTS AND LIMITATIONS: In a total of 503 patients, with median age of 64 yr, median PSA 5.4ng/ml, 14% African American, 70% Caucasian, 53% positive biopsy rate (22% GG1, 17% GG2, and 15% ≥ GG3), EPI was superior to an optimized model of standard clinical parameters with an area under the curve (AUC) 0.70 versus 0.62, respectively, comparable with previously published results (n=519 patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary prostate biopsies and 20% of total biopsies, with negative predictive value (NPV) 89% and missing 7% of ≥GG2 PCa. Alternative cut-point 20 would avoid 40% of unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of ≥GG2 PCa. The clinical investigators reached consensus recommending use of the 15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II will be reported separately. CONCLUSIONS: EPI is a noninvasive, easy-to-use, gene expression urine assay, which has now been successfully validated in over 1000 patients across two prospective validation trials to stratify risk of ≥GG2 from GG1 cancer and benign disease. The test improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies. PATIENT SUMMARY: It is challenging to predict which men are likely to have high-grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2-10ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore) test can predict ≥GG2 PCa at initial biopsy and defer unnecessary biopsies better than existing risk calculator's and standard clinical data.

Corrigendum: Incorrect Spelling of Author's Name: US Preventive Services Task Force prostate-specific antigen screening guidelines result in higher Gleason score diagnoses.

[This corrects the article on p. 423 in vol. 58.].

US Preventive Services Task Force prostate-specific antigen screening guidelines result in higher Gleason score diagnoses.

Purpose: To evaluate the impact that the 2012 US Preventive Services Task Force (USPSTF) prostate-specific antigen (PSA) screening guidelines have had on the diagnosis of prostate cancer, we compared the incidence and distribution of new cases diagnosed in 2011-before the USPSTF PSA screening recommendations versus 2014 at which time the guidelines were widely adopted. Materials and Methods: We identified all prostate biopsies performed by a large urology group practice utilizing a centralized pathology lab. We examined total biopsies performed, percentage of positive biopsies, and for those with positive biopsies examined for differences in patient age, PSA, and Gleason score. Results: A total of 4,178 biopsies were identified - 2,513 in 2011 and 1,665 in 2014. The percentage of positive biopsies was 27% in 2011 versus 34% in 2014 (p<0.0001). Among patients with positive biopsies, we found statistically significant differences between the 2 cohorts in the median ages and Gleason scores. Patients were about 1 year younger in 2014 compared to 2011 (t-test; p=0.043). High Gleason scores (8-10) were diagnosed in 19% of the 2014 positive biopsies versus 9% in the 2011 positive biopsies (chi square; p<0.0001). Conclusions: After the widespread implementation of the 2011 USPTF PSA screening guidelines, 34% fewer biopsies were performed with a 29% increase in positive biopsy rates. We found a significantly higher incidence of high grade disease in 2014 compared with 2011. The percentage of patients with positive biopsies having Gleason scores 8-10 more than doubled in 2014. The higher incidence of these more aggressive cancers must be part of the discussion regarding PSA screening.

Multidisciplinary management of a Jehovah's Witness patient for the removal of a renal cell carcinoma extending into the right atrium.

PURPOSE: To highlight the management of a Jehovah's witness surgical patient presenting for cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest. CLINICAL FEATURES: A 47-yr-old male, Jehovah's Witness, with renal cell carcinoma was admitted for left radical nephrectomy and excision of tumour thrombus extending into the junction of the inferior vena cava (IVC) and right atrium (RA). The preoperative goals were to maximize red blood cell mass, delineate the extent of tumour extension and develop a surgical plan incorporating blood conservation strategies to minimize blood loss. A midline abdominal incision was made to optimize removal of the non-caval portion of the tumour from the intra-abdominal region. CPB and deep hypothermic circulatory arrest were instituted to aid in removing the tumour from the IVC and RA. Intraoperative blood conservation strategies included the use of acute normovolemic hemodilution, antifibrinolytics, cell salvage, point-of-care monitoring of heparin and protamine blood concentrations, leukocyte-depleting filter, and meticulous surgical techniques. The patient was successfully weaned from CPB and was transported to the cardiothoracic intensive care unit without complication. The patient was discharged home one week after the operation with a hemoglobin of 10.2 g x dL(-1) and a hematocrit of 31.2%. CONCLUSION: Multiple blood conservation techniques were employed to manage this Jehovah's Witness patient through complex cardiac surgery, which was previously denied to him at other institutions. The successful outcome of this patient, while respecting the right to refuse allogeneic blood products, is a result of a multidisciplinary collaboration as well as the application of established blood conservation techniques.