Prostate cancer grade downgrading at time of prostatectomy provides risk-stratification insight into future tumor behavior after prostatectomy.

BACKGROUND: Prostate biopsy (Bx) sampling-based diagnosis of prostate cancer (PCa) has well-described inaccuracy when compared against whole gland analysis upon prostatectomy. Although upgrading of PCa Grade Group (GG) is often described, the occurrence and prognostic implications of downgrading PCa GG at the time of radical prostatectomy (RP) is less understood. Our objective was to evaluate whether downgrading PCa GG at the time of RP was associated with future tumor behavior. METHODS: The SEER database was searched from 2010 to 2017 and patients were included if they were assigned pathological grades on both Bx and RP specimen. Patients were stratified into Bx GG > RP GG and Bx GG ≤ RP GG groups, and tumor behavior after treatment was examined. Cox regression was used for the survival analysis. RESULTS: Here, 99,835 patients were included in this study. A total of 18,516 (18.5%) patients encountered downgrading from Bx GG to RP GG. A downgrading of 1 grade occurred in 13,969 (75.4%) of these patients and of 2 or more grades occurred in 4547 (24.6%) patients. A history of higher Bx GG compared with RP GG increased the risk of cancer-specific mortality (CSM) for each given RP GG controlling for age, race, preop prostate-specific antigen level, percentage of positive biopsy cores, and pathologic TNM stages. Specifically, a history of high Bx GG conferred a 45% increased risk of CSM for any given RP GG (hazard ratio = 1.45 95% confidence interval = 1.16-1.82, p < 0.001). CONCLUSION: A history of higher Bx GG, and hence downgrading at the time of RP, demonstrates some value as a risk-stratification tool for future cancer outcomes after prostatectomy.

Surgery associated with increased survival compared to radiation in clinically localized Gleason 9-10 prostate cancer: a SEER analysis.

PURPOSE: Men with Gleason score 9-10 prostate cancer have worse outcomes compared to those with Gleason 8 disease. Upfront treatments remain controversial for these patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, we evaluated the impact of initial treatment with external beam radiation therapy (EBRT), external beam radiation therapy with brachytherapy (EBRT + BT), or surgery on prostate cancer-specific mortality (PCSM) and overall mortality (OM) in Gleason 9-10 disease. METHODS: The SEER database was queried for men diagnosed with biopsy Gleason 9-10 prostate cancer from 2005 to 2014. Gathered data included demographic, pathologic, therapy received, and survival outcomes. Kaplan-Meier survival curves and crude and multivariate analyses were generated for initial therapy with EBRT, EBRT + BT, or surgery. RESULTS: A total of 7877 men were included, 4465 (56.7%) who underwent upfront treatment with EBRT alone, 623 (7.9%) with EBRT + BT, and 2789 (35.4%) with surgery. The 7 year PCSM rates were 29.2, 15.0, and 14.6% for EBRT, EBRT + BT, and surgery respectively (p < 0.001). The 7 year OM rates were 43.8, 27.2, and 20.0% for EBRT, EBRT + BT, and surgery, respectively (p < 0.001).When controlling for age, year of diagnosis, Gleason score, clinical T stage, and PSA level on multivariate analysis, EBRT had greater PCSM and OM than surgery (HR 0.41, 95% CI 0.28-0.61, p < 0.001 and HR 0.44, 95% CI 0.34-0.57, p < 0.001 respectively), but the mortality differences was not statistically significant between EBRT and EBRT + BT. CONCLUSION: Among men with localized Gleason 9-10 disease, surgery was associated with statistically significant improved survival outcomes compared to EBRT alone.

Race as a predictor of pathologic response to neoadjuvant chemotherapy at time of cystectomy for bladder cancer.

INTRODUCTION Complete pathologic response (pT0) at time of cystectomy after neoadjuvant chemotherapy (NAC) has been associated with significantly improved clinical outcomes. The goal of this study is to examine whether race is a predictor of pT0 response to NAC at time of cystectomy. MATERIALS AND METHODS: We analyzed the records of patients diagnosed with a non-metastatic (M0) muscle-invasive (cT2+) urothelial cell bladder cancer in the National Cancer Database (NCDB) who underwent a cystectomy from 2006 to 2014. The cohort was stratified by whether the patient received NAC prior to cystectomy. Univariate and multivariate logistic regression models were used to assess for the effect of race on pathologic complete response after NAC. RESULTS: We identified 16,036 patients of which 3,195 patients (19.9 %) were treated with NAC prior to cystectomy. The total number of African American (AA) patients in this study was 848 (5.3 %). Compared to Caucasian patients receiving NAC, AA patients had a greater proportion of females and had lower income and education. The rate of pT0 in the surgery only group was 2.7% compared to 15.0% (p < 0.001) for patients treated with NAC. On multivariate analysis, patients of AA race that received NAC were less likely to achieve pT0 (OR = 0.55, 95% CI: 0.31-0.98, p = 0.04) when controlling for age, sex, co-morbidities income, education and timing of cystectomy after starting NAC. CONCLUSIONS: Our results suggest that African American patients are less likely to achieve pathologic complete response to NAC prior to cystectomy.

Evaluation of Cancer Specific Mortality with Surgery versus Radiation as Primary Therapy for Localized High Grade Prostate Cancer in Men Younger Than 60 Years.

PURPOSE: The optimal primary treatment of localized high grade prostate cancer in younger men remains controversial. The objective of this project was to compare the impact of initial radical prostatectomy vs radiation therapy on survival outcomes in young men less than 60 years old with high grade prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed the records of men younger than 60 years in the SEER (Surveillance, Epidemiology and End Results) database who underwent initial surgery or radiation therapy of high grade (Gleason score 8 or greater) localized (N0M0 TNM stage) prostate cancer from 2004 to 2012. Univariate and multivariate Cox proportional hazards regression models were used to examine prostate cancer specific and overall mortality. RESULTS: A total of 2,228 men were identified, of whom 1,459 (65.5%) underwent initial surgery and had a median followup of 43 months and 769 (34.5%) underwent initial external beam radiation therapy with or without brachytherapy and had a median followup of 44 months. On multivariate analysis initial treatment with surgery was associated with improved prostate cancer specific and overall mortality compared with initial radiation treatment (HR 0.37, 95% CI 0.19-0.74, p = 0.005 vs HR 0.41, 95% CI 0.24-0.70, p = 0.001) when controlling for age, biopsy Gleason score, T stage and prostate specific antigen. CONCLUSIONS: Our data showed significant survival differences in young men treated initially with surgery vs external beam radiation therapy of high grade prostate cancer. Future prospective randomized trials are needed to confirm the long-term outcomes of these treatment approaches.

Can Women Facilitate Men's Prostate Cancer Screening Informed Decision-Making? The M-PACT Trial.

The M-PACT study compared an all-male with a mixed-sex intervention to increase informed decision-making for prostate cancer screening among African-American men in church settings. We recruited 262 men in 18 churches randomized to the two intervention approaches. Trained and certified lay peer community health advisors in each church led a series of four men's health workshops on informed decision-making for prostate cancer screening. African-American male workshop participants completed baseline, post-workshop, and 12-month follow-up surveys. Contrary to our expectations, including women in the workshops did not result in increased intervention efficacy for the informed decision-making outcomes as both groups showed significant improvement over time in several study outcomes including stage of decision-making for prostate cancer screening, preference for role in decision-making, prostate cancer knowledge, and self-reports of prostate specific antigen testing. Finally, men who attended multiple workshops had better informed decision-making outcomes on several indicators. The current findings suggest mixed results from including women in this men's health educational intervention. Future work should consider optimal ways of providing family support for African-American men's health promotion.

Recruitment and Participation of African American Men in Church-Based Health Promotion Workshops.

Health promotion interventions in African American communities are frequently delivered in church settings. The Men's Prostate Awareness Church Training (M-PACT) intervention aimed to increase informed decision making for prostate cancer screening among African American men through their churches. Given the significant proportion and role of women in African American churches, the M-PACT study examined whether including women in the intervention approach would have an effect on study outcomes compared with a men-only approach. The current analysis discusses the men's participation rates in the M-PACT intervention, which consisted of a series of 4 bimonthly men's health workshops in 18 African American churches. Data suggest that once enrolled, retention rates for men ranged from 62 to 69 % over the workshop series. Among the men who were encouraged to invite women in their lives (e.g., wife/partner, sister, daughter, friend) to the workshops with them, less than half did so (46 %), suggesting under-implementation of this "health partner" approach. Finally, men's participation in the mixed-sex workshops were half the rate as compared to the men-only workshops. We describe recruitment techniques, lessons learned, and possible reasons for the observed study group differences in participation, in order to inform future interventions to reach men of color with health information.

Informed Decision-Making and Satisfaction with a Church-Based Men's Health Workshop Series for African-American Men: Men-Only vs. Mixed-Gender Format.

Prostate cancer incidence and mortality are highest among African-American men, and coupled with the controversy around routine prostate cancer screening, reaching African-American men with interventions to help them make an informed decision about whether or not to be screened is critical. This study compares two approaches to delivering a church-based peer community health advisor intervention consisting of a series of four men's health workshops on informed decision-making for prostate cancer screening. In the men-only group, male community health advisors teach group workshops consisting only of men. In the health partner group, male-female pairs of community health advisors teach workshops in a mixed-gender format in which enrolled men are asked to invite a significant woman in their lives (e.g., wife/partner, sister, daughter, friend) with them to the workshops. Eighteen African-American churches were randomized to receive one of the two approaches, and 283 eligible men enrolled in the intervention. Main findings suggested that the workshops had an impact on stage of decision-making, and this increased significantly over time in the health partner group only. The intervention was highly rated by men in both groups, and these ratings increased over time, with some study group differences. Within-workshop study group differences favored the health partner group in some instances; however, men in the men-only groups reported greater increases in their ratings of trust in the workshops over time. The health partner intervention strategy appears to be promising for reaching men of color with health information.

MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer.

We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3'-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility.

Diagnostic Performance of Prostate-specific Antigen Density for Detecting Clinically Significant Prostate Cancer in the Era of Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

CONTEXT: There has been a dramatic increase in the use of prostate magnetic resonance imaging (MRI) in the diagnostic workup. With prostate volume calculated from MRI, prostate-specific antigen density (PSAD) now is a ready-to-use parameter for prostate cancer (PCa) risk stratification before prostate biopsy, especially among patients with negative MRI or equivocal lesions. OBJECTIVE: In this review, we aimed to evaluate the diagnostic performance of PSAD for clinically significant prostate cancer (CSPCa) among patients who received MRI before prostate biopsy. EVIDENCE ACQUISITION: Two investigators performed a systematic review according of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Studies (published between January 1, 2012, and December 31, 2021) reporting the diagnostic performance (outcomes) of PSAD (intervention) for CSPCa among men who received prebiopsy prostate MRI and subsequent prostate biopsy (patients), using biopsy pathology as the gold standard (comparison), were eligible for inclusion. EVIDENCE SYNTHESIS: A total of 1536 papers were identified in PubMed, Scopus, and Embase. Of these, 248 studies were reviewed in detail and 39 were qualified. The pooled sensitivity (SENS) and specificity (SPEC) for diagnosing CSPCa among patients with positive MRI were, respectively, 0.87 and 0.35 for PSAD of 0.1 ng/ml/ml, 0.74 and 0.61 for PSAD of 0.15 ng/ml/ml, and 0.51 and 0.81 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC for diagnosing CSPCa among patients with negative MRI were, respectively, 0.85 and 0.36 for PSAD of 0.1 ng/ml/ml, 0.60 and 0.66 for PSAD of 0.15 ng/ml/ml, and 0.33 and 0.84 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC among patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 or Likert 3 lesions were, respectively, 0.87 and 0.39 for PSAD of 0.1 ng/ml/ml, 0.61 and 0.69 for PSAD of 0.15 ng/ml/ml, and 0.42 and 0.82 for PSAD of 0.2 ng/ml/ml. The post-test probability for CSPCa among patients with negative MRI was 6% if PSAD was <0.15 ng/ml/ml and dropped to 4% if PSAD was <0.10 ng/ml/ml. CONCLUSIONS: In this systematic review, we quantitatively evaluated the diagnosis performance of PSAD for CSPCa in combination with prostate MRI. It demonstrated a complementary performance and predictive value, especially among patients with negative MRI and PI-RADS 3 or Likert 3 lesions. Integration of PSAD into decision-making for prostate biopsy may facilitate improved risk-adjusted care. PATIENT SUMMARY: Prostate-specific antigen density is a ready-to-use parameter in the era of increased magnetic resonance imaging (MRI) use in clinically significant prostate cancer (CSPCa) diagnosis. Findings suggest that the chance of having CSPCa was very low (4% or 6% for those with negative prebiopsy MRI or Prostate Imaging Reporting and Data System (Likert) score 3 lesion, respectively, if the PSAD was <0.10 ng/ml/ml), which may lower the need for biopsy in these patients.

Development of the men's prostate awareness church training: church-based workshops for African American men.

This article describes the development of a spiritually based intervention to increase informed decision making for prostate cancer screening through African American churches. The intervention used spiritually themed health messages, incorporated women as supportive health partners, and included a health information technology component. The Men's Prostate Awareness Church Training Project followed a community-based participatory research process to develop educational materials, and training for 40 community health advisors to implement the 4-part prostate health workshop series that will be implemented in 20 churches. Implications are discussed for designing culturally relevant interventions to reduce prostate cancer disparities impacting African American men.

Learning curve for magnetic resonance imaging/ultrasound fusion prostate biopsy in detecting prostate cancer using cumulative sum analysis.

Background: Targeted magnetic resonance (MR) with ultrasound (US) fusion-guided biopsy has been shown to improve detection of prostate cancer. The implementation of this approach requires integration of skills from radiologists and urologists. Objective methods for assessment of learning curves, such as cumulative sum (CUSUM) analysis, may be helpful in identifying the presence and duration of a learning curve. The aim of this study is to determine the learning curve for MR/US fusion-guided biopsy in detecting clinically significant prostate cancer using CUSUM analysis. Materials and methods: Retrospective analysis was performed in this institutional review board-approved study. Two urologists implemented an MR/US fusion-guided prostate biopsy program between March 2015 and September 2017. The primary outcome measure was cancer detection rate (CDR) stratified by Prostate Imaging Reporting and Data System (PI-RADS) scores assigned on the MR imaging. Cumulative sum analysis quantified actual cancer detection versus a predetermined target satisfactory CDR of MR/US fusion biopsies in a sequential case-by-case basis. For this analysis, satisfactory performance was defined as >80% CDR in patients with PI-RADS 5, >50% in PI-RADS 4, and <20% in PI-RADS 1-3. Results: Complete data were available for MR/US fusion-guided biopsies performed on 107 patients. The CUSUM learning curve analysis demonstrated intermittent underperformance until approximately 50 cases. After this inflection point, there was consistently good performance, evidence that no further learning curve was being encountered. Conclusions: At a new center implementing MR/US fusion-guided prostate biopsy, the learning curve was approximately 50 cases before a consistently high performance for prostate cancer detection.

PSA density is complementary to prostate MP-MRI PI-RADS scoring system for risk stratification of clinically significant prostate cancer.

BACKGROUND: While prostate multiparametric-magnetic resonance imaging (MP-MRI) has improved the diagnosis of clinically significant prostate cancer (CSPC), the complementary use of prostate-specific antigen (PSA) levels to risk-stratify for CSPC requires further study. The objective of this project was to determine if prostate MP-MRI and PSA can provide complementary insights into CSPC risk stratification. METHODS: In an IRB-approved study, pathologic outcomes from patients who underwent MR/US fusion-targeted prostate biopsy were stratified by various parameters including PSA, PSA density (PSAD), age, race, and PI-RADS v2 score. CSPC was defined as a Gleason score ≥7. Logistic regression was used to determine odds ratios (OR) with 95% confidence intervals (CI). P values were reported as two-sided with p < 0.05 considered statistically significant. ROC curves were generated for assessing the predictive value of tests and sensitivity + specificity optimization was performed to determine optimal testing cutoffs. RESULTS: A total of 327 patients with 709 lesions total were analyzed. PSAD and PI-RADS scores provided complementary predictive value for diagnosis of CSPC (AUC PSAD: 0.67, PI-RADS: 0.72, combined: 0.78, p < 0.001). When controlling for PI-RADS score, age, and race, multivariate analysis showed that PSAD was independently associated with CSPC (OR 1.03 per 0.01 PSAD increase, 95% CI 1.02-105, p < 0.001). The optimal cutoff of PSAD ≥ 0.1 ng/ml/cc shows that a high versus low PSAD was roughly equivalent to an increase in 1 in PI-RADS score for the presence of CSPC (4% of PI-RADS ≤3 PSAD low, 6% of PI-RADS 3 PSAD high vs. 5% of PI-RADS 4 PSAD low, 22% of PI-RADS 4 PSAD high vs. 29% of PI-RADS 5 PSAD low, 46% of PI-RADS 5 PSAD high were found to have CSPC). CONCLUSIONS: PSAD with a cutoff of 0.1 ng/ml/cc appears to be a useful marker that can stratify the risk of CSPC in a complementary manner to prostate MP-MRI.

Racial Analysis of Clinical and Biochemical Outcomes in Patients With Prostate Cancer Treated With Low-Dose-Rate Brachytherapy.

PURPOSE: Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa. METHODS: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure. RESULTS: One hundred and sixty-seven patients were included in the analysis (Black: n = 81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P = .011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = .114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P = .42). Overall survival was comparable between racial groups (P = .972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001). CONCLUSIONS: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes.

Associations between improvements in lower urinary tract symptoms and sleep disturbance over time in the CAMUS trial.

PURPOSE: We recently reported an association between the bother and severity of lower urinary tract symptoms secondary to benign prostatic hyperplasia and the severity of sleep disturbance. However, few studies have examined whether alterations in the severity of urinary symptoms influence the degree of sleep problems over time. MATERIALS AND METHODS: The severity of lower urinary tract symptoms in men enrolled in CAMUS (Complementary and Alternative Medicine for Urological Symptoms), a clinical trial of saw palmetto (Serenoa repens), was evaluated using AUASI (American Urological Association symptom index) and quality of life scores. Sleep disturbance was evaluated by the Jenkins sleep scale at 0, 24, 48 and 72 weeks. Statistical analyses were used to assess the relationship(s) between changes in lower urinary tract symptoms and sleep disturbance. RESULTS: The baseline characteristics of the 339 men (172 placebo arm and 167 saw palmetto arm) enrolled in the CAMUS trial with assessment of sleep disturbance and urinary symptoms were similar. There were no differences between improvements in the severity of sleep disturbance or urinary symptoms between the 2 experimental arms. Combined analyses of the entire cohort revealed significant associations (p <0.001) between the AUASI score and sleep disturbance severity with time. Multivariate analyses demonstrated that improvements in lower urinary tract symptoms other than nocturia were the most significant predictors of improvements in sleep disturbance. Specific analyses adjusting for other baseline characteristics demonstrated that a 3-point improvement in AUASI score was associated with a 0.73-point improvement in the Jenkins sleep scale with time. CONCLUSIONS: Improvements in lower urinary tract symptoms correlate with changes in sleeping abilities with time in men with benign prostatic hyperplasia. While nocturia is significantly associated with sleep disturbance, other changes in overall lower urinary tract symptoms are better predictors of changes in sleep dysfunction.

Validation of an MRI-based prostate cancer prebiopsy Gleason score predictive nomogram.

Background: Gleason score grading is a cornerstone of risk stratification and management of patients with prostate cancer (PCa). In this work, we derive and validate a nomogram that uses prostate multiparametric magnetic resonance imaging (MP-MRI) and clinical patient characteristics to predict biopsy Gleason scores (bGS). Materials and methods: A predictive nomogram was derived from 143 men who underwent MP-MRI prior to any prostate biopsy and then validated on an independent cohort of 235 men from a different institution who underwent MP-MRI for PCa workup. Screen positive lesions were defined as lesions positive on T2W and DWI sequences on MP-MRI. Prostate specific antigen (PSA) density, number of screen positive lesions, and MRI suspicion were associated with PCa Gleason score on biopsy and were used to generate a predictive nomogram. The independent cohort was tested on the nomogram and the most likely bGS was noted. Results: The mean PSA in the validation cohort was 9.25ng/mL versus 6.8ng/mL in the original cohort (p = 0.001). The distribution of Gleason scores between the 2 cohorts were not significantly different (p = 0.7). In the original cohort of men, the most probable nomogram generated Gleason score agreed with actual pathologic bGS findings in 61% of the men. In the validation cohort, the most likely nomogram predicted bGS agreed with actual pathologic bGS 51% of the time. The nomogram correctly identified any PCa versus non-PCa 63% of the time and clinically significant (Gleason score ≥ 7) PCa 69% of the time. The negative predictive value for clinically significant PCa using this prebiopsy nomogram was 74% in the validation group. Conclusions: A preintervention nomogram based on PSA and MRI findings can help narrow down the likely pathologic finding on biopsy. Validation of the nomogram demonstrated a significant ability to correctly identify the most likely bGS. This feasibility study demonstrates the potential of a prebiopsy prediction of bGS and based on the high negative predictive value, identification of men who may not need biopsies, which could impact future risk stratification for PCa.

The relationship between lower urinary tract symptom severity and sleep disturbance in the CAMUS trial.

PURPOSE: Bothersome lower urinary tract symptoms, including nocturia, significantly impact general health related quality of life in men, as does sleep disturbance. However, few groups have examined the relationship between urinary symptom severity and sleep disturbance. MATERIALS AND METHODS: Men enrolled in a clinical trial of saw palmetto (Serenoa repens) were studied at baseline. Lower urinary tract symptom severity, as determined by the American Urological Association symptom index and quality of life scores, and the degree of sleep disturbance were determined by the Jenkins sleep scale. Analysis was done, adjusting for baseline characteristics, to identify predictors of severe sleep disturbance. RESULTS: A total of 366 men with a mean ± SD age of 60.9 ± 8.3 years who had moderate-severe lower urinary tract symptoms (mean American Urological Association symptom index score 14.58 ± 4.6 points) and a mean Jenkins sleep score of 7.3 ± 4.7 points were included in analysis. Overall there were significant associations between the American Urological Association symptom index score and sleep disturbance severity. Multivariate analysis revealed that obstructive and irritative symptoms were significantly associated with severe sleep disturbance. Further analysis showed that lower serum prostate specific antigen and post-void residual urine volume were also significantly associated with the degree of sleep disturbance. CONCLUSIONS: Lower urinary tract symptom severity is a risk factor for severe sleep disturbance in men. While nocturia was significantly associated with sleep disturbance, other lower urinary tract symptoms were also independent predictors of sleep dysfunction.

Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial.

CONTEXT: Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). OBJECTIVE: To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. INTERVENTIONS: One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. MAIN OUTCOME MEASURES: Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. RESULTS: Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -1.36) [corrected]with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. CONCLUSION: Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603304.

Video-Based Coaching as an Educational Platform for Urological Residency Training: A Pilot Study.

INTRODUCTION: Surgical experience requires skills traditionally taught through real-time operating room education and a variety of supplemental educational strategies. Video-based coaching is a modality that may offer potential advantages of immediate, direct and targeted feedback. The objective of this study was to demonstrate and evaluate the utility and educational value of video-based coaching in urology by conducting a qualitative analysis with a coding schema. METHODS: Residents and attendings were recorded operating during randomly selected cases in the operating room. Video-based coaching sessions were held during urology grand rounds and required residents to describe a selected portion of the operating room video and attendings to provide teaching points. Audio recordings from the operating room and video-based coaching sessions were reviewed by 2 independent coders. A coding scale classifying surgical educational goals into 5 categories (information, operative technique, questioning, response to resident interaction and unrelated commenting) was used to identify the interactions and was adjusted for time. RESULTS: Four urological cases were selected for recording. In the video-based coaching sessions compared to the operating room, attendings made more teaching points per hour, provided more information to residents (mean teaching points 7.7 for video-based coaching vs 2.9 for operating room, p <0.005), emphasized operative skills and technique (mean teaching points 10.5 for video-based coaching vs 4.1 for operating room, p <0.005), and were more likely to ask open-ended discussion leading questions (mean teaching points 28.5 for video-based coaching vs 4.4 for operating room, p <0.05). CONCLUSIONS: Video-based coaching delivered in short time frames offers an easily implementable additional learning opportunity for resident education to further enhance skills learned in the urological operating room.

Performance of PI-RADS v2 assessment categories assigned prior to MR-US fusion biopsy in a new fusion biopsy program.

OBJECTIVE: To validate the performance of PI-RADS v2 for detection of clinically significant prostate cancer (csPca, Gleason ≥7) within the context of a new fusion biopsy program. MATERIAL AND METHODS: Patients with a PI-RADS v2 assessment category assigned on pre-biopsy mpMRI between March 2015 and November 2017 were identified. Diagnostic performance of PI-RADS v2 was calculated using fusion biopsy results as reference standard using receiver operating characteristic curve analysis. Patient and lesion characteristics were analyzed with one-way ANOVA and Wilcoxon rank sum test. RESULTS: Of 83 patients with 175 lesions, 115/175 (65.7%) were benign, 21/175 (12%) were Gleason 6, and 39/175 (22.3%) were Gleason ≥7. csPCa rates were 0% (0/5) for PI-RADS 1, 7.4% (2/27) for PI-RADS 2, 5.8% (3/52) for PI-RADS 3, 31.2% (24/77) for PI-RADS 4, and 71.4% (10/14) for PI-RADS 5 (p < 0.0001). For prediction of csPCa, patient-level AUC was 0.68 and lesion-level AUC was 0.77. Biopsy threshold of PI-RADS ≥3 was 92.6% sensitive and 22.1% specific. A threshold of PI-RADS ≥4 was 87.2% sensitive and 58.1% specific. Rate of csPca detection on concurrent standard 12 core biopsy only was 6.7%. CONCLUSION: PI-RADS v2 assessment categories assigned prior to biopsy predict pathologic outcome reasonably well in a new prostate fusion biopsy program. Biopsy threshold of PI-RADS ≥3 is highly sensitive. A threshold of ≥4 increases specificity but misses some csPCa.

Redesigning a large-scale clinical trial in response to negative external trial results: the CAMUS study of phytotherapy for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the US. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern US, and extracts of the bark of Pygeum africanum, the African plum tree. PURPOSE: The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH. METHODS: CAMUS was originally designed as a 3300-participant, four-arm trial of S. repens, P. africanum, an alpha-adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that S. repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at 1 year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6-18 months) symptom relief could be achieved with increasing doses of S. repens, the phytotherapy most commonly used in the US for BPH. RESULTS: Results are anticipated in 2011. CONCLUSIONS: Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of S. repens had to be established before proceeding to a long-term clinical trial.