332 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Tuesday, April 29, 2003

Source of Funding: National Institutes of Health (NIDDK).

Benign Prostatic Hyperplasia: Medicaland Hormonal Therapy (I)

PodiumTuesday, April 29, 2003 10:00 AM-12:00 PM

in the kidneys was increased in parallel to EG concentration. In OPN knockoutmice, however, with the introduction of 1% EG, crystal deposits developed in thedistal tubules of their kidneys.

CONCLUSIONS; Previously, renal toxicity tests of EG describedadministration of EG to mice and rats of both genders. Mineralization andpathological changes in the kidneys were found only in the male rat, not in thefemale rats or mice. In our examination, quite high-concentration EGadministration was performed rather than using these previous data, but there wasno crystal deposits found. We considered that there is a species difference betweenrats and mice regarding EG metabolism and renal protection. In knockout mouse,however, increased crystal deposits was observed and OPN seemed to play acrucial role in controlling stone formation.

Source of Funding: None.

1287BASELINE MEASURES PREDICT THE RISK OF BENIGNPROSTATIC HYPERPLASIA CLINICAL PROGRESSION INPLACEBO-TREATED PATIENTS John D McConnell*, Claus GRoehrborn, Dallas, TX.; Kevin M Slawin, Houston, TX.; Michael M Lieber,Rochester, MN; Joseph A Smith, Nashville, TN; Stephen A Kaplan, New York,NY; Oliver Bautista, Pam K Burrows, Rockville, MD; Leroy M Nyberg, JohnW Kusek, Bethesda, MD

INTRODUCTION AND OBJECTIVE; The Medical Therapy of ProstaticSymptoms (MTOPS) Study demonstrated that doxazosin and finasteride, aloneand in combination, significantly reduces the risk of BPH clinical progression.The decision, however, to recommend a risk-reduction strategy for treatmentshould be based upon an assessment of the patient's individual risk ofprogression. The MTOPS placebo group was analyzed to determine if therelative risk of BPH progression, acute urinary retention (AUR) or need forBPH-related surgery in untreated patients could be predicted from commonlyavailable baseline measures.

METHODS; In MTOPS, 737 patients were assigned to placebo andfollowed for an average of 4.5 years. Clinical progression of BPH waspre-defined as either a 2:4-point increase in AUA SS, acute urinary retention(AUR), incontinence, renal insufficiency or recurrent UTI. The need forBPH-related invasive therapy was a secondary outcome. Association ofabsolute risk with baseline levels of pre-specified covariates was assessedthrough regression models. The predictive value of baseline serum PSA wasanalyzed in detail. Receiver operator characteristic (ROC) curves were used toassess diagnostic test utility.

RESULTS; In placebo-treated patients, baseline PSA, Qmax, PVR, andprostate volume correlated significantly with the risk of BPH clinical progressionand the need for BPH-related invasive therapy (p=0.03 to <0.001). Baseline agealso correlated with risk of BPH clinical progression (p<O.OOI)and AUA SS withinvasive therapy (p=0.002). Baseline PSA and prostate volume also correlatedwith the risk of AUR (p=0.03 to 0.003). The risk of BPH progression increaseswith increasing baseline serum PSA (p<O.OOI; R2=1.l4%). The risk of AURdecreases as baseline serum PSA decreases (p=0.003; R2=4.41 %), The risk ofBPH-related invasive therapy decreases as baseline serum PSA decreases(p=0.018; R2= 1.45%). The area under the ROC curve for baseline PSA predictingclinical progression was 0.61, 0.70 for AUR, and 0.64 for BPH-related invasivetherapy.

CONCLUSIONS; Routinely available measures, including serum PSA, canpredict a patient's future risk of BPH clinical progression, AUR and BPH-relatedinvasive therapy, permitting an informed decision concerning the value of medicaltherapy over watchful-waiting.

BPH Risks (Rate per100 Patient Years)

1288PROGRESSION DELAY IN MEN WITH MILD SYMPTOMS OFBLADDER OUTLET OBSTRUCTION: A PROSPECTIVECOMPARATIVE STUDY OF PHYTOTHERAPY, WATCHFULWAITING, AND PLACEBO Stephan Hruby, Bob Djavan*, Vienna,Austria; Andreas Reissigl, Bregenz, Austria; Aziz Chaudr, London, UK; SaeidAlavi, Vienna, Austria; Theodore Anagnostou, Athens, Greece; FariborzBagheri, Budapest, Hungary; Mike Harik, Mesut Remzi, Michael Marberger,Vienna, Austria

INTRODUCTION AND OBJECTIVE: We recently reported the use of acombination of clinical and biochemical parmeters, as well as Artificial neuralnetworks for early identification of patients with bladder outlet obstruction (BOO)at risk for progression. Phytotherapy has been shown to be benefitial but no datawere available on their impact on the clinical course (i.e. disease progression). Thepurpose of this prospective multicenter matched trial was to evaluate the efficacyof Serenoa Repens in patients with mild symptoms of BOO (IPSS < 8).

METHODS: A total of 191 patients were included in the analysis. Eigty eightwere starded on Serenoa repens once daily and 103 matched patients included ina watchful waiting protocol. All were followed for up to 24 mo at 3 mo intervalls.Age, PSA, IPSS, OSS, IRR, QOL and the maximal and mean flow rate as well astotal and transition zone volume were recorded. Progression was defined as achange from the mild-IPSS group into the moderate- (IPSS 8-18) or severe IPSSgroup (IPSS > 18). The occurrence of urinary retention or the need for surgery(TURP) were also qualified as disease progression.

RESULTS; Cumulative progression rate was 1%,7%,9% and 16% at 6 mo, 12mo, 18 mo and 24 mo respectively for the active group (serenoa repens) and 6%,13%, 15% and 24%, respectively for the matched group on watchful waiting.Progression rates were significantly higher (p=O.OOI) when ANN calculated cutoffs for progression were used (PSA > 1.5 ng/mL and TZV > 25 cc.Whencompared to earlier matched patients on placebo, proression rates weresignificantly lower (p=0.003). IPSS, QoL, Qmax improved by 17%, 19% and 15%respectively versus 6%, 9%, 10%, respectively in the watchful waiting arm. PVR,PSA and TPV and TZV did not change significantly.

CONCLUSIONS: Progression rates in men with mild symptoms of BOO(IPSS<8) receiving Serenoa Repens was significantly reduced as compared topatients on watchful waiting and a matched group of patients on placebo. 1/3 ofpatients on watchful waiting and placbo progressed over the study periodsuggesting that phytotherapy may be an option in patients at risk for progression(i.e. PSA > 1.5 ng/mL and TZV > 25 cc).

Source of Funding: None.

1289BASELINE SYMPTOMS, UROFLOW, AND POST-VOIDRESIDUAL URINE AS PREDICTORS OF BPH CLINICAL

..PROGRESSION IN THE MEDICALLY TREATED ARMS OFTHE MTOPS TRIAL Steven A Kaplan*, New York, NY; Claus GRoehrborn, John D McConnell, Dallas, TX.; Karl J Kreder, Iowa City, IA;Michael L Lieber, Rochester, MN; Stephen C Jacobs, Baltimore, MD; KevinM Slawin, Houston, TX.; Oliver M Bautista, Pam K Burrows, Rockville, MD;Leroy M Nyberg, John W Kusek, Bethesda, MD

INTRODUCTION AND OBJECTIVE: The MTOPS (Medical Therapy ofProstate Symptoms) Study was designed to ascertain if medical therapy delaysprogressionof benign prostate hyperplasia(BPH) as categorizedby predefinedcriteria.The purpose of this abstract is to report the value of baseline AUA Symptom Score(Sx) urinary flow rate (Qmax) and post void residual urine (PVR) in predictingprogression of BPH in those patients randomzied to the medical treatment arms.

METHODS; MTOPS was a double-masked, placebo-controlled, multi-center,randomized clinical trial with 4 study arms (placebo, doxazosin (4 to 8 mg),finasteride (5 mg) and combination (Comb) of both doxazosin (Dox) andfinasteride (Fin). 3047 men were randomized equally to the 4 groups. Baselineparameters analyzed included age at randomization, transrectal ultrasound volume(TRUS), Sx, Qmax, PVR and PSA. Reduction in the risk of BPH progression wasanalyzed by one covariate at a time regression models of absolute risk of BPHprogression versus baseline covariates. Groups compared were Comb vs. Dox,Comb vs. Fin and Fin vs. Dox.

RESULTS; The predictive value of each baseline covariate on BPHprogression in each treatment arm is listed in Table 1. R2 values depicted werestatistically significant. (Ns is non significant). In all three pairwise comparisons ofactive therapy versus placebo, the risk reduction of BPH progression associatedwith active therapy applies uniformly to all levels of baseline parameters. In allpairwise comparisons, the risk of BPH progression is significantly associated' withbaseline age, TRUS, PSA and PVR.

CONCLUSIONS: Baseline parameters were variably predictive of BPHprogression in MTOPS in medically treated patients. However, baseline symptomswere the least predictive of progression and were not significantly associated withprogression when comparing active therapy to placebo.

0.61.332.13

Invasive Treal0.160,351.46

AUR3,103,477.21

ProgressionBasetine PSA Tertiles (nglml)<1.21.2·2.5>2.5

*Presenting author.

Vol. 169, No.4, Supplement, Tuesday, April 29, 2003 THE JOURNAL OF UROLOGY® 333

Source of Funding: Financial support was provided by Pfizer Inc.

1293PREDICTIVE MODEL FOR ACUTE URINARY RETENTION INMEN WITH BENIGN PROSTATIC HYPERPLASIA Peter Boyle*,Chris Robertson, Milan, Italy; Tim H Wilson, Research Triangle Park, NC;Jaques Benichou, Rouen, France

INTRODUCTION AND OBJECTIVE: Benign Prostatic Hyperplasia (BPH) isa progressive condition that is characterized by an increased risk of acute urinaryretention (AUR) and BPH-related surgery. AUR presents a high-risk in older menalthough there has been no attempt to predict individual men at high risk of thiscomplication.

METHODS: Three 2-year multi-center, double-blind, placebo-controlledstudies were conducted (n = 4325); dutasteride was administered at a dose of0.5 mg/day. Inclusion criteria were: moderate to severe symptoms (AmericanUrological Association Symptom Index, AUA-SI ~12); prostate volume ~30

ml; prostate-specific antigen ~ 1.5 nglml to s 10.0 ng/ml; and maximum flowrate (Qmax) sl5 ml/sec. AUR was defined as inability to urinate requiringcatheter; all BPH related surgical procedures were counted with TURP beingthe most common one performed. The three independent studies were designedfor a pooled analysis. The statistical analysis was restricted to the placebocontrol group.

RESULTS: There were 90 episodes of AUR determined among the 2,158 menin the control group in this study: the crude incidence of AUR was 4.2%. The rangeof the variables was divided into five equal groups (fifths). The risk of AUR wasindependently associated with Qmax, prostate volume and baseline PSA.Compared to the highest Qmax (13-33 mVsec)(Hazard Ratio (HR)= 1), the risk ofAUR in the group with the lowest Qmax «7 mils) was 4.5 (p for trend p<0.0006).For prostate volume, the risk in the group with the largest volume (69cc or more)

1292DUTASTERIDE PROVIDES SUSTAINED AND CONTINUEDIMPROVEMENT IN BPH-RELATED SYMPTOMS OVER 4YEARS Claus G Roehrborn*, Dallas, TX; Peter Boyle, Milan, Italy; JCurtis Nickel, Kingston, Canada

INTRODUCTION AND OBJECTIVE: Three large phase III clinical trialshave previously reported that dutasteride, a dual inhibitor of 5 alpha reductase, to

be safe and effective in the treatment of BPH for 2 years. An additional 2 yearopen-label extension phase was prospectively designed for all 3 studies in order toobtain additional safety and efficacy information with dutasteride. We report theinitial findings from one (ARIA3002) of the 3 studies.

METHODS: ARIA3002 was one of the 3 phase III clinical trials that hasrecently completed the open-label phase, thereby providing 4 years data withdutasteride treatment. The initial 2 year study was randomized, double-blind,placebo-controlled, evaluating the efficacy and tolerability of dutasteride 0.5mglday compared with placebo. Males ~ 50 years of age with BPH, anAUA-SI score ~ 12, urinary flow rate < 15 mLisec, serum prostate-specificantigen (PSA) ~ 1.5 nglml to s 10.0 nglml and a prostate volume ~ 30 cc wereincluded. Patients who completed the 2 year double-blind study were eligiblefor enrolment in the open-label phase. Of the original 1362 patients enrolledinto the double-blind portion of the study, 766 patients rolled over into theopen-label phase.

RESULTS: Mean AUA-SI scores were approximately 17 in both treatmentgroups at the initiation of the double-blind portion of the study. Approximately70% of the patients enrolled in the open-label phase completed the study. Mean(SD) changes from baseline AUA-SI are depicted in the table below.

CONCLUSIONS: Treatment with the dual 5ARI dutasteride providessustained and continued improvement in BPH-related symptoms out to 4 yearsproviding a 5.5 point improvement in AUA-SI . An additional 2 years treatmentwith dutasteride results in additional 2 point improvement in the AUA-SI. AUA-SIscores from patients treated with placebo in the initial 2 years of the trial had overa 3 point improvement in the AUA-SI which is consistent with the dutasterideresponse in the first 2 years of the study.

Placebo (Year 0·2)Outasteride (Year2-4)

18(7.1%)

Placebo (n=252)

-34 (6.2) n=370·4,9(64) n=347-4.7 (6.8) n=327-5,6 (6.5) n=290·5,5(6.4) n=275

9(34%)

P=0.0412

OOXlFIN(n=261)

Outasteride (Year 0.2)Outasteride (Year2·4)

14(5,9%)

P=0.5791

FIN(n=237)

10(4.0%)

P=0.1235

DOX(n=249)

-1,3 (6,4) n=378-2.9 (6,5) n=347-3.8 (6.7) n=319-44 (6,8) n=287-4.6 (7,0) n=260

Source of Funding: GSK.

Number (%) ofpatientsP valuevs placebo

Month 24Month 30Month 36Month 42Month 48

Oox Fin CombAge Ns 0.54% 1.22%PSA 1.88% Ns NsSx Ns 0,91% NsQmax 0.70% Ns NsPVR Ns Ns NsTRUS 1.12% Ns Ns

1291PROPORTION OF PATIENTS FROM THE PREDICT TRIALWITH AT LEAST A 4-POINT RISE IN INTERNATIONALPROSTATE SYMPTOM SCORE AT 1 YEAR Claus G Roehrbornon behalf of the PREDICT Steering Committee and Investigators",Dallas, TX

INTRODUCTION AND OBJECTIVE: Data from the Prospective EuropeanDoxazosin and Combination Therapy (PREDICT) trial demonstrated thatdoxazosin (DOX) and doxazosin in combination with finasteride (DOXIFIN) weremore effective than FIN alone or placebo in improving urinary symptoms in benignprostatic hyperplasia (BPH) patients after I year. It was also observed that FIN didnot provide any additional benefit beyond that achieved with DOX alone. Becauseclinical progression of BPH in the MTOPS trial was primarily evidenced by a risein total International Prostate Symptom Score (IPSS) by at least 4 points frombaseline, we conducted a post-hoc analysis of the PREDICT data to determine theproportion of patients with a 4 point rise at I year.

METHODS: PREDICT was a double-blind, parallel-group, placebo-controlledtrial comparing DOX, FIN, and DOXIFIN combination therapy over 52 weeks. ThePREDICT trial was I year in duration and was not powered to evaluate diseaseprogression. This post-hoc analysis evaluated the proportion of patients at I yearwith a rise in total IPSS by at least 4 points. All statistical analyses were conductedon an intent-to-treat (ITT) basis (ie, all patients who took at least I dose of studymedication during the double-blind treatment phase and had at least 1 post baselinetotal IPSS). Endpoint data were analyzed using Cochran Mantel Haenzsel chisquare test for difference in proportions stratified by country.

RESULTS: Presented here are the proportions of patients with at least a 4-pointrise from baseline in total IPSS by treatment group.

CONCLUSIONS: The proportion of patients with clinical progression of BPHas evidenced by a 4 point rise from baseline in total IPSS was lowest for thecombination therapy group, followed by the DOX group, then the FIN group, andhighest for the placebo group.

Table 1:Predictive valueofeach baselinecD'lariate

Source of Funding: National Institutes of Health (NIDDK).

1290ALFUZOSIN 10 MG ONCE DAILY FACILITATES RETURN TOVOIDING IN PATIENTS WITH ACUTE URINARY RETEN­TION: RESULTS OF A PLACEBO-CONTROLLED STUDY TimHargreave, Alan McNeill*, Edinburgh, UK; Jack Fitzsimmons, Malvern, PA;x ALFAUR Study Group, x, UK

INTRODUCTION AND OBJECTIVE: The ALFAUR study sought to confirmthe beneficial effect of alfuzosin on the outcome of a trial without catheter (TWOC)following an episode of acute urinary retention (AUR) (Phase one), and to assessthe effect of alfuzosin in the prevention of recurrence of AUR or the need forBPH-related surgery following a successful TWOC (Phase two). Phase one hasnow been completed and the results are presented.

METHODS: Patients presenting with AUR secondary to benign prostaticobstruction, were randomised to receive Alfuzosin 10 mg OD or placebo for2-3 days prior to a TWOC. The ratio of randomisation was 2: I, alfuzosin:placebo. The primary efficacy criterion was the percentage of patients with asuccessful TWOC.

RESULTS: 363 patients were randomised, results being evaluable from357. The mean age and mean volume of retention were comparable in eachtreatment group (69.3 ALF vs 69.4 Plac; 983.8mls ALF vs 966.7mls Plac)Alfuzosin significantly improved the likelihood of successful TWOC (61.9%versus 47.9%, p=0.012). In a multivariate analysis of risk factors, increasingage and retention volume reduced the likelihood of successful TWOC(p<O.OOI), whilst alfuzosin 10 mg OD almost doubled the likelihood of asuccessful TWOC (OR= 1.98, p=0.005). The safety profile of alfuzosin 10 mgOD was satisfactory.

CONCLUSIONS: The results from Phase one of the ALFAUR studydemonstrate a clear benefit to patients who received alfuzosin 10 mg OD prior toundergoing a trial without catheter fol1owing an episode of AUR. The probabilityof a successful voiding after TWOC in patients who receive alfuzosin 10 mg ODis almost twice as that of patients who receive placebo.

Source of Funding: Sanofi-Synthelabo.

334 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Tuesday, April 29, 2003

'P<O.OOI vsbaseline; tSlatistically signi~ant between groups.

BetweengroupPvalue

0.019t

0004t

0.589

-4.0±2.7"

-6.4±0.46'

-2.5±0.26'

EndPhaseIV AdjustedMeans

DOX GITS TAM (n=47)(n=47)

-8.0±.048'

-5.1±0.27"0.234

0.019t

BetweengroupPvalue

TAM(n=22)

-7.0±6.5*

-4.9±4.7"-6.4±4.1'

DOX GITS(n=23)

-11.7±6.3*

EndPhaseII (prewashout)unadjuated means

TotalIPSSIPSSObstrIPSSIrrit -5.2±3.2' -2.1±2.7" O.OOlt -2.8±0.25*

was 6.3 (95% CI (5.9,23))(P trend (p<O.OOOI) versus the smallest volume. ForPSA, the risk in the five categories was I (psa <2), 1.2 (2.1-2.9), 2.5 (2.9-4), 3.9(4.1-5.8) and 6.3 (PSA of greater than 5.9)(p trend (p<O.OOOI). After adjustmentthere was no association between risk of AUR and AUA-SI or age. Amultidimensional model has been developed to predict individual risk andvalidated in the treatment group with good results.

CONCLUSIONS: Risk factors for AUR have been identified and amultidimensional model has been developed. Identifying men at high risk of AURwould offer significant prospects for prevention since it has been clearlydemonstrated that 5-ARIs reduce the risk of this complication.

Source of Funding: GSK.

1294ANTIDIURETIC HORMONE IN ADULT NOCTURIA Du GeonMoon *, Suck Ho Kang, Jun Cheon, Jeong Gu Lee, Je Jong Kim, Ansan, SouthKorea

INTRODUCTION AND OBJECTIVE: Nocturia is generally regarded as anirritative or filling symptom, and has been closely associated with benign prostatichyperplasia and bladder outlet obstruction. However, operative decrease inprostatic volume and relief of obstruction do not eliminate nocturia. It still has notbeen clarified whether nocturia in BPH is an irritative symptom related to urinarytract obstruction or bladder function or circadian changes in nighttime urineproduction. We investigated the circadian variation of plasma antidiuretic hormoneand urine output in noturia patients. We also assessed the effect of desmopressin inurine output in nocturia patients.

METHODS: In 12 patients of nocturia 03 per night) and age matched normalcontrol of 5 healthy men, 24-hour circadian studies were performed during a72-hour admission. In 12 patients of nocturia, basal 24-hour urine output wascompared to 24-hour urine output after oral administration of DDAVP (0.2 mg,10 p.m.).

RESULTS: Compared to normal control, nocturia patients had a lack of diurnalvariation in urine output, and increased nocturnal urine production associated witha lack of nocturnal elevation of antidiuretic hormone level. Compared to basalurine output, administration of DDAVP significantly decreased nighttime (IIp.m.-8 a.m.) urine output in nocturia patients (p<0.05). Administration ofDDAVPsignificantly increased the osmolarlity of nighttime urine (p<0.05). There wassevere systemic adverse reaction.

CONCLUSIONS: Severe nocturia (3) patients in a large portion of elderlymen with lower urinary tract symptoms is caused by nocturnal polyuria andnatriuresis as a result of lack of nocturnal surge of antidiuretic hormone. Theseresults suggest that DDAVP may be an effective modality in nocturia, which doesnot respond to conventional treatment.

Source of Funding: None.

1295A CROSSOVER STUDY OF DOXAZOSIN GITS VERSUSTAMSULOSIN: CHANGES IN INTERNATIONAL PROSTATESYMPTOM SCORE AT THE END OF THE FIRST 8-WEEKEFFICACY PERIOD Roger S Kirby*, London, UK

INTRODUCTION AND OBJECTIVE: Introduction and Objectives: 8 wks oftreatment with doxazosin gastrointestinal therapeutic system (GITS), a controlled­release formulation, has been shown to be significantly more effective thantamsulosin (TAM) in relieving symptoms of BPA. A subanalysis evaluatingchanges in the International Prostate Symptom Score (IPSS) at the end of the first8 wk efficacy period, before washout, was undertaken to determine consistencywith the results of the 2 efficacy periods combined.

METHODS: METHODS: This was a randomized, double-blind, crossoverstudy of men aged 50-80 years with BPH, consisting of 4 phases: Phase I, placeborun-in for 2 wks; Phase II, first study drug DOX GITS or TAM for 8 wks; PhaseIII, washout with placebo for 2 wks; and Phase IV, second study drug TAM orDOX GITS for 8 wks. Therapy with DOX GITS 4mg/d and TAM O.4mg/d wasinitiated and then titrated to 8mg/d and 0.8mg/d, respectively, after 4 wk based onresponse. Efficacy data at the end of Phase II were evaluated using a t-test andefficacy data at the end of Phase IV were evaluated using an analysis of covariancemodel with terms for treatment, sequence, phase, and patient within sequence inaddition to the baseline as covariate.

RESULTS: RESULTS: Mean IPSS from baseline at end of Phase II and at endof Phase IV. Statistically significant improvements from baseline in total IPSS,obstructive subscore, and irritative subscore were observed in patients treated forthe first 8 wks (end of Phase II) with DOX GITS or TAM. DOX GITS was moreeffective than TAM in improving total IPSS (P=0.019) and irritative symptoms(P=O.OOl) at the end of the first 8 weeks.

CONCLUSIONS: CONCLUSIONS: After the first 8 wks of treatment, totalIPSS results are supportive of the previously reported data from the 2 efficacyperiods combined. Those results demonstrated that DOX GITS was significantlymore effective than TAM in improving total IPSS.

Source of Funding: Financial support was provided by Pfizer, Inc.

1296PATIENTS ON TAMSULOSIN EXPERIENCING ABNORMALEJACULATION CHOOSE TO REMAIN LONGER IN CLINICALTRIALS AND HAVE SLIGTHLY BETTER IMPROVEMENT INSYMPTOM SCORE THAN OTHER PATIENTS Mark J Speakman *,Taunton, UK; Robert J Snijder, Gaby Anthonijs, Leiderdorp, Netherlands;Caroline A Doyle, Ridgefield, CT

INTRODUCTION AND OBJECTIVE: Abnormal ejaculation has beenoccasionally associated with ",]-adrenoceptor (AR) antagonist treatment oflower urinary symptoms/benign prostatic hyperplasia (LUTS/BPH). Itis probably related to blockade of "',-ARs in the bladder neck, vas deferensand seminal vesicles. In controlled and open-label European clinical trialswith tamsulosin 0.4 mg once daily, 4.8% of patients had abnormal ejaculationbut only 0.6% of patients discontinued due to abnormal ejaculation. In USplacebo-controlled trials, 0% of patients receiving tamsulosin 0.4 mgdiscontinued due to abnormal ejaculation. The aim of this combined analysiswas to evaluate the impact of abnormal ejaculation in tamsulosin treatedLUTS/BPR patients.

METHODS: The combined database of 12 European and US clinical trials withtamsulosin 0.4 or 0.8 mg once daily (6 placebo-controlled, 2 active controlled, 4open-label extension studies) was used to evaluate the impact on total symptomscore, disease-specific quality of life (QoL: BPH Impact Index: BII) and studydiscontinuation in patients with or without abnormal ejaculation.

RESULTS: 2,543 patients (mean age 61.0 years) with a mean exposure totamsulosin of 696 days (range: 1-2,356 days) were included in the analysis. Theimprovement in symptom score was slightly better for patients with abnormalejaculation than for those without abnormal ejaculation, also in the longer term (seeTable). The improvement in BII was comparable for both groups. The percentageof all patients that remained in the study over time (up to 60 months) was larger inthe patients with abnormal ejaculation than in those without abnormal ejaculation.The decreased discontinuation in the patients with abnormal ejaculation wasmainly apparent in the first year.

CONCLUSIONS: Occasionally patients may experience abnormal ejaculationduring tamsulosin treatment. These patients have a slightly better improvement insymptom score in relation to patients without abnormal ejaculation. In addition,they are less likely to discontinue treatment than patients without abnormalejaculation.

1year 2years 3 years 4 years 5yearsPatientswith abnormal ejacula.lion~PSS : mean change -8.1 -9.1 -8.9 -8.9 -8.8Bll: mean change -1.8 -2.2 -1.9 -1.9 -2.0Palients Instudy: % 71.9% 57.1% 51.0% 45.2% 39.8%Patients without abnormal eJacula-tion~PSS : mean change -8.0 -8.1 -8.0 -8.0 -8.2811: mean change -1.7 -1.9 -1.9 -1.7 -1.7Patientsinstudy: % 51.5% 32.0% 26.1% 21.1% 12.7%

Source of Funding: Boehringer Ingelheim GmnH and Yamanouchi EuropeBV.

1297META-ANALYSIS OF PERMIXON IN TREATMENT OFSYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA: ANUPDATE Peter Boyle", Chris Robertson, Milan, Italy; Franck Lowe, NewYork, NY; Claus Roehrborn, Dallas, TX

INTRODUCTION AND OBJECTIVE: Permixon is a pharmacologicalcompound extracted from the fruit of the American dwarf palm, Serenoa repens,for the treatment of men with BPA. A previous meta-analysis, based on 2,857patients, demonstrated that Permixon effectively reduced nocturia and increased

*Presenting author.

Vol. 169, No.4, Supplement, Tuesday, April 29, 2003 THE JOURNAL OF UROLOGY® 335

Bladder Cancer: InvasivePodium

Tuesday, April 29, 2003 10:00 AM·12:00 PM

1300IS THERE A ROLE FOR PRE-OPERATIVE CHEMOTHERAPYIN SMALL CELL BLADDER CARCINOMA? THE M. D.ANDERSON EXPERIENCE Arlene 0 Siefker-Radtke", Colin P Dinney,Neil A Abrahams, Louis L Pisters, H Barton Grossman, David A Swanson,Randall E Millikan, Houston, TX

INTRODUCTION AND OBJECTIVE: Neuroendocrine tumors of the bladdercomprise a small subset of all bladder tumors. To improve our understanding ofsmall cell carcinoma of the bladder and define outcome with current management,we performed a retrospective revi~w of patients seen with this diagnosis at theM. D. Anderson Cancer Center.

METHODS: We reviewed records of 75 patients with small cell bladdercarcinoma evaluated at our institution from 1985 to 2002. Forty of thesepatients presented with resectable (i.e. <cT4b) cancers and form the basis forthis report.

RESULTS: Twenty patients had initial surgery, and 20 had pre-operativechemotherapy. For patients managed with initial resection, the median cancer­specific survival (CSS) was 13 months, with a 30% alive and disease-free at

1299FEMALE SEXUAL DYSFUNCTION (FSD) FOLLOWINGRADICAL CYSTECTOMY: IFSF-IO ANALYSIS Rupesh Raina*,Ashok Agarwal, Asha D Shah, Stephen Jones, James Ulchaker, Eric A Klein,Craig D Zippe, Cleveland, OH

INTRODUCTION AND OBJECTIVE: Outcome data following radicalcystectomy (RC) w/wo orthotopic diversion has focused primarily on cure, urethralrecurrence, and continence. In our contemporary RC series, we assessed FSD andwhether the type of diversion affected sexual dysfunction.

METHODS: Baseline and follow-up data from 27 (mean age 54.79 ± 12.7years) sexually active female patients (frequency limo. to every 3 days)undergoing RC from 1997-2002 for TCC of the bladder (16/27 (Tl-2); 11127(T3-4) were obtained. 13 women were pre-menopausal. 10/27 patients (37%) hadan orthotopic (Studor) diversion, 37% had a cutaneous continent (Indiana)diversion, and 7/27 (26%) had an ileal conduit diversion. A IO-item version of theself-administered Index of Female Sexual Function (IFSF) questionnaire, patternedon the validated multi-dimensional IIEF-15, was mailed to patients to assess sexualdysfunction following RC. Specific domains analyzed included: quality of sexualintercourse, desire, overall satisfaction with sexual function, orgasm, lubrication,and clitoral sensation with responses graded on a scale of I (almost never, never)to 5 (almost always, always).

RESULTS: With a mean follow-up of 24.2 months (range 1.5-65.1), thetotal mean baseline IFSF score decreased from 17.4 ± 7.23 to 10.6 ± 6.62 afterRC (p SO.05). The most common symptoms reported included: decreasedsexual desire, 37% (10/27); decreased lubrication, 41% (11/27); diminishedability or inability to achieve orgasm, 45% (12/27); dyspareunia, 22% (6/27).Only 48% (13/27) were able to have successful vaginal intercourse with 56%(15/27) reporting decreased satisfaction in overall sex life after RC. In 30%(8/27), there was a decrease in desire for sexual activity due to apprehensionfollowing cancer diagnosis and treatment. No difference in sexual functionswere observed between patient having orthoptic (Studor) diversion vscutaneous continent (Indiana) diversion.

CONCLUSIONS: Sexual dysfunction is a prevalent problem. Our earlyresults suggest that the type of continent diversion does not affect sexualfunction. Surgical modifications (urethral sparing) may improve FSD followingRC.

IFSF Domains: Baseline and afterRadical Cystectomy

0.0098

0.0306

0.0711

0,1262

0.0775

0.0067

P·valuesAfterRC

1.6 ± 2,01'

2.2 ± 2,09'

2 ± 2.22

2.1 ± 1.25

2.7 ± 1.53

10.6 + 6,62'

Domains Before RC

p' <0,05IFSF domains before vsafter RC (student t test).

Source of Funding: None.

Degree ofVaginal Lucrication 3.3 ± 1.90

Abilityto Achieve Orgasm 4 ± 1,83

Free of Pain During Intercourse 3.5 ± 1,99

Overall Sexual Desire 2.9 ± 1.3Overall Sexual Satisfaction 3.7 ± 1,23

Total Mean Value 17.4 + 7,23

1298IMPACT OF BASELINE SYMPTOM SEVERITY ON GENERALHEALTH AND SEXUAL SATISFACTION IN MEN WITH BPHTREATED WITH FINASTERIDE OR PLACEBO Steven AKaplan*, New York, NY; for the PLESS Study Group, USA

INTRODUCTION AND OBJECTIVE: In a previous analysis from theProscar" Long-Term Efficacy and Safety Study (PLESS), we reported thatfinasteride treatment led to an improvement relative to placebo in health-relatedquality of life measures, especially for men with a baseline serum prostate­specific antigen (PSA) level of 1.4 ng/mL or greater. The present analysis fromPLESS examined whether baseline symptom severity could impact the effect offinasteride treatment on general health and sexual satisfaction/drive in menwith BPH.

METHODS: PLESS was a four-year trial comparing the safety and efficacy offinasteride 5 mg to placebo in 3040 men with moderate to severe symptomatic BPHand enlarged prostates. Patients completed an annual health-related quality of lifequestionnaire, which included domains evaluating the level of general health, aswell as sexual satisfaction and sexual drive. Symptom severity was assessed usinga Quasi-AUA symptom score.

RESULTS: Finasteride treatment led to an improvement in general health, withthe greatest difference from placebo occurring in men with moderately-severe tosevere baseline symptoms. Additionally, over the entire 4-year study, sexualsatisfaction measures were similar in finasteride and placebo patients withmoderately-severe to severe baseline symptoms.

CONCLUSIONS: Finasteride treatment led to a sustained improvement ingeneral health in men with BPH, especially in patients with moderately-severe tosevere baseline symptoms. Although sexual satisfaction and sexual drive wereslightly worse relative to placebo for finasteride overall, little difference was seenin these measures for men who had moderately-severe to severe symptoms atbaseline.

Source of Funding: Study was funded by Merck & Co., Inc.

flow rates compare to placebo. This meta-analysis was unable to examine the effectof Permixon on symptom score.

METHODS: In addition to the original 13 studies involving 2,857 patients,there were a further 4 studies available for this meta-analysis involving anadditional 1,963 men. This analysis comprises 17 studies and 4,820 men. The database represents all clinical trial data published on Permixon. The additional studieswere randomized and allowed examination of the impact of Permixon on theInternational prostate Symptom Score (lPSS).

RESULTS: Overall the trials, the placebo was associated with an increasein flow rate of 1.09 (standard error 0.45) ml/sec. The effect of Permixon wasto increase flow rate by a further 2.28 (se 0.29) ml/sec. Placebo was associatedwith 0.63 (se 0.14) fewer reports of nocturia while the effect of Permixonwas to reduce this by a further 1.01 (se 0.13) episodes. The lPSS was usedin six studies. Permixon was associated with a fall of 4.7 (se 0.41) pointswhich was the same effect found with finasteride and tamsulosin in thesestudies.

CONCLUSIONS: This update of the original meta-analysis of all availablepublished trials of Permixon in the treatment of men with BPH reveals asignificant improvement in peak flow rate and reduction in nocturia aboveplacebo. There is also a significant reduction in symptoms as assessed bysymptom score.

Source of Funding: None.

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