Use of Monitoring Tests Among Patients With Localized Prostate Cancer Managed With Observation.

PURPOSE: It is unknown whether compliance with recommended monitoring tests during observation of localized prostate cancer has changed over time. MATERIALS AND METHODS: We performed a retrospective cohort study of Medicare beneficiaries diagnosed with low- or intermediate-risk prostate cancer in 2004-2016 who were initially managed with observation for a minimum of 12 months. The primary objective was to examine rates of PSA testing, prostate biopsy, and prostate MRI. We used multivariable mixed effects Poisson regression to determine whether rates of PSA testing and prostate biopsy increased over time. In addition, we identified clinical, sociodemographic, and provider factors associated with the frequency of monitoring tests during observation. RESULTS: We identified 10,639 patients diagnosed at a median age of 73 (IQR 69-77) years. The median follow-up time was 4.3 (IQR 2.7-6.6) years after diagnosis. Among patients managed without treatment for 5 years, 98% received at ≥1 PSA test, 48.0% ≥1 additional prostate biopsy, and 31.0% ≥1 prostate MRI. Among patients managed with observation for ≥12 months, mixed effects Poisson regression revealed that rates of PSA testing and biopsy increased over time (per calendar year: RR 1.02, 95% CI: 1.02-1.03 and RR 1.10, 95% CI: 1.08-1.11, respectively). Clinical and sociodemographic factors including age, clinical risk, race/ethnicity, census tract poverty, and region were associated with rates of biopsy and PSA testing. CONCLUSIONS: Use of recommended monitoring tests including repeat prostate biopsy remains low among Medicare beneficiaries undergoing observation for low- and intermediate-risk prostate cancer.

Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines.

BACKGROUND: For specific clinical indications, androgen deprivation therapy (ADT) will induce disease prostate cancer (PC) regression, relieve symptoms and prolong survival; however, ADT has a well-described range of side effects, which may have a detrimental effect on the patient's quality of life, necessitating additional interventions or changes in PC treatment. The risk-benefit analysis for initiating ADT in PC patients throughout the PC disease continuum warrants review. METHODS: A 14-member panel comprised of urologic and medical oncologists were chosen for an expert review panel, to provide guidance on a more judicious use of ADT in advanced PC patients. Panel members were chosen based upon their academic and community experience and expertise in the management of PC patients. Four academic members of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, and were tasked with addressing the role of ADT in specific PC settings. RESULTS: This article describes the practical recommendations of an expert panel for the use of ADT throughout the PC disease continuum, as well as an algorithm summarizing the key recommendations. The target for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting. CONCLUSION: The panel has provided recommendations for monitoring PC patients while on ADT, recognizing that PC patients will progress despite testosterone suppression and, therefore, early identification of conversion from castrate-sensitive to castration resistance is critical. Also, the requirement to both identify and mitigate side effects of ADT as well as the importance of quality of life maintenance are essential to the optimization of patient care, especially as more combinatorial therapeutic strategies with ADT continue to emerge.

Clinical significance of ureteric 'skip lesions' at the time of radical cystectomy: the M.D. Anderson experience and literature review.

OBJECTIVE: To assess the incidence and clinical significance of 'skip lesions' that are present in proximal but not in distal ureteric sections, which are occasionally found during the pathological examination of ureteric margins during radical cystectomy (RC). PATIENTS AND METHODS: We identified 660 patients who underwent a RC and had at least two permanent margins for a given ureter. In all, 1173 ureters were analysed and classified as follows: 'normal' (no tumour, reactive atypia, mild or moderate dysplasia) or 'abnormal' (severe dysplasia, carcinoma in situ (CIS), or tumour). Transitions from 'normal' distal pathology to 'abnormal' on proximal section(s) determined frequency of skip lesions. Fisher's exact test and the log-rank test were used to study correlations. RESULTS: Ureteric skip lesions were found in 4.8% patients (2.9% ureters). Pathology of skip lesions was CIS in 55.9%, transitional cell carcinoma in 23.5% and severe dysplasia in 20.6%. Skip lesions were associated with lymphovascular invasion (34.4% vs 13.7%, P = 0.004) and advanced pT stage (P = 0.007). On multivariate analysis, skip lesions correlated with lower median overall survival (OS) (inestimable vs 8.2 years, P = 0.014) in patients with pT0 or pTa disease and a trend towards lower OS (2.7 vs 8.8 years, P = 0.066) in pTis disease. Concordance between frozen distal margin and permanent proximal margin varied; sensitivity was 80% in those without and 20% in those with skip lesions. CONCLUSIONS: The presence of a ureteric skip lesion may be associated with lower survival in patients with pT0, pTa or pTis urothelial carcinoma. Thus, while uncommon, ureteric skip lesions should be reported in pathological findings.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Receptor heterodimerization: a new mechanism for platelet-derived growth factor induced resistance to anti-epidermal growth factor receptor therapy for bladder cancer.

PURPOSE: Human bladder cancer cells resistant to anti-epidermal growth factor receptor therapy often co-express platelet-derived growth factor receptor-ß. We determined whether there is functional crosstalk between epidermal growth factor receptor and platelet-derived growth factor receptor-ß, and how this regulates biological functions in bladder cancer cases. MATERIALS AND METHODS: We determined heterodimerization and co-localization of epidermal growth factor receptor and platelet-derived growth factor receptor-ß by immunoprecipitation and confocal microscopy, respectively. We tested the antiproliferative effects of specific inhibitory monoclonal antibodies to each receptor by (3)H-thymidine uptake assay. We transfected the nonplatelet-derived growth factor receptor-ß expressing bladder cancer cell line UMUC5 with the platelet-derived growth factor receptor-ß gene. These cells were analyzed in vitro by (3)H-thymidine uptake and by Matrigel™ invasion assay, and in vivo for tumorigenicity, metastatic potential and orthotopic growth. In a treatment study nude mice were inoculated with orthotopic tumors and treated with the inhibitory antibodies alone and in combination. RESULTS: Immunoprecipitation revealed epidermal growth factor receptor/platelet-derived growth factor receptor-ß heterodimers in all platelet-derived growth factor receptor-ß expressing cell lines. Forced expression of platelet-derived growth factor receptor-ß in epidermal growth factor receptor sensitive UMUC5 cells (50% inhibitory concentration less than 10 nM) significantly decreased responsiveness to epidermal growth factor receptor inhibition (50% inhibitory concentration greater than 100 nM) and increased invasive potential 3-fold as well as tumorigenicity. Increased invasiveness was associated with epidermal growth factor triggered platelet-derived growth factor receptor-ß transactivation, increased mitogen activated protein kinase and glycogen synthase kinase-3ß phosphorylation, and decreased E-cadherin. Inhibition of epidermal growth factor receptor and platelet-derived growth factor receptor-ß receptors blocked cell invasion, decreased cell proliferation, reduced xenograft tumor growth and increased E-cadherin expression. CONCLUSIONS: In epidermal growth factor receptor expressing bladder cancer co-expression of platelet-derived growth factor receptor-ß has implications for tumor biology. Thus, it should be further evaluated as a strategy involving dual receptor targeting.

Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis.

OBJECTIVE: To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy. MATERIALS AND METHODS: Orthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1-mm step-sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified. RESULTS: The correlation between MRI volume and BLI was weak in KU7 xenografts (R(2) < 0.1) but strong in 253J B-V (R(2) = 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R(2) = 0.42). CONCLUSION: The correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method.

The impact of variant histology on the outcome of bladder cancer treated with curative intent.

Patient risk stratification is essential for optimal management of patients with bladder cancer. Risk status determines the application and timing of therapeutic interventions such as repeat transurethral resection, intravesical chemo- and immunotherapy, systemic chemotherapy, and radical cystectomy. One key factor in such risk stratification appears to be the presence of variant histologic patterns in the bladder tumor. More than 90% of tumors are conventional urothelial carcinoma, and the rest consist of urothelial carcinoma with aberrant differentiation (squamous/glandular differentiation, small cell carcinoma, sarcomatoid carcinoma, and micropapillary carcinoma) or nonurothelial carcinoma (squamous cell carcinoma and adenocarcinoma). In this review, we focus on the implications of aberrant differentiation on the management of patients with bladder cancer. All of the variant histologies portend a worse prognosis than pure urothelial carcinoma. Although radical cystectomy remains the mainstay of treatment in all forms of bladder cancer, we highlight the use of neoadjuvant chemotherapy in patients with subtypes responsive to such therapy.

Sensitivity to epidermal growth factor receptor inhibitor requires E-cadherin expression in urothelial carcinoma cells.

PURPOSE: Epidermal growth factor receptor (EGFR) is an attractive target for the treatment of urothelial carcinoma, but a clinical response can be expected in only a small proportion of patients. The aim of this study was to define molecular markers of response to cetuximab therapy in a panel of urothelial carcinoma cell lines. EXPERIMENTAL DESIGN: Eleven cell lines were investigated for antiproliferative response to cetuximab based on [(3)H]thymidine incorporation. A variety of markers, including EGFR expression, phosphorylation, and gene amplification, as well as the expression of other growth factor receptors, their ligands, and markers of epithelial-to-mesenchymal transition were investigated. Cohen's kappa statistic was used to estimate the agreement between response and expression of these markers. E-cadherin was silenced by small interfering RNA in two sensitive cell lines, and the effect on the response to cetuximab was measured. RESULTS: We were able to identify a panel of relevant markers pertaining especially to alternate growth factor receptor expression and epithelial-to-mesenchymal transition that predicted response to cetuximab. The data suggested that expression of intact HER-4 (kappa, 1.00; P = 0.008), E-cadherin (kappa, 0.81; P = 0.015), and beta-catenin (kappa, 0.81; P = 0.015) and loss of expression of platelet-derived growth factor receptor beta (kappa, 0.57; P = 0.167) were associated with response to cetuximab therapy. Silencing E-cadherin in two sensitive cell lines reduced responsiveness to cetuximab in both (P < 0.001). CONCLUSIONS: A panel of predictive markers for cetuximab response has been established in vitro and is currently being evaluated in a prospective clinical trial of neoadjuvant EGFR-targeted therapy. Most importantly, E-cadherin seems to play a central role in modulation of EGFR response in urothelial carcinoma.

Is vascular endothelial growth factor modulation a predictor of the therapeutic efficacy of gefitinib for bladder cancer?

PURPOSE: The epidermal growth factor receptor inhibitor gefitinib (Iressa) is currently being studied in patients with bladder cancer and it has significant anti-angiogenic activity. We investigated the relationship between the modulation of vascular endothelial growth factor (Santa Cruz Biotechnology, Santa Cruz, California) expression and the biological efficacy of gefitinib for bladder cancer. MATERIALS AND METHODS: In vitro the 4 bladder cancer cell lines 253JB-V, UMUC-3, KU-7 and UMUC-13 were treated with gefitinib and vascular endothelial growth factor secretion was measured. The effects of gefitinib on vascular endothelial growth factor promoter, proliferation, cell cycle and downstream signals were evaluated. In vivo 253JB-V and UMUC-13 were injected into nude mice and tumors were treated with 2 mg gefitinib per day. Tumor kinetics were determined and the levels of phospho-epidermal growth factor receptor (Biosource), vascular endothelial growth factor, phospho-vascular endothelial growth factor (Cell Signaling Technology), angiogenesis and apoptosis were measured. RESULTS: Epidermal growth factor receptor (Neomarkers, Fremont, California) phosphorylation was blocked efficiently in all cell lines at concentrations of 0.5 microM or greater. Gefitinib (1 microM) induced an accumulation of cells in G0/G1 without apoptosis in 253J B-V cells, whereas it had no effect in other cell lines. Gefitinib inhibited vascular endothelial growth factor secretion in 253JB-V and UMUC-13 (concentration inhibiting a 50% response 0.5 and 0.1 microM, respectively) but not in UMUC-3 or KU-7. Gefitinib decreased vascular endothelial growth factor promoter activity in 253JB-V and UMUC-13 by 40% to 60%. In vivo the growth of 253JB-V tumors was significantly inhibited by gefitinib, whereas no effect was demonstrated in UMUC-13 tumors. Vascular endothelial growth factor expression and vascular endothelial growth factor receptor activation were significantly decreased in 253JB-V tumors and to a greater extent in resistant UMUC-13 tumors. Gefitinib inhibited angiogenesis and induced apoptosis in sensitive 253JB-V tumors only. CONCLUSIONS: Epidermal growth factor receptor blockade exerts an anti-angiogenic effect on bladder cancer cells, in part by modulating vascular endothelial growth factor expression. However, down-regulation of vascular endothelial growth factor expression is not sufficient to inhibit bladder cancer growth and it should not be used as a predictor of the therapeutic efficacy of gefitinib.

Prostatic urethral biopsy has limited usefulness in counseling patients regarding final urethral margin status during orthotopic neobladder reconstruction.

PURPOSE: We determined the value of preoperative transurethral prostatic urethral biopsy in predicting final distal urethral margin status at radical cystectomy. MATERIALS AND METHODS: Of 1,006 patients undergoing radical cystectomy at our institution between 1990 and 2004, 252 were men who underwent ileal neobladder and form the basis of this report. Variables collected include pathology of prostatic urethral biopsies, final pathology of the prostate, frozen section of the distal urethra, final urethral margins and survival data. RESULTS: Median patient age was 61 years. Data regarding preoperative transurethral resection prostatic urethral biopsy and/or frozen section of the urethra at the time of surgery were available for 245 of 252 patients (transurethral resection of the prostatic urethra alone in 127, urethral frozen section alone in 68 and both in 50). The incidence of positive distal urethral margin on final pathological examination was 1.1% (3 of 252) and urethral recurrence was 0.7% (2 of 252). The correlation between transurethral resection findings and frozen section margins was only 68%, and 16 patients with positive transurethral resection findings had negative frozen section margins. The negative predictive value of transurethral resection biopsy with respect to final margins was 99.4% and that of frozen section was 100%. CONCLUSIONS: While patients with no tumor on transurethral resection biopsy of the prostatic urethra have a high likelihood of negative urethral margins on final pathological evaluation, optimal negative predictive value is obtained with frozen sections. Furthermore, a positive transurethral resection prostatic urethral biopsy does not correlate with final margin and should not exclude patients from consideration for orthotopic diversion.

Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer.

PURPOSE: Expression of various members of the ErbB family (epidermal growth factor receptor/ErbB-1, ErbB-2, ErbB-3 and ErbB-4) is associated with disease stage and survival in patients with urothelial carcinoma. We examined the correlation of ErbB family receptor expression with the progression of urothelial carcinoma and survival. MATERIALS AND METHODS: A urothelial carcinoma tissue array was constructed from 248 archival paraffin blocks and quality control studies were ascertained. The tissue microarray was stained for epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4, and analyzed using an automated reader. Patient data included grade, stage, growth pattern, recurrence and survival. RESULTS: Kaplan-Meier estimates of 5-year overall and recurrence-free survival were 58% and 27%, respectively. Patients with high grade, invasive or nonpapillary disease had a worse prognosis than patients with low grade, superficial or papillary disease (p <0.0001). High epidermal growth factor receptor or low ErbB-4 expression was associated with nonpapillary, high grade and invasive tumors as well as with significantly shorter recurrence-free and overall survival (p <0.002, 0.028 and 0.047, respectively). Levels of ErbB-2 and ErbB-3 expression were not associated with overall or recurrence-free survival. CONCLUSIONS: The expression profiles of ErbB-4 and epidermal growth factor receptor are prognostic in urothelial carcinoma. They may help in selecting patients at high risk with bladder cancer for more aggressive therapy.

Differences in survival among patients with sarcomatoid carcinoma, carcinosarcoma and urothelial carcinoma of the bladder.

PURPOSE: Sarcomatoid carcinoma and carcinosarcoma of the bladder are rare tumors that contain epithelial and mesenchymal elements, and may portend a worse prognosis than conventional urothelial carcinoma. We investigated the survival of patients with the 2 tumor subtypes compared to survival in those with urothelial carcinoma. MATERIALS AND METHODS: Cases of sarcomatoid carcinoma, carcinosarcoma and high grade urothelial carcinoma of the bladder were identified from the Surveillance, Epidemiology and End Results Program. Demographic and pathological characteristics were compared. Differences in survival based on histological subtype were estimated using Kaplan-Meier analysis and multivariate Cox proportional hazards regression. RESULTS: Overall unadjusted survival rates for 46,515 patients with urothelial carcinoma, 135 with sarcomatoid carcinoma and 166 with carcinosarcoma were 77%, 54% and 48% at 1 year, and 47%, 37% and 17% at 5 years, respectively. Sarcomatoid carcinoma and carcinosarcoma presented at a similar age but at a higher T stage and with more frequent regional and distant metastases compared to urothelial carcinoma. On multivariate analysis patients with sarcomatoid carcinoma (HR 1.18, 95% CI 0.91-1.52) and carcinosarcoma (HR 2.00, 95% CI 1.65-2.41) were at higher risk for death compared to those with urothelial carcinoma. Overall mortality was worse with carcinosarcoma than with sarcomatoid carcinoma (HR 1.70, 95% CI 1.23-2.34). CONCLUSIONS: Compared to patients with urothelial carcinoma those with sarcomatoid carcinoma and carcinosarcoma present at a more advanced stage and are at greater risk for death even after adjusting for stage at presentation. The survival rate of sarcomatoid carcinoma is better than that of carcinosarcoma, offering some justification for the continued differentiation of these tumor types for clinical prognostication.

Pseudosarcomatous and sarcomatous proliferations of the bladder.

Pseudosarcomatous fibromyxoid tumor (PFT), postoperative spindle cell nodule (PSN), sarcoma, and sarcomatoid carcinoma of the bladder are frequently difficult to distinguish histopathologically with significant differences in disease-related outcomes. A retrospective review of our pathology registry over the last 25 years identified 7 PFT, 10 PSN, 18 primary bladder sarcomas, and 17 sarcomatoid carcinomas. Most patients with PFT, PSN, sarcoma, and sarcomatoid carcinoma were diagnosed between the ages of 50 to 60 years with PFT and PSN most commonly detected in women. A previous history of urological instrumentation and bladder cancer was present in all patients with PSN but none of the patients with PFT. Pseudosarcomatous fibromyxoid tumors were characterized by a tissue culture-like proliferation of myofibroblastic cells with focal atypia and overall cytoarchitectural features mimicking nodular fasciitis. Sarcomas and sarcomatoid carcinomas exhibited cellular atypia, mitotic activity with atypical mitosis, and the presence of necrosis. Transurethral resection was sufficient to control all PFT and PSN with no evidence of distant metastatic spread. In contrast, local recurrences and distant metastases frequently occurred in patients with primary sarcoma and sarcomatoid carcinoma despite aggressive surgical management, which was often combined with neoadjuvant chemotherapy (50% and 65% disease-specific mortality, respectively). Pseudosarcomatous fibromyxoid tumor and PSN have unique clinical and pathologic features that allow their distinction from primary bladder sarcoma and sarcomatoid carcinoma.

Laparoscopic partial nephrectomy: experience in 60 cases.

PURPOSE: To identify the factors associated with better outcomes in patients undergoing laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: We retrospectively analyzed the medical records of 36 men and 24 women aged 31 to 80 years (mean 60 years) in whom LPN was attempted at our institution over a 3.5-year period. Baseline patient characteristics and operative, pathologic, and postoperative outcomes were analyzed. The median duration of follow-up was 14.2 months (range 1-38 months). RESULTS: The median pathologic tumor size was 2.1 cm (range 0.7-6.0 cm). Final pathologic review revealed renal-cell carcinoma in 73% of patients. Six patients (10%) required conversion to either an open partial nephrectomy or a laparoscopic radical nephrectomy. Dense perinephric adipose tissue in the setting of a small renal tumor and unanticipated multifocal disease were factors associated with surgical conversion. The median overall estimated blood loss was 112 mL, and the median warm-ischemia time was 30 minutes. Blood loss was greater in patients who did not undergo hilar clamping (467 v 65 mL; P = 0.008). CONCLUSION: Factors influencing successful LPN outcomes include selecting a tumor commensurate with the surgeon's laparoscopic experience, performing routine hilar clamping, adjunctive use of hemostatic agents, and renal-parenchymal suture ligation. The presence of thick, fibrotic perinephric fat overlying a small tumor increases the technical difficulty.

Utilization of individualized prostate cancer and genomic biomarkers for the practicing urologist.

Prostate cancer encompasses a complex heterogeneous disease spectrum. Physicians and patients are faced with the ambiguity of who should be screened, biopsied, rebiopsied, treated, or provided with adjuvant therapy. Personalized outcomes and treatments are especially important given the varied nature of the disease, plethora of treatment options, risks of morbidity, and quality of life. Today's practicing urologist has a multitude of tests from which to choose, creating the difficult task of appropriate use. This review focuses on two blood-, one urine-, and five genomic-based tests, which, when used in the appropriate clinical setting, can facilitate the patient-physician decision-making process.

Barriers to accessing urethroplasty.

Urethroplasty is an effective treatment for men with anterior urethral strictures, but is utilized less frequently than ineffective treatments such as internal urethrotomy. We sought to identify provider-level barriers to urethroplasty. An anonymous online survey was emailed to all Mid-Atlantic American Urological Association members. Six scenarios in which urethroplasty was the most appropriate treatment were presented. Primary outcome was recommendation for urethroplasty in ≥ three clinical scenarios. Other factors measured include practice zip code, urethroplasty training, and proximity to a urethroplasty surgeon. Multivariate logistic regression identified factors associated with increased likelihood of urethroplasty recommendation. Of 670 members emailed, 109 (16%) completed the survey. Final analysis included 88 respondents. Mean years in practice was 17.2. Most respondents received formal training in urethroplasty: 43 (49%) in residency, 5 (6%) in fellowship, and 10 (11%) in both; 48 respondents (55%) had a urethroplasty surgeon in their practice, whereas 18 (20%) had a urethroplasty surgeon within 45 minutes of his or her primary practice location. The only covariate that was associated with an increased likelihood of recommending urethroplasty in ≥ three scenarios was formal urethroplasty training. Most members (68%) reported no barriers to referring patients for urethroplasty; the most common barriers cited were long distance to urethroplasty surgeon (n 5 13, 15%) and concern about complications (n 5 8, 9%). Urethroplasty continues to be underutilized in men with anterior urethral strictures, potentially due to lack of knowledge dissemination and access to a urethroplasty surgeon. Appropriate urethroplasty utilization may increase with greater exposure to urethroplasty in training.

Impact of the US Preventive Services Task Force Grade D Recommendation: Assessment of Evaluations for Elevated Prostate-specific Antigen and Prostate Biopsies in a Large Urology Group Practice Following Statement Revision.

On October 7, 2011, the United States Preventive Services Task Force (USPSTF) released their evidence statement and grade D recommendation against prostate-specific antigen (PSA)-based prostate cancer screening. Using a time series design, we assessed the effect of this recommendation upon evaluations for elevated PSA levels and prostate biopsies in our large urology group practice. We found that, despite a 24.1% increase in total visits, the 32 urologists in our practice completed 16.4% fewer evaluations for elevated PSA levels (317 fewer evaluations per month; P = .017) and 21.4% fewer prostate biopsies (42 fewer biopsies per month; P = .001) in the 2 years following the USPSTF grade D recommendation.

The Impact of a Biopsy Based 17-Gene Genomic Prostate Score on Treatment Recommendations in Men with Newly Diagnosed Clinically Prostate Cancer Who are Candidates for Active Surveillance.

INTRODUCTION: The biopsy based 17-gene GPS was clinically validated to predict the likelihood of adverse surgical pathology in men with NCCN® very low, low or low-intermediate risk prostate cancer. We performed a prospective study to assess the impact of incorporating GPS into treatment recommendations in 3 high volume urology practices. METHODS: Men with newly diagnosed prostate cancer meeting specific NCCN criteria were prospectively enrolled in the trial. Biopsy tissue was analyzed. Urologists indicated treatment recommendations on questionnaires administered before and after GPS. The primary study objectives were to assess all changes in treatment modality and/or treatment intensity after GPS. RESULTS: A total of 158 men were included in analysis, including 35, 71 and 52 at NCCN very low, low and low-intermediate risk. Biological risk predicted by GPS differed from NCCN clinical risk alone in 61 men (39%). Overall 18% of recommendations between active surveillance and immediate treatment changed after GPS. The relative increase in recommendations for active surveillance was 24% (absolute change 41% to 51%). In 41 of 158 men (26%) modality and/or intensity recommendations changed after GPS, including 25, 14 and 2 in whom recommendation intensity decreased, increased and were equivocal, respectively. All changes were directionally consistent with GPS. The NCCN low risk group showed the greatest absolute recommendation change after GPS (37%). In 17 of 57 men (30%) the initial recommendation of radical prostatectomy was changed to active surveillance after GPS. Urologists indicated greater confidence and found that incorporating GPS was useful in 85% and 79% of cases, respectively, including when biological risk confirmed the clinical risk category. CONCLUSIONS: This study demonstrates that the 17-gene GPS influenced treatment recommendations among urologists and provided increased confidence in these recommendations in patients at NCCN very low to low-intermediate risk.

A current review of medical therapy for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common diseases of aging men. It is estimated that by age 60 years, greater than 50% of men will have histologically documented evidence of the disease. Therapy for this disease has evolved considerably from its inception. Recent data from long-term population-based studies have shed new light on the treatment of this common problem in aging men. The authors review the current state of diagnosis of BPH and medical therapy for this condition in the primary care setting.