Ardalan E. Ahmad

Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer.

B‐cell translocation gene 3 (BTG3/ANA/APRO4) is a candidate tumor suppressor gene in some malignancies. We report here that B‐cell translocation gene 3 (BTG3) is transcriptionally down‐regulated in prostate cancer and the mechanism of inactivation is through promoter hypermethylation.

Geographic distribution of urologists throughout the United States using a county level approach.

PURPOSE The adequacy of the urologist work force in absolute numbers and relative distribution is unclear. To develop effective policies addressing the needs of an aging population we must better understand the urologist work force. We assessed the geographic distribution of urologists throughout the United States at the county level and determined the county characteristics associated with increased urologist density. MATERIALS AND METHODS County level data from the Department of Health and Human Services Area Resource File and the United States Census were analyzed in this ecological study. Logistic regression and ordinal logistic regression models were built to identify predictors of urologist density, defined as the number of urologists per 100,000 individuals. National patterns of urologist density were mapped graphically at the county level. RESULTS Overall 63% of the counties in the United States lack a urologist. Based on multivariate models urologists were less likely to be found in nonmetropolitan counties (OR 0.57, 95% CI 0.46-0.72) and rural counties (OR 0.03, 95% CI 0.02-0.06) than in metropolitan counties, which confirmed visually mapped models. Patterns of urologist density also appeared to be influenced by climate and county education levels rather than by traditional socioeconomic measures. Urologists younger than 45 years old were 3 times less likely to be located in nonmetropolitan and rural counties than their older counterparts. CONCLUSIONS The uneven distribution of urologists throughout the United States is likely to worsen as younger physicians continue to cluster in urban areas. Governing bodies must consider this distribution in their calls for increasing the number of training positions.

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer.

Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer‐specific survival. Lymph node counts are often a proxy for the extensiveness of a dissection. In the current study, the impact of an institutional policy requiring a minimum number of lymph nodes was assessed.

Urologist Density and County-Level Urologic Cancer Mortality

PURPOSE The surgical work force distribution at the county level varies widely across the United States, and the impact of differential access on cancer outcomes is unclear. We used urologists as a test case because they are the first care providers for urologic cancers, can easily be identified from available data sources, and are unevenly distributed throughout the country. The goal of this study was to determine the effect of increasing urologist density on local prostate, bladder, and kidney cancer mortality. PATIENTS AND METHODS Using county-level data from the Area Resource File, US Census, National Cancer Institute, and Centers for Disease Control, regression models were built for prostate, bladder, and kidney cancer mortality, controlling for categorized urologist density, county demographics, socioeconomic factors, and preexisting health care infrastructure. RESULTS For each of the three cancers, there was a statistically significant cancer-specific mortality reduction associated with counties that had more than zero urologists (16% to 22% reduction for prostate cancer, 17% to 20% reduction for bladder cancer, and 8% to 14% reduction for kidney cancer with increasing urologist density) relative to zero urologists. However, increasing density greater than two urologists per 100,000 people had no statistically significant impact on mortality for any of the tumors studied. CONCLUSION The presence of a urologist is associated with lower mortality for urologic cancers in that county, but increasing urologist density does not yield further improvements. Therefore, a nuanced and geographically aware policy toward the size and distribution of the future work force is most likely to provide the greatest population-level improvement in cancer mortality outcomes.

Bcl2 −938C/A Polymorphism Carries Increased Risk of Biochemical Recurrence After Radical Prostatectomy

PURPOSE Approximately 10% to 26% of patients show biochemical failure after radical prostatectomy or radiation therapy. The importance of cell cycle and apoptosis pathways in prostate cancer has been reported. However, to our knowledge there is currently no information on the role of apoptosis and cell cycle related gene polymorphisms in prostate cancer cases. We investigated several polymorphisms related to the cell cycle and apoptosis, and their role in biochemical failure after radical prostatectomy. MATERIALS AND METHODS We genotyped 6 single nucleotide polymorphisms in 6 genes, including p53 (rs1042522), p21 (rs1801270), MDM2 (rs2279744), PTEN (rs701848), GNAS1 (rs7121) and bcl2 (rs2279115), using polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequencing in 140 patients with prostate cancer and 167 age matched controls. The association of polymorphic variants with prostate specific antigen failure in patients with prostate cancer was analyzed by Kaplan-Meier curves. RESULTS A significant increase in the frequency of the C/C genotype of GNAS1 rs7121 was observed in patients compared with controls. Interestingly we found a significant difference in biochemical recurrence-free time between the bcl2 C/C and C/A+A/A genotypes. It was also noted that the bcl2 C/C genotype was an independent risk factor for biochemical recurrence after radical prostatectomy on multivariate analysis. There was no statistical difference in the genotype distributions of the other genes between patients and controls. CONCLUSIONS To our knowledge this is the first report documenting that bcl2 promoter region -938 C/C genotype carriers more frequently show biochemical recurrence than -938C/A+A/A carriers.

Reflex ImmunoCyt testing for the diagnosis of bladder cancer in patients with atypical urine cytology

BACKGROUND ImmunoCyt/uCyt (Scimedx, Denville, NJ, USA) is a well-established urinary marker assay with high sensitivity for the diagnosis of urothelial carcinoma (UC) and can function as a second-level test to arbitrate atypical reads of urine cytology. OBJECTIVE To determine the utility of uCyt as a reflex test for atypical cytology in patients undergoing a hematuria evaluation or surveillance with a history of UC. DESIGN, SETTING, AND PARTICIPANTS The uCyt assay was performed as a second-level reflex test on all voided urine cytology tests read as atypical between January 2007 and June 2010 in an academic medical center. Records were retrospectively reviewed. Three hundred twenty-four patients underwent a total of 506 uCyt assays. INTERVENTION Reflex uCyt assay on atypical urine cytology. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The uCyt test characteristics include sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS AND LIMITATIONS Reflex uCyt was performed on 506 atypical voided urine samples that were followed by cystoscopy within 90 d. Reflex uCyt with a history of UC showed a sensitivity of 73%, a specificity of 49%, and an NPV of 80%. In those with a history of low-grade UC, reflex uCyt had a sensitivity of 75%, a specificity of 50%, and an NPV of 82%, while in those with a history of high-grade UC, it had a sensitivity of 74%, a specificity of 44%, and an NPV of 79%. Without prior history of UC, reflex uCyt had a sensitivity of 85%, a specificity of 59%, and an NPV of 94%. This studys limitations include its retrospective design and interobserver variability inherent to cystoscopy, which was used as the reference test. CONCLUSIONS When used as a reflex test on atypical urine cytology, negative uCyt may predict a negative cystoscopy in select patients and modulate the urgency and further work-up in those with no prior history or low-grade disease.

Testicular Cancer Biomarkers: a role for precision medicine in testicular cancer

Abstract Testicular germ cell tumors (TGCTs) represent the most common solid tumors among men aged 15 to 34 years. Fortunately, recent advances have made testicular cancer a highly curable disease. Despite the high cure rates, there are still several areas in testis cancer care where treatment decisions are controversial and guided only with clinical factors and historic serum tumor markers. Unfortunately, unlike other genitourinary malignancies, modern research techniques have not been widely tested or applied to germ cell tumors, perhaps as a result of excellent prognosis in this cohort of young men. Despite this, there remain numerous challenges and pitfalls in testis cancer care that need to be addressed. A reliable set of biomarkers could be extremely useful in helping risk‐stratify patients, detect relapse early, guide surgical decision‐making, and tailor follow‐up. Current tumor markers (Alpha‐fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have low accuracy and low sensitivity when used not only as diagnostic but also as prognostic and predictive markers. In twenty‐first century medicine, there is a role for further prognostic stratification and the development of novel biomarkers that offer greater sensitivity and specificity for TGCTs. Despite the initial promising results, the majority of preclinical biomarkers do not, as yet have a proven validated role in clinical practice, and future prospective trials are needed to support and confirm the results of cohort studies. In this narrative review, we aimed to highlight the recent innovations in the development and implementation of novel testicular tumor markers and discuss their clinical applications and limitations in the management of this disease.

PD11-06 CYSTIC RENAL MASSES: IS THE BOSNIAK CLASSIFICATION SYSTEM AN ADEQUATE PREDICTOR OF SURVIVAL?

within 2 hours of one other for each patient to identify ureteral patency, the primary outcome for this study. Results from both imaging studies were reviewed in a blinded fashion by two experienced radiologists and compared. RESULTS: Eighty-six imaging studies were performed in 76 patients during the study period from September 2015 to September 2016. Females (58.3%) predominated males (41.7%) with a mean age of 51.2 16.1 years and a mean body mass index of 29.6 8.4 kg/m. Four studies were excluded due to technical factors preventing imaging interpretation. For the remaining 82 studies, 66 (80.5%) demonstrated concordance for detecting ureteral patency between the two imaging techniques. Within the 16 (19.5%) discordant studies,15 showed antegrade urine flow on contrast-enhanced ultrasound but not on fluoroscopic nephrostogram, and one antegrade flow on fluoroscopic nephrostogram but not on ultrasound. For discordant studies, 97.5% of tubes were managed according to ultrasound results. No adverse events were noted related to any contrast-enhanced ultrasound studies. While contrast-enhanced ultrasound utilized no ionizing radiation, fluoroscopic nephrostograms provided a mean radiation exposure dose of 13.1 17.5 mGycm for patients. CONCLUSIONS: Contrast-enhanced ultrasound can be used to perform a nephrostogram with ultrasound contrast administered via a nephrostomy tube. This novel imaging technique is non-inferior to fluoroscopic nephrostogram, safe for patients, and devoid of radiation exposure in evaluating ureteral patency following percutaneous nephrolithotomy.

MP38-05 DEFINING A COHORT OF MEN WHO MAY NOT REQUIRE REPEAT PROSTATE BIOPSY BASED ON PCA3 AND MRI: THE DOUBLE NEGATIVE EFFECT.

the outcome of 12-core transrectal ultrasound (TRUS) guided prostate biopsy. Herein, we aim to decipher the predictive value of mp-MRI in detection and exclusion of prostate cancer using TRUS prostate biopsy. METHODS: UK multicentre study. Data from 592 patients scheduled to undergo mp-MRI and/or 12-core TRUS-guided prostate biopsy from January till September 2016 was reviewed retrospectively from a prospective database. Mp-MRIs were reported using the Prostate Imaging Reporting and Data System (PI-RADS). Only patients who had pre biopsy mp-MRIs followed by prostate biopsy were included in the study. 108 patient were excluded as they did not have mp-MRI or biopsy due to contraindications. RESULTS: Prebiopsy mp-MRIs followed by a 12-core TRUSguided prostate biopsy were completed in 484 patients. The sensitivity and specificity of mp-MRI for prostate cancer detected on prostate biopsy were 92.6% and 74.4%, respectively. The negative predictive and positive predictive values of mp-MRI for prostate cancer detected on biopsy were 89.7% and 80.8%, respectively. 129 patients had a PIRADS score of 5 on mp-MRI, with prostate cancer detected in 92%(n1⁄4119) of patients on biopsy. The incidence of Gleason scores 6,7,8 and 9 in patients with PI-RADS 5 were 15.9%(n1⁄419), 51.2%(n1⁄461), 6.7%(n1⁄48) and 26%(n1⁄431), respectively. 117 patients had a PI-RADS score of 4 on mp-MRI, with prostate cancer detected in 53.8%(n1⁄463) of patients on biopsy. The incidence of Gleason scores 6,7,8 and 9 in patients with PI-RADS 4 were 60%(n1⁄436), 33.3% (n1⁄421), 4.7% (n1⁄43) and 1.5% (n1⁄41), respectively. 153 patients had a PI-RADS score of 3 on mp-MRI, with prostate cancer detected in 29% (n1⁄445) of patients on biopsy. The incidence of Gleason scores 6,7 and 9 cancers in patients with PI-RADS score of 3 were 68% (n1⁄431), 26.6% (n1⁄412) and 4.4% (n1⁄42), respectively. Overall there was a statistically significant association between patients with PIRADS scores 3 and cancer positive biopsies (p1⁄40.001). CONCLUSIONS: Mp-MRI has a high predictive value for both diagnosing and excluding prostate cancer. Patients with PI-RADS scores 3 had a significant association with detection of prostate cancer on biopsy. These findings could aid in guiding follow-up protocols in men suspected of prostate cancer.

PD03-04 LONG-TERM ONCOLOGIC OUTCOMES OF RADICAL PROSTATECTOMY IN A LARGE COHORT OF PATIENTS ON ACTIVE SURVEILLANCE

with detailed and validated clinicopathologic data for all patients with newly-diagnosed CaP. For this analysis, we identified all men who underwentRP for clinically low-riskCaP (defined as clinical stage T1 or T2a, prostate specific antigen (PSA) <10 ng/mL, and biopsy Gleason score 6) from 1/2011 through 8/2015. We compared differences in the frequency of adverse pathologic outcomes (e.g., Gleason score upgrading, seminal vesicle involvement, positive surgical margins) among patients selecting initial RP versus initial AS with subsequent transition to RP. RESULTS: During this interval, 2,858 patients with low-risk CaP were entered into the MUSIC registry. Among this group, 778 (27%) and 1,359 (48%) patients selected initial RP and initial AS, respectively. AS patients were older (63.4 vs. 60.1 years, p<0.001) with similar PSA levels (5.4 vs. 5.0 ng/mL, p1⁄40.08 for initial AS and RP groups, respectively), but less likely to have clinical T2a disease (5.1% vs 14.5%, p1⁄40.02). Among the AS cohort, the median follow-up was 506 days (IQR 280-793 days), and 79 (5.8%) transitioned to RP. Men managed with initial AS were more likely to have a pathological Gleason Score 7; however there were no other differences between these groups with respect to adverse pathology outcomes (Table 1). CONCLUSIONS: Patients with low risk CaP that enter AS have higher grade disease at RP compared to those undergoing initial RP. The lack of differences in other pathologic outcomes suggests that the surveillance process may be appropriately identifying patients with more aggressive cancers prior to stage progression.