Vitamin D and genetic ancestry are associated with apoptosis rates in benign and malignant prostatic epithelium.

PURPOSE: Vitamin D metabolites may be protective against prostate cancer (PCa). We conducted a cross-sectional analysis to evaluate associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. EXPERIMENTAL DESIGN: Benign and tumor epithelial punch biopsies of participants with clinically localized PCa underwent indirect TUNEL staining. Serum levels of 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D were assessed immediately before radical prostatectomy; levels of prostatic 25(OH)D were obtained from the specimen once the prostate was extracted. Ancestry informative markers were used to estimate the percentage of genetic West African, Native American, and European ancestry. RESULTS: One hundred twenty-one newly diagnosed men, age 40-79, were enrolled between 2013 and 2018. Serum 25(OH)D correlated positively with both tumor (ρ = 0.17, p = 0.03), and benign (ρ = 0.16, p = 0.04) prostatic epithelial TUNEL staining. Similarly, prostatic 25(OH)D correlated positively with both tumor (ρ = 0.31, p < 0.001) and benign (ρ = 0.20, p = 0.03) epithelial TUNEL staining. Only Native American ancestry was positively correlated with tumor (ρ = 0.22, p = 0.05) and benign (ρ = 0.27, p = 0.02) TUNEL staining. In multivariate regression models, increasing quartiles of prostatic 25(OH)D (ß = 0.25, p = 0.04) and Native American ancestry (ß = 0.327, p = 0.004) were independently associated with tumor TUNEL staining. CONCLUSIONS: Physiologic serum and prostatic 25(OH)D levels and Native American ancestry are positively associated with the degree of apoptosis in tumor and benign prostatic epithelium in clinically localized PCa. Vitamin D may have secondary chemoprevention benefits in preventing PCa progression in localized disease.

Prevalence of prostate cancer at autopsy in Nigeria-A preliminary report.

BACKGROUND AND OBJECTIVES: Prostate cancer is the most commonly diagnosed cancer in Nigerian men despite the lack of PSA based screening. Current prevalence estimates in Nigeria are based on cancer registry data obtained primarily from hospital admissions and therefore not truly reflective of prostate cancer incidence. Prior autopsy series did not adhere to modern pathologic quality practices. The aim of this study was to explore the prevalence of asymptomatic prostate cancer among Nigerian men at the time of autopsy. METHODS: Prostates were collected at autopsy at the Universities of Lagos and Calabar Teaching Hospitals from men aged more than 40 who died from causes other than prostate cancer. Thirty-nine prostates from Nigerian men autopsied in 2017 to 2018 were formalin-fixed, weighed, and sliced at 4 mm intervals. Haematoxylin and eosin-stained paraffin sections were prepared from these slices. Presence and Gleason grade of prostatic adenocarcinomas and presence of high-grade prostatic intraepithelial neoplasia (HGPIN) were recorded. RESULTS: Mean age of cases was 55 ± 11 years and mean prostatic weight was 23.0 ± 10.9 g. The crude prevalence of HGPIN was 20.6%. Overall crude prevalence of prostate cancer was 8.8% (n = 34), increasing from 8.3% for men aged 40-59 (n = 23) to 10.0% for men ≥60 years old (n = 10). Two tumors were small and had Gleason Grade 3 + 3 or 3 + 4, and one large stage T3 tumor with Gleason Grade 4 + 3 disease and neuroendocrine appearance was found in a 54-year-old man. CONCLUSIONS: The 8.8% prevalence of subclinical prostate cancer at autopsy was similar to previously reported Nigerian studies with more limited tissue sampling (6.7%-10%), but considerably lower than estimates in other populations, including African Americans. Our findings suggest that latent, clinically asymptomatic prostate cancer is less frequent in Nigerians than in African Americans, despite shared genetic ancestry. Future studies with increased sample size are warranted to provide insight in the natural history and true prevalence of prostate cancer in West Africa.

Performance of Prostate Health Index in Biopsy Naïve Black Men.

PURPOSE: The Prostate Health Index is validated for prostate cancer detection but has not been well validated for Gleason grade group 2-5 prostate cancer detection in Black men. We hypothesize that the Prostate Health Index has greater accuracy than prostate specific antigen for detection of Gleason grade group 2-5 prostate cancer. We estimated probability of overall and Gleason grade group 2-5 prostate cancer across previously established Prostate Health Index ranges and identified Prostate Health Index cutoffs that maximize specificity for Gleason grade group 2-5 prostate cancer with sensitivity >90%. MATERIALS AND METHODS: We recruited a "cancer-free" Black control cohort (135 patients) and a cohort of biopsy naïve Black men (158) biopsied for elevated prostate specific antigen. Descriptive statistics compared the prostate cancer cases and controls and the frequency of Gleason grade group 2-5 prostate cancer across Prostate Health Index scores. Receiver operating characteristics compared the discrimination of prostate specific antigen, Prostate Health Index and other prostate specific antigen related biomarkers. Sensitivity and specificity for Gleason grade group 2-5 prostate cancer detection were assessed at prostate specific antigen and Prostate Health Index thresholds alone and in series. RESULTS: Of biopsied subjects 32.9% had Gleason grade group 2-5 prostate cancer. In Blacks with prostate specific antigen from 4.0-10.0 ng/ml, Prostate Health Index and prostate specific antigen had similar discrimination for Gleason grade group 2-5 prostate cancer (0.63 vs 0.57, p=0.27). In Blacks with prostate specific antigen ≤10.0, a threshold of prostate specific antigen ≥4.0 had 90.4% sensitivity for Gleason grade group 2-5 prostate cancer; a threshold of prostate specific antigen ≥4.0 with Prostate Health Index ≥35.0 in series avoided unnecessary biopsy in 33.0% of men but missed 17.3% of Gleason grade group 2-5 prostate cancer. Prostate specific antigen ≥4.0 with Prostate Health Index ≥28.0 in series spared biopsy in 17.9%, while maintaining 90.4% sensitivity of Gleason grade group 2-5 prostate cancer. CONCLUSIONS: The Prostate Health Index has moderate accuracy in detecting Gleason grade group 2-5 prostate cancer in Blacks, but Prostate Health Index ≥28.0 can be safely used to avoid some unnecessary biopsies in Blacks.

Complications in adulthood for patients with paediatric genitourinary reconstruction.

BACKGROUND: Caring for adults with prior paediatric genitourinary reconstruction remains a challenge for adult providers. Reconstructions typically have occurred decades before; surgical records are not always available and patients and families may be unable to convey procedures performed. Spina bifida (SB) patients are vulnerable to cognitive decline which may compound these challenges. Changes in patient body habitus and loss of function may contribute to problems with previous reconstructions. METHODS: This is a non-systematic review of the literature and represents expert opinion where data are non-existent. This review focuses on the evaluation and management of complications arising from genitourinary reconstruction in congenital neurogenic bladder patients. RESULTS: Common complications experienced by congenital neurogenic bladder patients include recurrent urinary tract infection, incontinence of catheterizable channel and urinary reservoir as well as malignancy as this population ages. Preservation of renal function and prevention of urinary tract infection while optimizing continence are essential guiding principles in the care of these patients. Many of the recommendations, however, are gleaned from available data in the adult spinal cord patient (a more commonly studied population) or the paediatric urologic literature due to limited studies in adult management of such patients. CONCLUSION: Close follow-up and vigilance is warranted to monitor for infectious, mechanical and malignant complications while optimizing preservation of the upper urinary tracts and patient quality of life.

Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients.

PURPOSE: To investigate the correlation between serum 25 hydroxyvitamin D, prostatic 25 hydroxyvitamin D, and serum 1,25 dihydroxyvitamin D, and their respective associations with prostatic tumor proliferation at the time of radical prostatectomy. METHODS: In this cross-sectional analysis of 119 men undergoing radical prostatectomy, serum from whole blood and expressed prostatic fluid was collected on the day of surgery. Tumor proliferation was measured in the dominant tumor on formalin-fixed prostatectomy tissues by immunohistochemical staining for Ki67 and quantified by Aperio imaging analysis. RESULTS: The sample included 88 African Americans (74%) and 31 (26%) European Americans. Serum and prostatic levels of 25 hydroxyvitamin D were correlated with each other (Spearman's rho (ρ) = 0.27, p = 0.004), and there was also a correlation between serum 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D (ρ = 0.34, p < 0.001). Serum and prostatic 25 hydroxyvitamin D levels were not correlated with Ki67 staining in tumor cells. Serum 1,25 dihydroxyvitamin D was inversely correlated with Ki67 staining in tumor cells (ρ = - 0.30, p = 0.002). On linear regression, serum 1,25 dihydroxyvitamin D was negatively associated with Ki67 staining in tumor cells (ß - 0.46, 95% CI - 0.75, - 0.04, p = 0.04). CONCLUSION: The correlation between physiologic serum levels of 25 hydroxyvitamin D with both prostatic 25 hydroxyvitamin D and serum 1,25 dihydroxyvitamin D suggests that serum levels are reasonable biomarkers of vitamin D status. Furthermore, serum 1,25 dihydroxyvitamin D has an inverse association with Ki67 staining in tumor cells at physiologic levels and may protect against tumor progression.

Ureteral Complications of Pediatric Renal Transplantation.

PURPOSE: Ureteral complications following renal transplantation are more common in children than in adults. We identify potential risk factors for ureteral complications in pediatric patients. MATERIALS AND METHODS: We retrospectively studied a cohort of patients who underwent renal transplantation at Lurie Children's Hospital between 2004 and 2016. We analyzed the associations between patient characteristics, operative factors, graft characteristics and postoperative complications. RESULTS: A total of 224 renal transplantations in 219 patients were identified. Preexisting bladder pathology was present in 25% of cases. Overall rate of ureteral complications was 16%, with symptomatic vesicoureteral reflux being the most common. Ureteral complications were seen significantly more frequently in patients with underlying bladder pathology (26% vs 12%, p = 0.01). Rate of postoperative vesicoureteral reflux in patients with bladder pathology was lower when a urologist performed the reimplantation but the difference was not statistically significant (15% vs 27%, p = 0.35). Urologists were significantly more likely to perform the ureteral anastomosis in patients on clean intermittent catheterization (85% vs 43%, p = 0.004) and in patients with a history of complex bladder reconstruction (75% vs 28%, p <0.001). CONCLUSIONS: Patients with existing bladder pathology are at increased risk for ureteral complications, particularly vesicoureteral reflux. Since pediatric urologists routinely perform ureteral reimplantation in patients with existing bladder pathology, these patients may benefit from a multidisciplinary approach between urology and transplant surgery at renal transplantation.

Management of Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): an Evolving Treatment Paradigm.

OPINION STATEMENT: Combination systemic therapy is now standard of care for all men with metastatic, hormone-sensitive prostate cancer (mHSPC). Patients with mHSPC should be treated with standard androgen deprivation therapy (ADT) and abiraterone acetate with prednisone or docetaxel (chemohormoanl therapy) unless there are contraindications to combination therapy. Based on the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) study subgroup analysis, chemohormonal therapy may be most beneficial in men with high-volume disease burden, as men with low-volume metastatic disease do not appear to experience a survival benefit with chemohormonal therapy, while abiraterone in combination with ADT appears to be beneficial across both disease volume subgroups. Decisions regarding whether to use chemohormonal therapy or abiraterone and ADT for men with mHSPC should integrate consideration of volume of disease burden, quality of life effects, duration of therapy, and patient preferences for treatment as there is no formally powered prospective head-to-head comparison of these options demonstrating superiority of one approach over the other. Treatment of the primary tumor with radiation should be considered in men with de novo low-volume metastatic disease as radiation is associated with prolonged survival and a tolerable toxicity profile. Men with de novo high-volume metastatic disease do not appear to have improved survival with radiation of the primary tumor. Numerous clinical trials are ongoing to evaluate treatment approaches that may benefit men with mHSPC. Radical prostatectomy in men with mHSPC in combination with optimal systemic therapy is currently being assessed in a clinical trial, but should not be considered outside of a clinical trial. Metastasis-directed therapy with radiotherapy directed at metastatic lesions is still investigational, but can be considered in clinical trials in men with oligometastatic disease. Multiple studies are enrolling worldwide for men with mHSPC, and these should be considered for all interested patients.

A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort.

BACKGROUND: Predictive models that take race into account like the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) and the new Prostate Biopsy Collaborative Group (PBCG) RC have been developed to equitably mitigate the overdiagnosis of prostate specific antigen (PSA) screening. Few studies have compared the performance of both calculators across racial groups. METHODS: From 1485 prospectively recruited participants, 954 men were identified undergoing initial prostate biopsy for abnormal PSA or digital rectal examination in five Chicago hospitals between 2009 and 2014. Discrimination, calibration, and frequency of avoided biopsies were calculated to assess the performance of both risk calculators. RESULTS: Of 954 participants, 463 (48.5%) were Black, 355 (37.2%) were White, and 136 (14.2%) identified as Other. Biopsy results were as follows: 310 (32.5%) exhibited no cancer, 323 (33.9%) indolent prostate cancer, and 321 (33.6%) clinically significant prostate cancer (csPCa). Differences in area under the curve (AUC)s for the detection of csPCa between PCPT and PBCG were not statistically different across all racial groups. PBCG did not improve calibration plots in Blacks and Others, as it showed higher levels of overprediction at most risk thresholds. PCPT led to an increased number of avoidable biopsies in minorities compared to PBCG at the 30% threshold (68% vs. 28% of all patients) with roughly similar rates of missed csPCa (23% vs. 20%). CONCLUSION: Significant improvements were noticed in PBCG's calibrations and net benefits in Whites compared to PCPT. Since PBCG's improvements in Blacks are disputable and potentially biases a greater number of low risk Black and Other men towards unnecessary biopsies, PCPT may lead to better biopsy decisions in racial minority groups. Further comparisons of commonly used risk calculators across racial groups is warranted to minimize excessive biopsies and overdiagnosis in ethnic minorities.

A 17-Gene Panel Genomic Prostate Score Has Similar Predictive Accuracy for Adverse Pathology at Radical Prostatectomy in African American and European American Men.

OBJECTIVE: To validate the 17-gene Oncotype DX Genomic Prostate Score (GPS) as a predictor of adverse pathology (AP) in African American (AA) men and to assess the distribution of GPS in AA and European American (EA) men with localized prostate cancer. METHODS: The study populations were derived from 2 multi-institutional observational studies. Between February 2009 and September 2014, AA and EA men who elected immediate radical prostatectomy after a ≥10-core transrectal ultrasound biopsy were included in the study. Logistic regressions, area under the receiver operating characteristics curves (AUC), calibration curves, and predictive values were used to compare the accuracy of GPS. AP was defined as primary Gleason grade 4, presence of any Gleason pattern 5, and/or non-organ-confined disease (≥pT3aN0M0) at radical prostatectomy. RESULTS: Overall, 96 AA and 76 EA men were selected and 46 (26.7%) had AP. GPS result was a significant predictor of AP (odds ratio per 20 GPS units [OR/20 units] in AA: 4.58; 95% confidence interval (CI) 1.8-11.5, P = .001; and EA: 4.88; 95% CI 1.8-13.5, P = .002). On multivariate analysis, there was no significant interaction between GPS and race (P >.10). GPS remained significant in models adjusted for either National Comprehensive Cancer Network (NCCN) risk group or Cancer of the Prostate Risk Assessment (CAPRA) score. In race-stratified models, area under the receiver operating characteristics curves for GPS/20 units was 0.69 for AAs vs 0.74 for EAs (P = .79). The GPS distributions were not statistically different by race (all P >.05). CONCLUSION: In this clinical validation study, the Oncotype DX GPS is an independent predictor of AP at prostatectomy in AA and EA men with similar predictive accuracy and distributions.

Gender Representation in Urologic Subspecialties.

OBJECTIVE: To examine associations between urologic subspecialization, surgeon gender and practice patterns among certifying urologists over the last 13 years. MATERIALS AND METHODS: Demographic data of certifying and recertifying urologists (2004 to 2015) were obtained from the American Board of Urology. We investigated gender-specific trends in self-reported practice type (academic practice, private practice), subspecialization, and employment as a full-time vs part-time physician, relative to certification year and cycle. RESULTS: Of 9140 urologists applying for certification or recertification over the study period, 815 (8.9%) were women. The largest proportion of female surgeon candidates (65.0%) was first-time certifiers. Women represented 16.7% of first-time certifying urologists (P < .001) and reported practicing in academia more frequently (23.6%) compared with 13.7% of men (P < .001). Female surgeons identified as subspecialists in greater numbers (46.4%) than their male counterparts (23.4%) across all certification years and cycle cohorts (P < .001). Women reported subspecializing in female urology (24.2%) and pediatrics (10.2%) at higher frequencies than their male colleagues (4.6% and 3.1% respectively, both P < .001). Female and male surgeon candidates requested certification in equal proportion in andrology and infertility (P = .83) and endourology (3.6% female vs 5.8% male, P = .13), however differed in oncology (4.2% female vs 7.2% male, P = .001). CONCLUSION: A growing proportion of certifying urologists are women, with the greatest enrichment among those seeking first-time certification. Since 2004, female surgeons account for a disproportionate volume of urologists who practice in the academic setting and identify as subspecialists.

Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors.

INTRODUCTION AND OBJECTIVE: Studies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3 + 4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines. METHODS: We recruited 564 men age 40-79 undergoing initial prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three publicly funded and two private hospitals from 2009-2014. Univariate and multivariate analyses examined the associations between hospital type, race, West African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP diagnosis and Gleason ≥3 + 4 CaP. Given changes in CaP screening recommendations, we also assess the multivariate analyses for men aged 40-54. RESULTS: Black and White men had similar age, BMI, and prostate volume. Black men had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs. 0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs. 41.5%, p<0.001) and Gleason ≥3+4 CaP relative to Whites in both public (27.7% vs 11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models adjusted for age, first degree family history, prostate volume, 5-ARI use, hospital type, income, marital and educational status, Black race was independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There was a significant multiplicative interaction with Black race and abnormal DRE for Gleason ≥3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family history (OR = 4.98, p = 0.01) were independently positively associated with overall CaP diagnosis for men aged 40 to 54. CONCLUSIONS: Black race is independently associated with CaP and Gleason ≥3+4 CaP after accounting for clinical and socioeconomic risk factors including clinical setting and WAA, and has a higher odds ratio of CaP diagnosis in younger men. Further investigation into optimizing screening in Black men aged 40 to 54 is warranted.

Clinicopathological and immunohistochemical characteristics of papillary renal cell carcinoma with emphasis on subtyping.

Papillary renal cell carcinoma (PRCC), a morphologically and genetically distinct subtype of RCC, is morphologically separated into 2 subtypes for therapeutic and prognostic purposes. Type 2 tumors are generally believed to have a poorer prognosis than type 1 tumors. In spite of multiple studies, many clinicopathological issues about PRCC remain vague. We studied the clinicopathological features associated with type 1 versus type 2 PRCC, and we compared the immunohistochemical profiles in both subtypes of PRCC. We identified a total of 144 cases (74 type 1, 46 type 2, and 24 mixed), 29 female and 115 male. Mean age was 56 years for type 1 and 59 years for type 2. Mean tumor size was 3.6 cm for type 1 and 4.6 cm for type 2. Type 1 tumors were more likely to have nuclear grade 2 and less, whereas type 2 tumors were more likely to have nuclear grade 3 and above (P = .0001). There was no significant association between tumor type and renal sinus fat invasion, invasion of muscular branches of renal vein, perinephric fat invasion, microvascular angiolymphatic invasion, and main renal vein invasion. Type 2 tumors have higher nuclear grades than type 1 tumors. Based on long follow-up data, both subtypes appear to have excellent prognosis when diagnosed at early stage. The immunohistochemical profiles of both types 1 and 2 PRCC are essentially the same. The similar immunohistochemical profile suggests that PRCC is one entity with divergent histologic features.