Development and Validation of a Mixed-Reality Simulator for Reducing Biopsy Core Deviation During Simulated Freehand Systematic Prostate Biopsy.

INTRODUCTION: We describe the development and validation of a mixed-reality prostate biopsy (PBx) simulator with built-in guidance aids and real-time 3-dimensional visualization. METHODS: We evaluated our simulator during one-on-one training sessions with urology residents and attendings from 2018 to 2022. Participants performed freehand, side-fire, double-sextant transrectal ultrasound-guided systematic prostate biopsy (sPBx). After a baseline assessment (first set of 12 biopsy cores), participants trained for 25 minutes with visualization and cognitive aids activated. Training was followed by an exit set of 12 biopsy cores without visualization or cognitive aids and afterward, subjective assessment by trainees of the simulator. Deviation is the shortest distance of the center of a core from its intended template location. RESULTS: Baseline deviations (mean ± SD) for residents (n = 24) and attendings (n = 4) were 13.4 ± 8.9 mm and 8.5 ± 3.6 mm ( P < 0.001), respectively. Posttraining deviations were 8.7 ± 6.6 mm and 7.6 ± 3.7 mm ( P = 0.271), respectively. Deviations between baseline and exit were decreased significantly for residents ( P < 0.001) but not for attendings ( P = 0.093). Overall feedback from participants was positive. Confidence in performing a PBx increased in novices after training ( P = 0.011) and did not change among attendings ( P = 0.180). CONCLUSIONS: A new PBx simulator can quantify and improve accuracy during simulated freehand sPBx while providing visualization and graphical feedback. Improved simulated sPBx accuracy could lead to more even distribution of biopsy cores within the prostate when performed in clinical settings, possibly reducing the high risk of missing an existing lesion and thus decreasing the time to initiating treatment, if indicated.

Replacing surveillance cystoscopy with urinary biomarkers in followup of patients with non-muscle-invasive bladder cancer: Patients' and urologic oncologists' perspectives.

INTRODUCTION: Urinary biomarkers are being developed to detect bladder cancer recurrence/progression in patients with non-muscle-invasive bladder cancer (NMIBC). We conducted a questionnaire-based study to determine what diagnostic accuracy and cost would such test(s) need for both patients and urologic oncologists to comfortably forgo surveillance cystoscopy in favour of these tests. METHODS: Surveys were administered to NMIBC patients at followup cystoscopy visit and to physician members of the Society of Urologic Oncology. Participants were questioned about acceptable false-negative (FN) rates and costs for such alternatives, in addition to demographics that could influence chosen error rates and costs. RESULTS: A total of 137 patient and 51 urologic oncologist responses were obtained. Seventy-seven percent of patients were not comfortable with urinary biomarker(s) alternatives to repeat cystoscopy, with a further 14% willing to accept such alternatives only if the FN rate were 0.5% or lower. Seventy-five percent of urologic oncologists were comfortable with an alternative urinary biomarker test(s), with 37% and 33% willing to accept FN rates of 5% and 1%, respectively. Forty-seven percent of patients were not willing to pay out-of-pocket for such tests, while 61% of urologic oncologists felt that a price range of $100-500 would be reasonable. CONCLUSIONS: This is the first survey evaluating patient and urologic oncologist perspectives on acceptable error rates and costs for urinary biomarker alternatives to surveillance cystoscopy for patients with NMIBC. Despite potential responder bias, this study suggests that urinary biomarker(s) will require sensitivity equivalent to that of cystoscopy in order to completely replace it in surveillance of patients with NMIBC.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

PURPOSE: We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. MATERIALS AND METHODS: We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. RESULTS: Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. CONCLUSIONS: Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l.

Development and external validation of a biopsy-derived nomogram to predict risk of ipsilateral extraprostatic extension.

OBJECTIVES: To develop and externally validate a nomogram that predicts risk of side-specific extraprostatic extension (EPE) at time of surgery, using commonly available preoperative markers. MATERIALS AND METHODS: A consecutive sample of 753 men treated by radical prostatectomy (RP) at the University Health Network, Toronto, between 2009 and 2015, was used to develop the nomogram. The validation cohort consisted of 311 men treated by RP at Ottawa Hospital Research Institute, between 1992 and 2014. The study outcome was presence of ipsilateral EPE. The association between predictors considered and EPE was tested using univariate and multivariate logistic regression analyses. The predictive accuracy of the nomogram was determined using the area under the receiver-operating characteristic curve. RESULTS: The overall rate of EPE was 19.8% of all lobes in the developmental cohort and 28.9% in the validation cohort. Significant variables in the models were age, prostate-specific antigen and ipsilateral Gleason score, percentage of positive cores and highest core involvement (all P < 0.05). The nomogram predicting risk of EPE had a predictive accuracy of 0.74 in the external validation cohort. CONCLUSION: We developed and externally validated a nomogram that predicts the risk of ipsilateral EPE based on commonly used preoperative markers. This nomogram may be used to assist surgical decision-making prior to RP.

Citrate, malate and alkali content in commonly consumed diet sodas: implications for nephrolithiasis treatment.

PURPOSE: Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. MATERIALS AND METHODS: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. RESULTS: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist Orange, Diet 7Up, Sprite Zero, Diet Canada Dry Ginger Ale, Sierra Mist Free, Diet Orange Crush, Fresca and Diet Mountain Dew. Colas, including Caffeine Free Diet Coke, Coke Zero, Caffeine Free Diet Pepsi and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. CONCLUSIONS: Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH.