A 17-Gene Genomic Prostate Score as a Predictor of Adverse Pathology in Men on Active Surveillance.

PURPOSE: The GPS (Oncotype Dx® Genomic Prostate Score) test is a RNA expression assay which can be performed on prostate biopsies. We sought to determine whether the GPS was associated with an increased risk of adverse pathology findings in men enrolled on active surveillance who later underwent radical prostatectomy. MATERIALS AND METHODS: We identified all patients on active surveillance at University of California-San Francisco who had Gleason score 3 + 3 or low volume (33% or fewer positive cores) Gleason score 3 + 4 prostate cancer, GPS testing at diagnostic or confirmatory biopsy, clinical stage T1/T2, prostate specific antigen less than 20 and a clinical CAPRA (Cancer of the Prostate Risk Assessment) score less than 6. The primary outcome was adverse pathology, defined as Gleason score 4 + 3 or greater, stage pT3a or greater, or pN1. The secondary outcome was biochemical recurrence, defined as 2 consecutive prostate specific antigen measurements greater than 0.05 ng/ml following radical prostatectomy. RESULTS: Of the 215 men 179 (83%) were at low risk and 36 (17%) were at intermediate risk by CAPRA scoring. The median GPS was 26.4 (IQR 18.8-34.6). On multivariate analysis a higher GPS was associated with an increased risk of adverse pathology at delayed radical prostatectomy (HR/5 units 1.16, 95% CI 1.06-1.26, p <0.01). A higher GPS was also associated with an increased risk of biochemical recurrence (HR/5 units 1.10, 95% CI 1.00-1.21, p=0.04). CONCLUSIONS: In patients who undergo radical prostatectomy after a period on active surveillance, as in those who undergo immediate prostatectomy, a higher GPS is associated with an increased risk of adverse pathology. The GPS is also associated with biochemical recurrence following radical prostatectomy in such patients.

Genomic Prostate Score, PI-RADS™ version 2 and Progression in Men with Prostate Cancer on Active Surveillance.

PURPOSE: The OncotypeDx® GPS (Genomic Prostate Score®) is a 17-gene RNA expression assay intended to help guide treatment decisions in men diagnosed with prostate cancer. The PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 was developed to standardize the risk stratification of lesions identified on multiparametric prostate magnetic resonance imaging. We sought to determine whether these tests are associated with an increased risk of biopsy upgrading in men on active surveillance. MATERIALS AND METHODS: We identified all patients on active surveillance at the University of California-San Francisco who had low/intermediate risk prostate cancer (prostate specific antigen 20 ng/ml or less and clinical stage T1/T2) and Gleason score 6 disease who underwent multiple biopsies and had a GPS available and/or had undergone multiparametric prostate magnetic resonance imaging with an available PI-RADS version 2 score. The primary study outcome was biopsy upgrading, defined as an increase in the Gleason score from 3 + 3 to 3 + 4 or greater, which was analyzed by Cox proportional hazards regression. RESULTS: Of the men 140 had only GPS test findings, 169 had only a PI-RADS version 2 score and 131 had both data. Each 5-unit increase in the GPS was associated with an increased risk of biopsy upgrading (HR 1.28, 95% CI 1.19-1.39, p <0.01). PI-RADS scores of 5 vs 1-2 (HR 4.38, 95% CI 2.36-8.16, p <0.01) and 4 vs 1-2 (HR 2.62, 95% CI 1.45-4.76, p <0.01) were also associated with an increased risk of a biopsy upgrade. On subanalysis of patients with GPS and PI-RADS version 2 scores the GPS was associated with biopsy upgrading, adding value to the clinical covariates (partial likelihood ratio p = 0.01). CONCLUSIONS: A higher GPS or a PI-RADS version 2 score of 4 or 5 was associated with an increased risk of biopsy upgrading.

Remote Monitoring and Consultation of Inpatient Populations with Diabetes.

PURPOSE OF REVIEW: Inpatient hyperglycemia is common and is linked to increased morbidity and mortality. We review current and innovative ways diabetes specialists consult in the management of inpatient diabetes. RECENT FINDINGS: With electronic medical records (EMRs), remote monitoring and intervention may improve the management of inpatient hyperglycemia. Automated reports allow monitoring of glucose levels and allow diabetes teams to intervene through formal or remote consultation. Following a 2-year transition of our complex paper-based insulin order sets to be EMR based, we leveraged this change by developing new daily glycemic reports and a virtual glucose management service (vGMS). Based on a daily report identifying patients with two or more glucoses over 225 mg/dl and/or a glucose <70 mg/dl in the past 24 h, a vGMS note with management recommendations was placed in the chart. Following the introduction of the vGMS, the proportion of hyperglycemic patients decreased 39% from a baseline of 6.5 per 100 patient-days to 4.0 per 100 patient-days The hypoglycemia proportion decreased by 36%. Ninety-nine percent of surveyed medical and surgical residents said the vGMS was both important and helpful.

Inter-reader Agreement for Prostate Cancer Detection Using Micro-ultrasound: A Multi-institutional Study.

Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2-6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light's κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21-0.39). PPA was 33% (95% CI 25-42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.

Familial cortical myoclonus with a mutation in NOL3.

OBJECTIVE: Myoclonus is characterized by sudden, brief involuntary movements, and its presence is debilitating. We identified a family suffering from adult onset, cortical myoclonus without associated seizures. We performed clinical, electrophysiological, and genetic studies to define this phenotype. METHODS: A large, 4-generation family with a history of myoclonus underwent careful questioning, examination, and electrophysiological testing. Thirty-five family members donated blood samples for genetic analysis, which included single nucleotide polymorphism mapping, microsatellite linkage, targeted massively parallel sequencing, and Sanger sequencing. In silico and in vitro experiments were performed to investigate functional significance of the mutation. RESULTS: We identified 11 members of a Canadian Mennonite family suffering from adult onset, slowly progressive, disabling, multifocal myoclonus. Somatosensory evoked potentials indicated a cortical origin of the myoclonus. There were no associated seizures. Some severely affected individuals developed signs of progressive cerebellar ataxia of variable severity late in the course of their illness. The phenotype was inherited in an autosomal dominant fashion. We demonstrated linkage to chromosome 16q21-22.1. We then sequenced all coding sequence in the critical region, identifying only a single cosegregating, novel, nonsynonymous mutation, which resides in the gene NOL3. Furthermore, this mutation was found to alter post-translational modification of NOL3 protein in vitro. INTERPRETATION: We propose that familial cortical myoclonus is a novel movement disorder that may be caused by mutation in NOL3. Further investigation of the role of NOL3 in neuronal physiology may shed light on neuronal membrane hyperexcitability and pathophysiology of myoclonus and related disorders.

A Leak in the System: Addressing the Environmental Impact of Urologic Care.

As urologists we have an opportunity to reduce the carbon footprint of the procedures we perform. We highlight some areas of interest in urology and potential initiatives to reduce the energy and waste footprint of urology care. Urologists can and should make an impact on the growing climate crisis.

Practitioner counseling associated with improved opioid disposal among families of postoperative pediatric patients.

BACKGROUND: Death from opioid-related overdose has doubled in recent years. Interestingly, there has been a similar increase in the number of opioid prescriptions. Medical providers, unfortunately, have contributed towards this rise in prescriptions. To combat the opioid epidemic, numerous efforts have been made to focus on the medical field and its role in the opioid epidemic. Proposed solutions for reduction of circulating opioids have included such measures as education, monitoring programs, alternative pain management strategies, and improved opioid disposal. OBJECTIVES: We aimed to assess if counseling is associated with proper opioid disposal among families of post-operative pediatric patients. STUDY DESIGN: We conducted a cross-sectional, convenience sample study of families of post-surgical, pediatric patients at a single academic institution. Participants completed a survey during their postoperative visit assessing opioid requirements, storage and disposal during and after the postoperative period, and if they were counseled by any medical professional on proper disposal methods. We used multivariable logistic regression to evaluate the association between the independent variables and the primary outcome. RESULTS: We enrolled 180 participants, mean age of 8 years. Thirty-four percent reported having no opioid medication remaining at follow up because the medication was either consumed or the prescription was not filled. Sixty-six percent had leftover medication at the time of follow up. Sixty-six percent of participants knew the proper opioid disposal methods. However, only 22% of patients with leftover medication properly disposed of the medication. Patients who were counseled about proper opioid disposal were 3 times more likely to practice proper disposal practices than those who were not (p < 0.01). DISCUSSION: Our study uniquely look at opioid consumption, disposal rates, and the effect of counseling in a diverse post-surgical pediatric population. Our findings confirm similar observations in the literature with regards to low opioid consumption, but in a larger, more surgically diverse cohort with a 100% response rate. Limitations included a lack of demographic diversity and lack of data measuring the impact of timing or frequency of counseling on opioid disposal practices. Further research goals would be to evaluate the effectiveness of counseling on proper opioid disposal, and the influence of timing and various counseling methods. CONCLUSIONS: Most patients do not use all of their opioid medication prescription. Proper opioid disposal counseling by a medical professional may play an important role in adherence to recommended opioid disposal practices.

Genomic Risk Predicts Molecular Imaging-detected Metastatic Nodal Disease in Prostate Cancer.

BACKGROUND: The Decipher genomic classifier (GC) is increasingly being used to determine metastasis risk in men with localized prostate cancer (PCa). Whether GCs predict for the presence of occult metastatic disease at presentation or subsequent metastatic progression is unknown. OBJECTIVE: To determine if GC scores predict extraprostatic 68Ga prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET) positivity at presentation. DESIGN, SETTING, AND PARTICIPANTS: Between December 2015 and September 2018, 91 PCa patients with both GC scores and pretreatment 68Ga-PSMA-11 PET scans were identified. Risk stratification was performed using the National Comprehensive Cancer Network (NCCN), Cancer of the Prostate Risk Assessment (CAPRA), and GC scores. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to identify factors correlated with PSMA-positive disease. RESULTS AND LIMITATIONS: The NCCN criteria identified 23 (25.3%) and 68 patients (74.7%) as intermediate and high risk, while CAPRA scores revealed 28 (30.8%) and 63 (69.2%) as low/intermediate and high risk, respectively. By contrast, only 45 patients (49.4%) had high-risk GC scores. PSMA-avid pelvic nodal involvement was identified in 27 patients (29.7%). Higher GC score was significantly associated with pelvic nodal involvement (odds ratio [OR] 1.38 per 0.1 units; p=0.009) and any PSMA-avid nodal involvement (pelvic or distant; OR 1.40 per 0.1 units; p=0.007). However, higher GC score was not significantly associated with PSMA-avid osseous metastases (OR 1.11 per 0.1 units; p=0.50). Limitations include selection bias for patients able to receive both tests and the sample size. CONCLUSIONS: Each 0.1-unit increase in GC score was associated with an approximate 40% increase in the odds of PSMA-avid lymph node involvement. These data suggest that patients with GC high risk might benefit from more nodal imaging and treatment intensification, potentially via pelvic nodal dissection, pelvic nodal irradiation, and/or the addition of chemohormonal agents. PATIENT SUMMARY: Patients with higher genomic classifier scores were found to have more metastatic lymph node involvement on prostate-specific membrane antigen imaging.

Prostate cancer in the era of "Omic" medicine: recognizing the importance of DNA damage repair pathways.

Data from recent high-throughput studies analyzing local and advanced prostate cancer have revealed an incredible amount of biological diversity, which has led to the classification of distinct molecular tumor subtypes. While integrating prostate cancer genomics with clinical medicine is still at its infancy, new approaches to treat prostate cancer are well underway and being studied. With the recognition that DNA damage repair (DDR) mutations play an important role in the pathogenesis of this disease, clinicians can begin to utilize genomic information in complex treatment decisions for prostate cancer patients. In this Review, we discuss the role of DDR mutations in prostate cancer, including deficiencies in homologous repair and mismatch repair (MMR), and how this information is revolutionizing the treatment landscape. In addition, we highlight the potential resistance mechanisms that may result as we begin to target these pathways in isolation and discuss potential combinatorial approaches that may delay or overcome resistance.

Genomic biomarkers in prostate cancer.

Prostate cancer is the most common non-cutaneous cancer among men in the United States. In the last decade there has been a rapid expansion in the field of biomarker assays for diagnosis, prognosis, and treatment prediction in prostate cancer. The evidence base for these assays is rapidly evolving. With several commercial assays available at each stage of the disease, deciding which genomic assays are appropriate for which patients can be nuanced for physicians. In an effort to help guide these decisions in clinical practice, we aim to give an update on the current status of the biomarker field of prostate cancer.

Risk Factors for the Development of Bladder and Bowel Dysfunction.

BACKGROUND: Patients with vesicoureteral reflux and concomitant bladder and bowel dysfunction (BBD) are at high risk for febrile urinary tract infections. Risk factors for BBD have been identified in retrospective studies without validated measures. METHODS: We conducted a secondary analysis of the Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation trials. The outcome of interest in the analysis of these children was the development of BBD, defined by using the dysfunctional voiding questionnaire, during any time point in the studies. We used multivariable logistic regression to determine the independent effects of sex, baseline percentile BMI, cohort status (Randomized Intervention for Children with Vesicoureteral Reflux versus Careful Urinary Tract Infection Evaluation), continuous antibiotic prophylaxis (yes or no), and reflux status (dilating versus nondilating) on the development of BBD. RESULTS: Three hundred and eighteen patients met inclusion criteria. The majority of patients (244 patients, 77%) were not toilet trained at baseline visit. The median baseline age (interquartile range) was 21 months (11-35 months), and 299 (94%) patients were girls. During the study period, 111 (35%) developed BBD. Baseline BMI percentile was not associated with BBD development (adjusted odds ratio [aOR] = 1.0; 95% confidence interval [CI]: 0.9-1.1), whereas female sex was highly associated with BBD development (aOR = 12.7; 95% CI: 1.6-98). Patients with dilating reflux at baseline were 2.1 times more likely to develop BBD (95% CI: 1.2-3.7). Antibiotic prophylaxis was not associated with BBD development (aOR = 0.8; 95% CI: 0.4-1.4). CONCLUSIONS: Dilating reflux and female sex were identified as risk factors for development of BBD, but neither BMI nor prophylactic antibiotics was associated with the development of BBD.