Metastatic prostate cancer is associated with distinct higher frequency of genetic mutations at diagnosis.

INTRODUCTION AND OBJECTIVES: We explored characteristic genetic mutations associated with metastatic prostate cancer (PCa) by comparing next generation sequencing (NGS) data between men with or without metastatic disease at diagnosis. METHODS: We queried the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry for men diagnosed with PCa. Patients were categorized into with (M1) or without metastatic disease (M0) groups. The difference in the frequency of genetic mutations between the two groups and the prognostic significance of the mutations were analyzed using SPSS V28. We included frequency rate of > 5% and P values < 0.05 were considered statistically significant to maintain over 95% true positive detection rate. RESULTS: Of a total of 10,580 patients with diagnosis of PCa in the dataset, we selected a study cohort of 1268 patients without missing data; 700 (55.2%) had nonmetastatic PCa, 421 (33.2%) and 147 (11.6%) patients had metastatic castration sensitive and resistant PCa respectively. The median age at diagnosis and serum prostate specific antigen (PSA) level for the entire cohort was 62.8 years (IQR 56.3-68.4) and 8.0 ng/ml (IQR 4.9-20.9) respectively. A vast majority of the cohort were of Caucasian ancestry (89.1%). Of a total of 561 genes sequenced, there were mutations in 79 genes (14.1%). The mutation frequency was significantly higher in M1PCa compared to M0PCa, 35.7% and 23.3%, respectively (P = <0.001). The median tumor mutational burden was also significantly higher in the samples from M1PCa (2.59 mut/MB) compared to M0PCa (1.96 mut/MB) (P < 0.001). Compared to M0PCa patients, M1PCa patients demonstrated significantly higher rate of genetic mutations; TP53 (38.73% vs. 17.71% P < 0.001), PTEN (25.70% vs. 11.71% P < 0.001), AR (17.25% vs. 1.43% P < 0.001), APC (11.8% vs. 4.43% P < 0.001), TMPRSS2 (31.5% vs. 11.14% P < 0.001), ERG (23.59% vs. 13.13% P < 0.001), FOXA1 (17.43% vs. 6.33% P < 0.001), MYC (8.45% vs. 2.29% P < 0.001), RB1 (10.39% vs. 2.43% P < 0.001) and CDK12 (8.45% vs. 1.31% P < 0.001).  Of the various cellular signaling pathways, the androgen receptor signaling pathway was most often impacted. In the cohort with M1 disease, compared to men without genetic mutations the men with genetic mutations demonstrated worse survival (P = <0.001, log rank test). Compared to castration sensitive M1 patients, AR (57% vs. 4% P < 0.001), TP53 (50.7% vs. 34% P < 0.001), PTEN (35.2% vs. 22.1% P < 0.001), RB1(23.9% vs. 4.75% P < 0.001) were significantly more frequently mutated in castration resistant M1 patients. In contrast, mutations of SPOP (13.3% vs. 7.9% P < 0.001), FOXA1 (17.6% vs. 5.3% P < 0.001) and CDK12 (12% vs. 6.45% P < 0.001) were significantly more frequently found in castration sensitive M1 patients compared to castration resistant patients. CONCLUSION: Patients with M1PCa demonstrated characteristic genetic mutations compared to M0PCa, which most often influenced androgen receptor signaling and is associated with worse survival. In addition, we identified distinct genetic mutations between castration sensitive and resistant M1PCa. These findings may be used to further our understanding and management of men with PCa.

Genetic mutations in smoking-associated prostate cancer.

OBJECTIVES: Tobacco smoking is known to cause cancers potentially predisposed by genetic risks. We compared the frequency of gene mutations using a next generation sequencing database of smokers and nonsmokers with prostate cancer (PCa) to identify subsets of patients with potential genetic risks. MATERIALS AND METHODS: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry was analyzed. The GENIE registry contains clinically annotated sequenced tumor samples. We included 1832 men with PCa in our cohort, categorized as smokers and nonsmokers, and compared the frequency of mutations (point mutations, copy number variations, and structural variants) of 47 genes with more than 5% mutation rate between the two categories and correlated with overall survival using logistic regression analysis. RESULTS: Overall, 1007 (55%) patients were nonsmokers, and 825 (45%) were smokers. The mutation frequency was significantly higher in smokers compared to nonsmokers, 47.6% and 41.3%, respectively (p = 0.02). The median tumor mutational burden was also significantly higher in the samples from smokers (3.59 mut/MB) compared to nonsmokers (1.87 mut/MB) (p < 0.001). Patients with a smoking history had a significantly higher frequency of PREX2, PTEN, AGO2, KMT2C, and a lower frequency of adenomatous polyposis coli (APC) and KMT2A mutations than compared to nonsmokers. The overall mortality rate (28.5% vs. 22.8%) was significantly higher among smokers (p = 0.006). On a multivariate logistic regression analysis, the presence of metastatic disease at the time of diagnosis (OR: 2.26, 95% CI: 1.78-2.89, p < 0.001), smoking history (OR: 1.32, 95% CI: 1.05-1.65, p = 0.02), and higher frequency of PTEN somatic gene mutation (OR: 1.89, 95% CI: 1.46-2.45, p < 0.001) were independent predictors of increased overall mortality among patients with PCa. Patients with PTEN mutation had poorer overall survival compared to men without PTEN mutations: 96.00 (95% CI: 65.36-113.98) and 120.00 (95% CI: 115.05-160.00) months, respectively (p < 0.001) irrespective of smoking history although the G129R PTEN mutation was characteristically detected in smokers. CONCLUSIONS: PCa patients with a tobacco smoking history demonstrated a significantly higher frequency of somatic genetic mutations. Whereas mutations of PREX2, KMT2C, AGO2, and PTEN genes were higher in smokers, the APC and KMT2A mutations were higher in nonsmokers. The PTEN somatic gene mutation was associated with increased overall mortality among patients with PCa irrespective of smoking history. We found that G129R PTEN mutation known to reduce the PTEN phosphatase activity and K267Rfs*9 a frameshift deletion mutation in the C2 domain of PTEN associated with membrane binding exclusively detected in smokers and nonsmokers, respectively. These findings may be used to further our understanding of PCa associated with smoking.

Urinary stone disease burden is increased in patients with cognitive impairment.

Mental illness and brain disorders such as dementia are commonly encountered in patients with cognitive impairment in urology. In this cohort study, we assessed the prevalence and outcomes of inpatient admissions for stone disease in patients with cognitive impairment. Using the National Inpatient Sample database, we identified adults (>18 years) with stone disease between 2015 and 2019. The patients were dichotomized based on the presence or absence of cognitive impairment. The groups were compared for baseline differences in inpatient admissions and hospital complications. We evaluated the independent factors associated with urinary complications in the population using multivariate logistic regression. We identified 223,072 patients with stone disease. Patients with cognitive impairment were significantly (P<0.001) older (68 vs. 62 years), female (55.7% vs. 47.4%), had government-issued insurance (77.5% vs. 64.4%), and were discharged to a nursing facility (31.7% vs. 14.2%). Patients with cognitive impairment had significantly higher rates of urinary tract infection (29.7% vs. 21.5%, P<0.001), pneumonia (5.6% vs. 4.6%, P<0.001), systemic sepsis (4.3% vs. 3.8%, P<0.001), and acute renal failure (0.9% vs. 0.7%, P = 0.008). Female sex, low income, and cognitive impairment were all independently more likely to experience a urinary complication, with significant differences (P<0.001). Patients with cognitive impairment have a higher prevalence of stone disease and urinary complications associated with inpatient admissions than the rest of the population. Health care inequities among cognitively impaired patients should be a topic of further study.

The impact of socioeconomic status on the survival of men with early-onset prostate cancer.

Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.

Extramural venous invasion: a novel magnetic resonance imaging biomarker for adverse pathology in bladder cancer.

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

Magnetic resonance imaging radiomic features for recurrent prostate cancer following proton radiation therapy-A pilot study.

OBJECTIVE: The role of multiparametric MRI (mp-MRI) for postproton radiation evaluation is unclear. In this pilot study, we characterize the mp-MRI features using the Prostate Imaging-Reporting and Data System (PI-RADS) for recurrent prostate cancer (PCa) following proton radiation therapy. METHODS: After obtaining IRB approval, we identified 163 consecutive cases who underwent MRI-fusion prostate biopsy at our institution from November 2017 to May 2020. This study evaluated patients with prostate cancer (PCa) with biochemical recurrence following proton radiation. Patients were excluded if they had grossly metastatic disease, metal fragments, implanted devices, or with surgically removed prostates. The mpMRI studies were reviewed in depth and scored by 2 fellowship-trained radiologists. Following MRI-fusion biopsy of lesions of interest (LOI), slides were read by fellowship-trained pathologists. RESULTS: We found 14 patients with 16 lesions who met the study inclusion criteria. The median age was 69 years (range 57-79) and median time to biochemical recurrence was 7.3 years (range 3-13). On post-treatment imaging, decreases in prostate size and diffusely decreased T2 signal intensity were observed, making the use of apparent diffusion coefficient (ADC) and early enhancement at dynamic contrast enhanced (DCE) imaging often necessary for diagnosis of disease recurrence. We identified a total of 16 lesions with PIRADS scores of 3 or higher. Of these lesions, there were 5 PIRADS 3 lesions (4/5 (80%) without prostate cancer), 7 PIRADS 4-5 lesions (6 (86%) had high risk Pca), and 4 lesions with unassigned PIRADS scores (100% had high risk cancers). Among the MRI variables, diffusion weighted imaging (DWI) heterogeneity had the strongest association with recurrence of PCa (P < 0.001). CONCLUSIONS: Results of our pilot study showed that the PIRADS scoring system in the postproton radiation therapy setting has some correlations with prostate cancer recurrence; However, the clinical value of these findings are unclear. While definitive PIRADS categorization of lesions demonstrated expected frequency of cancer consistent with the scoring system, all unassigned lesions also harbored malignancy suggesting a cautious approach to PIRADS scoring system in postproton radiation setting. The findings from this study may be validated using a larger cohort.

Inter-reader reliability of the vesical imaging-reporting and data system (VI-RADS) for muscle-invasive bladder cancer: a systematic review and meta-analysis.

To evaluate the diagnostic agreement between readers in VI-RADS interpretation to detect muscle-invasive bladder cancer (MIBC) preoperatively, we conducted a systematic review and meta-analysis of the available data. Scopus, PubMed, Web of Science, and Embase databases were systematically searched up to November 13, 2021. Case reports, review articles, editorials, and studies with insufficient data were eliminated. The Quality Appraisal of the Diagnostic Reliability Checklist was used to assess the risk of bias. The degree of agreement was determined by Cohen's kappa coefficient (κ) for comparison of data. The heterogeneity of these studies was explored using subgroup analysis and meta-regression analysis. The level of confidence was set at 0.05. All analyses were conducted in STATA 16.0. Overall, 19 eligible studies, consisting of 2439 participants, were included in this meta-analysis. The inter-reader agreement for VI-RADS in MIBC detection ranged from κ of 0.45 to 0.96 among included studies. The pooled inter-reader reliability was calculated as 0.76 [95% CI 0.73-0.80; I2 = 92.13%, Q(50) = 635.08, p < 0.01]. Sources of heterogeneity included magnetic strength, T2WI slice thickness, number of readers, sample size, study design, number of centers, year of publication, proportion of male patients, and mean age. There is substantial reliability in VI-RADS interpretation for MIBC among radiologists with various levels of expertise. The high degree of inter-reader agreement for MIBC detection supports the implementation of VI-RADS in routine clinical practice for the staging paradigm of bladder cancer.

Prospective Observational Study of a Racially Diverse Group of Men on Active Surveillance for Prostate Cancer.

OBJECTIVE: To evaluate the risk upgrading of active surveillance (AS), we reviewed the outcomes of African American men (AA) after electing AS. AS is the standard of care for men with low-grade prostate cancer (PCa). AA are known to have more advanced PCa features and are more likely to die from PCa, thus subsequent disease progression for AA on AS is unclear. METHODS: A prospectively maintained AS database from the Southeast Louisiana Veterans Administration Medical Center, New Orleans, Lousiana was queried. We identified men with low- and very low-risk PCa (Gleason 3 + 3, PSA <10, ≤CT2a) who had undergone at least 2 prostate biopsies, including initial diagnostic and subsequent confirmatory prostate biopsies. Descriptive and comparative statistical analysis was performed using R version 3.5.1. RESULTS: From a total of 274 men on AS (70% AA), 158 men met inclusion criteria (104 AA [66%]). All patients underwent at least 2 biopsies, and 29% underwent 3 or more biopsies. The median follow-up was 2.7 years. At 3 years on AS protocol, 57% AA and 61% Caucasians demonstrated no evidence of upgrading or treatment. No significant difference was observed between upgrading or progression to treatment when comparing racial groups. Seven (4%) patients in this cohort died from non PCa-specific causes, but no patients demonstrated metastasis or death from PCa over the course of study. CONCLUSION: AA men with low-risk PCa can be safely followed with the same AS protocol as non-AA men. Further analysis with longer follow up is ongoing.

Clinical Characteristics and Outcomes Based on Race of Hospitalized Patients With COVID-19 in a New Orleans Cohort.

BACKGROUND: In Louisiana, deaths related to COVID-19 have disproportionately occurred in Black persons. Granular data are needed to better understand inequities and develop prevention strategies to mitigate further impact on Black communities. METHODS: We conducted a retrospective study of patients admitted to an urban safety net hospital in New Orleans, Louisiana, with reactive SARS-CoV-2 testing from March 9 to 31, 2020. Clinical characteristics of Black and other racial/ethnic group patients were compared using Wilcoxon rank-sum test and Fisher exact tests. The relationship between race and outcome was assessed using day 14 status on an ordinal scale. RESULTS: This study included 249 patients. The median age was 59, 44% were male, and 86% were age ≥65 years or had ≥1 comorbidity. Overall, 87% were Black, relative to 55% Black patients typically hospitalized at our center. Black patients had longer symptom duration at presentation (6.41 vs 5.88 days; P = .05) and were more likely to have asthma (P = .008) but less likely to have dementia (P = .002). There were no racial differences in initial respiratory status or laboratory values except for higher lactate dehydrogenase in Black patients. Patient age and initial oxygen requirement, but not race (adjusted proportional odds ratio, 0.92; 95% CI, 0.70-1.20), were associated with worse day 14 outcomes. CONCLUSIONS: Our results demonstrate minor racial differences in comorbidities or disease severity at presentation, and day 14 outcomes were not different between groups. However, Black patients were disproportionately represented in hospitalizations, suggesting that prevention efforts should include strategies to limit SARS-CoV-2 exposures and transmission in Black communities as one step toward reducing COVID-19-related racial inequities.

Early prostate-specific antigen response post-abiraterone as predictor of overall survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: Abiraterone is an important agent in the treatment of advanced prostate cancer. Early changes in prostate-specific antigen while on abiraterone in patients with metastatic castrate-resistant prostate cancer potentially have financial and health implications for patients. Limited data is available on early prostate-specific antigen change and subsequent survival given phase III trials did not measure prostate-specific antigen changes before 12 weeks. METHODS: A single-center retrospective study was performed. Metastatic castrate-resistant prostate cancer patients treated with abiraterone (without prior enzalutamide) at Tulane Cancer Center were reviewed with a focus on early prostate-specific antigen decline and relationship to overall survival. RESULTS: A total of 110 patients were analyzed for prostate-specific antigen response of ≥ 30 and > 50% at 4, 8, and 12 weeks. A prostate-specific antigen response of either > 30% or > 50% at 4, 8, or 12 weeks was associated with improved overall survival at all time points except > 50% decline at 8 weeks. Multivariate analysis indicated, for all time points, that early prostate-specific antigen declines were predictive of overall survival. The neutrophil to lymphocyte ratio and docetaxel pretreatment also were predictive in many, but not all, of the multivariate analyses. CONCLUSIONS: A > 30% or > 50% prostate-specific antigen decline at 4, 8, or 12 weeks provides important information regarding subsequent overall survival for patients with metastatic castrate-resistant prostate cancer. While these data require validation with a large, multi-institutional trial, they can provide physicians with information regarding prognosis and the timing of expected outcomes. These data affirms the notion that prostate-specific antigen responses as early as 4 weeks after abiraterone initiation can be used to inform both patients and physicians about metastatic castrate-resistant prostate cancer outcomes after initiating treatment with this important but costly therapeutic choice.

Factors Affecting the Completion of Genitourinary Physical Examinations Prior to Urologic Consultation.

BACKGROUND: Proper instruction during medical training regarding performing adequate physical examinations prior to urologic consultations greatly improves patient care. We evaluated the frequency of genitourinary (GU) physical examinations performed prior to urologic consultation to determine the influence of factors affecting the completion of these examinations. METHODS: Between January 2013 and December 2014, 1,596 consultations were requested by primary providers and completed by the urology department at a major tertiary care teaching institution. We reviewed patient medical records retrospectively and recorded the number of GU examinations performed prior to consultation. Patient demographics were evaluated for trends in the rates of examination. A total of 9 available urology residents saw at least one consult each. RESULTS: We identified a total of 1,596 urologic consultations during the study period, of which 233 of 407 (57.2%) (51 female and 182 male patients) received GU examinations prior to the urologic consult in the emergency department (ED) and 394 of 1,189 (33.1%) (118 female and 276 male patients) received GU examinations by the inpatient care team. Staff in the ED were 3.11 times more likely to perform a GU examination on a male patient than a female patient, and the inpatient teams were 1.48 times more likely to perform a GU examination on a male patient than a female patient. The likelihood of examination by either team was low in patients aged ≥65 years. CONCLUSION: Prior to urologic consultation, GU examinations are inconsistently performed. This variability may affect patient care and could be the subject of a future study.

3D-printed soft-tissue physical models of renal malignancies for individualized surgical simulation: a feasibility study.

To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.

Racial Variation in the Outcome of Subsequent Prostate Biopsies in Men With an Initial Diagnosis of Atypical Small Acinar Proliferation.

BACKGROUND: African American (AA) men are known to have more aggressive prostate cancer (PCa) compared with Caucasian American men. We sought to determine predictors of subsequent detection and risk stratification of PCa in a racially diverse group of men with atypical small acinar proliferation (ASAP) on initial prostate biopsy. MATERIALS AND METHODS: A retrospective analysis was conducted on data from men with ASAP on initial prostate biopsy who subsequently received confirmatory biopsies between September 2000 and July 2015. Biopsies with more than 3 years between initial and confirmatory biopsies were excluded. Race, age, body mass index, transrectal ultrasound volume, serum prostate-specific antigen (PSA), PSA velocity, PSA density, and elapsed time between biopsies were assessed for predictive value in subsequent PCa diagnosis after an initial finding of ASAP. RESULTS: Of 106 men analyzed, 75 (71%) were AA and 31 (29%) were non-AA. Baseline variables revealed AA men had higher PSA levels, PSA velocity, and PSA density (all P < .05). PCa was diagnosed in subsequent biopsy in 42 (40%) patients without significant racial variation; 30 (40%) AA versus 12 (39%) non-AA. Of the 42 PCa patients, 25 (24%) met Epstein criteria for significant disease without racial variation; 18 (24%) AA versus 7 (23%) non-AA. Only 10 (9%) patients had any component of Gleason 4; 7 (9%) AA versus 3 (10%) non-AA. In multivariate analysis, increasing age, PSA level, and PSA density were significant predictors of PCa. CONCLUSION: AA men diagnosed with ASAP on initial prostate biopsy do not have increased risk of PCa on confirmatory biopsy compared with non-AA men.

A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer.

PURPOSE: Most prostate cancer mortality can be attributed to metastatic castration resistant prostate cancer, an advanced stage that remains incurable despite recent advances. The AR (androgen receptor) signaling axis remains active in castration resistant prostate cancer. Recent studies suggest that expression of the AR-V (AR splice variant) AR-V7 may underlie resistance to abiraterone and enzalutamide. However, controversy exists over the optimal assay. Our objective was to develop a fast and sensitive assay for AR-Vs in patients. MATERIALS AND METHODS: Two approaches were assessed in this study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene® tubes. Transcript expression was analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS: Through a side-by-side comparison we found that the whole blood approach was suitable to detect AR-Vs. The specificity of the assay was corroborated in a cancer-free cohort. Using the PAXgene assay samples from a cohort of 46 patients with castration resistant prostate cancer were analyzed. Overall, AR-V7 and ARv567es were detected in 67.53% and 29.87% of samples, respectively. Statistical analysis revealed a strong association of AR-V positivity with a history of second line hormonal therapies. CONCLUSIONS: To our knowledge this is the first study to demonstrate that PAXgene preserved whole blood can be used to obtain clinically relevant information regarding the expression of 2 AR-Vs. These data on a castration resistant prostate cancer cohort support a role for AR-Vs in resistance to therapies targeting the AR ligand-binding domain.

Clinical Use of PCA3 and TMPRSS2:ERG Urinary Biomarkers in African-American Men Undergoing Prostate Biopsy.

PURPOSE: Prostate specific antigen has decreased performance characteristics for the detection of prostate cancer in African-American men. We evaluated urinary PCA3 and TMPRSS2:ERG in a racially diverse group of men. MATERIALS AND METHODS: After institutional review board approval, post-examination urine was prospectively collected before prostate biopsy. PCA3 and TMPRSS2:ERG RNA copies were quantified using transcription mediated amplification assays (Hologic, San Diego, California). Prediction models were created using standard of care variables (age, race, family history, prior biopsy, abnormal digital rectal examination) plus prostate specific antigen. Decision curve analysis was performed to compare the net benefit of PCA3 and TMPRSS2:ERG. RESULTS: Of 304 patients 182 (60%) were African-American and 139 (46%) were diagnosed with prostate cancer (69% African-American). PCA3 and TMPRSS2:ERG scores were greater in men with prostate cancer, 3 or more cores, 33.3% or more cores, greater than 50% involvement of greatest biopsy core and Epstein significant prostate cancer (p <0.01). PCA3 added to the standard of care plus prostate specific antigen model for the detection of any prostate cancer in the overall cohort (0.747 vs 0.677, p <0.0001) in African-American men only (0.711 vs 0.638, p=0.0002) and nonAfrican-American men (0.781 vs 0.732, p=0.0016). PCA3 added to the model for the prediction of high grade prostate cancer for the overall cohort (0.804 vs 0.78, p=0.0002) and African-American men only (0.759 vs 0.717, p=0.0003) but not nonAfrican-American men. Decision curve analysis demonstrated improvement with the addition of PCA3. For African-American men TMPRSS2:ERG did not improve concordance statistics for the detection of prostate cancer. CONCLUSIONS: For African-American men urinary PCA3 improves the ability to predict the presence of any and high grade prostate cancer. However, the TMPRSS2:ERG urinary assay does not add significantly to standard tools.

Racial variation in prostate needle biopsy templates directed anterior to the peripheral zone.

OBJECTIVES: African Americans (AA) have been reported to have both increased incidence and increased aggressiveness of prostate cancer (PCa) located anterior to the peripheral zone (APZ). We sought to evaluate the utility of prostate biopsies directed toward the APZ in a predominantly AA cohort. METHODS AND MATERIALS: We reviewed all patients with PCa found on biopsy schema that included needle biopsies directed at both the peripheral zone (PZ) and APZ from 2010 to 2014. Self-identified race was recorded for all patients. To evaluate the reliability of APZ-directed prostate biopsies, we performed pathologic secondary review of 25 radical prostatectomy specimens. A series of the Mann-Whitney U and Chi-square tests were used to compare variables. RESULTS: We identified 398 men, of which 277 (70%) were AA. Compared with non-AA, AA had more National Comprehensive Cancer Network-defined intermediate or high-risk (50% vs. 39%, P = 0.25) PCa. Most patients had PCa limited to the PZ only (n = 190) or in both the PZ and APZ (n = 191). For 17 patients (4%), PCa was limited only to the APZ core(s), 14 (5%) AA vs. 3 (2%) non-AA (P = 0.24). Most of these 17 patients (n = 14, 82%) had Gleason 6 disease. Patients with PCa in both the PZ and APZ had higher serum prostate-specific antigen, prostate-specific antigen density, volume of disease, and increased grade and National Comprehensive Cancer Network category (all P<0.01). Of these patients, there were no differences in race (AA = 135, 71% vs. non-AA = 56, 29%; P = 0.48). In only 21 men (11%), without racial variation, APZ tumor grade was greater than PZ. Radical prostatectomy and APZ-directed biopsies demonstrated a concordance rate of 80% (20/25), false positive rate of 8% (2/25), and false negative rate of 12% (3/25). CONCLUSIONS: APZ-directed prostate biopsies are rarely the sole location of PCa and do not show a clear racial predilection. In those men with PCa identified in both regions, the APZ biopsy did not frequently change treatment recommendations. Biopsies directed at the APZ are not of greater benefit to AA than non-AA.

Characterizations of Clinical and Therapeutic Histories for Men With Prostate Cancer-Specific Mortality.

BACKGROUND: Careful descriptions of men with prostate cancer (PCa)-specific mortality are scant in nontrial settings. The present retrospective review describes the clinical characteristics, timelines, and treatment histories from initial presentation to death in a cohort of men with metastatic, castrate-resistant PCa (mCRPC). Unique to the present study is the unequivocal attribution of PCa death by a single experienced clinician. PATIENTS AND METHODS: A total of 119 patients who had been treated at Tulane Cancer Center and had died of mCRPC from 2008 to 2015 were studied through a retrospective review of the medical records. RESULTS: The median age at diagnosis was 65 years (range, 40-85 years), and 34.4% of the patients presented with metastatic disease (stage M1). Of these patients, 56% had received definitive primary therapy, all had received androgen-deprivation therapy, and 52% had received docetaxel. The patients had received a median of 7 (1-14) systemic therapies before death. Most were secondary hormonal manipulations after the diagnosis of mCRPC (median, 4; range, 0-9). The median survival was 69 months (range, 5-270 months) after diagnosis, and the median age at death was 73 years (range, 47-95 years). The presence of metastases at diagnosis was a significant predictor of early death (hazard ratio, 4.33; P < .001), and definitive primary therapy was a significant predictor of longer survival (P < .001). The median survival for patients presenting with metastases was 39 months (range, 5-235 months) compared with 100 months (range, 6-270 months) for those with localized disease (P < .001). The median age at diagnosis between the docetaxel- and non-docetaxel-treated patients was significantly different at 62 and 71 years, respectively (P = .002). CONCLUSION: The present retrospective analysis provides initial views clarifying the clinical characteristics of men dying of mCRPC and the therapies they received before death. Additional data are needed in multi-institutional settings to confirm these findings.

Individualized Physical 3-dimensional Kidney Tumor Models Constructed From 3-dimensional Printers Result in Improved Trainee Anatomic Understanding.

OBJECTIVE: To evaluate the effect of 3-dimensionally (3D) printed physical renal models with enhancing masses on medical trainee characterization, localization, and understanding of renal malignancy. METHODS: Proprietary software was used to import standard computed tomography (CT) cross-sectional imaging into 3D printers to create physical models of renal units with enhancing renal lesions in situ. Six different models were printed from a transparent plastic resin; the normal parenchyma was printed in a clear, translucent plastic, with a red hue delineating the suspicious renal lesion. Medical students, who had completed their first year of training, were given an overview and tasked with completion of RENAL nephrometry scores, separately using CT imaging and 3D models. Trainees were also asked to complete a questionnaire about their experience. Variability between trainees was assessed by intraclass correlation coefficients (ICCs), and kappa statistics were used to compare the trainee to experts. RESULTS: Overall trainee nephrometry score accuracy was significantly improved with the 3D model vs CT scan (P <.01). Furthermore, 3 of the 4 components of the nephrometry score (radius, nearness to collecting system, and location) showed significant improvement (P <.001) using the models. There was also more consistent agreement among trainees when using the 3D models compared with CT scans to assess the nephrometry score (intraclass correlation coefficient, 0.28 for CT scan vs 0.72 for 3D models). Qualitative evaluation with questionnaires filled out by the trainees further confirmed that the 3D models improved their ability to understand and conceptualize the renal mass. CONCLUSION: Physical 3D models using readily available printing techniques improve trainees' understanding and characterization of individual patients' enhancing renal lesions.

3D Printing and Its Urologic Applications.

3D printing is the development of 3D objects via an additive process in which successive layers of material are applied under computer control. This article discusses 3D printing, with an emphasis on its historical context and its potential use in the field of urology.

Benign prostatic hyperplasia and urinary symptoms: Evaluation and treatment.

Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting middle-aged men. This condition can be microscopic, macroscopic, symptomatic, or asymptomatic. Up to 15% to 25% of men aged 50-65 years have lower urinary tract symptoms (LUTS) consisting of nocturia, urgency, frequency, a sensation of not completely emptying the bladder, stop-start urination, straining to urinate, a need to urinate soon after voiding, and weak urinary stream. These symptoms usually are associated with benign enlargement of the prostate gland that is of sufficient severity to interfere with a man's quality of life. Although LUTS is often associated with BPH, LUTS can also be due to various unrelated syndromes such as heart failure, urinary tract infections, and diabetes. Most men will have benign hyperplasia of the prostate gland and this benign growth compresses the urethra resulting in LUTS. This article will discuss the evaluation, pharmacological management, minimally invasive treatment, and surgical therapy of this common condition affecting millions of American men.