The impact of smoking on sexual function.

OBJECTIVES: To evaluate the hypothesis that there is an improvement in sexual function following smoking cessation (as smoking is a well-established risk factor for sexual dysfunction), we analysed the association between cigarette smoking and smoking cessation with sexual function among participants of the REduction by DUtasteride of prostate Cancer Events (REDUCE) study. SUBJECTS AND METHODS: We analysed baseline data of 6754 men, aged 50-75 years divided into: lifelong non-smokers, former smokers, and current smokers. We examined total testosterone (TT, normal range ≥10 nmol/L) and sexual function variables: self-reported sexual activity, low libido, and erectile dysfunction (ED). Differences between current vs non-smokers and former vs current smokers were analysed using the chi-square test, linear and logistic regressions. RESULTS: A total of 3069 (45.4%) men were non-smokers, 2673 (39.6%) former smokers, and 1012 (15%) current smokers. Current smokers were significantly younger than former and non-smokers (mean age 61.6, 63.2, and 62.7 years, respectively), leaner (mean body mass index 27.0, 27.7, and 27.2 kg/m2 , respectively), and had less hypertension (32.4%, 41.6%, and 36.8%, respectively; all P < 0.01). In uni- and multivariable analysis, current smokers had higher mean TT than non-smokers (485.4 vs 451.2 nmol/L, P < 0.001), higher prevalence of low libido (25.6% vs 21.0%, P = 0.002) and ED (31.6% vs 26.0%, P < 0.001) with comparable sexual activity (81.7% vs 82.8%, P = 0.420). In multivariable analysis, former smokers had statistically significantly less prevalence of low libido (odds ratio [OR] 0.8, P = 0.013) and ED (OR 0.8, P = 0.006) compared to current smokers. CONCLUSION: Cigarette smoking was associated with worse sexual health compared to non-smokers, while former smokers had better erectile function and libido than current smokers. Smoking cessation may improve male sexual health and counselling on smoking cessation may be considered at the time of sexual health evaluations.

Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study.

PURPOSE: We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade in 2-year repeat biopsies. MATERIALS AND METHODS: Retrospective analyses were conducted of 889 men aged 50 to 75 years old with negative baseline prostate biopsy and 2-year repeat biopsy positive for prostate cancer in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Acute and chronic prostate inflammation and cancer grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and prostate cancer grade in 2-year repeat biopsy was evaluated with Student's t-test, chi-squared test and multivariable logistic regression. RESULTS: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low grade (Gleason scores 2-6) and 268 (30%) were high grade (Gleason scores 7-10). In univariable and multivariable analyses, men with baseline chronic inflammation had significantly fewer high grade tumors (univariable OR 0.64, 95% CI 0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR 0.74, 95% CI 0.45-1.20, p=0.22; multivariable OR 0.78, 95% CI 0.48-1.29, p=0.34). CONCLUSIONS: Chronic inflammation in a negative biopsy was associated with lower prostate cancer grade among men with cancer on follow-up 2-year biopsy.

Dutasteride Improves Nocturia but Does Not Lead to Better Sleep: Results from the REDUCE Clinical Trial.

PURPOSE: In men, complaints of nocturia causing poor sleep are often attributed to benign prostatic hyperplasia and treated with benign prostatic hyperplasia medications. We assessed whether treating lower urinary tract symptoms with dutasteride altered either nocturia or sleep quality using data from REDUCE. MATERIALS AND METHODS: REDUCE was a 4-year randomized, multicenter trial comparing dutasteride 0.5 mg/day vs placebo for prostate cancer chemoprevention. Study participants were men considered at increased risk for prostate cancer. Eligibility included age 50-75 years, prostate specific antigen 2.5-10 ng/ml, and 1 negative prostate biopsy. At baseline, 2 years and 4 years, men completed the International Prostate Symptom Score and Medical Outcomes Study Sleep Scale, a 6-item scale assessing sleep. To test differences in nocturia and Medical Outcomes Study Sleep Scale over time, we used linear mixed models adjusted for baseline confounders. Subanalyses were conducted in men symptomatic from lower urinary tract symptoms, nocturia, poor sleep, or combinations thereof. RESULTS: Of 6,914 men with complete baseline data, 80% and 59% were assessed at 2 and 4-year followup, respectively. Baseline characteristics were balanced between treatment arms. Dutasteride improved nocturia at 2 (-0.15, 95% CI -0.21, -0.09) and 4 years (-0.24, 95% CI -0.31, -0.18) but did not improve sleep. When limited to men symptomatic from lower urinary tract symptoms, nocturia, poor sleep or combinations thereof, results mirrored findings from the full cohort. CONCLUSIONS: In men with poor sleep who complain of nocturia, treatment of lower urinary tract symptoms with dutasteride modestly improves nocturia but has no effect on sleep. These results suggest men with poor sleep who complain of nocturia may not benefit from oral benign prostatic hyperplasia treatment.

Partial Validation of the Sleep Health Construct in the Medical Outcomes Study Sleep Questionnaire.

Sleep health is postulated as a multi-dimensional construct comprised of sleepiness/alertness, timing, duration, efficiency, and satisfaction. New questionnaires for its measurement have been proposed. We performed secondary data analyses and analyzed responses on a widely used, well-established sleep questionnaire to determine whether the construct might be detectable with an existing questionnaire. Healthy men (n = 7604) aged 55-75 completed the six-item Medical Outcomes Study Sleep Questionnaire (MOSSQ) at baseline in a large, randomized clinical trial [the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial). Two components clearly emerged from a Principal Components Analysis, suggesting that both sleep disturbance and sleep satisfaction are differentiated by the MOSSQ. Selected elements of sleep health are accessible with relatively few questionnaire items. Widespread previous usage of the MOSSQ in both descriptive and interventional research suggests that many previously collected databases could address at least two components of this construct.

Sleep quality and prostate cancer aggressiveness: Results from the REDUCE trial.

BACKGROUND: Disrupted sleep has been associated with increased risk of certain cancers. Little data exist in prostate cancer. We tested the association between sleep quality and prostate cancer diagnosis overall and by tumor grade in the Reduction by Dutasteride of Prostate Cancer Events chemoprevention trial. We hypothesized that worse sleep quality would be associated with increased tumor aggressiveness. METHODS: At baseline, 5614 men completed a validated six-item questionnaire on sleep quality. We generated a composite score categorized into tertiles to measure overall sleep quality and assessed each sleep quality question individually. Logistic regression was used to test associations between baseline sleep quality and overall, low-grade and high-grade prostate cancer diagnosis at 2-year study-mandated biopsy. Models were stratified by nocturia. RESULTS: Overall sleep quality was unrelated to overall or low-grade prostate cancer. Worse overall sleep quality was associated with elevated odds of high-grade prostate cancer (odds ratio [OR]T3vsT1 1.15; 95% confidence interval [CI]: 0.83-1.60 and ORT2vsT1 1.39; 95% CI: 1.01-1.92). Men reporting trouble falling asleep at night sometimes vs never had elevated odds of high-grade prostate cancer (OR: 1.51; 95% CI: 1.08-2.09) while trouble staying awake during the day was associated with decreased odds of low-grade prostate cancer (OR: 0.65; 95% CI: 0.49-0.86). Results were similar within strata of nocturia severity. CONCLUSIONS: Overall, associations between sleep quality and prostate cancer were inconsistent. However, there was some evidence for a positive association between insomnia and high-grade prostate cancer, and an inverse relationship between daytime sleepiness and low-grade prostate cancer; findings that should be validated by future studies.

Statin use and longitudinal changes in prostate volume; results from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

OBJECTIVE: To test the association between statin use and prostate volume (PV) change over time using data from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, a 4-year randomised controlled trial testing dutasteride for prostate cancer chemoprevention. SUBJECTS/PATIENTS AND METHODS: We identified men with a baseline negative prostate biopsy from REDUCE who did not undergo prostate surgery or develop prostate cancer over the trial period. Men reported statin use at baseline. PV was determined from transrectal ultrasonography performed to guide prostate biopsy at baseline, and 2- and 4-years after randomisation. Multivariable generalised estimating equations tested differences in PV change over time by statin use, overall and stratified by treatment arm. We tested for interactions between statins and time in association with PV using the Wald test. RESULTS: Of 4106 men, 17% used statins at baseline. Baseline PV did not differ by statin use. Relative to non-users, statin users had decreasing PVs over the trial period (P = 0.027). Similar patterns were seen in the dutasteride and placebo arms, although neither reached statistical significance. The mean estimated PV was modestly but significantly lower in statin users relative to non-users in the dutasteride arm at 2-years (4.5%, P = 0.032) and 4-years (4.0%, P = 0.033), with similar (3-3.3%) but non-significant effects in the placebo arm. CONCLUSION: If confirmed, our present findings support a role for statins in modestly attenuating PV growth, with a magnitude of effect in line with previously reported prostate-specific antigen-lowering effects of statins (~4%). Future studies are needed to assess whether this putative role for statins in PV growth could impact lower urinary tract symptom development or progression.

Helping Men Find Their Way: Improving Prostate Cancer Clinic Attendance via Patient Navigation.

Navigation programs aim to help patients overcome barriers to cancer diagnosis and treatment. Missed clinic appointments have undesirable effects on the patient, health system, and society, and treatment delays have been shown to result in inferior surgical cure rates for men with prostate cancer (CaP). We sought to measure the impact of patient navigation on CaP clinic adherence. Patient navigators contacted patients prior to their first encounter for known or suspected CaP between 7/1/2016 and 6/30/2017. Encounters from 7/1/2014 to 6/30/2015 were used as a historical control. Patient-variables were analyzed including age, health insurance status, home address, zip code, race, ethnicity, and referring primary care clinic. Encounter-level variables included diagnosis (categorized as known or suspected CaP), date of appointment, type of appointment [new vs. return], and provider. The associations between several factors including navigation contact and these variables with missed appointment were analyzed using generalized linear mixed effects multivariate logistic regression. A total of 2854 scheduled clinic encounters from 986 unique patients were analyzed. Patient navigation resulted in a lower missed appointment rate (8.8% vs. 13.9%, OR = 0.64, IQR 0.44-0.93, p = 0.02 on multivariable analysis). Lack of health insurance (OR = 13.18 [5.13-33.83]), suspected but not confirmed CaP diagnosis (OR = 7.44 [4.85-11.42]), and Black (1.97 [1.06-3.65]) or Hispanic (OR = 3.61 [1.42-9.16]) race, were associated with missed appointment. Implementation of patient navigation reduced missed appointment rates for CaP related ambulatory encounters. Identifying risk factors for missed appointment may aid in targeting navigation services to those most likely to benefit from this intervention.

Both acute and chronic inflammation are associated with less perineural invasion in men with prostate cancer on repeat biopsy.

OBJECTIVES: To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). MATERIAL AND METHODS: We conducted a retrospective analysis of 1 399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation and PNI were assessed by central pathology review. The association between acute and chronic inflammation with PNI was evaluated using chi-squared and Kruskal-Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. RESULTS: The presence of PNI was identified in 133 biopsies (9.5%). In all, 267 biopsies (19.1%) had acute inflammation, 1 038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of both acute and chronic inflammation had a mutual association (P < 0.001). Chronic inflammation was associated with a lower Gleason score (P = 0.009) and lower tumour volume (P < 0.001), while acute inflammation was associated with lower Gleason score (P = 0.04), lower tumour volume (P = 0.004) and higher prostate-specific antigen levels (P = 0.05). In both univariable and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable odds ratio [OR] 0.54, 95% confidence interval [CI] 0.37-0.79, P = 0.001; multivariable OR 0.65, 95% CI 0.43-0.99, P = 0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR 0.51, 95% CI 0.29-0.89, P = 0.018; multivariable OR 0.63, 95% CI 0.35-1.13, P = 0.12). CONCLUSION: Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in patients with PCa.

Implementation of multiparametric magnetic resonance imaging technology for evaluation of patients with suspicion for prostate cancer in the clinical practice setting.

OBJECTIVES: To investigate the impact of implementing magnetic resonance imaging (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa) detection rates in men presenting with clinical suspicion for PCa in the clinical practice setting. PATIENTS AND METHODS: We performed a review of 1 808 consecutive men referred for elevated prostate-specific antigen (PSA) level between 2011 and 2014. The study population was divided into two groups based on whether MRI was used as a risk stratification tool. Univariable and multivariable analyses of biopsy rates and overall and clinically significant PCa detection rates between groups were performed. RESULTS: The MRI and PSA-only groups consisted of 1 020 and 788 patients, respectively. A total of 465 patients (45.6%) in the MRI group and 442 (56.1%) in the PSA-only group underwent biopsy, corresponding to an 18.7% decrease in the proportion of patients receiving biopsy in the MRI group (P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was significantly higher in the MRI vs the PSA-only group. In logistic regression analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.29-2.35; P < 0.001) and clinically significant PCa detection (OR 2.04, 95% CI 1.48-2.80; P < 0.001) were higher in the MRI than in the PSA-only group after adjusting for clinically relevant PCa variables. CONCLUSION: Among men presenting with clinical suspicion for PCa, addition of MRI increases detection of clinically significant cancers while reducing prostate biopsy rates when implemented in a clinical practice setting.

Inflammation on Prostate Needle Biopsy is Associated with Lower Prostate Cancer Risk: A Meta-Analysis.

PURPOSE: We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. MATERIALS AND METHODS: We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. RESULTS: Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337-0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450-0.913 and OR 0.499, 95% CI 0.334-0.665, respectively). CONCLUSIONS: In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis.

The Association of Previous Prostate Biopsy Related Complications and the Type of Complication with Patient Compliance with Rebiopsy Scheme.

PURPOSE: Prostate biopsy complications have important consequences that may affect patient compliance with rebiopsy schemes. However, to our knowledge this has not been studied in earnest. Thus, we evaluated whether previous prostate biopsy related complications and the type of complication were associated with repeat prostate biopsy compliance in a clinical trial with study mandated systematic biopsies. MATERIALS AND METHODS: We retrospectively analyzed the records of 4,939 men 50 to 75 years old who underwent 2-year prostate biopsy and were recommended to undergo 4-year prostate rebiopsy in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study. The analyzed biopsy complications were hematuria, urinary tract infection, acute urinary retention and hemospermia. RESULTS: A total of 260 men (5.3%) had a 2-year prostate biopsy related complication, including hematuria in 180 (3.6%), urinary tract infection in 36 (0.7%), acute urinary retention in 26 (0.5%) and hemospermia in 102 (2.1%). A total of 474 men (9.6%) were noncompliant with 4-year rebiopsy. On univariable analysis any previous complication (OR 1.56, 95% CI 1.08-2.24, p = 0.018), urinary tract infection (OR 2.72, 95% CI 1.23-6.00, p = 0.013), acute urinary retention (OR 4.24, 95% CI 1.83-9.81, p = 0.016) and hemospermia (OR 1.78, 95% CI 1.03-3.06, p = 0.037) were associated with rebiopsy noncompliance. Hematuria was not associated with rebiopsy noncompliance (OR 1.19, 95% CI 0.74-1.91, p = 0.483). Results were unchanged on multivariable analysis, including for any complication (OR 1.65, 95% CI 1.08-2.26, p = 0.018), for urinary tract infection (OR 2.62, 95% CI 1.07-3.21, p = 0.029), for acute urinary retention (OR 4.51, 95% CI 1.93-10.54, p = 0.001), for hemospermia (OR 1.85, 95% CI 1.07-3.21, p = 0.029) and for hematuria (OR 1.19, 95% CI 0.74-1.93, p = 0.472). CONCLUSIONS: In men who undergo repeat prostate biopsy a previous biopsy related complication and the type of complication were associated with lower compliance with rebiopsy schemes. Patients who experience biopsy related complications are ideal candidates to receive intervention regarding the importance of prostate rebiopsy to prevent noncompliance.

Sleep Problems are Associated with Development and Progression of Lower Urinary Tract Symptoms: Results from REDUCE.

PURPOSE: Although lower urinary tract symptoms and sleep problems often develop together, to our knowledge it is unknown whether sleep disturbances are linked to lower urinary tract symptoms development and progression. As measured by the 6-item MOS-Sleep (Medical Outcomes Study Sleep Scale) survey we examined the relationship between sleep problems, and the development and progression of lower urinary tract symptoms in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study. MATERIALS AND METHODS: REDUCE was a randomized trial testing prostate cancer chemoprevention with dutasteride in men with prostate specific antigen 2.5 to 10 ng/ml and a negative biopsy. At baseline men completed MOS-Sleep and a scaled average was used to calculate the sleep score. Men were followed for 4 years and I-PSS (International Prostate Symptom Score) was completed at baseline and every 6 months. Asymptomatic men had I-PSS less than 8 while symptomatic men had I-PSS 8 or greater. In the placebo arm of 2,588 men not receiving α-blockers or 5α-reductase inhibitors at baseline we tested the association between sleep problems and lower urinary tract symptom development and progression using Cox models. RESULTS: During followup lower urinary tract symptoms developed in 209 of 1,452 asymptomatic men (14%) and 580 of 1,136 (51%) with lower urinary tract symptoms demonstrated progression. On multivariable analysis higher sleep scores were suggestively associated with increased lower urinary tract symptoms in asymptomatic men (quartile 4 vs 1 HR 1.41, 95% CI 0.92-2.17, p = 0.12) and with lower urinary tract symptom progression in symptomatic men (per 10 points of sleep score HR 1.06, 95% CI 1.01-1.12, p = 0.029). CONCLUSIONS: Among men with lower urinary tract symptoms worse sleep scores were associated with the progression of lower urinary tract symptoms and among asymptomatic men worse sleep scores were suggestively associated with the development of lower urinary tract symptoms. If confirmed, these data suggest that sleep problems may precede such symptoms. Whether treating sleep problems would improve lower urinary tract symptoms requires further testing.

Radical prostatectomy and the effect of close surgical margins: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

OBJECTIVE: To evaluate biochemical recurrence (BCR) patterns amongst men undergoing radical prostatectomy (RP) with specimens having negative (NSM), positive (PSM), and close surgical margins (CSM) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. PATIENTS AND METHODS: Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM, PSM, and CSM. CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate-specific antigen (PSA) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR, metastases, and mortality were analysed using Cox proportional hazard models. RESULTS: Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM, 1902 (44%) had PSM, and 372 (8%) had CSM. On multivariable analysis, relative to NSM, men with CSM had a higher risk of BCR (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.25-1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM (HR 2.09, 95% CI 1.86-2.36; P < 0.001). Metastases, prostate cancer-specific mortality and all-cause mortality did not differ based on margin status alone. CONCLUSIONS: Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.

Determinants of Clinic Absenteeism: A Novel Method of Examining Distance from Clinic and Transportation.

Delayed treatment and non-adherence are associated with inferior prostate cancer (CaP) outcomes. Missed clinic appointments (MA) are one form of non-adherence that may be preventable. We conducted a retrospective cohort study of 1341 scheduled clinic encounters for men referred to an academic urology clinic for evaluation of known or suspected CaP. Driving distance and public transit times were calculated using a Google Distance Matrix API algorithm. Zip code level data regarding socioeconomic status was obtained from the 2013 American Community Survey. Logistic regression multivariate analysis was used to identify MA predictors. Of scheduled clinic encounters, 14% were missed. Public health insurance was associated with MA (Private insurance 10%, Public insurance 19%), (p < 0.01) Calendar month was associated with MA with December showing the highest rate (21.2%) and June the lowest (5.3%) rates. (p = 0.02) Appointments for suspected CaP were more likely to be missed (19.3%) than those for known CaP (10.5%), p < 0.01. Driving distance was inversely associated with rate of MA (CA median 11.8 miles, MA median 10.4 miles, p = 0.04) while public transit times were not (66.7 min for CA, 65.3 min for MA, p = 0.36). Men that missed appointments were from areas with lower household incomes and educational attainment. Patient encounter type, insurance status, and reason for referral remained significantly associated with MA after multivariable adjusted analysis. By computing public transit time to the clinic using a mapping engine, we present a novel way to measure this parameter for studies of urban health care.

Association of Obesity-Related Hemodilution of Prostate-Specific Antigen, Dihydrotestosterone, and Testosterone.

BACKGROUND: Prostate-specific antigen (PSA) hemodilution is the leading theory for lower PSA values in obese men. However, testosterone and dihydrotestosterone (DHT), which are necessary for PSA production, are reduced in obese men. We assessed the relationship of body mass index (BMI) and PSA, taking into consideration the effect of testosterone and DHT. METHODS: Among 8,122 participants in Reduction by Dutasteride of Prostate Cancer Events (REDUCE), complete data were available for 7,275. BMI was categorized as normal (<25 kg/m2 ), overweight (25-29.9 kg/m2 ), obese (30-34.9 kg/m2 ), or moderate + severely obese (≥35 kg/m2 ). Associations between BMI, testosterone, and DHT and the outcome variable of PSA were examined using linear regression. RESULTS: There were 1,964 (27.0%) normal weight, 3,826 (52.6%) overweight, 1,200 (16.5%) obese, and 285 (3.9%) moderately + severely obese patients. With increasing BMI, there was a progressive decrease in PSA (P = 0.02), increase in prostate volume (P < 0.001), and decrease in both testosterone (P < 0.001) and DHT (P < 0.001). Using linear regression, increasing BMI was associated with decreasing serum PSA values. Furthermore, BMI remained inversely associated with PSA after individually adjusting for testosterone and DHT, as well as when adjusting for testosterone and DHT in the same model. Decreased androgen levels accounted for only 19% of the lower PSA in men with higher BMI. CONCLUSIONS: Only a fraction of lower PSA in obese men could be attributed to testosterone and DHT levels. The remaining factors explaining lower PSA are unaccounted for, presumably secondary to hemodilution associated with increased plasma volume in obese men. Prostate 77:466-470, 2017. © 2016 Wiley Periodicals, Inc.

Chronic Prostate Inflammation Predicts Symptom Progression in Patients with Chronic Prostatitis/Chronic Pelvic Pain.

PURPOSE: We examined the 4-year longitudinal association between histological prostate inflammation and chronic prostatitis/chronic pelvic pain syndrome. We also studied the development of new and progressing existing chronic prostatitis/chronic pelvic pain syndrome in men randomized to placebo in the REDUCE (REduction by DUtasteride of prostate Cancer Events) population. MATERIALS AND METHODS: At multiple time points during 4 years univariable and multivariable analyses were performed between acute and chronic inflammation detected on baseline biopsies and the incidence of chronic pelvic pain syndrome-like symptoms, defined as a positive response to CPSI (Chronic Prostatitis Symptom Index) question 1a-perineal pain and/or question 2b-ejaculatory pain and a total pain subscore of at least 4, and progression of chronic prostatitis/chronic pelvic pain syndrome, defined as a 4-point or greater increase from baseline in total CPSI score, in patients with a baseline categorization of chronic prostatitis/chronic pelvic pain syndrome. RESULTS: Of the 4,109 men in the study acute and chronic inflammation was detected in 641 (15.6%) and 3,216 (78.3%), respectively. Chronic prostatitis/chronic pelvic pain syndrome symptom status was available for 2,816 at baseline. Chronic prostatitis/chronic pelvic pain syndrome-like symptoms developed in 317 of 2,150 men without the condition at baseline who had followup data. Acute and chronic inflammation was not associated with the incidence of the symptoms (p >0.1). At a median followup of 12.0 months 109 of 145 men with baseline chronic prostatitis/chronic pelvic pain syndrome and followup data showed symptomatic progression. Chronic but not acute inflammation was significantly associated with shorter time to progression on univariable and multivariable analyses (p = 0.029 and 0.018, respectively). CONCLUSIONS: Inflammation is not associated with an increased risk of chronic prostatitis/chronic pelvic pain syndrome. However, chronic inflammation predicts the risk of symptomatic progression in men in whom chronic prostatitis/chronic pelvic pain syndrome symptoms have been identified.

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.

Lymph Node Dissection is Not Associated with Improved Survival among Patients Undergoing Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: A Propensity Score Based Analysis.

PURPOSE: The oncologic benefit of lymph node dissection for patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma is uncertain. Therefore, we evaluated the association of lymph node dissection with oncologic outcomes among patients undergoing cytoreductive nephrectomy. MATERIALS AND METHODS: We identified 305 patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma between 1990 and 2010, of whom 188 (62%) underwent lymph node dissection. Several propensity score techniques were used to evaluate cancer specific and all cause mortality. Internally predicted probabilities for pN1 disease were estimated using logistic regression. RESULTS: Overall 74 (24%) patients had pN1 disease and median followup was 8.5 years (IQR 5.6-10.7). After propensity score adjustment there were no significant differences in clinicopathological features according to whether lymph node dissection was performed. In the overall cohort lymph node dissection was not significantly associated with cancer specific or all cause mortality using any of the propensity score techniques. Moreover, lymph node dissection was not associated with survival outcomes in patients at increased risk for pN1 disease, including patients with preoperative radiographic lymphadenopathy (cN1) or across increasing probability thresholds for pN1 disease from 0.20 to 0.80. Nodal metastases were associated with more aggressive primary tumor features and significantly shorter cancer specific survival. CONCLUSIONS: Among patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma, lymph node dissection was not associated with improved oncologic outcomes in the overall cohort, for patients with preoperative radiographic lymphadenopathy or across increasing probability thresholds for pN1 disease. These findings suggest that lymph node dissection at cytoreductive nephrectomy does not confer an oncologic benefit by cytoreduction of nodal metastases. The presence of nodal metastases is associated with more aggressive tumor biology.

Redefining and Contextualizing the Hospital Volume-Outcome Relationship for Robot-Assisted Radical Prostatectomy: Implications for Centralization of Care.

PURPOSE: Robot-assisted radical prostatectomy has undergone rapid dissemination driven in part by market forces to become the most frequently used surgical approach in the management of prostate cancer. Accordingly, a critical analysis of its volume-outcome relationship has important health policy implications. Therefore, we evaluated the association of hospital robot-assisted radical prostatectomy volume with perioperative outcomes, and examined the distribution of hospital procedure volume to contextualize the volume-outcome relationship. MATERIALS AND METHODS: We identified 140,671 men who underwent robot-assisted radical prostatectomy from 2009 to 2011 in NIS (Nationwide Inpatient Sample). The associations of hospital volume with perioperative outcomes and total hospital costs were evaluated using multivariable logistic regression and generalized linear models. RESULTS: In 2011, 70% of hospitals averaged 1 robot-assisted radical prostatectomy per week or less, accounting for 28% of surgeries. Compared to patients treated at the lowest quartile hospitals, those treated at the highest quartile hospitals had significantly lower rates of intraoperative complications (0.6% vs 1.4%), postoperative complications (4.8% vs 13.9%), perioperative blood transfusion (1.5% vs 4.0%), prolonged hospitalization (4.3% vs 13.8%) and mean total hospital costs ($12,647 vs $15,394, all ptrend <0.001). When modeled as a nonlinear continuous variable, increasing hospital volume was independently associated with improved rates of each perioperative end point up to approximately 100 robot-assisted radical prostatectomies per year, beyond which there appeared to be marginal improvement. CONCLUSIONS: Increasing hospital robot-assisted radical prostatectomy volume was associated with improved perioperative outcomes up to approximately 100 surgeries per year, beyond which there appeared to be marginal improvement. A substantial proportion of these procedures is performed at low volume hospitals.

Biopsy Detected Gleason Pattern 5 is Associated with Recurrence, Metastasis and Mortality in a Cohort of Men with High Risk Prostate Cancer.

PURPOSE: We evaluated the relative risk of biochemical recurrence, metastasis and death from prostate cancer contributed by biopsy Gleason pattern 5 among men at high risk with Gleason 8-10 disease in the SEARCH (Shared Equal Access Regional Cancer Hospital) cohort. MATERIALS AND METHODS: Men with biopsy Gleason sum 8-10 prostate cancer treated with radical prostatectomy were evaluated. The cohort was divided into men with Gleason 4 + 4 vs those with any pattern 5 (ie Gleason 3 + 5, 5 + 3, 4 + 5, 5 + 4 or 5 + 5). Predictors of biochemical recurrence, metastases, and prostate cancer specific and overall survival were analyzed using Kaplan-Meier, log rank test and Cox proportional hazards models. RESULTS: We identified 634 men at high risk in the SEARCH database, of whom 394 (62%) had Gleason 4 + 4 and 240 (38%) had Gleason pattern 5 on biopsy. Baseline characteristics did not significantly differ between the groups. On multivariable analysis relative to Gleason 4 + 4 men at high risk with Gleason pattern 5 showed no difference in the risk of biochemical recurrence (HR 1.26, 95% CI 0.99-1.61, p = 0.065). However, they were at significantly greater risk for metastasis (HR 2.55, 95% CI 1.50-4.35, p = 0.001), prostate cancer specific mortality (HR 2.67, 95% CI 0.1.26-5.66, p = 0.010) and overall mortality (HR 1.60, 95% CI 1.09-2.34, p = 0.016). CONCLUSIONS: Preoperative subclassification of high risk prostate cancer by biopsy Gleason grade (4 + 4 vs any Gleason pattern 5) identified men at highest risk for progression. Any Gleason 5 on biopsy is associated with a greater risk of metastasis, and prostate cancer specific and overall mortality. Grouping all Gleason 8-10 tumors together as high risk lesions may fail to fully stratify men at highest risk for poor outcomes.