Evaluation of an epigenetic assay for predicting repeat prostate biopsy outcome in African American men

OBJECTIVE: To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. MATERIALS AND METHODS: The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). RESULTS: Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) = 7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS >= 7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS >= 7 PCa were 78.8% and 94.2%, respectively. CONCLUSION: In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy

Neoadjuvant Clinical Trial With Sorafenib for Patients With Stage II or Higher Renal Cell Carcinoma

The multitargeted tyrosine kinase inhibitor sorafenib is used for the treatment of advanced-stage renal cell carcinoma. However, the safety and efficacy of this agent have yet to be evaluated in the preoperative period, where there may be potential advantages including tumor downstaging. This prospective trial evaluates the safety and feasibility of sorafenib in the preoperative setting

Management of female stress urinary incontinence with single-incision mini-sling (Altis®): 36 month multicenter outcomes.

PURPOSE: To assess noninferiority of the safety and effectiveness of the Altis® Single Incision Sling (SIS) with standard midurethral transobturator and/or retropubic slings through 36 months in a prospective, longitudinal, nonrandomized US Food and Drug Administration (FDA) 522 cohort study. MATERIALS AND METHODS: Adult females with confirmed predominant stress urinary incontinence (UI) through cough stress test (CST) or urodynamics and failed two noninvasive incontinence therapies. Effectiveness endpoints included objective dryness, negative CST, adverse events, and revision/resurgery through 36 months. The primary effectiveness endpoint was reduction from baseline in 24-h pad weight of ≥50% at 6 months, as requested by the FDA, and is included as a study point in this paper. Primary safety endpoint was rate of related serious adverse events (SAE) through 36 months. Noninferiority margins of 15% and 10% were prespecified for the effectiveness and safety endpoints. Due to the observational nature of the cohort study, a propensity methodology was conducted to assess the effect of potential confounding variables on the primary endpoints between groups. RESULTS: Three hundred fifty-five women underwent the sling procedure (n = 184 Altis; n = 171 Comparator). One hundred fourty (76%) Altis subjects and 101 (59%) Comparator subjects completed follow-up through 36 months. At 36 months, for the effectiveness endpoint, the difference in proportions of -0.005 for Altis versus Comparator (95% confidence interval [CI]: -0.102 to 0.092) was statistically significant (p = 0.002), supporting the hypothesis that Altis is noninferior to Comparator. Furthermore, both groups demonstrated high objective efficacy; in the Altis arm n = 99 (81.8%) subjects were a success, and in the Comparator arm, n = 79 (82.3%) subjects were a success. Additionally, regarding the CST, Altis was found to be noninferior to the Comparator at every study visit, and the rate of negative CST remained above 80% for both groups (p \u3c 0.001). At 36 months, Altis (n = 2; 1.1%) and Comparator (n = 4; 2.3%) subjects experienced a device and/or procedure-related SAE. The difference in proportions of 0.013 for Altis versus Comparator (95% CI: -0.023 to 0.048) was statistically significant (p \u3c 0.001), demonstrating that Altis is noninferior to Comparator with respect to the primary safety endpoint throughout the study. There were 62 (36.3%) retropubic midurethral slings (RMUS), 96 (56.1%) transobturator midurethral slings (TMUS), and 13 (7.6%) SIS slings in the Comparator group. For the 36 month effectiveness endpoint, assessing the noninferiority of Altis versus RMUS and Altis versus TMUS, 99 (81.8%) Altis and 37 (90.2%) RMUS were a success, trending toward statistical significance, however, it cannot be determined to be noninferior (p = 0.092). Ninty-nine (81.8%) Altis and 33 (71.7%) TMUS were a success; this was statistically significant (p \u3c 0.001), demonstrating Altis was noninferior to TMUS. Rates of negative CST were 122 (87.1%) Altis, 40 (93.0%) RMUS (p \u3c 0.001), and 44 (91.7%) TMUS (p \u3c 0.001). CST demonstrated that Altis was noninferior to RMUS and Altis was noninferior to TMUS at 36 months. CONCLUSION: Altis single-incision sling was noninferior to standard midurethral sling for treatment of stress UI, throughout the study and at 36 months. Furthermore, adverse event rates were low