Search

Background: To use the European Association of Urology Research Foundation (EAURF) registry data to determine the proportion of contemporary Lower Urinary Tract Symptoms associated with Benign Prostatic Enlargement (LUTS/BPE) patients prescribed phytotherapy, and to determine their subjective quality of life and clinical progression responses., Methods: This was a prospective multicenter multinational observational registry study, conducted over 2 years. Men ≥ 50 years seeking LUTS/BPE were divided at baseline into two cohorts, presently/recently untreated patients (PUP) commencing pharmacotherapy at baseline and presently/recently treated patients (c-PTP) continuing previously received pharmacotherapy, with 24-month follow-up (FU)., Results: Overall, 2175 patients were enrolled with 1838 analyzed. Of the PUP cohort (n = 575), 92 (16%) received phytotherapy and 65 (71%, n = 65/92) completed 24-month FU, with France prescribing 34% (n = 30/89) the highest proportion of phytotherapy among all LUTS/BPE medications. In the c-PTP group (n = 1263), only 69 (5%) patients were using phytotherapy, falling to n = 35/69 (51%) at 24-month FU (highest in France 20% (n = 43/210)). Though defined disease progression occurred in ≤ 20%, with only 1% proceeding to surgical intervention, in both groups, clinically meaningful improvement was lower and symptom persistence was higher in PUP but similar in the treated (c-PTP) patients on phytotherapy compared to the other LUTS/BPE medication., Conclusion: Low heterogeneous prescribing rates for phytotherapy were reported in both PUP and c-PTP cohorts over the 24-month FU. Although phytotherapy led to subjective improvements, healthcare practitioners should prescribe them with caution until higher quality evidence and guideline recommendations supporting its use are available., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lower urinary tract symptoms due to benign prostate enlargement (LUTS/BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease specific and generic QOL measures., Methods: Evolution was a European prospective, multicenter multi-national, observational registry collecting real-life clinical data over 2 years on the management of LUTS/BPE in primary and secondary care. This study investigated disease-specific QOL using questionnaires such as IPSS Q8, BPH Impact Index (BII) and generic QOL using questionnaires like EuroQOL Five Dimension (EQ5D) which encompassed EQ5D VAS and EQ5D health index., Results: The registry enrolled 1838 BPE patients and 1246 patients were evaluable at the end of 24 months. Nearly 70% of patients in the study were previously treated with medical therapy and 17% of these had already discontinued medical treatment previously for various reasons with lack of efficacy being the most common. The mean time since diagnosis of LUTS in the previously treated group was 4.7 years (0-26 years). Medical management produced statistically significant improvement in QOL (disease specific and generic) in previously untreated patients and an insignificant change in generic QOL in previously treated patients., Conclusions: After 5-years from the onset of symptoms, LUTS/BPE patients previously treated with medication had significantly impaired QOL in patients in a manner comparable to other chronic diseases. Earlier intervention with minimally invasive surgical techniques (MIT) should be considered in LUTS/BPE patients that do not show a significant improvement in QOL with medical therapy.

Purpose: A cost minimisation analysis compares the costs of different interventions' to ascertain the least expensive over time. We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement (BPE)., Methods: The Evolution registry is a prospective, multicentre registry, conducted by the European Association of Urology Research Foundation (EAUrf) for 24 months in 5 European countries. Evolution was designed to register the management of symptomatic BPE in clinical practice settings in 5 European countries. Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed., Results: In total, 1838 men were enrolled with 1246 evaluable at 24 months. Medical therapies were more cost saving than TURP for treatment durations ranging from 2.9 to 70.4 years. Cost saving depended on both medication class and individual country assessed. Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy. Daily finasteride monotherapy was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain. Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany., Conclusions: BPE medical management was more cost saving than TURP for different specific treatment durations. Information from this study will allow clinicians to convey medical and surgical costs over time, to both patients and payors alike, when considering BPE treatment.

Context: Bacillus Calmette-Guérin (BCG) is currently the most effective intravesical therapy for nonmuscle invasive bladder cancer, reducing not only recurrence rates but also preventing progression and reducing deaths. However, response rates to BCG vary widely and are dependent on a multitude of factors., Objective: To review existing data on clinical, pathologic, immune, and molecular markers that allow prediction of BCG response., Evidence Acquisition: PubMed and MEDLINE search of English language literature was conducted from its inception to July 2017 using appropriate search terms. Following systematic literature review and analysis of data, consensus voting was used to generate the content of this review., Evidence Synthesis: As seen in the EORTC and CUETO risk nomograms, clinicopathologic features, especially tumor stage and grade, are the most effective predictors of BCG response. Data are less robust with regards to the association of response with age, female sex, recurrent tumors, multiplicity of tumors, and the presence of carcinoma in situ. Single biomarkers, such as tumor p53 and urinary interleukin-2 expression, have had limited success in predicting BCG response, possibly due to the multifaceted nature of the generated immune response. More comprehensive biomarker panels (eg, urinary cytokines), have a more robust correlation with response, as do patterns of urinary cytologic fluorescent in-situ hybridization examination. Gene expression data correlate with disease progression, but studies examining potential associations with BCG response are limited., Conclusions: Currently, the best predictors of BCG response are clinicopathologic features such as tumor grade and stage. Panels of urinary cytokines, as well as fluorescent in-situ hybridization patterns of cytologic anomalies, appear to be promising biomarkers. The complexity of the immune response to BCG and the heterogeneity of bladder cancer suggest that future studies should amalgamate measures reflecting innate immune response and tumor/stromal gene expression before these can be adopted for clinical use., Patient Summary: Bacillus Calmette-Guérin (BCG) immunotherapy is an effective treatment for many patients with nonmuscle invasive bladder cancer. An individual's response to BCG can be predicted by using various features of the cancer. In the future, predictive markers using molecular measures of the tumor type and the immune response to BCG may allow us to precisely know an individual's likely outcome after BCG treatment., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Compare the efficacy and tolerability of dutasteride in combination with bicalutamide to bicalutamide monotherapy in the treatment of locally advanced and metastatic prostate cancer (PCa)., Methods: One-hundred-fifty PCa patients with locally advanced or metastatic disease were prospectively enrolled and randomly assigned to receive either bicalutamide monotherapy 150 mg once daily (79 patients) or bicalutamide 150 mg plus dutasteride 0.5 mg once daily (71 patients). Treatment response was assessed by serum PSA level measurement, and standard procedures for diagnosis of clinical progression were used during follow-up. Patient-reported quality of life (QoL) was assessed using validated questionnaires (EORTC QLQ-C30 and QLQ-PR25)., Results: At 3 years follow-up, PSA progression was found in 52 patients [65.8 %; 95 % confidence interval (CI) 55.4-76.3] in the monotherapy group compared to 38 patients (53.5 %; 95 % CI 41.9-65.1) in the combined therapy group (p = 0.134). At the time of analysis 37 men (46.8 %; 95 % CI 35.8-57.8) in the monotherapy group had died versus 30 men (42.3 %; 95 % CI 30.8-53.7) in the combined therapy group. Median survival time was 5.4 and 5.8 years, respectively (p = 0.694). There was no statistically significant difference in the presentation frequency of adverse events between groups (p = 0.683). QoL was good and comparable between the two groups., Conclusions: Both therapies were well tolerated with a good QoL. However, despite a trend toward higher efficacy of the combined therapy, progression-free survival and overall survival was not significantly different between the groups. Further research on this therapy should be performed.

Purpose: To develop a model to predict recurrence for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) treated with intravesical chemotherapy which can be challenging because of the heterogeneous characteristics of these patients., Methods: Data from three Dutch trials were combined. Patients treated with intravesical chemotherapy with characteristics according to the IR definition of the EAU guideline 2013 were included. Uni- and multivariable Cox regression with selection methods were used to identify predictors of recurrence at 1, 2, and 5 years. An easy-readable table for recurrence probabilities was developed. An external validation was done using data from Spanish patients., Results: A total of 724 patients were available for analyses, of which 305 were primary patients. Recurrences occurred in 413 patients (57%). History of recurrences, history of intravesical treatment, grade 2, multiple tumors, and adjuvant treatment with epirubicin were relevant predictors for recurrence-free survival with hazard ratios of 1.48, 1.38, 1.22, 1.56, and 1.27, respectively. A table for recurrence probabilities was developed using these five predictors. Based on the probability of recurrence, three risk groups were identified. Patients in each of the separate risk groups should be scheduled for less or more aggressive treatment. The model showed sufficient discrimination and good predictive accuracy. External validation showed good validity., Conclusion: In our model, we identified five relevant predictors for recurrence-free survival in IR-NMIBC patients treated with intravesical chemotherapy. These recurrence predictors allow the urologists to stratify patients in risk groups for recurrence that could help in deciding for an individualized treatment approach.

Objective: To compare the risks according to the American Urological Association (AUA), EAU, European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncologico (CUETO) classifications with real outcomes in a cohort of patients in the Netherlands, and to confirm that patients who were undertreated according to these risk models have worse outcomes than adequately treated patients., Patients and Methods: Patients treated with complete transurethral resection of bladder tumour and intravesical chemotherapy were included. Not all patients would have received intravesical chemotherapy had they been treated to current standards, and thus comparison of the observed outcomes in our Dutch cohort vs expected outcomes based on the EORTC risk tables and CUETO scoring model was possible. The cohort was reclassified according to the definitions of five index patients (IPs), as defined by the AUA guidelines, and three risk groups, defined according to the EAU guidelines, to compare the outcomes of undertreated patients with those of adequately treated patients., Results: A total of 1001 patients were available for comparison with the AUA definitions and 728 patients were available for comparison with the EORTC and CUETO models. There was a large overlap between the observed outcomes and expected recurrence and progression probabilities when comparison was made using the EORTC risk tables. The observed recurrence outcomes were in general higher than the expected probabilities according to the CUETO risk classification, especially in the long term. No differences in progression were found when comparing these two models to the Dutch cohort. Patients who were undertreated according to the guidelines showed, in general, a higher risk of developing recurrence and progression. Limitations are i.a. its retrospective nature and the differences in grading system., Conclusion: Comparisons between the observed outcomes in our Dutch cohort and the expected outcomes based on EAU and CUETO risk models and the EORTC and AUA guidelines showed that lack of adherence to existing guidelines translates into worse outcomes., (© 2013 The Authors. BJU International © 2013 BJU International.)

The European Association of Urology Research Foundation has proposed that alternatives to perioperative chemotherapy should be evaluated. The MAGNOLIA study represents a unique opportunity to investigate the concept of immunotherapy in muscle-invasive bladder cancer., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The aim of our survey was to evaluate the usage and indications of various metastatic prostate cancer (PCa) therapies, and to identify barriers to usage of bisphosphonates (BPs)., Materials and Methods: Between March and June 2009, an internet-based survey was performed among board-certified urologists of the EAU who treated ≥ 10 patients with metastatic PCa annually., Results: Questionnaires completed by 200 urologists from 12 European countries including 27,442 PCa patients were used for analyses. On average, 22% of the patients presented in stage IV, 15% had bone metastases and 10% received BPs. In most countries, BPs were used to the same extent in hormone-naïve and castration-resistant PCa (CRPC). A total of 23% of urologists prescribed chemotherapy in patients with hormone-sensitive PCa, and 55% of the urologists did not administer androgen deprivation maintenance therapy in patients with CRPC., Conclusions: BPs were frequently used in PCa with bone metastases, although current guidelines recommend their use only in CRPC. Standardized multidisciplinary educational programs should be developed in order to prevent non-indicated early chemotherapy in hormone-sensitive patients and to stimulate maintenance of androgen deprivation therapy in CRPC patients. Also, programs facilitating home infusions for patients who need intravenous BPs are needed in specific countries to optimize treatment of CRPC., (Copyright © 2012 S. Karger AG, Basel.)

Background: Cigarette smoking is the most well-established risk factor for developing bladder cancer., Objective: To investigate the role of smoking status on the clinical outcome of patients with non-muscle-invasive bladder cancer., Design, Setting, and Participants: Data obtained during a prospective phase 3 study with three schedules of epirubicin were used for statistical analysis. Smoking status (obtained when entering the study), other prognostic variables, and clinical outcome measures of 718 patients were analyzed. Mean follow-up was 2.5 yr., Measurements: The primary outcome measure was recurrence-free survival (RFS)., Results and Limitations: Demographics were similar for nonsmokers versus ex-smokers and current smokers, except for gender (p<0.001) and grade (p=0.022). In univariate analyses, RFS was significantly shorter in male patients (p=0.020), in patients with a history of recurrences (p<0.003), in patients with multiple tumors (p<0.004), in patients with a history of intravesical therapy (p=0.037), and in ex-smokers and current smokers (p=0.005). In multivariate analyses, a history of recurrences, multiplicity, and smoking status remained significant factors for predicting RFS. Gender and initial therapy were no longer a significant influence on RFS. Because progression was uncommon (n=25) and follow-up was short and focused only on recurrences, no conclusion can be drawn on progression-free survival. A limitation of the study were the questionnaires. They were only used when entering the study, and there were no questions about passive smoking and other causal factors., Conclusions: In this prospective study, the significance of known factors (history of recurrences and number of tumors) in predicting RFS was confirmed. Another significant factor that appears to predict RFS is smoking status: ex-smokers and current smokers had a significantly shorter RFS compared with nonsmokers., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To study the additive effect of either an early instillation or maintenance instillations of adjuvant intravesical epirubicin, as compared to the epirubicin "standard" treatment schedule only, in patients with non-muscle-invasive bladder cancer., Methods: Patients with intermediate- and high-risk urothelial cell carcinoma of the bladder, except carcinoma in situ, were randomised for adjuvant intravesical instillations with 50mg epirubicin/50 ml NaCl for 1h. Group 1 received 4 weekly and 5 monthly instillations (standard schedule), group 2 received the same schedule as group 1, but with an additional instillation <48 h after transurethral resection of bladder tumour (TURBT), and group 3 received the same scheme as group 1, but with additional instillations at 9 and 12 mo (maintenance schedule). Standard follow-up was 5 yr and consisted of cystoscopy, cytology, and registration of adverse events., Results: A total of 731 patients were eligible for quasi intention-to-treat analysis. Side-effects were minimal for all treatment groups. After 5-yr follow-up, respectively, 44.4%, 42.7%, and 45.0% (log-rank test, p=0.712) of the patients in groups 1, 2, and 3 were recurrence free, and 90.0%, 87.7%, and 88.2% (log-rank test, p=0.593) of the patients, respectively, were progression free., Conclusions: In the quasi intention-to-treat analysis there is no difference in the 5-yr recurrence-free period between the treatment groups, despite one instillation within 48 h of TURBT or two maintenance instillations up to 1 yr, in addition to the "standard" schedule.

The treatment of hormone resistant prostate cancer) with epirubicin 25 mg/m(2)(Epi25) on a weekly intravenous regimen may be better in terms of health related quality of life (HRQOL) than with 100 mg/m(2)(Epi100) on a 4-weekly regimen. A total of 79 patients who filled out the EORTC-QLQ-C30 questionnaire for the assessment of HRQOL could be evaluated. Compared with the baseline, no changes in HRQOL function scales or significant changes in the following HRQOL symptom scales were found. The Epi25 group reported less pain during the first 3 months and the Epi100 group more dyspnoea after 4 weeks and less pain and less insomnia but more loss of appetite after 8 weeks. In both groups, toxicity was comparable, except for World Health Organisation grade II-III alopecia occurring in 82% in the Epi100 versus 31% in the Epi25 group. There were no significant differences between groups in response rates and survival. In this study, HRQOL was not improved which is in line with other studies using only epirubicine. Epirubicin as single agent therapy should not be used in future treatment of patients with HRPC.

Objectives: To investigate whether volume adjustment can be used to reduce the within-patient variability of the maximal urinary flow rate (Qmax) without affecting the variability between patients., Methods: We analyzed 2049 urinary flow curves of 208 men with lower urinary tract symptoms suggestive of bladder outlet obstruction and studied the relation between Qmax and voided volume (VV) in individual patients using multilevel regression analysis., Results: In agreement with most previous studies, we found a hyperbolic relation between the VV and Qmax. Although hyperbolic on average, the slope of the regression line relating the VV to Qmax differed substantially across individual patients. In some patients, Qmax even tended to be lower with an increased VV., Conclusions: The reproducibility of Qmax is poor, in part because of its dependence on the VV. The current methods to adjust Qmax for VV, such as the Siroky nomogram, minimize between-patient dependency, whereas our findings emphasize the importance of within-patient variability. A common approach to adjust Qmax for VV, however, is not feasible, because the relation of Qmax to VV differs substantially across patients. The only valid, although impractical option, remains to record a large number of urinary flow curves for each patient.

Objectives: To evaluate the relative accuracy of a computerised method to quantitatively assess maximum urinary flow., Methods: A total of 1147 uroflows were evaluated by the computerised method and by three experts from different European countries. The sample consisted of uroflows from the respective visits by a 20% sample of randomly chosen patients (n = 223) with lower urinary tract symptoms with participation in two clinical trials in which the efficacy and safety of Permixon was evaluated. The proportions of automated maximum flow values included in the 10% extended range of experts (and their 95% confidence intervals) were assessed, as well as the concordance coefficients between experts and the computerised method and the paired Student's t-test for the average differences between experts and computer., Results: The rate of agreement between experts and computer varied between about 95 and 100% over factor levels for visit, type of machine and country. Concordance coefficients indicated good agreement between experts and the automated method. When looking at average differences between experts and the computer, the smallest differences were observed between experts 2, 3 and the computer (differences not statistically significant). Statistically significant average differences were observed between expert 1 and the other experts as well as between expert 1 and the computer., Conclusions: The computerised assessment decreases the fraction of variability of maximum urinary flow caused by artifacts as well as intra- and inter-expert variation. The computerised assessment of maximum urinary flow is an efficient, consistent and valid approach to quantitatively assess maximum urinary flow in clinical trials.

Objectives: To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer., Methods: We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only., Results: 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41)., Conclusions: In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.

Background and Purpose: Neoadjuvant hormonal therapy (NHT) has been used for more than a decade for prostate cancer, but the results of clinical trials are only now becoming available, and the value of the treatment is not yet clear. The authors reviewed the results of the European randomized trials to increase our understanding of the role of this treatment., Patients and Methods: We report the results of 402 patients with prostate cancer (220 clinical stage T(2) and 182 clinical T(3) tumor), of whom 192 were randomly assigned to NHT using an LHRH analog (goserelin) plus flutamide for a period of 3 months (NHT) and 210 underwent radical prostatectomy only (RP)., Results: "Pathologic downstaging" occurred in 15% and 7% of the NHT and the RP group, respectively (P < 0.01). Fifty of the 189 patients in the NHT group (26%) and 68 of the 209 patients in the RP group (33%) developed disease progression, as determined by rising serum prostate specific antigen (PSA) concentration. Regarding local disease progression, the advantage for the use of NHT approached but did not reach statistical significance:18 of 189 patients (10%) in the NHT group and 33 of 209 patients (16%) in the RP group (P = 0. 07)., Conclusions: Although there was a trend in favor of the NHT group with respect to the number of patients with PSA progression and the number with local disease progression, it did not reach statistical significance. These results may be attributable to a true lack of benefit of adjuvant hormonal ablation or to a lack of statistical power to demonstrate a difference in a subset of patients who might benefit from this therapy.

Objectives: This European phase III clinical trial was part of an intercontinental study which was closed prematurely by the sponsor. The study was designed to compare the effects of oral bropirimine with intravesical BCG, the current standard treatment in patients with newly diagnosed bladder carcinoma in situ (CIS)., Methods: A total of 55 BCG-naive patients with bladder CIS were randomized to receive bropirimine (n = 27) or BCG (n = 28). Bropirimine was orally administered at a dose of 3 g/day for 3 consecutive days with a 4-day drug-free interval for up to 1 year. BCG-Tice instillations were administered weekly for 2 x 6 weeks. Both biopsies and cytology had to be negative for the patient to be considered a complete responder (CR)., Results: The percentage of dropouts for all of the adverse events was 4% for bropirimine and 14% for BCG. The most frequently reported local events in the bropirimine- versus the BCG-treated group were irritative complaints, 64 vs. 89% (p = 0.03) and hematuria, 24 vs. 61% (p < 0.01). The most frequently reported systemic events in the bropirimine- versus the BCG-treated group were fever 4 vs. 21%, flu syndrome 24 vs. 7%, headache 28 vs. 11% and nausea 24 vs. 11% (all p > 0.05). A total of 92% of the patients treated with bropirimine had a CR with a mean duration of 12.6 months (95% CI 9.2-15.9). In the BCG group, all of the patients had a CR with a mean of 12.3 months (95% CI 8.5-16.0)., Conclusions: This study shows that bropirimine, an orally administered drug that can be self-administered to outpatients with more acceptable local toxicity compared to BCG, could be an effective first-line therapy in patients with CIS of the urinary bladder. Continued investigation of bropirimine is warranted to increase its clinical utility., (Copyright 1999 S. Karger AG, Basel.)

Purpose: We study toxicity and efficacy of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin (BCG) in patients with intermediate or high risk superficial bladder cancer compared to the use of intravesical mitomycin C alone., Materials and Methods: Patients with intermediate and high risk papillary superficial bladder cancer and carcinoma in situ were randomized after transurethral resection between 4 weekly instillations with 40 mg. mitomycin C followed by 6 weekly instillations with BCG (group 1, 90 patients) or 10 weekly instillations with mitomycin C (group 2, 92 patients)., Results: The frequency of bacterial and chemical cystitis, and other local side effects was similar in both groups. Allergic reactions, including skin rash, were more frequent in the mitomycin C only group (12 of 92 patients versus 5 of 90, p = 0.08), and other systemic side effects were more frequent in the sequential group (16 of 90 versus 8 of 92, p = 0.07). After a median followup of 32 months the number of recurrences (sequential 35 of 90 patients versus mitomycin C only 42 of 92, p = 0.36) and progression (5 of 90 versus 4 of 92 respectively, p = 0.70) were similar in both groups., Conclusions: We did not find any major differences in toxicity or treatment efficacy with intravesical mitomycin C and the sequential use of BCG or mitomycin C for intermediate and high risk superficial papillary bladder cancer.

Objectives: To determine long-term efficacy of intravesical mitomycin C (MMC) versus bacille Calmette-Guérin (BCG) in patients with superficial bladder cancer with regard to recurrences and progression., Methods: Patients with superficial bladder cancer (pTa, pT1, pTis) were treated with intravesical MMC (30 mg, weekly for 4 weeks, and thereafter monthly for 5 months) or BCG (weekly for 6 weeks)., Results: Three hundred forty-four patients were eligible (171 in the BCG group, 173 in the MMC group). The median follow-up was 7.2 years. Toxicity was not significantly different between the two treatment groups. Efficacy of the two treatment policies was similar with regard to tumor recurrence. With regard to progression to invasive disease, MMC was more effective than BCG in patients without carcinoma in situ (CIS) (P = 0.006)., Conclusions: We can confirm the conclusions of other studies that intravesical treatment with 30 mg of MMC remains an effective treatment option that can also be used in high-risk patients. Like others, we could not confirm that a 6-week course of BCG is more effective in the prevention of tumor progression. Of the 33 patients with tumor progression after intravesical therapy, 20 died of bladder cancer, confirming that tumor progression after intravesical therapy carries a poor prognosis. In this study the difference in toxicity between BCG and MMC was not significant. When comparing studies with MMC and BCG, differences in treatment schedule and/or patient selection should be kept in mind.

Objectives: To assess the additive benefit of combining an alpha1-blocker and a 5alpha-reductase inhibitor., Methods: This European, randomized, double-blind, multicenter trial involved 1.051 patients with lower urinary tract symptoms related to benign prostatic hyperplasia. Patients received sustained release (SR) alfuzosin (n = 358), a selective alpha1-blocker given at a dose of 5 mg twice daily without dose titration; finasteride (n = 344), 5 mg once daily, or both drugs (n = 349), for 6 months. Primary efficacy criteria were symptomatic improvement (International Prostate Symptom Score: I-PSS) and maximum flow rate (Qmax). Safety was assessed by monitoring adverse events., Results: Symptomatic improvement was significantly higher from the 1st month of treatment with SR alfuzosin, alone or in combination; mean changes in I-PSS versus baseline at end-point were -6.3 and -6.1, respectively, compared with -5.2 with finasteride alone (SR alfuzosin vs. finasteride, p = 0.01; combination vs. finasteride, p = 0.03). The percentages of patients with a decrease in I-PSS of at least 50% were 43, 42 and 33% for SR alfuzosin, the combination and finasteride, respectively (SR alfuzosin vs. finasteride, p = 0.008; combination vs. finasteride, p = 0.009). In the overall population, increases in Qmax were greater with SR alfuzosin and the combination, compared with finasteride alone after 1 month of therapy, but changes at end-point were similar in the three treatment groups. In those 47% of patients likely to be obstructed (baseline Qmax <10 ml/s), however, mean increases in Qmax were significantly higher with SR alfuzosin, alone or in combination, whatever the visit. Finasteride, alone or in combination, significantly impaired sexual function. The incidence of postural symptoms was low and similar in the three treatment groups., Conclusion: In this 6-month trial, SR alfuzosin was more effective than finasteride, with no additional benefit in combining both drugs.

Objective: To evaluate the outcome and durability of high-energy transurethral microwave thermotherapy (HE-TUMT) in comparison with transurethral resection of the prostate (TURP)., Patients and Methods: Fifty-two patients with BPH and lower urinary tract symptoms were randomized and treated either by TURP (21 patients; mean prostate volume 45 mL, SD 15) or HE-TUMT (31 patients, mean prostate volume 43 mL, SD 12). Long-term results were obtained at a mean (SD) follow-up of 2.4 (0.5) years., Results: During the follow-up, the mean symptomatic improvement stabilized at 56% after TUMT and 74% after TURP. The mean maximum urinary flow rate increased by 62% after TUMT and 105% after TURP. Before treatment, 78% of patients in the TURP group were obstructed according to urodynamic investigation and after treatment, 14% remained obstructed. In the TUMT group, 67% of patients were obstructed before treatment and 33% remained so afterward. Six patients (19%) underwent TURP after TUMT (four after 1 year) and two patients were also treated with medication. One patient underwent a bladder neck incision after TURP to treat bladder neck sclerosis. Three patients were not satisfied with the outcome after the additional TURP., Conclusion: Both treatment modalities show good symptomatic and objective results at > 2 years of follow-up. Most re-treatments were performed > or = 1 year after treatment and were based on subjective findings.

Despite the lack of evidence in the literature for close relationships between lower urinary tract symptoms and bladder outlet obstruction, the majority of urologists rely on symptomatology when selecting patients for prostatic surgery. We investigated the relationships between a wide range of lower urinary tract symptoms from the ICSmale questionnaire and the results of urodynamic pressure and flow studies. We evaluated 933 patients with lower urinary tract symptoms suggestive for bladder outlet obstruction from 12 countries who participated in the ICS-"BPH" study with the ICSmale questionnaire and urodynamic pressure and flow studies. Spearman rank correlation coefficients were obtained between symptoms and measures of bladder outlet obstruction. There was little or no correlation between a wide range of symptoms and the results of free uroflowmetry and pressure and flow studies. From symptoms alone, it is not possible to diagnose bladder outlet obstruction. Pressure and flow studies and symptom profiles measure different aspects of the clinical condition that should be viewed separately in the evaluation and treatment decision of the patient presenting with lower urinary tract symptoms.

Objectives: To evaluate a computerized method of artifact detection and correction of uroflow and compare the quantitative assessment of maximum flow obtained by the computer with visual correction by experts., Methods: A total of 90 randomly chosen flows was scanned into the computer whereafter automated artifact detection and correction was performed according to pre-established rules implemented in the software. Three experts visually corrected the flows using the same artifact detection and correction specifications as the computer. Measuring agreement between different methods of assessment of maximum flow was evaluated by calculating the difference and the standard deviation (SD) of the differences. The repeatability of assessing the maximum flow value by the computer and by expert 1 was assessed by calculating the difference between 2 readings and the coefficient of repeatability., Results: The coefficient of repeatability of maximum flow after detection and correction of artifacts by the computer (0.38 ml/s) was slightly better when compared with the coefficient of repeatability between 2 observations by 1 expert (1.12 ml/s). The interobserver variation for the quantitative assessment of maximum flow appeared to be great. A total of 51% of the maximum flow values assessed by expert 2 was 1 ml/s or more greater than those assessed by expert 1. When comparing the results of the computer with those of the experts, the mean value of maximum flow from expert 1 was 0.71 ml/s smaller than the computer value (p < 0.01), the mean value from expert 2 was 0.53 ml/s greater (p < 0.01) and the mean value from expert 3 was not significantly different (0.25 ml/s greater). The SD of maximum flow after correction by the computer was 0.3 ml/s smaller than the SD of the raw data from the flowmeter and the corrected values by 2 experts., Conclusions: Computerized artifact detection and correction eliminates an important fraction of the variability of manually corrected maximum flow values. This may lead to smaller sample size requirements, especially in studies where the primary objective is to assess a small (+/- 1 ml/s) difference in mean maximum flow between groups.

Objective: To compare the efficacy and tolerability of the alpha 1 A-subtype selective drug tamsulosin with the nonsubtype-selective agent alfuzosin in the treatment of patients with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction (BOO), often termed symptomatic benign prostatic hyperplasia (BPH)., Patients and Methods: The study comprised 256 patients with benign prostatic enlargement and LUTS suggestive of BOO (symptomatic BPH) who received tamsulosin 0.4 mg once daily or alfuzosin 2.5 mg three times daily during 12 weeks of treatment. The response was assessed by measurements of maximum urinary flow rate (Qmax), a symptom score (Boyarsky) and blood pressure at regular intervals., Results: Tamsulosin and alfuzosin produced comparable improvements in Qmax and total Boyarsky symptom score. Both treatments were well tolerated with respect to adverse events. Tamsulosin had no statistically significant effect on blood pressure compared with baseline but alfuzosin induced a significant reduction in both standing and supine blood pressure, compared with baseline (P < 0.05)., Conclusion: Tamsulosin is the first adrenoceptor antagonist that is selective for the alpha 1 A-subtype; this specificity may explain its lack of effect on blood pressure compared with alfuzosin, an agent that is not receptor subtype specific. Moreover, this finding may partly explain why tamsulosin, in contrast to other currently available alpha 1-adrenoceptor antagonists, can be administered without dose titration. Another advantage compared with alfuzosin (and prazosin) is the once-daily dosing regimen of tamsulosin.

Objectives: To investigate if the circadian rhythm of urinary flow values varies within groups of patients with varying degrees of bladder outlet obstruction., Methods: A total of 170 patients with lower urinary tract symptoms suggestive of bladder outlet obstruction used a home-based uroflowmeter and produced a total of 1670 correctly measured flows at home. These patients also underwent a screening program with free urinary flowmetry in the hospital and a urodynamic pressure and flow study., Results: There is a circadian variability in urinary flow values in men with higher grades of obstruction. These men have a higher peak urinary flow with a smaller voided volume and thus a shorter flow time in the early afternoon when compared with late evening, early morning, and the midnight to morning periods., Conclusions: This significantly greater maximum flow in the afternoon in men with higher grades of obstruction can be an important bias in studies where the primary end point is to assess a small improvement in maximum flow. Therefore, the circadian rhythm of uroflow has to be taken into account in the evaluation of the efficacy of treatment. Patients participating in clinical research studies should produce their urinary flow in the clinic always during the same time period, either in the morning or in the afternoon, and should not switch their appointment time.

Objective: To determine if, in patients with lower urinary tract symptoms (LUTS), measurement of the transition zone (TZ) of the prostate by transrectal ultrasonography (TRUS) and the ratio between the TZ volume and total prostate volume (TZ index) correlates better with clinical and urodynamic investigations than total prostate volume alone., Patients and Methods: In total, 150 consecutive patients with LUTS underwent a standardized screening programme including the International Prostate Symptom Sore (IPSS), a physical examination, TRUS of the prostate and urodynamic investigations with pressure-flow studies. The total prostate volume and TZ volume were assessed from TRUS using the ellipsoid formula. Spearman's rank correlation coefficients were calculated between different prostate volume measurements and specific symptomatic and urodynamic variables., Results: The relationships between specific IPSS symptoms, symptom scores and the prostate volume measurements were not statistically significant except for one domain, nocturia, that appeared to be statistically significantly correlated with the TZ index (r = 0.25). The correlations for free flow, pressure-flow variables and prostate volume measurements were stronger, but only moderate at best. The highest correlations were between TZ volume and the linear passive urethral resistance obstruction category, urethral resistance factor and detrusor pressure at maximum flow (r = 0.43, 0.44 and 0.40, respectively). The differences between the correlations of prostate volume and TZ index and these variables were small (r = 0.39, 0.38 and 0.37, respectively for prostate volume and r = 0.38, 0.40 and 0.33 respectively for TZ index)., Conclusions: There were very small differences between the correlations of total prostate volume, TZ volume and TZ index, and clinical and pressure-flow variables. In the assessment of the last two, the estimation of the total prostate volume by TRUS was a reasonable way to obtain the required information about prostate size and measuring TZ volume and calculating TZ index was of limited additional value. Symptoms and bladder outlet obstruction were mainly determined by other factors than the prostate and, specifically, TZ volume. As earlier studies have indicated that including pressure-flow data in the pre-operative evaluation and selection of patients for interventional therapies may improve the overall clinical results, we think that prostate volume, TZ volume or symptoms alone should not be used as the main indication for deciding on the appropriate invasive treatment options.

Objectives: We investigated the symptomatic and urodynamic effects of several noninvasive and minimally invasive treatment modalities to quantify these effects and to compare subjective and objective results within groups with various degrees of obstruction., Methods: In a prospective study at one center, 487 patients who completed a full screening program including urodynamic investigation started treatment with watchful waiting, terazosin, transurethral microwave thermotherapy, or laser treatment of the prostate; they were re-evaluated symptomatically and urodynamically after 6 months of therapy. The symptomatic and urodynamic results of 87 patients from another center who underwent transurethral resection of the prostate and who had their second urodynamic evaluation 6 months after surgery were also included., Results: In patients without bladder outlet obstruction (BOO), improvement in maximum flow and symptom scores with little change in the degree of obstruction was most apparent, whereas a decrease of detrusor pressure at maximum flow was observed mainly in patients with BOO. The urodynamic effect but not the symptomatic effect of treatments depended on the initial grade of BOO. Urodynamic changes were more marked in the minimally invasive treatment groups compared with the noninvasive treatment groups., Conclusions: In symptomatic patients with benign prostatic hyperplasia, symptomatic improvement in the short term does not seem to depend on changes in urodynamic parameters. Future well-controlled studies focusing on the durability of symptomatic and urodynamic effects will be needed to illustrate the relative potential of urodynamic and other clinical parameters to predict a favorable response to current and innovative treatments.

Purpose: We compared the outcome of transurethral resection of the prostate and high energy microwave thermotherapy in patients with benign prostatic hyperplasia., Materials and Methods: Of 52 patients with symptomatic benign prostatic hyperplasia 21 (mean age plus or minus standard deviation 69.6 +/- 8.5 years) were treated with transurethral resection of the prostate and 31 (mean age 69.3 +/- 5.9 years) were treated with high energy microwave thermotherapy. Patients were assessed using the Madsen symptom score, measurements of voiding parameters, transrectal ultrasound and cystometry, including pressure-flow analyses. Examinations were repeated at fixed intervals for up to 12 months after treatment., Results: After transurethral resection and thermotherapy there was significant improvement in all clinical parameters. At 1 year of followup symptomatic improvement was 78% in the transurethral resection group versus 68% in the thermotherapy group, with improvements in free flow rate of 100 and 69%, respectively. Both groups had significant relief of bladder outlet symptoms. No serious complications occurred in either group, while 1 patient in each group required repeat treatment., Conclusions: Satisfactory results were obtained after both treatments, with improvements following high energy microwave thermotherapy being in the same range as those after transurethral resection of the prostate.

Purpose: We investigated the international differences in the reporting of lower urinary tract symptoms and related bother in patients with symptoms suggestive of bladder outlet obstruction., Materials and Methods: Multiple logistic regression analysis was used to evaluate international differences in the reporting of lower urinary tract symptoms and related bother in 1,271 patients from 12 countries who participated in the International Continence Society "benign prostatic hyperplasia" study., Results: Country of origin was significantly associated with the prevalence of a large number of lower urinary tract symptoms (10 of 20), even after adjusting for potentially confounding variables, including physical and socio-demographic factors. Country of origin was also significantly associated with the reporting of bother but for a much smaller number of symptoms (2)., Conclusions: In different countries lower urinary tract symptoms may be reported to different extents. Therefore, the results of studies in particular countries may not be generally applicable to other countries. It is likely that symptom scores will conceal this variation, necessitating consideration of individual symptoms (as in the International Continence Society "benign prostatic hyperplasia" study) or the development of country specific scoring systems. An alternative would be to focus on bother, which appeared to be much less sensitive to international differences.

Objectives: To evaluate the short- and long-term effects of neoadjuvant hormonal treatment in locally confined prostate cancer., Methods: We report the preliminary results of 354 patients (199 with a clinical T2 tumor and 155 with a clinical T3 tumor) of whom 164 randomly received neoadjuvant total androgen deprivation using a luteinizing-hormone-releasing hormone (LHRH) analog (goserelin) plus flutamide for a period of 3 months., Results: Serum prostate-specific antigen (PSA) levels and prostatic volume decreased from a mean of 19.9 ng/mL and 37.7 cm3 to a mean of 0.8 ng/mL and 26.5 cm3 after 3 months of neoadjuvant therapy. "Clinical down-staging" was seen in 32% in the neoadjuvantly treated group. "Pathological downstaging" percentages were 6% and 16% in the direct radical prostatectomy group and neoadjuvantly-treated group, respectively (P < 0.01). In patients with clinical T2 tumors, a significant difference in number of positive margins was shown in favor of the neoadjuvantly treated group (P < 0.01). In patients with clinical T3 tumors, a significant difference could not be detected (P = 0.14). In 215 patients with a mean follow-up time of 15 months, the calculated 95% confidence intervals of mean time of PSA progression-free survival were 26 to 35 months in the neoadjuvantly-treated group and 28 to 37 months in the direct radical prostatectomy group, indicating no significant differences between treatment groups. However, follow-up time is currently too short to draw definite conclusions., Conclusions: These early data confirm high understaging percentages in clinical staging. The clinical relevance of the statistically significant smaller numbers of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor will have to be confirmed when further follow-up allows an accurate evaluation of time to PSA progression, local recurrence, and distant metastases. Presently, neoadjuvant therapy is not advisable outside clinical research settings.

Objectives: To evaluate clinical and urodynamic changes in patients with and without bladder outlet obstruction (BOO) and to compare the clinical and urodynamic results of terazosin treatment between patients with and without BOO., Methods: In a prospective study, 97 patients who completed a full screening program including urodynamic investigation with pressure-flow study analysis started treatment with terazosin. A total of 60 patients completed 6 months of treatment and were re-evaluated with International Prostate Symptom Scores (IPSS), uroflowmetry, and urodynamic investigation with pressure-flow study analysis. Patients were stratified using the linear passive urethral resistance relation (lin-PURR) classification according to Schäfer. Patients with a lin-PURR of 3 or more were classified as patients with BOO and patients with a lin-PURR of 2 or less were classified as patients without BOO. The clinical and urodynamic changes within and between the groups with and without BOO were evaluated., Results: Terazosin resulted in significant symptomatic relief (9 points on the IPSS scale; P < 0.01) and a significant improvement of free urinary flow (3.0 mL/s; P < 0.01). In patients with BOO, a statistically significant improvement of all urodynamic obstruction variables (P < 0.01) was shown. In patients without BOO, a significant improvement of free urinary flow (4.4 mL/s; P < 0.01), a statistically significantly improved bladder capacity (increase of 70 mL; P = 0.01), and no statistically significant changes in urodynamic obstruction variables (P > 0.05) were shown. Patients with a hypoactive detrusor were more prone to early dropout. When comparing the changes of symptoms (P = 0.89), quality of life (P = 0.85), and the number of patients with improvements of free uroflow of at least 30% (P = 0.15), there appeared to be no significant difference between the groups with and without BOO., Conclusions: Although there is a statistically significant difference in urodynamic response to terazosin treatment between patients with and without BOO, we cannot recommend the use of pressure-flow studies in the selection of patients for terazosin treatment because the clinical results of treatment appear not to be significantly different between patients with and without BOO. It seems more useful, and certainly less expensive and less invasive, to start alpha 1-blocker therapy if, on clinical grounds, the urologist considers the patient to be a candidate for alpha 1-blocker therapy, and to continue therapy in those who respond.

Objectives: To compare the pharmacodynamics and tolerability of the new goserelin acetate 10.8-mg depot with the 3.6-mg depot in patients with advanced prostate cancer during the first 3 months of therapy., Methods: One hundred sixty patients were randomized in two comparative studies to receive either the 10.8-mg goserelin acetate depot every 12 weeks or the 3.6-mg goserelin acetate depot every 4 weeks for 12 weeks and then the 10.8-mg depot every 12 weeks thereafter. Data for pharmacodynamic assessments were collected prospectively, whereas clinical response data were collected retrospectively., Results: Serum testosterone profiles of the 10.8-mg goserelin acetate depot and the 3.6-mg goserelin acetate depot were similar; testosterone levels in both groups fell below castrate levels by day 21 after administration. Decreases in serum prostate-specific antigen level after 3 months of therapy were also similar in both groups: 94% with the 10.8-mg depot and 92.5% with the 3.6-mg depot. For all patients, the median time to progression was 152.7 weeks and the median time to death was 213.6 weeks. The safety profile of the 10.8-mg goserelin acetate depot was similar to that of the 3.6-mg depot; hot flashes was the most common adverse event. The incidence of injection site reactions was very low (2 [0.3%] of 614 administrations)., Conclusions: The new 10.8-mg depot was pharmacodynamically equivalent to the current 3.6-mg depot and was well tolerated, both locally and systemically. The observed times to progression and survival were as expected in this patient population. The 10.8-mg goserelin-acetate depot provided a dosing schedule that was convenient for the patient and the physician, and it has the potential to reduce health care costs while maintaining the quality of life in patients being treated for advanced prostate cancer.

Objective: To characterize the serum kinetics of prostate specific antigen (PSA) after visual laser ablation of the prostate (VLAP)., Patients and Methods: The PSA values of 45 patients were measured at 24 h and at 1, 4, 12, 26 and 52 weeks after VLAP and the changes assessed in relation to symptom scores, urinary flow rates and prostate size., Results: After an initial rise immediately after VLAP, the serum PSA level declined. At 24 h, the PSA value reached a mean level 23 times higher than the PSA level before VLAP and then took a mean of 78 days to reach a new baseline. The mean decrease of the subsequent baseline value relative to that before treatment was 1.7 ng/mL. The prostatic size and energy applied correlated positively with the rise in PSA 24 h after VLAP. The rise in maximal urinary flow after VLAP, the decrease in the symptom score and residual urine volume did not correlate with the rise in PSA level 24 h after VLAP or with the time to reach a value halfway between the level at 24 h and the new baseline value., Conclusions: The pattern of the increase in serum PSA level and decline after VLAP was not predictive of the clinical outcome of therapy.

Purpose: We quantified the physiological variability of clinical and pressure-flow study variables in patients with symptomatic benign prostatic enlargement., Materials and Methods: Symptom scores were measured, and advanced urodynamic studies with pressure-flow analysis were performed in 178 patients before and 6 months after a period a watchful waiting., Results: Patients without bladder outlet obstruction experienced significant symptomatic improvement. Symptoms in patients with obvious bladder outlet obstruction did not improve significantly. The reproducibility of mean pressure-flow variables was evident. However, there was an important intra-individual variability. Patients with obvious bladder outlet obstruction showed a significant decreases in detrusor pressure at maximal flow of 14cm. water, a significant decrease in the urethral resistance factor of 7 cm. water and a significant decrease of 1 obstruction class on the linear passive urethral resistance relation nomogram, indicating less severe bladder outlet obstruction., Conclusions: Mean differences among therapy groups must be regarded critically, especially when the difference are slight and possibly within physiological variability.

Objectives: To compare the results obtained using a portable home-based uroflowmeter with the results of traditional flowmetry performed in the out-patient department (OPD)., Patients and Methods: Sixty-seven patients (mean age 61 years, range 38-79) with lower urinary tract symptoms and/or benign prostatic enlargement used a home-based uroflowmeter comprising a datalogger and specially designed fluid sensors incorporated into disposable beakers. The results of these measurements were compared with those from uroflowmetry in the OPD and with other clinical variables., Results: There was a good correlation between the uroflow results obtained when voiding at home and at the OPD. The highest measured maximum flow and voided volume were obtained with the home-based uroflowmeter system. However, the mean of all consecutive home-based maximum flow and voided volume measurements were lower than those obtained by single-void uroflowmetry in the OPD., Conclusions: Home-based uroflowmetry provides reliable voiding results which are comparable with those obtained in the OPD.

Purpose: We evaluated the urodynamic and clinical effects of terazosin in patients with symptomatic benign prostatic hyperplasia (BPH)., Materials and Methods: A total of 45 patients who participated in a multicenter trial was evaluated with urodynamic pressure-flow studies before and after 26 weeks of treatment., Results: Maximum flow rate and symptom score improved significantly in 22 patients with and 11 without bladder outlet obstruction who completed 26 weeks of treatment. In patients with bladder outlet obstruction the condition was significantly reduced and in patients without obstruction, significant urodynamic changes could not be detected., Conclusions: Terazosin treatment results in symptomatic relief and improved urinary flow in patients with and without bladder outlet obstruction, and in significant improvement in patients with urodynamically proved obstruction.

Purpose: To assess the pharmacodynamic equivalence of the new 10.8 mg. goserelin depot with the current 3.6 mg. depot 3 studies were performed in patients with advanced prostate cancer., Materials and Methods: In 2 comparative studies 160 patients were randomized for dosing every 12 weeks using the 10.8 mg. depot or every 4 weeks using the 3.6 mg. depot. In the noncomparative study 35 patients received the 10.8 mg. depot. Blood sampling for serum testosterone and evaluation of toxicity was done during the 48-week study period., Results: Serum testosterone profiles of the 10.8 and 3.6 mg. goserlin depots were similar with testosterone levels decreasing into the castrate range by day 21 after depot administration. The safety profile of 10.8 mg. goserelin is comparable to that of the current monthly depot with the main side effects related to androgen deprivation., Conclusions: The new long acting depot was pharmacologically equivalent, and well tolerated locally and systemically, and will offer added convenience to patients and health care personnel.

Objective: To determine the gain in lead time obtained when using ultrasensitive prostate-specific antigen (PSA) assays in the diagnosis of biochemical progression after radical prostatectomy., Patients and Methods: The post-operative PSA serum concentrations of 137 patients who had undergone radical prostatectomy were evaluated retrospectively. From these patients, 12 were selected who showed biochemical recurrence, as measured by the Hybritech Tandem-E Singlepoint PSA assay. Samples of the serum frozen at the time of the initial analysis were thawed and PSA values were remeasured by the Abbott IMx PSA assay and the Tandem-E Multipoint PSA assay. Analytical thresholds (zero-dose + 3 SD) for the Tandem-E Singlepoint, IMx and Tandem-E Multipoint assay were 1.0, 0.04 and 0.04 ng/mL, respectively. The lead time to the detection of a recurrence obtained when using the IMx and the Tandem-E Multipoint PSA assay was compared with that attained using the Tandem-E Singlepoint PSA assay. As a control, PSA values were determined in 58 serum specimens of nine patients having no evidence of recurrence after radical prostatectomy., Results: All 58 control specimens had PSA levels below the analytical thresholds of the three assays, except one which had a PSA serum concentration of 0.08 ng/mL, estimated by the IMx assay. When compared with the lead time obtained with the Tandem-E Singlepoint assay, the 12 patients with a biochemical recurrence had a median gain in lead time of 327 days (range 60-627) with the IMx assay and of 369 days (range 60-639) with the Tandem-E Multipoint assay., Conclusion: A PSA value > 0.04 ng/mL after radical prostatectomy heralds further biochemical progression. The use of the ultrasensitive IMx and the Tandem-E Multipoint assays provided more lead time, but there is no clear evidence that this gain is necessarily of benefit to the patient.

Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy.

Objective: To evaluate the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia (BPH)., Methods: Thirty-three sites in 13 countries enrolled men with BPH who had an International Prostate Symptom Score (IPSS) > or = 12 [corrected]. After a 2-week, no-treatment lead-in period and a 26-week, single-blind treatment period, patients responding to terazosin were randomly assigned to receive either terazosin or placebo for a 24-week, double-blind withdrawal period., Results: Of the initial 427 patients enrolled, 378 were evaluable, 273 of whom completed the single-blind period, of which 186 patients were randomized. During the single-blind treatment period, IPSS, quality-of-life score (QOL), peak flow rate (PFR), and nocturia score (NOC) improved significantly (p < or = 0.05). During the double-blind withdrawal period, IPSS, QOL, PFR, and NOC deteriorated significantly in the placebo group compared with the terazosin group. The most common adverse event resulting in premature termination from the study was dizziness. There were no clinically important mean reductions in diastolic blood pressure (DBP) for patients normotensive at baseline. Terazosin significantly reduced mean DBP in hypertensive patients during the single-blind period and maintained the reduction during the double-blind period., Conclusion: Treatment with terazosin has a beneficial effect on BPH, continuing for at least 12 months, and can be safely considered for medium- to long-term use in those who benefit.

Background: The total prostate-specific antigen (t-PSA) in serum measured by PSA assays represents the sum of free (f-PSA) and PSA complexed with alpha 1-antichymotrypsin. The f-PSA/t-PSA (F/T) ratio in prostate cancer (PCA) patients is lower than in patients suffering from benign prostatic hyperplasia (BPH). This review summarizes the current literature on the clinical relevance of measurement of the F/T PSA ratio., Methods: Discussed are: physiology of PSA, assays for t-PSA and F/T ratio, factors which bias the F/T PSA ratio, use of F/T PSA ratio in the detection of PCA, correlation with histological features, and pathological stage., Results: Using the F/T ratio in the intermediate t-PSA range, a reduction of approximately 30% in biopsies can be accomplished in the detection of prostate cancer., Conclusions: The F/T PSA ratio could become a valuable tool in the differentiation of BPH from PCA. To accomplish this goal, an international standardization not only for the t-PSA measurement but also for the F/T PSA ratio must be a priority for manufacturers of PSA assays.

Objective: To assess the additional value of prostate-specific antigen density in the diagnosis of prostate cancer in patients who undergo prostate biopsies., Patients and Methods: The study comprised 376 patients with symptoms of prostatism who were undergoing prostate biopsy. Digital rectal examination (DRE) and transrectal ultrasonography (TRUS) were performed and the prostate specific antigen level (PSA) and density (PSAD) were determined for each patient., Results: Both PSA and PSAD significantly differentiated (P < 0.001) between benign and malignant histology. Of the 376 patients, 91 (24%) had a PSA level in the intermediate range (4.0-10.0 ng/mL). In these patients PSAD was significantly better than PSA in differentiating between benign and malignant histology (P = 0.027 vs 0.316). With a PSAD limit of 0.15 ng/mL/cm3 in these patients, the sensitivity was 92% and the specificity was 54% for the diagnosis of prostate cancer. No patient with a positive biopsy had a PSAD < 0.11 ng/mL/cm3. No limiting value could be found for PSAD that combined both an acceptable sensitivity and specificity. Of the patients with a malignancy detected by the biopsy, 92% also had a suspect DRE., Conclusion: In patients with intermediate PSA levels, PSAD is of limited additional value when compared to DRE in correctly diagnosing prostate cancer. Acute prostatitis is also a possible cause of elevated PSA. Both PSA and PSAD had no additional value in differentiating between benign prostatic hyperplasia (BPH) and histologically proven extensive prostatitis.

Objectives: In this article we describe the long-term follow-up of patients with carcinoma in situ (CIS) of the urinary bladder and examine whether the extent of CIS, the presence of associated papillary tumors, or the response to treatment influence the course of the disease., Methods: Fifty-two patients with CIS of the bladder, treated in a randomized prospective study, are described. In 23 patients with concomitant papillary tumors all macroscopically visible lesions were completely resected transurethrally (TUR). CIS was histologically confirmed in all patients by biopsy, 29 of whom had primary CIS. The patients were treated with intravesical mitomycin, bacille Calmette-Guérin (BCG)-RIVM or BCG-Tice and followed regularly by urine cytology, cystoscopy, and biopsy., Results: Complete response was achieved in 65% of the patients. Of these responders, 24% later had a recurrence of CIS or a superficial tumor and 18% had progressive disease (PD). In the nonresponding patients, progression occurred in 67%. In the whole group, PD was seen in 35% of the patients, and radical cystectomy was performed in 21%. The disease-related death rate was 13%. The risk for recurrence or PD was not higher in patients with more extensive CIS, defined as three or more positive biopsy results or when CIS was associated with papillary tumors compared to patients with one or two biopsy specimens positive for CIS or CIS alone. Nonresponding patients showed a significantly higher progression rate and cystectomy rate than responding patients (P = 0.0012 and 0.008, respectively)., Conclusions: CIS of the bladder is a malignancy with a poor prognosis, especially in patients not responding after intravesical treatment. Early detection and adjuvant intravesical treatment after TUR of concomitant papillary tumors are required. In patients not responding after intravesical treatment, radical surgery is necessary before progression occurs. The number of biopsies positive for CIS, not the presence of concomitant superficial tumors, was an indicator for progression or recurrence.

Results of a randomized prospective study are reported in which mitomycin C, Tice bacillus Calmette-Guerin (BCG) and RIVM-BCG were compared in 437 patients with primary or recurrent pTa and pT1 bladder tumors, including carcinoma in situ. The followup (or time in study) varied from 2 to 81 months (mean 36 months). After complete transurethral resection of all visible tumors the patients were treated with 30 mg. mitomycin C once a week for 4 consecutive weeks and thereafter every month for a total of 6 months, and 5 x 10(8) colony-forming units Tice BCG or RIVM-BCG once a week for 6 consecutive weeks. For papillary tumors mitomycin C and RIVM-BCG treatments were equally effective (p = 0.53), and mitomycin C was more effective than Tice BCG therapy (p = 0.01).