Michael Kearney

Prevalence of TMPRSS2-ERG Fusion Prostate Cancer among Men Undergoing Prostate Biopsy in the United States

Purpose: Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen–screened men undergoing prostate biopsy in the United States. Experimental Design: We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable. Results:ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion–positive prostate cancer biopsies than gene fusion–negative prostate cancer biopsies (P ≤ 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02). Conclusions: This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.

Buccal Mucosa Grafts for Hypospadias surgery: Long-term Results

PURPOSE We review the long-term results of buccal mucosa grafts used as part of secondary hypospadias repair. MATERIALS AND METHODS We evaluated 47 patients for 10 years and analyzed long-term results of buccal mucosa grafts for hypospadias repair. Of the 47 patients 40 have been followed for more than 3 years. RESULTS The overall complication rate was 32% (13 of 47 cases). All complications occurred in the first 6 months following surgery, and the complication rate was significantly lower in the last 7 years of the series (19%) compared to the first 3 years (60%) (p = 0.01). All 3 patients in this series with a preoperative diagnosis of balanitis xerotica obliterans had a significant postoperative complication. CONCLUSIONS Buccal mucosa appears to be a durable source of nongenital tissue for urethral replacement. Attention to detail in terms of graft harvest, graft preparation and graft fixation helps to avoid major postoperative complications. Onlay grafts appear to be preferable to tube grafts, and patients with the diagnosis of balanitis xerotica obliterans would appear not to be candidates for 1-stage urethral reconstruction using buccal mucosa.

Interactive spaced education to assess and improve knowledge of clinical practice guidelines: a randomized controlled trial.

Objective:To determine whether Interactive Spaced Education (ISE) is an effective and acceptable form of graduate and continuing medical education (GME/CME), using clinical practice guideline (CPG) education as an experimental system. Summary Background Data:ISE is a novel form of online education, which combines the pedagogical merits of the spacing and testing effects. Its efficacy for GME and CME is not known. Methods:One-hundred sixty urologists and 320 urology residents were randomized to 1 of 2 cohorts. We developed and validated 48 ISE items (questions and answers) on 5 urology CPGs (hematuria and priapism [HP]; staghorn calculi, infertility, and antibiotic use [SIA]). Physicians were sent 3 emails a week, each containing 2 questions. Content was repeated 3 times over 20 weeks. Cohort A physicians received the 3-cycle ISE course on HP, with 24 control items on SIA in cycle 3. Cohort B physicians received the 3-cycle ISE course on SIA, with 24 control items on HP in cycle 3. Results:The ISE program was completed by 71% urologists and 83% residents. Cohort A scores on HP increased from mean 44.9% in cycle 1% to 75.7% in cycle 3, a 57% relative increase compared with controls (P < 0.001; Cohen effect size, 2.2). Similarly, cohort B scores on SIA increased from 45.2% in cycle 1% to 69.5% in cycle 3, a 56% relative increase compared with controls (P < 0.001; effect size, 2.2). Eighty-four percent of all participants requested to enroll in further ISE programs. Conclusions:ISE is an effective and well-accepted form of GME and CME and is a promising new methodology to improve CPG knowledge.

Validation in a multiple urology practice cohort of the prostate cancer prevention trial calculator for predicting prostate cancer detection.

PURPOSE The Prostate Cancer Prevention Trial prostate cancer risk calculator was developed in a clinical trial cohort that does not represent men routinely referred for prostate biopsy. We assessed the generalizability of the Prostate Cancer Prevention Trial calculator in a cohort more representative of patients referred for consideration of prostate biopsy in American urology practice. MATERIALS AND METHODS Patients undergoing prostate biopsy by 12 urologists at 5 sites were enrolled in an Early Detection Research Network cohort. The Prostate Cancer Prevention Trial risk calculator was validated by examining area underneath the receiver operating characteristic curve, sensitivity, specificity and calibration comparing observed vs predicted risk of prostate cancer detection. RESULTS Cancer incidence was greater (43% vs 22%, p = 0.001) in the Early Detection Research Network validation cohort (645) compared to the Prostate Cancer Prevention Trial group (5,519). Early Detection Research Network participants were younger and more racially diverse, and had more abnormal digital rectal examinations and higher prostate specific antigen than Prostate Cancer Prevention Trial participants (all p <0.001). Cancer severity was worse in the Early Detection Research Network cohort than in the Prostate Cancer Prevention Trial (Gleason 7 or higher 60% vs 21%, p <0.001). Nevertheless, the Prostate Cancer Prevention Trial risk calculator was superior to prostate specific antigen alone for predicting cancer in the Early Detection Research Network (AUC 0.691 vs 0.655, p = 0.009) and calibration confirmed that the Prostate Cancer Prevention Trial risk score accurately predicted individual risks in the Early Detection Research Network cohort. CONCLUSIONS Differences between the Early Detection Research Network validation cohort and the Prostate Cancer Prevention Trial cohort underscore the importance of validating calculator performance in the multicenter urology practice setting. Our findings extend the applicability of the Prostate Cancer Prevention Trial calculator for measuring the risk of prostate cancer detection on biopsy to the routine American urology practice setting.

CLINICAL PREDICTORS IN THE USE OF FINASTERIDE FOR CONTROL OF GROSS HEMATURIA DUE TO BENIGN PROSTATIC HYPERPLASIA

PURPOSE We identify predictors of clinical response as well as response time in patients treated with finasteride for gross hematuria due to benign prostatic hyperplasia. MATERIALS AND METHODS A retrospective chart review was preformed of 53 patients who had been given 5 mg. finasteride daily for the treatment of active bleeding or a recent history of recurrent bleeding. Urological evaluations were negative for tumor in all patients. A history of prostatectomy, anticoagulant status and prostate size was determined. The degree of hematuria was then graded before and after finasteride treatment according to our previously described system. Of the 53 patients who were actively bleeding at initial evaluation 16 were followed to determine time required for complete resolution of hematuria. RESULTS Hematuria grade improved after finasteride in 50 (94%) patients. Overall 77% of patients (41 of 53) experienced no further bleeding while taking finasteride. Mean followup was 38 months (range 3 to 86). Of the patients 86% (12 of 14) taking coumadin, 77% (10 of 13) taking aspirin and 73% (19 of 26) on no anticoagulants had no further bleeding once on finasteride. Of the patients who had undergone prior transurethral prostatectomy 84% (26 of 31) experienced no further bleeding versus 68% (15 of 22) of those who had not undergone previous surgery. In the 16 patients who began finasteride while actively bleeding the average time to clear urine was 12 days (range 2 to 45). Prostatic volume correlated with the average time needed for resolution of hematuria, which was 2.7 days or longer for small (less than 40 gm.), 10.3 days or longer for large (40 to 100), 19 days or longer for extra large (100 to 150) and 45 days or longer for extra extra large (greater than 150) glands. Hematuria resolved an average of 5.5 days versus 18.6 days in those who had or had not undergone previous prostatectomy, respectively. CONCLUSIONS Our long-term followup demonstrates finasteride as a useful treatment for benign prostatic hyperplasia related gross hematuria, which is effective in patients who are on anticoagulants. In patients with larger prostatic volumes a longer time to response and higher incidence of recurrent but lower grade bleeding should be anticipated compared to those who have undergone prior prostatectomy or have a smaller prostate.

Epigenetic risk score improves prostate cancer risk assessment

Early detection of aggressive prostate cancer (PCa) remains crucial for effective treatment of patients. However, PCa screening remains controversial due to a high rate of overdiagnosis and overtreatment. To better reconcile both objectives, more effective methods for assessing disease severity at the time of diagnosis are needed.