PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study.

BACKGROUND: The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. METHODS: A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. RESULTS: A total of 1534 men with baseline IPSS <8 were included in the study cohort. At baseline, there were 335 men with PSA 2.5-4 ng/mL, 589 with PSA 4.1-6 ng/mL, and 610 with PSA 6-10 ng/mL. During the 4-year study, 196 men progressed to incident LUTS (50.5% medical treatment, 9% surgery, and 40.5% new symptoms). As a continuous variable, higher PSA was associated with increased incident LUTS on univariable (HR 1.09, p = 0.019) and multivariable (HR 1.08, p = 0.040) analysis. Likewise, baseline PSA 6-10 ng/mL was associated with increased incident LUTS vs. PSA 2.5-4 ng/mL in adjusted models (HR 1.68, p = 0.016). This association was also observed in men with PSA 4.1-6 ng/mL vs. PSA 2.5-4 ng/mL (HR 1.60, p = 0.032). CONCLUSIONS: Men with mild to no LUTS but increased baseline PSA are at increased risk of developing incident LUTS presumed due to benign prostatic hyperplasia.

Predictors of operative time during radical retropubic prostatectomy and robot-assisted laparoscopic prostatectomy.

OBJECTIVES: To better predict operative time using patient/surgical characteristics among men undergoing radical retropubic prostatectomy or robot-assisted laparoscopic prostatectomy in order to achieve more efficient operative scheduling and potentially decrease costs in the Veterans Health System. METHODS: We analyzed 2619 men treated with radical retropubic prostatectomy (n = 2005) or robot-assisted laparoscopic prostatectomy (n = 614) from 1993 to 2013 from six Veterans Affairs Hospitals in the Shared Equal Access Regional Cancer Hospital database. Age, body mass index, race, biopsy Gleason, prostate weight, undergoing a nerve-sparing procedure or lymph node dissection, and hospital surgical volume were analyzed in multivariable linear regression to identify predictors of operative time and to quantify the increase/decrease observed. RESULTS: In men undergoing radical retropubic prostatectomy, body mass index, black race, prostate weight and a lymph node dissection all predicted longer operative times (all P ≤ 0.004). In men undergoing robot-assisted laparoscopic prostatectomy, biopsy Gleason score and a lymph node dissection were associated with increased operative time (P ≤ 0.048). In both surgical methods, a lymph node dissection added 25-40 min to the operation. Also, in both, each additional operation per year per center predicted a 0.80-0.89-min decrease in operative time (P ≤ 0.001). CONCLUSIONS: Overall, several factors seem to be associated with quantifiable changes in operative time. If confirmed in future studies, these findings can allow for a more precise estimate of operative time, which could decrease the overall cost to the patient and hospital by aiding in operating room time management.

Does Peak Urine Flow Rate Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from REDUCE.

PURPOSE: We determined whether decreased peak urine flow is associated with future incident lower urinary tract symptoms in men with mild to no lower urinary tract symptoms. MATERIALS AND METHODS: Our population consisted of 3,140 men from the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial with mild to no lower urinary tract symptoms, defined as I-PSS (International Prostate Symptom Score) less than 8. REDUCE was a randomized trial of dutasteride vs placebo for prostate cancer prevention in men with elevated prostate specific antigen and negative biopsy. I-PSS measures were obtained every 6 months throughout the 4-year study. The association between peak urine flow rate and progression to incident lower urinary tract symptoms, defined as the first of medical treatment, surgery or sustained and clinically significant lower urinary tract symptoms, was tested by multivariable Cox models, adjusting for various baseline characteristics and treatment arm. RESULTS: On multivariable analysis as a continuous variable, decreased peak urine flow rate was significantly associated with an increased risk of incident lower urinary tract symptoms (p = 0.002). Results were similar in the dutasteride and placebo arms. On univariable analysis when peak flow was categorized as 15 or greater, 10 to 14.9 and less than 10 ml per second, flow rates of 10 to 14.9 and less than 10 ml per second were associated with a significantly increased risk of incident lower urinary tract symptoms (HR 1.39, p = 0.011 and 1.67, p <0.001, respectively). Results were similar on multivariable analysis, although in the 10 to 14.9 ml per second group findings were no longer statistically significant (HR 1.26, p = 0.071). CONCLUSIONS: In men with mild to no lower urinary tract symptoms a decreased peak urine flow rate is independently associated with incident lower urinary tract symptoms. If confirmed, these men should be followed closer for incident lower urinary tract symptoms.

The association between sexual function and prostate cancer risk in US veterans.

Sexual dysfunction and prostate cancer are common among older men. Few studies explored the association between these two illnesses. We examined whether sexual function is associated with prostate cancer risk among older men. Among 448 men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, sexual function was ascertained from the Expanded Prostate Cancer Index Composite sexual assessment. We tested the link between sexual function and prostate cancer risk adjusting for multiple demographic and clinical characteristics using logistic regression. Multinomial logistic regression was used to test the associations with risk of low-grade (Gleason ≤6) and high-grade (Gleason ≥7 or ≥4 + 3) disease versus no cancer. Of 448 men, 209 (47%) had a positive biopsy; these men were less likely to be white (43% vs 55%, P = 0.013), had higher prostate-specific antigen (PSA) (6.0 vs 5.4 ng ml-1 , P < 0.001), but with lower mean sexual function score (47 vs 54, P = 0.007). There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. After adjusting for baseline differences, sexual function was linked with a decreased risk of overall prostate cancer risk (OR: 0.91 per 10-point change in sexual function, P = 0.004) and high-grade disease whether defined as Gleason ≥7 (OR: 0.86, P = 0.001) or ≥4 + 3 (OR: 0.85, P = 0.009). Sexual function was unrelated to low-grade prostate cancer (OR: 0.94, P = 0.13). Thus, among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade prostate cancer. Confirmatory studies are needed.

Does Prostate Size Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from the REDUCE Trial.

BACKGROUND: It has been shown that increased prostate size is a risk factor for lower urinary tract symptom (LUTS) progression in men who currently have LUTS presumed due to benign prostatic hyperplasia (BPH). OBJECTIVE: To determine if prostate size is a risk factor for incident LUTS in men with mild to no symptoms. DESIGN, SETTING, AND PARTICIPANTS: We conducted a post hoc analysis of the REDUCE study, which contained a substantial number of men (n=3090) with mild to no LUTS (International Prostate Symptom Score [IPSS] <8). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome was determination of the effect of prostate size on incident LUTS presumed due to BPH defined as two consecutive IPSS values >14, or receiving any medical (α-blockers) or surgical treatment for BPH throughout the study course. To determine the risk of developing incident LUTS, we used univariable and multivariable Cox models, as well as Kaplan-Meier curves and the log-rank test. RESULTS AND LIMITATIONS: Among men treated with placebo during the REDUCE study, those with a prostate size of 40.1-80ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23-2.26, p=0.001) of developing incident LUTS compared to men with a prostate size 40.0ml or smaller. There was no association between prostate size and risk of incident LUTS in men treated with 0.5mg of dutasteride. The post hoc nature of our study design is a potential limitation. CONCLUSIONS: Men with mild to no LUTS but increased prostate size are at higher risk of incident LUTS presumed due to BPH. This association was negated by dutasteride treatment. PATIENT SUMMARY: Benign prostatic hyperplasia (BPH) is a very common problem among older men, which often manifests as lower urinary tract symptoms (LUTS), and can lead to potentially serious side effects. In our study we determined that men with mild to no current LUTS but increased prostate size are much more likely to develop LUTS presumed due to BPH in the future. This association was not seen in men treated with dutasteride, a drug approved for treatment of BPH. Our study reveals that men with a prostate size of 40.1-80ml are potential candidates for closer follow-up.

Do all men with pathological Gleason score 8-10 prostate cancer have poor outcomes? Results from the SEARCH database.

OBJECTIVE: To determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI). MATERIALS AND METHODS: We identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI. Cox proportional hazards models and the log-rank test were used to compare BCR among the groups. RESULTS: At 2 years after RP, pathological group was significantly correlated with BCR (log-rank, P < 0.001) with patients in group 5 (+SVI) having the highest BCR risk (66%) and those in group 1 (NSMs and no ECE) having the lowest risk (14%). When we compared groups 2, 3, and 4, with each other, there was no significant difference in BCR among the groups (~50% 2-year BCR risk; log-rank P = 0.28). Results were similar when adjusting for prostate-specific antigen, age, pathological Gleason sum and clinical stage, or after excluding men who received adjuvant therapy. CONCLUSIONS: In patients with high grade (Gleason score 8-10) prostate cancer after RP, the presence of either PSMs, ECE or SVI was associated with an increased risk of early BCR, with a 2-year BCR risk of ≥50%. Conversely, men with organ-confined margin-negative disease had a very low risk of early BCR despite Gleason score 8-10 disease.

Adverse pathology and undetectable ultrasensitive prostate-specific antigen after radical prostatectomy: is adjuvant radiation warranted?

OBJECTIVES: To determine if men with adverse pathology but undetectable ultrasensitive (<0.01 ng/mL) PSA are at high-risk for biochemical recurrence (BCR), or if there is a subset of patients at low-risk for whom the benefit of adjuvant radiation therapy might be limited. PATIENTS AND METHODS: We evaluated 411 patients treated with RP from 2001 to 2013 without adjuvant radiation who had an undetectable (<0.01 ng/mL) PSA level after RP but with adverse pathology [positive surgical margins (PSMs), extraprostatic extension (EPE), and/or seminal vesicle invasion (SVI)]. Multivariable Cox regression analyses tested the relationship between pathological characteristics and BCR to identify groups of men at highest risk of early BCR. RESULTS: On multivariable analysis, only pathological Gleason 7 (4 + 3), Gleason ≥8, and SVI independently predicted BCR (P = 0.019, P < 0.001, and P = 0.001, respectively), although on two-way analysis men with Gleason 7 (4 + 3) did not have significantly higher rates of BCR compared with patients with Gleason ≤6 (log-rank, P = 0.074). Men with either Gleason ≥8 (with PSMs or EPE) or SVI (15% of the cohort) defined a high-risk group vs men without these characteristics (3-year BCR risk of 50.4% vs 11.9%, log-rank, P < 0.001). CONCLUSIONS: Among men with adverse pathology but an undetectable (<0.01 ng/mL) PSA level after RP, the benefits of adjuvant radiation are probably limited except for men with Gleason 8-10 (with PSMs or EPE) or SVI who are at high-risk of early BCR.

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy.

PURPOSE: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. MATERIALS AND METHODS: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. RESULTS: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. CONCLUSION: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy

ABSTRACT Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. Results: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. Conclusion: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.

The association of exercise with both erectile and sexual function in black and white men.

INTRODUCTION: There is growing interest in using exercise to treat. Although many studies have highlighted the relationship between better erectile function and exercise, black men have been underrepresented in the literature. AIMS: This study aims to determine whether or not exercise is associated with better erectile as well as sexual function in black men and define a minimum exercise threshold for which better erectile/sexual function is seen in a cross-sectional study. METHODS: Our study population consisted of 295 healthy controls from a case-control study assessing risk factors for prostate cancer conducted at the Durham Veterans Affairs Medical Center, which contained a substantial proportion of black men (n = 93; 32%). Exercise and erectile/sexual function were both determined from self-reported questionnaires. Subjects were stratified into four exercise groups: <3 (sedentary), 3-8.9 (mildly active), 9-17.9 (moderately active), and ≥18 (highly active) metabolic equivalents (MET) hours/week. The association between exercise and erectile/sexual function was addressed utilizing multivariable linear regression analyses. MAIN OUTCOME MEASURES: Erectile/sexual function was defined by the validated Expanded Prostate Cancer Index Composite sexual assessment, which was analyzed as a continuous variable (sexual function score). Clinically significant better function was defined as half a standard deviation (SD) (16.5 points). RESULTS: Median sexual function score was 53 (SD = 33). Higher exercise was associated with a better sexual function score (P < 0.001). Importantly, there was no interaction between black race and exercise (P-interaction = 0.772), meaning more exercise was linked with better erectile/sexual function regardless of race. Overall, exercise ≥18 MET hours/week predicted better erectile/sexual function (P < 0.001) with a clinically significant 17.3-point higher function. Exercise at lower levels was not statistically (P > 0.147) or clinically (≤8.14 points higher function) associated with erectile/sexual function. CONCLUSIONS: In a racially diverse population, exercise ≥18 MET hours/week is highly associated with better erectile/sexual function regardless of race.

Spinal Cord Injury survey to determine pressure ulcer vulnerability in the outpatient population.

Pressure ulcers are one of the most common causes of morbidity, mortality and rehospitalization for those living with Spinal Cord Injury (SCI). Literature examining risk and recurrence of pressure ulcers (PrUs) has primarily focused on the nursing home elderly who do not have SCI. More than 200 factors that increase PrU risk have been identified. Yet unlike the elderly who incur pressure ulcers in nursing homes or when hospitalized, most persons with SCI develop their pressure ulcers as outpatients, while residing in the community. The Veterans Health Administration (VHA) provides medical care for a large number of persons with chronic SCI. Included in the VHA SCI model of chronic disease management is the provision of an annual Comprehensive Preventive Health Evaluation, a tool that has potential to identify individuals at high risk for PrUs. This research was motivated by the clinical observation that some individuals appear to be protected from developing PrUs despite apparently 'risky' behaviors while others develop PrUs despite vigilant use of the currently known preventative measures. There is limited literature regarding protective factors and specific risk factors that reduce PrU occurrence in the community dwelling person with chronic SCI have not been delineated. The purpose of this study is to examine the preliminary hypothesis that there are biological and/or psychosocial factors that increase or reduce vulnerability to PrUs among persons with SCI. A limited number of refined hypotheses will be generated for testing in a prospective fashion. A retrospective cross-sectional survey of 119 randomly selected Veterans with SCI undergoing the Comprehensive Health Prevention Evaluation during the year 2009 was performed. Factors that differed between patients with 0, 1 or ⩾2 PrUs were identified and stratified, with an emphasis on modifiable risk factors. Three hypotheses generated from this study warrant further investigation: (1) cumulative smoking history increases the risk of PrUs independent of co-morbidities, (2) being moderately overweight, BMI>25, with or without spasticity, is a modifiable factor that may be protective and (3) increased use of a caregiver does not reduce PrU risk. Prospective studies that focus on these hypotheses will lead to evidence-based risk assessment tools and customized interventions to prevent PrUs in persons with SCI in the outpatient setting.