The evolving clinical picture of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): A look at 1310 patients over 16 years.

INTRODUCTION: Two decades of increasing understanding of etiopathogenesis and clinical phenotyping produces an impression the clinical face of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is changing. We sought to retrospectively analyze trends in CP/CPPS patients presenting to our clinic for evaluation over a 16-year period. METHODS: Patients with CP/CPPS presenting to a tertiary clinic were evaluated prospectively from 1998-2014 with Chronic Prostatitis Symptom Index (CPSI) and UPOINT (urinary, psychosocial, organ-specific, infection, neurogenic, and tenderness) categorization. Patients were stratified in four cohorts, based on year of presentation, and we retrospectively analyzed variations in symptom scores and patterns, UPOINT categorization, and treatment modalities amongst cohorts. RESULTS: Mean age of the 1310 CP/CPPS patients was 44.7 years, while mean CPSI pain, urination, and total scores were 10.6, 4.8, and 23.3, respectively. The most prevalent UPOINT domain, urinary (U) (71.8%) was associated with a higher CPSI urination score (6.3), more frequent penile tip pain (37%), dysuria (48%), and more treatment with alpha-blockers (70%). Increase in UPOINT domains was associated with higher CPSI pain, quality of life (QoL), and total scores. Trends over time included increased prevalence of psychosocial (P), organ (O), and tenderness (T) domains, as well as increased use of alpha-blockers, neuromodulation, and phytotherapy as treatment modalities. There was little variation in age, CPSI scores, and pain locations over time. CONCLUSIONS: The changing clinical face of CP/CPPS reflects the increased recognition of psychosocial (P domain) and pelvic floor pain (T domain), along with the concomitant use of associated therapies. There was little variation of pain/urinary symptom patterns and QoL.

Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

CONTEXT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that causes severe symptoms, bother, and quality-of-life impact in the 8.2% of men who are believed to be affected. Research suggests a complex pathophysiology underlying this syndrome that is mirrored by its heterogeneous clinical presentation. Management of patients diagnosed with CP/CPPS has always been a formidable task in clinical practice. Due to its enigmatic etiology, a plethora of clinical trials failed to identify an efficient monotherapy. OBJECTIVE: A comprehensive review of published randomized controlled trials (RCTs) on the treatment of CP/CPPS and practical best evidence recommendations for management. EVIDENCE ACQUISITION: Medline and the Cochrane database were screened for RCTs on the treatment of CP/CPPS from 1998 to December 2014, using the National Institutes of Health Chronic Prostatitis Symptom Index as an objective outcome measure. Published data in concert with expert opinion were used to formulate a practical best evidence statement for the management of CP/CPPS. EVIDENCE SYNTHESIS: Twenty-eight RCTs identified were eligible for this review and presented. Trials evaluating antibiotics, α-blockers, anti-inflammatory and immune-modulating substances, hormonal agents, phytotherapeutics, neuromodulatory drugs, agents that modify bladder function, and physical treatment options failed to reveal a clear therapeutic benefit. With its multifactorial pathophysiology and its various clinical presentations, the management of CP/CPPS demands a phenotypic-directed approach addressing the individual clinical profile of each patient. Different categorization algorithms have been proposed. First studies applying the UPOINTs classification system provided promising results. Introducing three index patients with CP/CPPS, we present practical best evidence recommendations for management. CONCLUSIONS: Our current understanding of the pathophysiology underlying CP/CPPS resulting in this highly variable syndrome does not speak in favor of a monotherapy for management. No efficient monotherapeutic option is available. The best evidence-based management of CP/CPPS strongly suggests a multimodal therapeutic approach addressing the individual clinical phenotypic profile. PATIENT SUMMARY: Chronic prostatitis/chronic pelvic pain syndrome presents a variable syndrome. Successful management of this condition is challenging. It appears that a tailored treatment strategy addressing individual patient characteristics is more effective than one single therapy.

Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: insights from a randomized, double-blind, placebo controlled study.

PURPOSE: We compared the efficacy and safety of the currently recommended dose of pentosan polysulfate sodium with a third of the daily dose and with placebo. MATERIALS AND METHODS: In this multicenter, double-blind, randomized, placebo controlled study 368 adults with interstitial cystitis/bladder pain syndrome, defined as an ICSI total score of 8 or greater and a score of greater than 0 on the 4 ICSI component items, received pentosan polysulfate sodium 100 mg once daily or 3 times daily, or matching placebo for 24 weeks. Study eligibility was not based on cystoscopy findings. ICSI was administered at baseline, and at weeks 4, 8, 12, 18 and 24. Unblinded interim analysis performed at 6 years with 54% of the target number of 645 patients enrolled resulted in early study termination. RESULTS: There was no statistically significant difference between the pentosan polysulfate sodium group and the placebo group or between the 2 pentosan polysulfate sodium groups for the primary end point, defined as responder achieving a 30% or greater reduction from the baseline ICSI total score at study end. This primary end point was achieved by 48 of 118 patients (40.7%) in the placebo group, and by 51 of 128 (39.8%) and 52 of 122 (42.6%) in the pentosan polysulfate sodium 100 mg once daily and 3 times daily groups, respectively. Pentosan polysulfate sodium was well tolerated with a similar percent of patients (range 10.2% to 13.3%) across the groups discontinuing due to an adverse event. CONCLUSIONS: Results of this study in a broad population of patients with symptoms consistent with interstitial cystitis revealed no treatment effect vs placebo for pentosan polysulfate sodium at the currently established dose or at a third of the daily dose.

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

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

Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis.

CONTEXT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial. OBJECTIVE: To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among α-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo. DATA SOURCES: We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines. STUDY SELECTION: Randomized controlled trials comparing drug treatments in CP/CPPS patients. DATA EXTRACTION: Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and random-effects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects. DATA SYNTHESIS: Twenty-three of 262 studies identified were eligible. Compared with placebo, α-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of -1.7 (95% confidence interval [CI], -2.8 to -0.6), -1.1 (95% CI, -1.8 to -0.3), -1.4 (95% CI, -2.3 to -0.5), and -1.0 (95% CI, -1.8 to -0.2), respectively. Patients receiving α-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1-2.3) and 1.8 (95% CI, 1.2-2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of α-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (-9.8; 95% CI, -15.1 to -4.6), pain scores (-4.4; 95% CI, -7.0 to -1.9), voiding scores (-2.8; 95% CI, -4.1 to -1.6), and quality-of-life scores (-1.9; 95% CI, -3.6 to -0.2) compared with placebo. Combining α-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of -13.8 (95% CI, -17.5 to -10.2) for total symptom scores, -5.7 (95% CI, -7.8 to -3.6) for pain scores, -3.7 (95% CI, -5.2 to -2.1) for voiding, and -2.8 (95% CI, -4.7 to -0.9) for quality-of-life scores. CONCLUSIONS: α-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti-inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of α-blockers may be overestimated because of publication bias.

Impact of medical therapy on transurethral resection of the prostate: two decades of change.

OBJECTIVE: • To examine how the introduction of medical therapy for symptomatic benign prostatic hyperplasia (BPH) might have changed the indications, patient characteristics and outcomes in men undergoing transurethral resection of the prostate (TURP) over two decades (1988-2008). PATIENTS AND METHODS: • All patients who underwent TURP for symptomatic BPH in a geographically defined area at our institution in 1988 (before the introduction of medical therapy for BPH), 1998 (when medical therapy was becoming an important therapy for BPH), and 2008 (when medical therapy was the primary first line therapy for BPH) were reviewed. • We assessed the total number of TURPs, indications for surgery, patient age, health status, weight of resected tissue, and pre- and postoperative events/complications. RESULTS: • There was a 60% decrease in TURPs from 1988 to 1998 with a moderate increase in number in 2008. • Failure of medical therapy was not an indication for TURP in 1988, but was at least one of the indications in 36% and 87% of patients in 1998 and 2008, respectively. • There was a substantial rise in the percentage of patients (but not total number or percentage of men at risk for BPH) presenting with acute or chronic urinary retention (AUR or CUR) at the time of their TURP (from 22.9% in 1988 to 42.9% in 2008, and from 14.6% in 1988 to 39.3% in 2008 for AUR and CUR, respectively). There was also a rise in the percentage of patients presenting with preoperative hydronephrosis (1.3% in 1988, 12.5% in 1998, 7.1% in 2008). • Inpatient stays decreased (from 4.1 day in 1988 to 2.7 days in 1998, and to 2.1 day in 2008), but the number of patients discharged with a catheter increased over the two decades (from 3.2% in 1988 to 12.5% in 1998, and to 28.6% in 2008). CONCLUSIONS: • The increasing use of medical therapy as a first line treatment for BPH has resulted in a dramatic decrease in TURPs which, in turn, has been associated with an apparent increase in risk of poor pre- and postoperative outcomes. However, the actual number (either the total number or as a percentage of men at risk for BPH) who have experienced these progression events has not changed and the postoperative outcomes are probably related to earlier catheter removal and hospital discharge. • It appears that we are performing TURP on the right patients.

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

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

The relationship among symptoms, sleep disturbances and quality of life in patients with interstitial cystitis.

PURPOSE: We conducted a retrospective analysis to determine associations among symptoms, sleep disturbances and quality of life in responder and nonresponder groups of patients with interstitial cystitis. MATERIALS AND METHODS: Patients in a multidose pentosan polysulfate sodium clinical trial with a diagnosis of interstitial cystitis who were randomized to 300 mg pentosan polysulfate sodium per day (128) completed the Interstitial Cystitis Symptom Index, an adapted Medical Outcomes Study Sleep scale and the Medical Outcomes Study Short Form-12 Health Survey at baseline, and at weeks 8, 16, 24 and 32. Responders were defined as those achieving a 30% or greater reduction in Interstitial Cystitis Symptom Index score from baseline to study end point (week 32 or last observation carried forward). RESULTS: A positive correlation at baseline was observed between sleep scores and Short Form-12 physical and mental components (r = 0.43 and 0.37, respectively, p <0.0001). Patients showed statistically significant improvement in Interstitial Cystitis Symptom Index and sleep scores by week 32. Responders (48, 43%) had a mean change in sleep score of 11.8 +/- 22.4 while nonresponders (64, 57%) had a mean change of 1.6 +/- 15.7 (p = 0.0055 between groups). The reduction in Interstitial Cystitis Symptom Index score correlated with improvement in sleep score from baseline to study end point (r = -0.33, p = 0.0003). At the study end point responders demonstrated a significant improvement in the Short Form-12 physical component compared with baseline (p <0.0001). CONCLUSIONS: Reduction in interstitial cystitis symptoms may be associated with patient reported improvement in sleep and quality of life.

Association between response to pentosan polysulfate sodium therapy for interstitial cystitis and patient questionnaire-based treatment satisfaction.

OBJECTIVE: To evaluate the relationship between symptom reduction and satisfaction with pentosan polysulfate sodium (PPS) therapy in subjects with interstitial cystitis (IC). METHODS: A secondary analysis was conducted in 128 subjects treated with PPS 300 mg/day (US Food and Drug Administration-approved dose) from a 32-week multicenter, randomized, double-blind study of 380 subjects with IC who were treated with PPS 300 mg/day, 600 mg/day, or 900 mg/day. Self-rated outcome measures included the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and a treatment satisfaction questionnaire. Treatment responders were defined as subjects having > or =30% reduction in ICSI from baseline to study end point. RESULTS: A reduction in IC symptoms was associated with significantly higher satisfaction with PPS (p < 0.05). Compared with nonresponders, subjects achieving a > or = 30% reduction in ICSI were more likely to be pleased with PPS for IC symptoms, to have benefited from PPS for their IC symptoms, to recommend PPS for IC symptoms to others with the same condition, and to say that PPS provides better relief, based on prior experience with other IC treatments. Among all subjects at week 32, 75% said they would recommend PPS therapy for IC symptoms to others with the condition. CONCLUSION: Despite limitations (lack of placebo control, use of a nonvalidated instrument), this analysis demonstrated significantly increased treatment satisfaction with PPS therapy among treatment responders versus nonresponders. There was a significant positive correlation between ICSI scores and response on the treatment satisfaction questionnaire. Treatment response and patient satisfaction with treatment are important clinical considerations in the management of patients with IC.

Time to initiation of pentosan polysulfate sodium treatment after interstitial cystitis diagnosis: effect on symptom improvement.

OBJECTIVES: Interstitial cystitis (IC) is a chronic, debilitating condition that is often associated with late diagnosis and a delay in initiation of appropriate IC-specific therapy. The purpose of this study was to determine whether the length of time from initial diagnosis to start of treatment impacts subsequent symptom improvement. METHODS: A retrospective analysis was conducted in 128 patients with IC who had been treated with pentosan polysulfate sodium (PPS) 300 mg/day for 32 weeks in a multicenter, randomized, double-blind, parallel-group clinical trial. Outcome measures included the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and the O'Leary-Sant Interstitial Cystitis Problem Index (ICPI). Early treatment was defined as treatment initiation 6 months or less after IC diagnosis, whereas late treatment was defined as treatment initiation 24 months or more after IC diagnosis. Efficacy data were analyzed by using the intent-to-treat, last-observation-carried-forward population. RESULTS: At the end of the study, mean changes from baseline in total ICSI and ICPI scores (+/- SEM) for early treatment (6 months or less) versus late treatment (24 months or more) were 3.97 +/- 0.59 versus 2.15 +/- 0.70 (P = 0.0472) and 3.94 +/- 0.56 versus 1.77 +/- 0.63 (P = 0.0117), respectively. Similar trends for both measures were observed when examining other times from IC diagnosis (3 months or less versus 24 months or more, 3 months or less versus 36 months or more, and 6 months or less versus 36 months or more). CONCLUSIONS: Initiation of PPS treatment within 6 months of establishing the diagnosis of IC may be associated with greater improvement in patient symptoms and symptom bother.

Clinical significance of nontraditional bacterial uropathogens in the management of chronic prostatitis.

PURPOSE: We compared the clinical benefits of eradicating traditional accepted uropathogens and nontraditional uropathogens (gram-positive bacteria other than enterococci) in prostate specific specimens in men with clinical prostatitis. MATERIALS AND METHODS: Men with prostatitis-like symptoms and any bacteria localized to prostate specific specimens were treated with levofloxacin or ciprofloxacin for 4 weeks with 6 months of followup. Rates of bacterial eradication and clinical responses in group 1, who had uropathogenic localization (eg Escherichia coli and Enterococcus faecalis), were compared to those in group 2, who had bacteria considered nonuropathogens (eg coagulase negative Staphylococcus species and Streptococcus species). RESULTS: Of the men 261, including 146 in group 1 and 115 in group 2, were available for analyses. Mean age was 51.3 years and mean symptom duration was 8.4 weeks (median 3.5). Of the patients 107 (41%) had received previous antibiotic treatment. Bacteria eradication rates were similar in groups 1 and 2 (74.0% and 78.3%, respectively, p = 0.47). Clinical response rates were also similar in groups 1 and 2 (76.6% and 70.4%, respectively, p = 0.26). In groups 1 and 2 there was a statistically significant correlation between clinical and microbiological outcomes (chi-square analysis correlation p = 0.0014 and 0.0055, respectively). At 6 months of followup 70.5% of successfully treated group 1 patients were still considered to have a positive clinical response compared to 72.8% in group 2 (p = 0.75). CONCLUSIONS: Clinically acceptable short and long-term microbiological and clinical responses to fluoroquinolone therapy for clinical prostatitis did not depend on whether traditional uropathogenic bacteria or nontraditional uropathogens were isolated in prostate specific specimens.

Improvement in sexual functioning in patients with interstitial cystitis/painful bladder syndrome.

INTRODUCTION: Sexual functioning is one of the strongest predictors of poorer quality of life (QOL) in patients diagnosed with interstitial cystitis/painful bladder syndrome (IC/PBS). AIMS: To examine the relationship between symptom reduction and sexual functioning in patients with IC/PBS. METHODS: Patients with IC/PBS were treated with 300 mg/day pentosan polysulfate sodium for 32 weeks. MAIN OUTCOME MEASURES: Patients completed the O'Leary-Sant Interstitial Cystitis Symptom Index, Short Form-12 QOL, and Medical Outcomes Study Sexual Functioning Scale at baseline, and at 8, 16, 24, and 32 weeks. Treatment responders were defined as those achieving a >/=30% reduction in symptom index from baseline. RESULTS: A total of 128 patients were included in the analyses. At baseline, mean symptom index, QOL (physical and mental), and sexual functioning scores were 12.3, 41.7, 45.9, and 56.1, respectively. Patients showed statistically significant improvement in symptom and sexual functioning scores at weeks 8, 16, 24, and 32. At week 32, the mean change in symptom index score from baseline was -2.97 (standard deviation [SD] = 4.66, P < 0.0001), and the mean change in sexual functioning score from baseline was 8.9 (SD = 32.9, P = 0.0054). Reduction in symptom index score was moderately correlated with improvement in sexual functioning score at the end of study (r = -35, P = 0.0002). Positive correlation was observed at the end of the study between the mean change scores of sexual functioning score and physical and mental QOL components (r = 0.46, P < 0.0001 and r = 0.29, P = 0.0023, respectively). Patients achieving a >/=30% reduction in symptom index (responder, N = 47; 44%) had an adjusted mean change in sexual functioning score of 19.8 (standard error [SE] = 4.69), while nonresponders (N = 59, 56%) had an adjusted mean change -0.49 (SE = 4.17) (between groups, P = 0.0020). CONCLUSIONS: Sexual dysfunction is moderate to severe in patients with IC/PBS and impacts significantly on QOL. Reduction in symptoms was associated with improvement in the patient-reported outcomes of sexual function.

The economics of medical therapy for lower urinary tract symptoms associated with benign prostatic hyperplasia.

Medical therapy is currently the most popular treatment choice for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Because medical therapy of BPH-related LUTS is considered a life-long strategy, short- and long-term cost considerations should play a major role in therapeutic decision-making. The effectiveness in terms of long and short amelioration of symptoms, flow rate, and quality of life are well documented for 5alpha-blockers and 5alpha-reductase inhibitors as well as for the gold standard treatment for BPH, transurethral resection of the prostate and minimally invasive therapies. Short- and long-term safety concerns also are well documented for these various treatment options. On the contrary, short- and long-term costs have been less well studied and comparisons depend on the model or analyses undertaken in the few studies available. However, the economic studies based on prospective clinical trial data that have become available throughout the past several decades allow us to rationalize our use of alpha- blockers, 5alpha-reductase inhibitors, and combination therapy, taking into consideration age, severity of symptoms, prostate volume, prostate-specific antigen, and the differential response of the various medications (and combination) in selected patients. Based on current studies, 5alpha-blockers generally provide cost-effective therapy for most patients, whereas 5alpha-reductase therapy and combination therapy provide cost-effective treatment for patients with larger prostate glands or higher baseline prostate-specific antigen levels.

How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?

PURPOSE: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Stamey results were calculated from 2 x 2 contingency tables. RESULTS: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p <0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or VB3 confirms a positive 4-glass Meares-Stamey localization test. The sensitivity and specificity of a VB3 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. CONCLUSIONS: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained.

The overlapping lower urinary tract symptoms of benign prostatic hyperplasia and prostatitis.

PURPOSE OF REVIEW: To investigate the relationship, diagnosis and treatment of the overlapping lower urinary tract symptoms experienced by men diagnosed with benign prostatic hyperplasia and prostatitis. RECENT FINDINGS: Recent studies have clearly shown that men can suffer from both benign prostatic hyperplasia and prostatitis. Approximately 5-20% of men diagnosed with benign prostatic hyperplasia suffer from prostatitis-like symptoms, while over one third of men diagnosed with benign prostatic hyperplasia have had a diagnosis of prostatitis in the past. Differentiation between these two symptom-based medical conditions can be difficult because of overlapping symptoms, but pain clearly identifies those patients with chronic prostatitis. Treatment for men with co-occurring benign prostatic hyperplasia and prostatitis may include alpha-blockers, 5alpha-reductase inhibitors and phytotherapies (saw palmetto and bee pollen extract), with evidence clearly showing the benefits of alpha-blocker therapy. SUMMARY: Benign prostatic hyperplasia and chronic prostatitis are a common cause of lower urinary tract symptoms and frequently co-occur in older men. The best treatment for men with lower urinary tract symptoms associated with both benign prostatic hyperplasia and prostatitis is alpha-blockers.

Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study.

PURPOSE: We evaluated the efficacy and tolerability of pentosan polysulfate sodium (PPS) for the treatment of men with chronic pelvic pain syndrome (CPPS), National Institutes of Health (NIH) category III. MATERIALS AND METHODS: In a 16-week double-blind study 100 men with a clinical diagnosis of CPPS were randomized to receive 300 mg PPS or placebo 3 times daily. Clinical Global Improvement (CGI) was the primary outcome measure. Additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (CPSI), Subjective Global Assessment and Symptom Severity Index assessment tools. RESULTS: Significantly more patients receiving PPS experienced moderate to marked improvement based on CGI assessment (18 or 37% vs 8 or 18%, p = 0.04). However, mean CGI scores were not significantly different between the PPS group (1.0) and placebo groups (1.0 vs 0.6, p = 0.107). All NIH-CPSI domains suggested a positive effect for PPS and for total NIH-CPSI the difference approached statistical significance (-5.9 or 22% vs -3.2 or 12%, p = 0.068). The PPS group showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (-2.0 or 22% vs -1.0 or 12%, p = 0.031). Of patients receiving PPS 67% and 80% of those receiving placebo completed the 16-week study. Diarrhea, nausea and headache were the most common adverse events. CONCLUSIONS: Pentosan polysulfate (900 mg daily) was more likely than placebo to provide relief for CPPS symptoms.

Management of urinary tract infections: historical perspective and current strategies: Part 1--Before antibiotics.

PURPOSE: Urinary tract infections (UTIs) have plagued mankind long before bacteria were recognized as the causative agents of disease and before urology became an established medical specialty. To our knowledge a comprehensive review of the recorded medical history of UTI from its first description in ancient Egyptian papyri through today has not been attempted until now. MATERIALS AND METHODS: Numerous resources were used to collect the information described in this review. Older textbooks from the school of medicine library at our institution were used to collect information on UTI in ancient times. Medical texts from the 19th century contains information regarding the treatment of UTI during that era. Early volumes of the Journal of Urology from the beginning of the 20th century are rich with information on the first attempts at chemotherapy for UTI. MEDLINE searches were used to collect appropriate information after 1969. RESULTS: The Ebers papyrus from ancient Egypt recommended herbal treatments to ameliorate urinary symptoms without providing insight into pathological mechanisms. Hippocrates believed that disease was caused by disharmony of the 4 humors and accordingly diagnosed urinary disorders. Roman medicine further expanded the conservative approach (bed rest, diet, narcotics and herbs) advocated by Greek physicians, while also improving invasive techniques (surgical lithotomy for stones and catheterization for retention). The Arabian physician Aetius refined uroscopy and created a detailed classification and interpretation of urinary disease based on this technique. During the Middle Ages no major advances occurred, although existing therapies were refined and treatments for gonococcal urethritis were well described. The early 19th century provided vivid and detailed descriptions of UTIs without the knowledge that they were caused by microorganisms. Management included hospitalization, bed rest, attention to diet, plasters, narcotics, herbal enemas and douches, judicious bleeding (direct bleeding, cupping and leeches), and surgery for stones, abscess and retention. The discovery of microorganisms as the etiological agents of infectious diseases in general and inflammation associated with urinary diseases in particular provided an impetus for physicians critically to examine management approaches and develop evidence based strategies for UTI treatment. Various antibacterial agents, such as hexamine, mercurochrome and others (hexylresorcinol, methylene blue, pyridium, acriflavin and mandelic acid), showed promise in laboratory studies but their efficacy in clinical investigations was disappointing. CONCLUSIONS: Treatments for UTI until the discovery of antibiotics were largely palliative because the bacterial origin of UTI was not recognized and no specific antimicrobial therapies were available.

Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used. OBJECTIVE: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS. DESIGN: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo. SETTING: Urology outpatient clinics at 10 tertiary care medical centers in North America. PATIENTS: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment. MEASUREMENTS: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events. INTERVENTIONS: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo. RESULTS: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes. LIMITATIONS: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently. CONCLUSION: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.

Acupuncture for chronic prostatitis/chronic pelvic pain syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is prevalent in urological practice and has a significant impact on quality of life. Standard therapies often fail to achieve sustainable amelioration of symptoms. This article attempts to show that neuromodulatory treatment in the form of electroacupuncture can be a minimally invasive and effective treatment for CP/CPPS that is refractory to standard therapies. This neuromodulatory therapy lends support to the hypothesis that the end stage of CP/CPPS may be a neuropathic pain syndrome.