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Purpose: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease., Methods: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements., Results: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including non-invasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB., Conclusion: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences.

Purpose: The impact of nonurological factors on male lower urinary tract symptoms (LUTS) remains unclear. We investigated cross-sectional and longitudinal associations among anxiety, depression, physical function, sleep quality and urinary symptom subdomains., Materials and Methods: Data from 518 men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study were analyzed to identify associations between Patient-Reported Outcomes Measurement Information System® (PROMIS®) depression, anxiety, sleep disturbance and physical function measures and LUTS subdomains, as derived from the American Urological Association Symptom Index and LUTS Tool. Multivariable linear regression was used to assess the relationships between PROMIS measures and LUTS subdomains at baseline and at 3- and 12-month followup., Results: Baseline depression and anxiety were associated with urinary incontinence (p <0.001), voiding symptoms (p <0.001) and quality of life (p=0.002), whereas baseline sleep disturbance was associated with voiding and storage symptoms and quality of life (p <0.001 for all). Urinary symptom severity improved in all subdomains at 3 and 12 months. Similar associations between PROMIS measures and LUTS subdomains were observed at all time points, but baseline depression, anxiety, sleep disturbance and physical function measures were not associated with longitudinal trajectories of LUTS., Conclusions: Urinary symptom subdomains are independently associated with modifiable clinical variables including sleep quality and depression at all time points, but these variables do not predict the degree of improvement in LUTS following urological evaluation and treatment over the medium term. Bidirectional assessment and randomized experiments may improve our understanding of these relationships.

Purpose: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer., Materials and Methods: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses., Results: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry., Conclusions: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

Purpose: Lower urinary tract symptoms are common in men and women. Members of the LURN (Lower Urinary Tract Dysfunction Research Network) sought to create a brief, clinically relevant tool to improve existing measurements of lower urinary tract symptoms in men and women., Materials and Methods: Using a modified Delphi methodology during an expert consensus meeting we reduced the LURN CASUS (Comprehensive Assessment of Self-Reported Urinary Symptoms) questionnaire to a brief set of clinically relevant items measuring lower urinary tract symptoms. The sum score of these items was evaluated by comparing it to the AUA SI (American Urological Association Symptom Index), the UDI-6 (Urinary Distress Inventory Short Form) in women only and the CASUS lower urinary tract symptoms screening questions using the Pearson correlation, regression analysis and ROC curves., Results: The LURN SI-10 (10-Item LURN Symptom Index) assesses urinary frequency, nocturia, urgency, incontinence, bladder pain, voiding and post-micturition symptoms (score range 0 to 38). The correlation between LURN SI-10 and AUA SI scores was 0.77 in men and 0.70 in women. The UDI-6 and the LURN SI-10 correlated highly in women (r=0.76). The LURN SI-10 showed good accuracy to predict moderate and severe lower urinary tract symptoms as defined by the AUA SI (ROC AUC range 0.82-0.90). Similar accuracy was shown in predicting different levels of symptom status using the UDI-6 (AUC range 0.84-0.86)., Conclusions: The LURN SI-10 correlates well with the AUA SI and the UDI-6. It includes items related to a broader spectrum of lower urinary tract symptoms, particularly incontinence, bladder pain and post-micturition symptoms, and it applies to men and women.

Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms., Materials and Methods: PubMed®, EMBASE® and Web of Science® were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways., Results: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were cross-sectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder syndrome and cell migration/cytoskeleton remodeling pathways that were enriched in female stress incontinence., Conclusions: Major deficiencies in the existing biomarker literature include poor reproducibility of laboratory data, unclear classification of patients with lower urinary tract symptoms and lack of adjustment for clinical covariates. Despite these limitations we identified multiple putative pathways in which panels of biological markers need further research.

Purpose: Women with lower urinary tract symptoms are often diagnosed based on a predefined symptom complex or a predominant symptom. There are many limitations to this paradigm as often patients present with multiple urinary symptoms which do not perfectly fit the preestablished diagnoses. We used cluster analysis to identify novel, symptom based subtypes of women with lower urinary tract symptoms., Materials and Methods: We analyzed baseline urinary symptom questionnaire data obtained from 545 care seeking female participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms were measured with the LUTS (lower urinary tract symptoms) Tool and the AUA SI (American Urological Association Symptom Index), and analyzed using a probability based consensus clustering algorithm., Results: Four clusters were identified. The 138 women in cluster F1 did not report incontinence but experienced post-void dribbling, frequency and voiding symptoms. The 80 women in cluster F2 reported urgency incontinence as well as urgency and frequency but minimal voiding symptoms or stress incontinence. Cluster F3 included 244 women who reported all types of incontinence, urgency, frequency and mild voiding symptoms. The 83 women in cluster F4 reported all lower urinary tract symptoms at uniformly high levels. All but 2 of 44 LUTS Tool and 8 AUA SI questions significantly differed between at least 2 clusters (p <0.05). All clusters contained at least 1 member from each conventional group, including continence, and stress, urgency, mixed and other incontinence., Conclusions: Women seeking care for lower urinary tract symptoms cluster into 4 distinct symptom groups which differ from conventional clinical diagnostic groups. Further validation is needed to determine whether management improves using this new classification., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Male urinary incontinence is thought to be infrequent. We sought to describe the prevalence of urinary incontinence in a male treatment seeking cohort enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network)., Materials and Methods: Study inclusion and exclusion criteria, including men with prostate cancer or neurogenic bladder, were previously reported. LURN participants prospectively completed questionnaires regarding lower urinary tract symptoms and other clinical variables. Men were grouped based on incontinence type, including 1) no urinary incontinence, 2) post-void dribbling only and 3) urinary incontinence. Comparisons were made using ANOVA and multivariable regression., Results: Of the 477 men 24% reported no urinary incontinence, 44% reported post-void dribbling only and 32% reported urinary incontinence. African American men and those with sleep apnea were more likely to be in the urinary incontinence group than in the no urinary incontinence group (OR 3.2, p = 0.02 and OR 2.73, p = 0.003, respectively). Urinary incontinence was associated with significantly higher bother compared to men without leakage (p <0.001). Compared to men without urinary incontinence and men with only post-void dribbling those with urinary incontinence were significantly more likely to report higher scores (more severe symptoms) on the PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaires regarding bowel issues, depression and anxiety than men without urinary incontinence (p <0.01)., Conclusions: Urinary incontinence is common among treatment seeking men. This is concerning because the guideline recommended questionnaires to assess male lower urinary tract symptoms do not query for urinary incontinence. Thus, clinicians may be missing an opportunity to intervene and improve patient care. This provides a substantial rationale for a new or updated symptom questionnaire which provides a more comprehensive symptom assessment., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: It is well established that sleep disorders are associated with the nocturia prevalence in men. While previous literature supports that patients with sleep disorders are at increased risk for nocturia, the risk of daytime lower urinary tract symptoms has not been well established., Materials and Methods: We examined the NHANES (National Health and Nutrition Examination Survey) database between 2006 and 2008. Men older than 40 years who completed the sleep, prostate and kidney questionnaires were included in study. The presence of lower urinary tract symptoms was defined as 2 or more symptoms, including hesitancy, incomplete emptying and/or nocturia. Multivariable models using logistic regression were constructed to compare groups of men with and without a sleep disorder., Results: Of the 3,071 men who completed all survey questions 270 (8.8%) reported a sleep disorder. Men with a sleep disorder had a significantly higher body mass index (30.8 vs 27.4 kg/m 2 ), a greater likelihood of reporting diabetes (20.3% vs 10.2%) and more comorbidities (72.6% vs 45.2%, all p <0.01) than men without a sleep disorder. Multivariable logistic regressions demonstrated that men with a sleep disorder were more likely to report nocturia (OR 1.23), 2 or more lower urinary tract symptoms (OR 1.12) and daytime lower urinary tract symptoms (OR 1.27, all p <0.01)., Conclusions: Sleep disorders are associated with an increased risk of nocturia and daytime lower urinary tract symptoms independent of body mass index, diabetes and an increased number of comorbidities. Based on the current data clinicians should consider assessing lower urinary tract symptoms in men with a sleep disorder since intervention could improve lower urinary tract symptoms and sleep disorders as well as daytime urinary symptoms., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We described and compared the frequency and type of lower urinary tract symptoms reported by men and women at the time that they were recruited from urology and urogynecology clinics into the Symptoms of Lower Urinary Tract Dysfunction Research Network multicenter, prospective, observational cohort study., Materials and Methods: At 6 research sites treatment seeking men and women were enrolled who reported any lower urinary tract symptoms at a frequency more than rarely during the last month on the LUTS (Lower Urinary Tract Symptoms) Tool. At baseline the study participants underwent a standardized clinical evaluation and completed validated questionnaires. Urological tests were performed, including pelvic/rectal examination, post-void residual urine measurement and urinalysis., Results: A total of 545 women and 519 men were enrolled in the study. Mean ± SD age was 58.8 ± 14.1 years. At baseline nocturia, frequency and a sensation of incomplete emptying were similar in men and women but men experienced more voiding symptoms (90% vs 85%, p = 0.007) and women reported more urgency (85% vs 66%, p <0.001). Women also reported more of any type of urinary incontinence than men (82% vs 51% p <0.001), which was mixed incontinence in 57%. Only 1% of men reported stress incontinence but they had other urinary incontinence, including post-void dribbling in 44% and urgency incontinence in 46%. Older participants had higher odds of reporting symptoms of nocturia and urgency., Conclusions: In this large, treatment seeking cohort of men and women lower urinary tract symptoms varied widely by gender and age. Men reported more voiding symptoms and nonstress or urgency urinary incontinence while women reported more incontinence overall and urgency. Older participants had greater odds of urgency and nocturia., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The primary objective of this study was to evaluate reasons for seeking care among men and women with lower urinary tract symptoms., Materials and Methods: Participants were recruited from urology and urogynecology clinics, and the community. The sample was enriched with persons expected to have abnormal or diminished bladder sensations (eg participants with lower back surgery and participants 65 years old or older). Interviews were performed in person beginning with an open-ended assessment of urinary symptoms and associated bother followed by more directed questions, including reasons for seeking or not seeking treatment. We also examined the relationship between symptom frequency and bother using the LUTS (Lower Urinary Tract Symptoms) Tool., Results: A total of 88 participants, including 38 men and 50 women, with a mean ± SD age of 52.2 ± 14.3 years provided information about urinary symptoms, including a range of quality of life consequences and coping behaviors. They sought treatment mostly because of new, continuing or bothersome symptoms. Factors associated with not seeking treatment included low symptom severity and concerns about the costs vs the benefits of treatment (eg side effects of medication). Symptom frequency and bother were associated with each other across symptoms assessed by the LUTS Tool., Conclusions: In this large qualitative study we obtained useful insights into the impact of lower urinary tract symptoms from the perspective of the person with the symptoms. Removing barriers and misconceptions about the treatment of lower urinary tract symptoms may increase the number of people who seek clinical care and improve the clinical course of men and women who experience lower urinary tract symptoms., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Several case reports have documented rare spontaneous cancer regression following systemic infections. Immune related targeted therapies are now available for many cancers, including renal cell carcinoma. We hypothesized that perioperative infection after nephrectomy for renal cell carcinoma may impact long-term cancer specific survival., Materials and Methods: We performed a retrospective cohort study using SEER (Surveillance, Epidemiology and End Results)-Medicare claims data from 2004 to 2011. ICD-9 and CPT codes were used to identify patients older than 65 years who underwent radical or partial nephrectomy for renal cell carcinoma. Patients hospitalized for infection within 30 days of surgery were identified. Study exclusion criteria included death within 90 days of surgery, immunodeficiency and metastatic disease at diagnosis. Kaplan-Meier curves were used to evaluate cancer specific survival between infection vs no infection groups. A Cox proportional hazards model was created to assess survival while controlling for age, gender, race, Elixhauser index, tumor grade, tumor size, histological subtype, AJCC (American Joint Committee on Cancer) stage, systemic therapy and geographic region., Results: Of 8,967 patients 493 (5.5%) were hospitalized for infection after nephrectomy. Median age was 74 years (IQR 69-79), the mean ± SD Elixhauser index was 4.9 ± 7.4 and median followup was 42 months (IQR 22-67). Following nephrectomy univariable Cox regression showed a nonsignificant improvement in cancer specific survival in patients with a serious infection requiring hospitalization (HR 0.84, 95% CI 0.69-1.00, p = 0.054). Cox multivariable regression revealed significant improvement in cancer specific survival for the same population (HR 0.75, 95% CI 0.57-0.99, p = 0.04). This effect was primarily due to patients with larger (7 cm or greater) tumors (HR 0.67, 95% CI 0.44-0.99, p = 0.049). No impact was observed among patients with smaller (less than 7 cm) tumors (HR 0.82, 95% CI 0.57-1.19, p = 0.3)., Conclusions: In patients with T2 (7 cm or greater) renal cell carcinoma who undergo nephrectomy perioperative infection may improve cancer specific survival., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Using patient reported outcomes measures we identified the most informative set of factors associated with quality of life in a large sample of men treated for localized prostate cancer., Materials and Methods: We examined relationships with quality of life using FACIT (Functional Assessment of Chronic Illness Therapy). We also hypothesized variables in a sample of men diagnosed with localized prostate cancer who represented different time points since treatment, including less than 12 months in 70, 1 to 3 years in 344, greater than 3 to 5 years in 291 and greater than 5 years in 97. Correlative measures included subscales of MAX-PC (Memorial Anxiety Scale for Prostate Cancer), short forms of PROMIS® and SOMS (Surgical Outcomes Measurement System), TDM-SATS (Treatment Decision-Making Satisfaction Scale) and subscales of the BFI (Big Five Inventory) of personality., Results: Quality of life was significantly associated with hypothesized variables across different time cohorts. In regression models several factors accounted for most of the variability in quality of life scores depending on time since treatment, including 47%, 22%, 29% and 27% at less than 12 months, 1 to 3 years, greater than 3 to 5 years and greater than 5 years, respectively. Upon examining the unique contribution of these variables, treatment decision making satisfaction was the only variable to have a significant and unique contribution to quality of life across all 4 time cohorts (standardized coefficients 0.33, 0.27, 0.31 and 0.49, respectively, p <0.01). In the cohort with 1 to 3 years since treatment erectile function and neurotic personality style also had unique associations with quality of life (standardized coefficients 0.25 and -0.20, respectively)., Conclusions: When considering the short-term and the longer term quality of life of a man after treatment for localized prostate cancer, our findings highlight the importance of treatment decision making satisfaction, erectile function and personality., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume., Materials and Methods: The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes., Results: On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p=0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p=0.02 and 0.01, respectively)., Conclusions: Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Recent studies have identified genetic variants associated with increased serum prostate specific antigen concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on prostate specific antigen, it may be possible to create a personalized prostate specific antigen cutoff to more accurately identify individuals for whom biopsy is recommended. Therefore, we determined how many men would continue to meet common biopsy criteria after genetic correction of their measured prostate specific antigen concentrations., Materials and Methods: The genotypes of 4 single nucleotide polymorphisms previously associated with serum prostate specific antigen levels (rs2736098, rs10788160, rs11067228 and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of prostate specific antigen was performed by dividing an individual's prostate specific antigen value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds (2.5 ng/ml or greater, or 4.0 ng/ml or greater) before and after genetic correction., Results: Genetic correction of serum prostate specific antigen results was associated with a significantly decreased percentage of men meeting biopsy thresholds. Genetic correction could lead to a 15% or 20% relative reduction in the total number of biopsies using a biopsy threshold of 2.5 ng/ml or greater, or 4.0 ng/ml or greater, respectively. In addition, genetic correction could result in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses., Conclusions: Our results suggest that 4 single nucleotide polymorphisms can be used to adjust a man's measured prostate specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: While a clear heritable component underlies lower urinary tract symptoms and benign prostatic hyperplasia, few studies have identified specific genetic factors. In contrast, recent genome-wide association studies identified single nucleotide polymorphisms that increase prostate cancer risk. Some of these single nucleotide polymorphisms may also predispose to surgical intervention for benign prostatic hyperplasia. We determined whether these single nucleotide polymorphisms are also associated with lower urinary tract symptom severity and benign prostatic hyperplasia medication use., Materials and Methods: The genotypes of 38 single nucleotide polymorphisms previously associated with prostate cancer risk were determined for 1,168 healthy white male volunteers. American Urological Association symptom index score and medication for benign prostatic hyperplasia were documented prospectively. Statistical analyses were done to compare the frequency of the single nucleotide polymorphisms with American Urological Association symptom index and benign prostatic hyperplasia medication use., Results: Several single nucleotide polymorphisms, including rs2736098 on chromosome 5p15, showed a significant relationship with benign prostatic hyperplasia medication. After adjusting for the other genetic variants, patient age and medication use, rs1571801 on chromosome 9q33.2 (OR 1.31, 95% CI 1.0-1.74) and rs5945572 on chromosome Xp11 (OR 1.28, 95% CI 1.04-1.59) were significantly associated with increased urinary symptoms. In contrast, rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms (OR 0.83, 95% CI 0.66-1.01)., Conclusions: Of 38 single nucleotide polymorphisms that predispose to prostate cancer we identified 3 that are also associated with a well characterized lower urinary tract symptom phenotype. These single nucleotide polymorphisms may aid in the improved characterization of men with lower urinary tract symptoms/benign prostatic hyperplasia., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Survival to reproductive age among men with cancer has steadily increased and yet cancer therapy and cancer itself may carry the risk of infertility. Since 2006, we have used a formalized fertility preservation program with expedited fertility care at our institution. We assessed the impact of this program by comparing the frequency of sperm cryopreservation and patient characteristics before and after its implementation., Materials and Methods: Men 18 to 55 years old diagnosed with cancer at our institution from 2002 to 2010 were included in our study. We retrospectively reviewed patient charts to identify those who were offered and subsequently used fertility preservation services before and after program formalization., Results: From 2002 to 2010 at our institution 4,818 men 18 to 55 years old were diagnosed with cancer, of whom 411 were offered fertility preservation consultation and 249 underwent sperm cryopreservation. Since program implementation, the annual number of men receiving fertility preservation consultation and undergoing sperm cryopreservation increased by 2.4 and 2.7-fold, respectively, while the total number diagnosed with cancer remained fairly constant. Upon substratifying patients into the more conventional reproductive age range of 18 to 40 years 23.4% of all men with cancer in this group were offered consultation before formalization vs 43.3% after formalization (p <0.05). The overall sperm use and discard rates were 8.4% and 14.8%, respectively., Conclusions: A formalized institutional fertility preservation program significantly increased the overall number and percent of male patients with cancer who received fertility preservation consultation and pursued sperm cryopreservation. These increases were seen in men with all types of cancer and across all demographics assessed at our institution., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Treatment options for patients with low risk prostate cancer include radical prostatectomy, radiation therapy, and active surveillance. Among patients treated with radical prostatectomy, prior studies have demonstrated significantly higher biochemical progression rates with surgical delays of 6 months or greater. We determined the impact of surgical delay on radical prostatectomy outcomes specifically in low risk patients., Materials and Methods: From our radical prostatectomy database we identified men who fulfilled the D'Amico low risk criteria (clinical stage T1c/T2a, prostate specific antigen less than 10 ng/ml, and biopsy Gleason 6 or less). Pathological tumor features and biochemical progression rates were compared between men with and without surgical delay. We used Cox proportional hazards models to examine predictors of biochemical progression., Results: Of 1,111 men who fulfilled the D'Amico low risk criteria, those with a surgical delay of 6 months or more were significantly older, had a higher proportion of African American men, and a lower proportion of clinical stage T2a (vs T1). A surgical delay of 6 months or more was associated with a greater risk of high grade disease at prostatectomy (p = 0.001) and biochemical progression (p = 0.04). The progression-free survival rate was significantly lower among men with a surgical delay. On multivariate analysis with prostate specific antigen and clinical stage, surgical delays of 6 months or more were significantly and independently associated with time to biochemical progression., Conclusions: In men who met the D'Amico low risk criteria, a surgical delay of 6 months or more was associated with significantly worse radical prostatectomy outcomes, including more pathology upgrading and a higher rate of biochemical progression. Low risk patients choosing to defer initial definitive therapy should be counseled regarding the possibility of worse treatment outcomes at a later date., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Five genetic variants along chromosomes 8q24 and 17q have a cumulative association with prostate cancer risk. Our research group previously reported an association between these variants and clinicopathological characteristics. More recently 4 additional prostate cancer susceptibility variants were identified on chromosomes 2p15, 10q11, 11q13 and Xp11. We performed cumulative risk assessment incorporating all 9 genetic variants and determined the relationship of the new variants to clinicopathological tumor features., Materials and Methods: The genotype of 9 variants was determined in 687 men of European ancestry who underwent radical prostatectomy from 2002 to 2008 and in 777 healthy volunteer controls. We compared the incidence of these variants in prostate cancer cases and controls, and assessed their cumulative risk. We also determined the relationship of carrier status for the 4 new variants and clinicopathological tumor features., Results: Prostate cancer cases had an increased incidence of all 9 risk variants compared to controls. A cumulative model including the 9 single nucleotide polymorphisms provided greater prostate cancer risk stratification than a model restricted to the original 5 single nucleotide polymorphisms described. Specifically men with 6 or more variants were at greater than 6-fold increased risk for prostate cancer. Although 2p15 and 11q13 carriers were more likely to have aggressive features, other clinicopathological features were similar in carriers and noncarriers., Conclusions: Genetic variants located in 9 regions have a cumulative association with prostate cancer risk. Identification of an increasing number of single nucleotide polymorphisms may provide greater understanding of their combined relationship with CaP risk and disease aggressiveness., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The 5alpha-reductase inhibitors improve urinary symptoms related to benign prostatic hyperplasia, deter benign prostatic hyperplasia progression and provide prostate cancer chemoprevention. Currently there are a number of 5alpha-reductase inhibitor formularies, including Proscar, generic finasteride and dutasteride. While all formularies decrease serum prostate specific antigen (a proxy for prostate volume), they may not accomplish this to the same degree, which may have dramatic effects on prostate specific antigen kinetics in men changing 5alpha-reductase inhibitor formularies. We examined prostate specific antigen velocity after changes in 5alpha-reductase inhibitor formularies., Materials and Methods: We identified patients treated with 2 or more 5alpha-reductase inhibitor formularies who had sufficient prostate specific antigen values to calculate prostate specific antigen velocity during each 5alpha-reductase inhibitor treatment. Patient data were grouped depending on the formularies received. Statistical analysis was done to compare prostate specific antigen velocity at various time points while on different 5alpha-reductase inhibitors., Results: Eight men changed from dutasteride to generic finasteride (group 1), 21 changed from dutasteride to Proscar (group 2), 49 changed from Proscar to dutasteride (group 3) and 77 changed from Proscar to generic finasteride (group 4). We noted a significant increase in prostate specific antigen velocity in groups 1 and 2 (p <0.05), and 4 (p <0.005). The increase was greater than 0.35 ng/ml per year, the common cutoff for prostate biopsy recommendations, in more than a third of patients., Conclusions: Results confirm that changing 5alpha-reductase inhibitors drugs can be associated with a clinically significant change in prostate specific antigen velocity. These prostate specific antigen velocity changes could place patients at risk for unnecessary prostate biopsy. Additional prospective studies are warranted., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer. Because PSA kinetics were previously linked to prostate cancer specific mortality, we determined whether prostate specific antigen velocity is associated with clinically significant prostate cancer., Materials and Methods: A total of 1,073 men underwent radical prostatectomy from 1992 to 2008 with data available on prostate specific antigen velocity and tumor volume. Insignificant cancer was defined by the Ohori criteria as organ confined, tumor volume 0.5 cc or less and no primary or secondary Gleason pattern 4 or 5. We calculated the proportion of men with pathologically insignificant prostate cancer stratified by prostate specific antigen velocity., Results: Preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year was significantly associated with high grade disease (p = 0.008), positive surgical margins (p = 0.003) and seminal vesicle invasion (p = 0.007) at radical prostatectomy. Median tumor volume was also significantly higher in men with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year (3.1 vs 2.4 cc, p = 0.0001). Overall 69 men (6%) met the Ohori criteria for insignificant cancer. Patients with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year were 50% less likely to have insignificant disease (10% vs 5%, p = 0.003)., Conclusions: A prostate specific antigen velocity threshold of 0.4 ng/ml per year was associated with the likelihood of insignificant prostate cancer. This suggests that prostate specific antigen velocity may be a useful adjunct in prostate cancer screening to increase specificity for identifying patients with clinically significant disease.

Purpose: A decreased percent of differential function is a common indication for infant pyeloplasty but there is no recognized fetal ultrasound parameter to predict this deficit. We determined whether there is a correlation between fetal pyelectasis and the newborn percent differential function that may enhance prenatal counseling and guide postnatal evaluation., Materials and Methods: Our database was queried for fetal and newborn measures with fetal pyelectasis on ultrasound and the percent of differential function on renal scintigraphy. Fetal pyelectasis data were stratified by estimated gestational age and the percent of differential function. The affected cohort was defined as having 35% or less differential function and the unaffected cohort was defined as having greater than 35%. The Wilcoxon 2-sample test was used for statistical analysis with logistic regression to generate estimated probability models of a decreased percent of differential function vs mm fetal pyelectasis., Results: A total of 831 cases had fetal and newborn ultrasound data available with a total of 229 renal scans identified. Of the 229 cases 36 (16%) had 35% or less differential function on scintigraphy. At estimated gestational age 33 weeks or less the affected cohort had 8 mm greater pyelectasis than the unaffected cohort (OR 1.2, p <0.0001). At estimated gestational age greater than 33 weeks the affected cohort had 4 mm greater pyelectasis than the unaffected cohort (OR 1.07, p <0.07). Subgroup analysis before 33 weeks of estimated gestational age showed similar significance (OR >1, p

Purpose: The Prostate Cancer Prevention Trial reported that 15% of men with a prostate specific antigen less than 4 ng/ml and a normal digital rectal examination have biopsy detectable prostate cancer. However, limited published data describe the tumor features of prostate cancer detected at low prostate specific antigen levels (less than 2.5 ng/ml)., Materials and Methods: A total of 1,278 men underwent radical retropubic prostatectomy by 1 surgeon between 2003 and 2008. We describe the clinicopathological features of 77 patients with a preoperative prostate specific antigen of less than 2.5 ng/ml., Results: Of the men with a low prostate specific antigen (less than 2.5 ng/ml) tumor 51 (66%) had findings suspicious for prostate cancer on digital rectal examination. Indications for prostate biopsy in the remainder of men included an increased prostate specific antigen velocity, hematospermia and abnormal transrectal ultrasound findings. Prostate cancer was detected at transurethral resection of the prostate in the remaining 8% of men. Despite having a low prostate specific antigen at diagnosis 8 (10.4%) and 20 (26%) men, respectively, had biopsy and radical retropubic prostatectomy Gleason grade 7 disease or greater, while 7 (9%) and 6 (7.8%), respectively, had extracapsular tumor extension or positive surgical margins. Compared to men with a normal digital rectal examination mean tumor volume was significantly higher in those with a suspicious digital rectal examination (3.3 vs 1.7 cc, p = 0.018)., Conclusions: Despite having a prostate specific antigen of less than 2.5 ng/ml at diagnosis, a considerable proportion of men had aggressive pathological features at radical retropubic prostatectomy. Digital rectal examination remains an important component of early prostate cancer detection.

Purpose: The primary responsibility of institutional review boards is to protect human research subjects and, therefore, ensure that studies are performed in accordance with a standard set of ethical principles. A number of groups have compared the responses of institutional review boards in multicenter clinical trials involving medical therapies. To our knowledge no such studies have been performed to date of trials investigating surgical intervention. We investigated the consistency of the recommendations issued by various institutional review boards in the Minimally Invasive Surgical Therapies study for benign prostatic hyperplasia, a multicenter trial with a uniform consent and study protocol., Materials and Methods: We obtained the institutional review board response from 6 of the 7 participating institutions after initial submission of the Minimally Invasive Surgical Therapies study protocol and classified the responses. We then redistributed the approved protocols to an institutional review board at another participating institution and analyzed that review of these protocols., Results: We found that the number and type of responses required for institutional review board approval of an identical study protocol varied significantly among participating institutions. We also found that institutional review board responses were inconsistent in the second review, although all protocols were ultimately approved., Conclusions: The current system of local institutional review board review in the context of a multicenter surgical trial is inefficient in the review process and may not provide expertise for overseeing surgical trials. Based on these results a central surgical institutional review board may be needed to improve the ethical review process in multicenter trials.

Purpose: Recent studies have identified 2 distinct genetic variants along chromosome 17, including allele T of single nucleotide polymorphism rs4430796 on 17q12 and allele G of single nucleotide polymorphism rs1859962 on 17q24, that have been linked to prostate cancer risk. Less is known about tumor pathological features in carriers of these variants., Materials and Methods: Genotypes for regions 17q12 and 17q24 were determined in 759 white men with prostate cancer and compared to those in 790 healthy control volunteers using logistic regression. In patients with prostate cancer the Fisher exact or Kruskal-Wallis test was used as appropriate to assess the relationship(s) between clinical and pathological characteristics with 17q carrier status., Results: The frequency of the 17q12 and 17q24 genetic variants was significantly higher in patients with prostate cancer compared to that in controls (OR 1.32, 1.15, respectively). Of patients with prostate cancer 83% and 77% were carriers of the 17q12 and 17q24 variants as well as 75% and 75% of controls, respectively. Carriers of 17q12 risk variants were significantly more likely to have high grade disease using an additive best fit genetic model. In addition, there were trends toward adverse pathological features associated with 17q12 independent of the best fit genetic model., Conclusions: Sequence variants along 17q12 and 17q24 were present in a significantly higher proportion of our prostate cancer cases than in our controls. Adverse pathological features, including higher Gleason grade and pathological stage, were more frequent in 17q12 carriers. Since these alleles may act in conjunction with variants on other chromosomes to influence prostate cancer risk, additional research is required to determine the cumulative associations of genetic risk variants with prognosis.

Purpose: In collaboration with deCODE Genetics Inc. we previously reported on the association between genetic variants on chromosome 8q24 and prostate cancer susceptibility. Several prior studies have examined the relationship between these 8q24 alleles and clinical tumor features. In this study we examine the differences in clinical and pathological tumor features between carriers and noncarriers of these 8q24 alleles in patients with prostate cancer., Materials and Methods: We genotyped 551 white men who underwent radical prostatectomy or radiation therapy for clinically localized prostate cancer at single institution between 2002 and 2005. Of these men 177 (32.1%) were carriers of the -8 allele of the microsatellite marker DG8S737, the A allele of the single nucleotide polymorphism rs1447295 and/or the A allele of the rs16901979 (a surrogate single nucleotide polymorphism of HapC) 8q24 alleles. We used statistical analyses to compare the distribution of clinical characteristics and pathological outcomes between carriers and noncarriers., Results: The -8, A and HapC surrogate single nucleotide polymorphism alleles were present in 77 (14%), 128 (23%) and 61 (14%) patients with prostate cancer, respectively. Carriers of the -8 or multiple 8q24 alleles were significantly more likely to have a Gleason score of 7 or greater and lymph node metastases. Among men with a family history of prostate cancer, carriers of the -8 allele had a significantly greater risk of high grade disease (64% vs 39%, p = 0.04)., Conclusions: In our predominantly surgically treated population there was a significant association between 8q24 prostate cancer susceptibility alleles, particularly the -8 allele, and high grade disease. In men with a family history of prostate cancer the presence of 1 or more of these alleles also conferred a greater risk of some adverse pathological features.

Purpose: Despite the tremendous stage migration associated with prostate cancer screening to our knowledge it remains unproven whether prostate specific antigen based screening decreases prostate cancer specific mortality. Recent studies have shown that prostate specific antigen velocity more than 2 ng/ml per year in the year before diagnosis is associated with a significantly greater risk of prostate cancer specific mortality after treatment. This may serve as a surrogate marker for prostate cancer outcomes. We compared the prostate specific antigen velocity profile between patients with prostate cancer in whom the tumor was detected in a formal screening study and those who were referred for treatment., Materials and Methods: We evaluated prostate specific antigen velocity in 1,101 men from a prostate cancer screening study and in 368 not enrolled in a screening study who were referred for treatment. All patients underwent radical prostatectomy for clinically localized disease and had multiple preoperative prostate specific antigen measurements to calculate prostate specific antigen velocity., Results: Median prostate specific antigen velocity before diagnosis was significantly higher in referred vs screened men (1.35 vs 0.68 ng/ml per year, p <0.0001). In addition, a significantly greater proportion of referred patients had prostate specific antigen velocity more than 2 ng/ml per year (38% vs 17%, p <0.0001). On multivariate analysis using prostate specific antigen, clinical stage and biopsy Gleason score screened vs referred status was a significant independent predictor of prostate specific antigen velocity more than 2 ng/ml per year (p <0.0004)., Conclusions: Prostate specific antigen velocity more than 2 ng/ml per year has been linked to a significantly greater risk of prostate cancer specific mortality. Patients who underwent serial screening had a more favorable prostate specific antigen velocity profile at diagnosis, suggesting that screen detected prostate cancer may be more likely to be cured with definitive therapy.