254 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Monday, April 28, 2003

performed using scrotal approach. In 1898 Narath described "radical operation ofthe varicocele" via inguinal incision.This approach was further developed intocommonly used procedures by Ivanissevich (1918) and Palomo (1949) from SouthAmerica.Possible influence of varicocele on fertility and successful pregnanciesafter varicocelectomy was reported since 19th century (Barwell, Bennet, Hammen,Wilhelm, Macomber and Sanders). Recent interest to varicocelectomy as atreatment of male infertility was ignited by Tulloch's report in 1952. Since thattime, the first and most important indication for varicocelectomy was defined andwidely accepted.Further technical improvement and refinement of varicocelectomywas associated with microsurgery. Microsurgical technique was applied to thevaricoicelectomy by Ishigami who performed anastomosis between spermatic andsaphenous vein. Later microsurgical techniques were modified and improved byMarmar and Goldstein.

CONCLUSIONS: Varicocelectomy is one of the oldest surgical procedures inhistory. Nevertheless, the best technique has yet to be developed.

Source of Funding: None.

985EVOLUTION OF SURGICAL TREATMENT OF URETERO­PELVIC JUNCTION OBSTRUCTION Bijan Shekarriz: GaurangShah*, Jyoti Upadhyay, Zahi Makhuli, Syracuse, NY

INTRODUCTION AND OBJECTIVE: Management of ureteropelvic junction(UPJ) obstruction has benefited from advancement in minimally invasiveprocedures. The purpose of this study was to review the changing pattern ofsurgical management of UPJ obstruction.

METHODS: A comprehensive review of original literature of surgicaltreatment of UPJ obstruction was performed including MEDLINE andPu1:)Med.

RESULTS: The open repair for treatment of UPJ obstruction was describedby Trendelenberg (1886). Kuster (1891) performed the first dismemberedpyeloplasty. Since that time, various modifications for pyeloplasty weredescribed by Schwyzer (1916), Foley (1937). Anderson and Hayes (1949)introduced dismembered reduction pyeloplasty. Culp and De Weed (1951),Scardino and Prince (1953) described flap pyeloplasty. In 1903, Albarrandescribed incision of stenotic UPJ. He made full thickness incision through aureter and placed catheter within the ureter, during healing. He described it as"urethrotome externe". In 1943, Davis promoted "Albarran procedure" andnamed it "intubated ureterotomy". He did full thickness incision of stricture,placed stent within the ureter and coapted edges with a few sutures. Althoughdismembered pyeloplasty was gold standard in treating UPJ obstruction withthe success rate in the 90 % range, improvement in endourological outcomesmade endopyelotomy a first-line minimally invasive therapy option. In 1983,Wickham and Miller performed incision of stenotic UPJ obstruction throughnephrostomy tract, using a Sachs urethrotome. They called this procedure"Percutaneous Pyelolysis". Smith and Badlani (1986) popularized thistechnique in United States and renamed it "endopyelotomy", Their techniqueoffered direct visual incision of the UPJ. The antegrade endopyelotomy wastraditionally used for UPJ obstruction associated with calculus disease. Tofurther decrease the morbidity, a variety of investigators have treated UPJobstruction by retrograde endoscopic approach in early 90's (Bageley,Clayman, Kavoussi, Gallucci, Thomas, Preminger). Although endoscopicapproaches to UPJ obstruction were less invasive, their long-term success ratewas less compared to open pyeloplasty. With the introduction of laparoscopyinto urology, the technique for laproscopic pyeloplasty can combine the highsuccess rate of open pyeloplasty with decreased morbidity (Kavoussi, 1998).

CONCLUSIONS: Surgical management of UPJ obstruction has moved fromopen repair to minimally invasive procedures including endoscopic repair andlaproscopic techniques.

Source of Funding: None.

986THE VOIDING CYSTOURETHROGRAM: A HISTORICALPERSPECTIVE Sovrin M Shah *, Kenneth I Glassberg, Brooklyn, NY

INTRODUCTION AND OBJECTIVE: The voiding cystourethrogram(VCUG) provides the opportunity to visualize voluntary antegrade flow of urinethrough the urethra while also allowing observation of the dynamic relationshipbetween the bladder, urethra, and uretero-vesicaljunction. We sought to determinethe historical roots of this procedure.

METHODS: We investigated early urologic and radiologic literature relating tothe beginnings of the VCUG and communicated with some of the pioneers of theearly 1950s.

RESULTS: In 1895 the first roentgenogram and in 1905 the first cystogramwere performed by Roentgen and Voelker, respectively. In 1920 Blum and hiscolleagues first introduced the use of fluoroscopy during cystograms to study

*Presenting author.

the act of micturition. Only sparse use of this technique was reported between1920 and mid 1940s. In 1947, FD Stephens from Australia, working in Englandat the Hospital for Sick Children, Great Ormond Street, began to implementVCUG in the study of children. He is given credit by his mentor and colleagues(TT Twistington, DI Williams, and DFE Nash) for impressing upon them thevalue of voiding cystourethrography. Case studies and various pathologiesresulting from these studies were subsequently presented in 1954 and 1955 byWilliams and Stephens. At about the same time in the United States, Muellnerand Fleischner (1948), from the Beth Israel Hospital, Boston, Massachusetts,examined bladder behavior during voiding under the fluoroscope. At theAnnual Meeting of the American Urological Association in St. Louis in May1953 Frank Hinman Jr and his colleagues at the University of California Schoolof Medicine, San Francisco, presented the use of cineradiography and serialroentgenography during voiding. Their findings differed slightly from those ofMuellner and Fleischner. The paper was published in May 1954. With theincreasing use of the VCUG, Williams noted that reflux occurs with chronicretention and the VCUG was able to demonstrate the urethra, ureters, and renalpelves simultaneously. In the late 1950s and early 1960s Keith Waterhouse,from the State University of New York, Downstate Medical School, Brooklyn,employed VCUG in the identification of posterior urethral valves.

CONCLUSIONS: The VCUG not only improved the urologist's ability tostudy and treat lower urinary tract anomalies, it also opened the door to theemergence of a new specialty - pediatric urology.

Source of Funding: None.

Bladder Cancer: SuperficialModerated Poster

Monday, April 28, 2003 3:30-5:30 PM

987FLUORQUINOLONE PROPHYLAXIS FOR SUPERFICIALBLADDER CANCER: RESULTS OF A RANDOMIZED STUDYJon A Lovisolo*, Giuseppe Gianesini, Paolo Maggio, AIda V Bono, Varese,Italy

INTRODUCTION AND OBJECTIVE: In vitro studies have shown thatantibiotics of the fluorquinolone class possess strong inhibitory effects ontransitional cell carcinoma (TCC) cells at concentrations easily obtainable in urineafter oral or parenteral dosing. A retrospective study showed that perioperativepefloxacin, a fluorquinolone, might be able to reduce the recurrence rate ofsuperficial TCC after TURBT. Herein, we present the results of a prospectiverandomized trial designed to study the possible antineoplastic effects of pefloxacinon superficial bladder cancer.

METHODS: Patients who underwent TURBT for presumed Ta, T1 or insitu TCC were eligible for randomization to receive either ceftriaxone l gm iv1 hour before and 12, 24 and 36 hours after TURBT (control group) orpefloxacin 800mg iv one hour before and 8 and 12 hours after TURBT. Ifpathology confirmed superficial TCC, the patient was kept on study, whilethose without tumor (TO) or with muscle invasive disease (T2) were excluded.Pefloxacin was to be continued 400mg po bid one day a week for 6 months afterdischarge.

RESULTS: 163 patients were randomized, and 113 were eligible tocontinue the study. Reasons for ineligibility were finding of either TO or T2disease. One hundred patients were evaluable for this analysis. Reasons fornon-evaluability were: early discontinuation of pefloxacin due to toxicity in 5cases, loss to follow-up in 6 cases, early non-cancer related death in 1 case andearly progression of disease in 1 case. There were 80 males and 20 females withan average age of 69 years. Fifty-three patients had been randomized to thecontrol group and 47 had received pefloxacin. Among the patients in the controland pefloxacin groups 34 (64% land 37 (78%) had never been treated forbladder cancer and 19 (36%) and 10 (22%) had recurrent TCe respectively. Thedistribution of stages and grades on enrollment were similar between the 2groups. The average follow-up period was 53 months. 34 patients (34%) hadrecurrent tumors during follow-up. The recuurence rates in the 2 groups were30.2% (16/53) in the control group and 38.3% (18/47) in the pefloxacin group.(Fisher Exact test, p= 0.39). Five patients had progression of disease to stageT2 or greater. All 5 of these patients were in the pefloxacin group. Only onepatient has died due to his bladder cancer.

CONCLUSIONS: This study suggests that perioperative pefloxacin does notreduce the recurrence rate of superficial bladder cancer in patients undergoingTURBT. This casts doubt on the clinical utility of fluorquinolones for prophylaxisin these patients.

Source of Funding: None.

Vol. 169, No.4, Supplement, Monday, April 28, 2003 THE JOURNAL OF UROLOGY® 255

Source of Funding: None.

988ANTI-TUMOR ACTIVITY OF COMMON ANTIBIOTICSAGAINST SUPERFICIAL BLADDER CANCER Ashish M Kamat*,Houston, TX; Dale Riggs, Morgantown, WV; Donald L Lamm, Scottsdale, AZ

INTRODUCTION AND OBJECTIVE: Despite complete resection ofsuperficial bladder tumors, the recurrence rate averages 88%. Intravesicalchemotherapy decreases the recurrence rate by only 14%. Recent evidencesuggests that immediate postoperative instillation is most effective, presumably bypreventing tumor implantation at the time of resection. Oral intake of antibioticsresults in significantly higher concentrations in the urine compared to serum. Weevaluated four commonly used antibiotics for cytotoxic effects against bladdercancer cells at clinically relevant concentrations.

METHODS: Three human transitional cell carcinoma lines - HTB9 (grade 2),T24 (grade 3), and TccSup (grade 4) - were exposed to Bactrim®, cephelexin,nitrofurantoin or ciprofloxacin in concentrations from 0 (control) to 1000, 5000,2000 and 1000 /Lg/mlrespectively, for 96 hours. Cytotoxicity was evaluated usingthe MTT colorimetric assay. Six replicates were used for each data point.

RESULTS: Significant cytotoxicity (p<O.OOl) was seen starting at 31.25/Lg/ml(HTB9, TccSup) and 62.5 /Lg/ml (T24) for Bactrim®, at 19.5 /Lg/ml(HTB9)and 156.3 /Lg/ml(T24, TccSup) for cephelexin, at 7.8 ug/ml (HTB9, T24, TccSup)for nitrofurantoin, and at 12.5 ug/ml (HTB9, TccSup) and 50 ug/ml (T24) forciprofloxacin. Maximum cytotoxicity results are shown in the table.

CONCLUSIONS: Commonly used antibiotics exhibit significant dosedependent cytotoxicity against high grade bladder cancer cells at concentrationsachievable in urine after oral administration. Post surgical antibiotic use mightprove beneficial in preventing seeding of cancer cells after transurethral resectionof bladder tumors thereby decreasing tumor recurrences. Pre-clinical data such asthese must be taken into consideration when designing clinical trials addressing theissue of recurrences after TURBT.

Cytotoxic Effect ofAntibiotics

989MAINTENANCE BACILLUS CALMETTE-GUERIN FOR TA, T1BLADDER CANCER IS NOT ASSOCIATED WITH INCREASEDTOXICITY. RESULTS FROM AN EUROPEAN ORGANIZATIONFOR RESEARCH AND TREATMENT OF CANCER GENITO­URINARY GROUP PHASE III TRIAL Adrian P Van der Meijden,Hertogenbosch, Netherlands; Richard J Sylvester", Brussels, Belgium;Willem Oosterlinck, Gent, Belgium; Giovanni Casetta, Torino, Italy;Wolfgang Hoeltl, Vienna, Austria; Aida V Bono, Varese, Italy

INTRODUCTION AND OBJECTIVE: After transurethral resection, weassessed the side effects (local and systemic) of weekly instillations with BacillusCalmette-Guerin (BCG) during a 6-week induction course followed by 3-weeklymaintenance courses at 3, 6, 12, 18, 24, 30 and 36 months to determine if BCGtoxicity increases over time.

METHODS: A total of 520 patients randomized in a multicenter phase III trialwere eligible and received BCG. The treatment regimen was divided into 5 periods:induction, months 3 and 6, month 12, the second year of maintenance and the thirdyear of maintenance.

RESULTS: During the 36-month treatment period, 19.4% of the patientsstopped BCG instillations due to side effects, 32.7% completed their treatment,17.1% stopped due to inefficacy and 30.8% stopped due to other reasons. 14.2%stopped due to local side effects: bacterial cystitis 2%, BCG induced cystitis 11.5%and other local side effects 3.3%. Treatment was withheld due to systemic sideeffects in 8.8%: fever 4.4%, lung infection 0.2%, skin rash 0.2%, general malaise2.9%, sepsis 0%, and other 1.2%. Of the 60 patients who stopped instillations dueto BCG induced cystitis, 34 stopped during the first 6 months, 5 at 12 months, 10during the second year and 11 during the third. Of the 23 patients who ceasedinstillations due to high fever, 19 stopped within 6 months, 1 at 12 months, 2 in thesecond and 1 in the third year. Fifteen patients stopped due to general malaise: 12within 6 months, 1 at 12 months, 1 in the second year and 1 in the third. 68% ofpatients who stopped treatment due to side effects did so during the first 6 months.The percent of patients delaying or stopping treatment after 6 months due to localside effects does not increase and actually decreases for systemic side effects.

CONCLUSIONS: To be effective for the treatment of Ta, T1 bladder tumors,a recent meta-analysis has shown that maintenance BCG is required. IntravesicalBCG provokes both local and systemic side effects. The majority of adverse events

Maximal Cytotoxicity (%),Dose (~g/ml)

990FAILURE TO ACHIEVE A COMPLETE RESPONSE TOINDUCTION BeG THERAPY IS ASSOCIATED WITH IN­CREASED RISK OF PROGRESSION AND DEATH IN PATIENTSWITH HIGH RISK SUPERFICIAL BLADDER CANCER Seth PLerner*, Houston, TX; Cathy Tangen, Heidi Caron, Seattle, WA; David PWood, Ann Arbor, MI; Donald Lamm, Scottsdale, AZ; E David Crawford,Aurora, CO

INTRODUCTION AND OBJECTIVE: The Southwest Oncology Groupconducted a randomized trial of BCG with or without maintenance BCG. Inadditional retrospective analyses, we demonstrated that patients who achieved acomplete response (CR) or remained NED during induction therapy hadsignificantly improved survival relative to those who did not achieve a CR. We alsoanalyzed all randomized patients in order to define prognostic groups forsubsequent progression-free survival based on covariates collected at study entry.

METHODS: Patients must have been alive and evaluable at the end ofinduction therapy. Patients randomized to maintenance BCG were excluded fromthe CR analysis since subsequent treatment with BCG could confound survivalresults. Comparisons were therefore made only among those who did not receiveBCG maintenance. Outcome measures of progression-free and overall survivalwere assessed using Kaplan Meier estimates and proportional hazards regressionmodels. Survival was defined from three months post-registration to death due toany cause. 412 patients randomized to maintenance vs. no maintenance therapy hadcomplete covariate information and could be used for identifying prognostic groupsby implementing Classification and Regression Tree (CART) analysis.

RESULTS: 593 patients were evaluable at the end of induction BCG therapy,and 341 of these were not randomized to maintenance BCG. Patients who achieveda prior complete response during induction BCG had a 5-year survival probabilityof 77% compared to 61% for patients who did not (Hazard ratio 0.60, 95%confidence interval 0.46, 0.78; p < 0.0001). Prior complete response retainedsignificance when adjusted for age, gender, prior intravesical chemotherapy, andpapillary disease versus CIS (HR=0.63, p=O.OOI). CART analysis identified 4prognostic groups. Older patients (2 73 years old) previously treated withintravesical therapy who failed to achieve a complete response had a 3-fold higherrisk of progression relative to those who achieved a CR (Hazard ratio 3.19,p=O.OOOl).

CONCLUSIONS: Failure to achieve a complete response during inductionBCG is associated with a significant risk of progression and death for patients withCIS or recurrent Ta, Tis, or T1 bladder cancer.

Source of Funding: National Cancer Institute.

are seen during the induction course and the first half-year of maintenance. Duringfurther maintenance BCG toxicity does not increase and instillations are welltolerated.

Source of Funding: US National Cancer Institute.

991THE SIDE EFFECTS OF BACILLUS CALMETTE-GUERIN INTHE TREATMENT OF TA T1 BLADDER CANCER DO NOTPREDICT ITS EFFICACY: RESULTS FROM AN EUROPEANORGANISATION FOR RESEARCH AND TREATMENT OFCANCER GENITO-URINARY GROUP PHASE III TRIALRichard J Sylvester", Brussels, Belgium; Adrian P Van der Meijden, 'sHertogenbosch, Netherlands; Willem Oosterlinck, Gent, Belgium; GiovanniCasetta, Torino, Italy; Wolfgang Hoeltl, Vienna, Austria; Aldo V Bono,Varese, Italy

INTRODUCTION AND OBJECTIVE: Previous publications have indicatedthat there may be a correlation between the local and systemic side effects of BCGand its efficacy. It has been suggested that patients with side effects have a betterclinical outcome than those without. The EORTC has investigated this claim in alarge-scale randomized trial.

METHODS: After transurethral resection, intravesical instillations of BacillusCalmette-Guerin (BCG) were given during a 6-week induction course followed by3-weekly maintenance courses at 3, 6, 12, 18, 24, 30 and 36 months. Theprognostic importance of delaying or stopping BCG due to local or systemic sideeffects prior to the 6 months maintenance was investigated with respect to the timeto first recurrence at or after 6 months (landmark method).

RESULTS: 87 out of 520 patients (16.7%) delayed or stopped treatment priorto 6 months: 40 (7.7%) due to local toxicity only, 23 (4.4%) due to systemictoxicity only, and 24 (4.6%) due to both. 168 patients (32.3%) recurred at or after6 months. Neither the delay nor stop of BCG due to local toxicity (HR = 1.29, P =0.25), systemic toxicity (HR = 1.04, P = 0.88) or either local or systemic toxicity(HR = 1.15, p = 0.49) prior to 6 months was related to the time to subsequentrecurrence. Likewise there was no relationship to the particular type of local(chemical cystitis, frequency, hematuria) or systemic (general malaise, fever, skinrash, lung infection) toxicity. Similar conclusions were reached when analyzing the

HTB9

95A±OA,400

87.9±1.1,500

89.2±1.7,1250

85.9+1.2,1000

TccSUP

93.2±OA, 400

90.2±1.1,1000

91.8±3.4,5OO0

91.6+1.9,2000

T24

91.3±0.4,4oo

88.3±0.6,1oo0

86.6±0.9, 1250

90.8+1.6,1000

Ciprofloxacin

Bactrim®

Cephelexin

Nitrofurantoin

256 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Monday, April 28, 2003

presence or absence of side effects and side effects requiring stop of treatment.Likewise changing the landmark to include the 6 months maintenance did notchange the conclusions.

CONCLUSIONS: This large study does not confirm suggestions from previoustrials that patients with BCG related toxicity have a better clinical outcome thanthose without such toxicity.

Source of Funding: US National Cancer Institute.

992MYCOBACTERIAL CELL WALL COMPLEX (MCC) IN THETREATMENT OF CIS OF THE BLADDER: 2 YEAR FOLLOW­UP AND DOSE ESCALATION RESULTS Alvaro Morales*,Kingston, ON, Canada; Gary E Steinhoff, Victoria, BC, Canada; CatherineHildebrand, London, ON, Canada; Marc Riviere, Montreal, PQ, Canada

INTRODUCTION AND OBJECTIVE: Mycobacterial cell wall complex(MCC) is effective and safe at a dose of 4 mg in patients with carcinoma in situ(CIS) of the bladder failing intravesical BCG and/or chemotherapy (I). A doseescalation (8 mg) study in a similar patient population has been conducted. Wereport on the intermediate-term results of the low dose study and the preliminaryefficacy and safety of MCC at an increased dose in refractory patients with CIS.

METHODS: 25 patients with CIS of the bladder who failed one or morecourses of BCG and/or chemotherapy were treated with 4 mg of MCC in 50 mLof saline weekly for 6 weeks and then weekly for 3 weeks at 3 and 6 months.Response to therapy was assessed quarterly by cystoscopic examination, bladderbiopsies and urinary cytology. Negative cystoscopy, biopsy and cytologyconstituted a complete response (CR). A second study entered 30 patients with thesame characteristics who were treated with an increased dose (8 mg) of MCC.

RESULTS: Patients treated with 4 mg MCC and evaluated at 18 monthsobtained a CR of 24% (intent-to-treat population) and 8% achieved a partialresponse (negative cystoscopy and biopsies but positive/suspicious cytology. A 2year follow-up for this cohort will be a vailable by January 30, 2003. Althoughencouraging, the results suggested that the dose and duration of MCC treatmentmight be sub-optimal. Therefore, 30 patients with refractory CIS were enrolled ina dose escalation study and treated with an identical protocol but at the dose of 8mg of MCC. All these patients have completed the initial evaluation with a CR rateof 43%, thus doubling the efficacy observed with the lower dose (4 mg). Notoxicity associated with the increased dose was observed even when the MCC wasadministered in the presence of a disrupted urothelium (immediately after thebiopsies).

CONCLUSIONS: Continuing observation provides strong support for MCC asa safe, effective and durable option for bladder cancer patients failing first linetherapy. At an escalated dose, the effectiveness of MCC appears to be enhancedwithout compromising its safety profile. Long-term follow-up data are needed toconfirm the durability of the response rates documented in the initial study.However, the clinical results to date indicate that MCC is an effective alternativeto current treatments for refractory CIS of the bladder. (I) Morales A. et al. J Urol167 SuppI4):187, 2002.

Source of Funding: Bioniche Life Sciencesn.

993INTERIM RESULTS FROM A NATIONAL MULTICENTERPHASE II TRIAL OF COMBINATION BCG PLUS INTER­FERON-ALFA-2B FOR SUPERFICIAL BLADDER CANCERMichael A Odonnell*, Kathleen Lilli, Christina Leopold, Iowa City, IA

INTRODUCTION AND OBJECTIVE: This report provides interim resultsfrom a large multicenter trial of combination BCG plus interferon alfa-2B (IFN) forboth BCG naive (N) and previous BCG failure (F) patients with superficial bladdercancer (SBC).

METHODS: 337 evaluable patients with moderate to high risk SBC (83%grade 2-3, 70% recurrent, 55% multifocal, 49% stage TI or CIS) enrolled fromMay 1999 to May 2000 with median 24 months follow up are included for analysis.BCG N patients (n=206) were treated with a 6-week induction course of standarddose BCG plus 50 million units (MU) of IFN followed by three 3-weekmaintenance cycles ofreduced dose BCG (1/3-1/10) plus 50 MU IFN at 3, 9, and15 months post induction. BCG F patients (n= 131) were treated similarlyexcepting induction therapy began at a reduced (1/3-1/10) BCG dose plus 50 MUIFN. Patients were evaluated for recurrence with quarterly cystoscopy + cytologyand biopsy/resection as appropriate. Patient tolerance was assessed with a dailysymptom questionnaire and toxicity estimated using a weekly physiciandetermined toxicity scale.

RESULTS: The simple tumor recurrence rates for BCG N and BCG F patientswere 35% and 53%, respectively. The Kaplan-Meier estimates for freedom fromdisease were 71%, 61%, and 58% for BCG N patients at I, 2, and 3 years. Thecorresponding results for prior BCG F patients were 53%, 40% and 40%. Femalegender, age <50 or >70, and papillary-only disease were associated with greaterrecurrence in BCG N patients while multifocality, complete lack of prior BCG

'Presenting author.

response, duration> 2 years and CIS were adverse prognostic factors for priorBCG failures. During the induction phase, moderate to severe local symptoms werepresent in 6% (N) and 17% (F). Toxicity-related premature dropout; treatmentdelay and/or further BCG dose reduction; and need for symptomatic drugs were3.7%,3.5% & 13% during BCG Nand 7.3%, 4.3% & 16% during BCG F inductiontreatments. Moderate-severe systemic side effects were uncommon (1.8% and5.6%, N vs. F). Symptoms and toxicity remained relatively constant duringmaintenance therapy for BCG F but increased to a commensurate level for BCG Npatients.

CONCLUSIONS: This multicenter trial substantiates the previous earlyencouraging reports of the efficacy of combination BCG + IFN as upfront andsalvage therapy for patients with moderate to high risk SBC with a high level ofpatient tolerance and minimal serious toxicity. While this study is still immature,tumor recurrences in the first year following protocol completion appear rare.

Source of Funding: Schering.

9945-AMINOLEVULINIC ACID-INDUCED FLUORESCENCEDIAGNOSIS REDUCES RECURRENCE OF SUPERFICIALBLADDER CANCER: FINAL RESULTS WITH A MEDIANFOLLOW-UP OF 3.5 YEARS Thomas N Filbeck*, Regensburg,Germany; Pichlmeier Uwe, Hamburg, Germany; Ruth Knuechel, WolfWieland, Wolfgang Roessler, Regensburg, Germany

INTRODUCTION AND OBJECTIVE: 5-aminolevulinic acid (ALA)-inducedfluorescence diagnosis (FD) allows for a more thorough transurethral resection(TUR) of superficial bladder carcinoma (BC) compared to conventional white light(WL). A prospective single institution randomized trial was performed toinvestigate whether residual tumor rate and long-term tumor recurrence can bereduced by means of FD. Preliminary data with a median follow-up of 21 monthshave been presented at the AUA meeting 2001 (Anaheim/CA). After completingthe study we present now the final results of the study with a median follow-up of42 months (range 24-61).

METHODS: Between May 1997 and August 2000, 301 patients underwentTUR of bladder tumors either with WL or FD. Patients with muscle invasivetumors or without any evidence of superficial BC during the 1st TUR wereexcluded from further evaluation. A second TUR was performed 5-6 weeks later toevaluate the residual tumor rate. To evaluate recurrence-free survival (RFS) patientfollow-up was performed every 3 months by WL cystoscopy and urine cytology.RFS was analysed via Kaplan-Meier methods and multivariable Cox regressionanalysis.

RESULTS: 191 patients with superficial BC were available for efficacyanalysis. The residual tumor rate was 25.2% in the WL arm vs. 4.5% in the FD arm(p<O.OOOI). Median follow up of the patients (n=103) in the WL arm was 42months (range 25-61) compared to 43 (range 24-61) in the (n=88) FD arm. RFSafter 12, 24 and 48 months was 90.9%, 90.9% und 85 % in the FD group,respectively compared to 78.6%, 69.9% und 60.7 % in the WL group (p=0.OO05).This superiority proved to be independent of risk groups. The adjusted Hazard­Ratio of the FD TUR in comparison to the WL TUR is 0.29 (95% CI: 0.15;0.56).

CONCLUSIONS: Fluorescence diagnosis is significantly superior toconventional white light transurethral resection with respect to residual tumor rateand recurrence-free survival. The differences in recurrence-free survival imply thatfluorescence diagnosis offers a clinically relevant procedure to reduce the numberof tumor recurrences.

Source of Funding: None.

995DO WE NEED P53 IMMUNOHISTOCHEMISTRY INSUPERFICIAL BLADDER CANCER? - FINAL RESULTS OFTHE ISBC COMBINED ANALYSIS Peter J Goebell*, Essen,Germany; Bernd J Schmitz-Drager, Furth, Germany; Susan Groshen, LosAngeles, CA; Manfred Heydthausen, Dusseldorf, Germany; The InternationalBladder Cancer Network, Barcelona, Spain

INTRODUCTION AND OBJECTIVE: For nearly one decade the putativeprognostic value of p53 immunohistochemistry in bladder cancer has beencontroversially discussed. Aim of this paper was to elucidate the different findingsusing the new concept of a combined analysis of raw data from previouslypublished material.

METHODS: 26 institutions contributed a total of 3421 patient data setsaccording to the protocol requirements. The entire study group (mean age: 66.7years) comprised 2697 males (78.8 %). 2298 patients (68%) had superficial tumorsTa (1314), TIS (37) and TI (947) (38.9, 1.1, and 28%, respectively), while theremaining 1082 patients (32%) had advanced tumors (>T2).

RESULTS: With regard to gender, age and tumor stage the patients includedreflected a normal bladder cancer population. Statistical analysis revealed a highlysignificant correlation (p<.OOl) between p53 positivity vs. tumor grade and tumorstage. Uni- and multivariat analysis showed that p53 positivity was significantly

Vol. 169, No.4, Supplement, Monday, April 28, 2003 THE JOURNAL OF UROLOGY® 257

and BCG therapy. Mortality is significantly higher in patients with previousbladder tumors and/or showing recurrence and progression.

Source of Funding: None.

999PROGNOSTIC FACTORS RELATED TO PROGRESSION INTRANSITIONAL CELL CARCINOMA OF THE BLADDERSTAGE G2Tl Joan Palou*, Felix Millan, Antonio Rosales, AntonioAlcaraz, Jose Salvador, Humberto Villavicencio, Barcelona, Spain

INTRODUCTION AND OBJECTIVE: High grade, association to carcinomain situ and/or stage Tl are characteristics of the primary superficial bladder tumors,often associated to progression to muscle invasive disease. But when dealing withtransitional cell carcinoma G2Tl, only 5.2 % progress. We evaluate the prognosticfactors of progression in primary superficial TCC G2T1.

METHODS: A cohort of 565 patients with primary TCC G2Tl treated withtransurethral resection and random bladder biopsies was studied. Independentvariables were; multiplicity, association to CIS, tumor size, tumor recurrence at 3or 6 months, grade and association to CIS at the first recurrence. The dependentvariable was progression to muscle invasive disesase. Univariate and multivariateanalysis was done by means of Cox regression.

RESULTS: On multivariate analysis multiple tumors (relative risk 4.5,95 % IC1.3-15.9), recurrence at 6 months (RR 5.5, 95 % IC 1.3-22.6) and high grade at thefirst recurrence (RR 12.9, 95 % IC 1.4-118.7) were the main prognostic factors forprogression to invasive disease.

CONCLUSIONS; In primary TCC G2Tl, solitary tumor and low grade at thefirst recurrence have a very low potential to progress. High grade at the firstrecurrence is the main prognostic factor related to progression.

Univariate Analysis

998INTRAVESICAL CHEMOTHERAPY ALONE VERSUS INTRA­VESICAL THERMO-CHEMOTHERAPY FOR PROPHYLAXISOF RECURRENCE OF SUPERFICIAL TRANSITIONAL CELLCARCINOMA: A MULTICENTRIC STUDY Renzo Colombo*, LuigiF Da Pozzo. Andrea Salonia, Patrizio Rigatti, Milan, Italy; Zvi Leib, JackBaniel, Tel-Aviv, Israel; Emanuele Caldarera, Michele Pavone-Macaluso,Palermo, Italy

INTRODUCTION AND OBJECTIVE: To compare the efficacy and localtoxicity of the intravesical instillation of Mitomycin C (MMC) versus the samecytostatic agent in combination with local hyperthermia as an adjuvant treatment,after complete transurethral resection (TURB) of superficial transitional cellcarcinoma of the bladder.

METHODS: The study was designed as a prospective, multicentric,randomized trial. Eighty-three patients suffering from primary or recurrentsuperficial (Ta-Tl) transitional cell carcinoma of the bladder, after a completeTURB, were randomly assigned to receive intravesical instillations of MMC alonein 41 cases (Group 2) and MMC in combination with local microwave-inducedhyperthermia in 42 cases (Group I). For the combined approach a new systemnamed Synergo 10I-I was used. The effectiveness evaluation endpoints of thestudy included duration of disease-free interval and recurrence rate. The safetyevaluation endpoints included subjective and objective side effects and clinicalcomplications. Minimum follow-up was 24 months.

RESULTS: The statistical analysis of seventy-five evaluable patientsdemonstrated a highly significant difference in both disease-free interval andrecurrence rate in favor of thermo-chemotherapy. Six and 23 recurrences were seenin group 1 and 2 respectively, the 2 - year recurrence rate being 14.3% and 56.1%.Tumor recurrence in the chemotherapy alone group is significantly earlier and morefrequent. The mean time to first recurrence was 9.5 months in group 1 and 6.6months in group B. The Kaplan-Meier curves showed that there was a highlysignificant (p = 0.0002) difference between the two treatments groups. Subjectiveintolerance as well as clinical complications were significantly higher, but transientand moderate, in the combined treatment group.

CONCLUSIONS: In our series, endovesical thermo-chemotherapy appears tobe more effective than standard endovesical chemotherapy as an adjuvant treatmentof superficial bladder tumors at 24 month follow-up, despite an increased butacceptable local toxicity.

Source of Funding: None.

correlated with tumor progression (as defined by the different centers) in Tl(p<.OOl), but not in Ta tumors. Adjusting for different endpoint definitions usingprogression of superficial lesions into muscle invasive disease, progression in stageor grade, similar results were obtained.

CONCLUSIONS: Since P53 positivity is less likely to be found in papillarylesions or lesions of low grade, a p53 accumulation seems to represent a marker forlesions with a higher malignant potential. Thus p53 immunohistochemistry appearsbe predictive for the prognosis of superficial bladder cancer. However, themagnitude of this association varies among tumor stages, suggesting that theconditions for the use of a given marker need to be well defined. This trial providesa solid basis to define suitable patient populations, a statistically adequate size forstudy cohorts and optimized immunohistochemical techniques for prospectivetrials. This initiative contributes to the combined efforts of a large number ofinvestigators to standardize of marker development and use.

Source of Funding: None.

996SURVIVAL OF PATIENTS WITH HIGH GRADE SUPERFICIALBLADDER TUMORS (TlG3) TREATED WITH TRANS­URETHRAL RESECTION (TUR) ALONE Thomas Otto*, Julia Suhr,Peter J Goebell, Kurt W Schmid, Herbert Riibben, Essen, Germany

INTRODUCTION AND OBJECTIVE: Survival of patients with high-gradesuperficial bladder tumors (TlG3) treated with TUR only followed up for 9 years(mean) are evaluated. The patients received initially no adjuvant chemo- orimmunotherapy.

METHODS: A total of 404 patients (median age 67 years) with referencehistopathology Tl G3 transitional cell carcinoma of the bladder are evaluated. Thepatients underwent a re-TUR to be confirmed as free of residual cancer. Follow-upis 8 to 12 years (median: 9 years).

RESULTS: After 9 years median follow-up 40 % of 404 patients died tumorrelated. The corrected rate of survival I, 2 an 3 years after initial diagnosis isdetermined with 81%,70% and 60%. Stratifying the patients in age ranges from <50years up to >80 years no significant differences are observed. All tumor related deathappeared within 3 years after initial diagnosis of Tl G3 bladder cancer.

CONCLUSIONS: Early treatment decision within 6 month after initialdiagnosis of a TIG3 bladder carcinoma is mandatory. Patients without progressionwithin 3 years after the first diagnosis have an excellent prognosis and can betreated by organ preserving therapy.

Source of Funding: None.

997CONSERVATIVE MANAGEMENT OF TlG3 TRANSITIONALCELL CARCINOMA OF THE BLADDER. RISK FACTORANALYSIS IN 165 SELECTED PATIENTS Vincenzo Serretta*,Carlo Pavone, Giovanbattista Ingargiola, Rosalinda Allegro, GiuseppeSalamone, Michele Pavone-Macaluso, Palermo, Italy

INTRODUCTION AND OBJECTIVE: The management of TlG3 transitionalcell carcinoma of the bladder (TCCB), is still controversial. Some Authors supportan immediate radical cystectomy. BCG is considered the treatment of choice.Limited encouraging experiences are reported with intravesical chemotherapy.Objectives; Evaluating a selected population of 165 patients with TlG3 TCCB, inabsence of Tis, treated conservatively with TUR plus adjuvant intravesical therapy.

METHODS: Between January 1976 and December 1999, 165 patients withTlG3 bladder tumors were treated by TUR plus adjuvant intravesical therapy.Patients with previuos T1G3, Tis, more than 3 tumors or greater than 3 em wereexcluded. A sequential combination of mitomycin C and epirubicin was adopted in91 patients (55%). BCG or other agents were used intravesically in 28 (17%) and46 (28%) patients respectively. In case of Ta-Tl recurrence, TUR was repeated andone year of adjuvant intravesical therapy completed. Patients went off study if Tisor invasive tumor (T-category over TI) were detected. Age (less or more than 70),previuos history, multiplicity, time to recurrence, adjuvant therapy were consideredin multivariate analysis.

RESULTS: At a mean follow-up period of 48 months (12- 240 months), 74patients (44.8%) recurred. The recurring tumor was Tl in 32 (19%) cases andTlG3 in 23 cases (14%). In 8 additional patients (5%) a Tis was detected. Fourteenpatients (8.4%) progressed and 10 patients (6%) underwent cystectomy. Medianprogression-free survival was 149 months. Twenty-three patients (14%) died, 9(5.5%) of whom due to bladder cancer. Median overall survival was 144 months.Recurrence was found related only to number of the tumors (p=0.0007) and toBCG (p=O.0013). No factor was found significantly correlated to progression.Previous history (p=0.0021), recurrence after adjuvant therapy (p<O.OOOl), andprogression (p<O.OOOl),were statistically related to survival.

CONCLUSIONS; If no concomitant Tis exists a conservative approach is alegitimate option as an initial treatment of patients with primary TlG3 bladdertumors. Time to progression and overall survival are comparable to those obtainedby cystectomy. Recurrence is statistically influenced by initial number of tumors

Primary TumorSolitary/multipleNoCIS/CISFirstRecurrenceNoCIS/CISNorecur/3m/>3mNorecur/6m/>6mG1/G2IG3

Source of Funding: None.

Progression (%)3.2/10.24,2/16.7

Progression ('!oj3,3/3890/7.7/17

0/13.7/16,50/14.9/30.3

Pvalue0,020,001

PValue0.00010.00010.00010.0001

258 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Monday, April 28, 2003

1000PROSPECTIVE VALIDATION OF P53 AS A PROGNOSTICMARKER IN TRANSITIONAL CELL CARCINOMA (TCC) OFTHE BLADDER Guido Dalbagni*, Madhu Mazumdar, Harry W Herr,Victor E Reuter, New York, NY

INTRODUCTION AND OBJECTIVE: The aim of this study is toprospectively validate p53 overexpression as a prognostic marker of progressionand survival in patients with Tl TCC of the bladder.

METHODS: Eighty-nine patients with first time Tl TCC were enrolled with amale to female ratio of 4:1. The median follow-up was 26 months. Fourteenpatients underwent an immediate cystectomy and 75 patients were initiallymanaged with TUR with or without intravesical BCG. Eighty-two patients werehigh grade using the WHOIISUP 1998 grading system. Sixty-eight patients hadunifocal tumors and 34 patients had associated Tis. P53 overexpression was testedby immunohistochemistry (IRC) using both MoAb 1801 and DO-7.

RESULTS: During the course of the follow-up, 32 additional patients underwenta radical cystectomy and 12 patients died, 8 of bladder cancer. P53 overexpression didnot predict progression nor survival. The effect of immediate cystectomy in the overallsurvival could not be assessed due to the small number of events.

CONCLUSIONS: P53 tissue typing by IRC in a prospective cohort ofpatients with Tl bladder cancer did not prove to be a clinically usefulprognostic marker.

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1001BLADDER WASHING CYTOLOGY IMMEDIATELY AFTERTRANSURETHRAL RESECTION PREDICTS RECURRENCEOF URETHELIAL CARCINOMA Giora Katz*, Lake City, FL;Kenneth Iczkowski, Gainesville, FL; Carl Cascione, Gainesville, FL; RicardoE Rodriguez, Lake City, FL

INTRODUCTION AND OBJECTIVE: We assess the abili ty of postoperativebladder washing cytology, performed immediately after transurethral resection ofbladder tumors, to predict early recurrence.

METHODS: During a one-year period, pre- and postoperative bladder washingcytology specimens were sampled from patients undergoing transurethralresections, in which all visible tumor was considered by the surgeon to have beenremoved. Post resection bladder washing was obtained at the end of the procedureafter draining and cycling the bladder at least once with sterile water. The pre andpost bladder washing cytology specimen was examined with the submitted bladdertumor and was determined to be either positive or negative for bladder tumor cellsas part of the work up of the submitted specimen of bladder tumor. Recurrence wasdetermined based on submitted pathology specimens during the follow up period.

RESULTS: A mean follow-up of 13.7 months was obtained after 38 resectionsin 32 patients. Postoperative cytology was satisfactory in 35 of 38 cases andpositive in 17 (49%). Follow-up of these 35 transurethral resections disclosed a15/17 (88%) recurrence rate after post procedure positive washing cytology, and4/18 (22%) recurrences after negative cytology (p<O.OOI). Postoperative cytologydemonstrated a sensitivity for recurrence = 79%, specificity = 88%, positivepredictive value = 88%, and negative predictive value = 77%. In contrast, tumorin the transurethral resection specimen had a positive predictive value of 54% forrecurrence, and its grade or stage was inferior to cytology in predicting recurrence.

CONCLUSIONS: Post-operative bladder washing cytology status may beuseful information for the decision making process in the management of bladdertumors. A positive result should promote early consideration of repeat transurethralevaluation and intravesical treatment.

*Presenting author.

Source of Funding: This material is the result of work supported withresources and the use of facilities at the the North Florida South Georgia VeteranHealth System.

1002EFFICACY OF OFFICE FULGURATION FOR RECURRENTLOW GRADE PAPILLARY BLADDER TUMORS UNDER 0.5CENTIMETERS (CM) Sherri M Donat, Amanda North", GuidoDalbagni, Harry W Herr, New York City, NY

INTRODUCTION AND OBJECTIVE: Recurrent superficial papillary bladdertumors are most commonly treated by transurethral resection (TUR) underanesthesia. Low-grade non-invasive tumors rarely progress and can be reliablyidentified visually at flexible cystoscopy in conjunction with urine cytology. Wereport our experience with office fulguration of small tumors using flexiblecystodiathermy.

METHODS: We conducted a prospective single institution analysis of267 consecutive patients with superficial bladder cancer undergoing routinebladder cancer surveillance between January 1998 and December 2001. Urinecytology was routinely performed at each surveillance cystoscopy. Bothcytological and histologic recurrences were recorded. Criteria for fulguration inthe office were: < 5 low-grade appearing papillary tumors, < 0.5cm tumorsize, negative urine cytology, and patient desire. All patients completed theirinitial treatment (TUR, partial cystectomy, andlor intravesical therapy) and aminimum of 6 months on surveillance without a tumor recurrence (median11.57 months).

RESULTS: Flexible cystodiathermy for small low-grade recurrent papillarytumors was efficacious and well tolerated. Forty-six percent of patients (N = 123)experienced one or more tumor recurrences (range I-ll) in a median follow uptime of 2.6 years. Of these 74/123 (60%) underwent office cystodiathermy. Nodifference was seen in disease specific survival (p=0.1633) or progression ofdisease (p=0.860). When stratified by risk of recurrence, high-risk patients 2021267 (76%) with low-grade papillary recurrences undergoing office cystodiathermydid not risk progression of disease (p=0.9025) and had a better overall survival(p=0.0477). Overall median time from diagnosis was 6.84 years, with the mediantime from the last tumor 20.4 months.

CONCLUSIONS: Office cystodiathermy for small low-grade papillaryrecurrences is safe and efficacious when patients are properly selected. This changein practice can potentially improve patient quality of life and have a majoreconomic impact on health care.

Source of Funding: None.

1003URINARY IL-2 ASSAY FOR MONITORING INTRAVESICALBACILLUS CAL METTE-GUeRIN (BCG) RESPONSE OFSUPERFICIAL BLADDER CANCER DURING INDUCTIONCOURSE AND MAINTENANCE THERAPY Fabien Saint*, PascaleMaille, Dimitri Vordos, Andras Hoznek, Pascale Soyeux, Jean JacquesPatard, Claude Abbou, Dominique Chopin, creteil, France

INTRODUCTION AND OBJECTIVE: We evaluated the clinical significanceof Thl(IL-2)/Th2(IL-IO) urinary profiles during a six weekly induction coursefollowed by a three weekly maintenance therapy schedule.

METHODS: Urinary IL-2/IL-1O were measured by ELISA assay in 39 patientsreceiving BCG for superficial bladder cancer or carcinoma in situ. Measurementswere made after each instillations of 81 mg ofBCG Connaught (Immucyst), duringinduction course and the three-weekly maintenance therapy (given at 3, 6, 12, 18,24, 30 and 36 months). Cytokine levels have been correlated with the risk ofrecurrence, progression, leucocyturia, and the adverse events.

RESULTS: Median follow-up was 35 months (range 7 to 72 months).Complete response to BCG were obtained in 30 patients (77%); the remaining ninepatients relapsed (23%), and 4 of these patients progressed (10.2%). Failure todetect urinary IL-2 during BCG induction and the first re-induction courses (6+ 3schedule) correlated with times to recurrence and progression (p=O.OI; p=O.OI).During re-induction courses, the first instillation was associated with a Thlcytokine profile, whereas the second and third instillations were associated with aswitch to a Th2 profile. This switch was associated with leukocyturia (p=O.OOOI)and adverse events (p=0.03).

CONCLUSIONS: The 6+3 instillations schedule is associated with an urinaryIL-2 overproduction and improved recurrence- and progression-free survival.During BCG re-induction course, the favourable Thl urinary cytokine patterngradually switches to a Th2 profile suggesting that the schedule based on threeweekly instillations may be unsuitable for some patients, and that the dose andfrequency of maintenance BCG instillations may be adapted to individual urinarycytokine levels.

Source of Funding: This work was supported by Fondation de I Avenir pourla Recherche Medicale Appliquee, Fondation pour la Recherche Medicale,universite Paris XII, AP-HP Hopitaux de Paris, and I Association Claude Bernard.

Vol. 169, No.4, Supplement, Monday, April 28, 2003 THE JOURNAL OF UROLOGY® 259

1004NEO ADJUVANT TREATMENT IN INTERMEDIATE- HIGHRISK SUPERFICIAL TRANSITIONAL CELL CARCINOMA OFTHE BLADDER (STCCB) FACING CYSTECTOMY: AMULTICENTER STUDY Abraham Ami Sidi». Holon, Israel; OferNativ, Haifa, Israel; Ja Witjes, Nijmegen, Netherlands; Michele Pavone,Palermo. Italy; Peter Aiken, Mannheim, Germany; Amos Shapiro, Jerusalem,Israel; Zvi Leib, Petach Tiqva, Israel; Vincenzo Serretta, Palermo. Italy;Michael Siegsmund, Mannheim, Germany; Albert Tarnopolsky, Holan,Israel; Ofer Gofrit, Jerusalem, Israel; Ag Van der Heijden, Nijmegen,Netherlands; LfDa Pozzo, Andera Salonia, Milan, Italy; Moshe Wald, Haifa,Israel; Alberto Florio, Dominico De Carolis, Ascoli Piceno, Italy; RenzoColombo, Milan, Italy

INTRODUCTION AND OBJECTIVE: STCCB. especially intermediate-highrisk patients, tends to recur despite conventional treatment by surgery andintravesical instillations, and may require cystectomy. Patients, exemplified withexcessive tumor burden and! or multifocality, for whom a single surgery will notaccomplish complete resection, pose a therapeutic challenge. Herein we report ourexperience with neo adjuvant treatment for these patients.

METHODS: Synergo® technology is designed to treat STCCB by deliveringhyperthermia at 42 ± 2aC to the bladder wall concomitant with intravesicalchemotherapy. Data of 81 intermediate-high risk STCCB patients treated bySynergo® during 1994-2002 was analyzed. Patients' characteristics: stage Ta-38,Tl-35 (8 unspecified), grade GI-9, G2-50, G3-16 (6 unspecified), all had perviousrecurrences (average of 4.8). Tumor size> 2 cm was in 26 patients, and multiplesites (25) were in 45. Previous intravesical BCG was administered to 49 patients,and 37 failed I or more intravesical chemotherapeutic instillations. Treatmentconsisted of 12 sessions: 8 weekly followed by 4 monthly, each lasted one hour.Mitomycin C 20 or 40 mg was used in 76 patients and Epirubicin 50 mg in 5.Disease free interval was determined by video-cystoscopy every 3-6 months for aperiod of 2 years. Biopsies and urine cytology were performed as indicated.Primary end point was complete tumor eradication. This was induced by Synergo®alone, and in some patients assisted by a single surgery. Also, disease free intervalwas recorded ensuing complete eradication.

RESULTS: Synergo® neo adjuvant treatment induced complete tumoreradication in 88% (71/81): 58 (72%) patients with the Synergo® alone, while 13(16%) with a single surgical resection following tumor burden reduction. Tenpatients (12%) did not respond. Median time to acheive complete tumor eradicationwas 61 days. Side effects included mainly mild pain during session, dysuria,hematuria and frequency the first day after treatment. Reduced bladder capacityoccurred in 3 patients. Cystectomy was performed in 13 patients: 10 non­responders; 1 stage progression; 2 reduced bladder capacity. Disease free state wasmaintained in 47171 (66%) in an average follow-up of 13 months.

CONCLUSIONS: Synergo® technology is efficacious and safe, accomplishing88% complete eradication, thus, offering potential treatment option for thisobstinate patients group. After an average follow up of 13 months 66% of patientsremained tumor free.

Source of Funding: The study was partially supported by Medical Enterprises.

1005URINE FLUORESCENCE IN SITU HYBRIDIZATIONANALYSIS DURING BACILLUS CALMETTE·GUERINTREATMENTS IN UROTHELIAL CARCINOMA Robert JKarnes", Kevin C Halling, Michael M Lieber, Horst Zincke, Michael L Blute,Rochester, MN

INTRODUCTION AND OBJECTIVE: Fluorescence in situ hybridization(FISH) can detect chromosomal alterations (aneusomy) indicative of malignancy inurinary cells. Urine FISH has been shown to be a sensitive and specific marker ofurothelial carcinoma (UC). FISH analysis does not appear to be affected byinflammtion. Predicting the response to bacillus Calmette-Guerin (BCG)intravesical treatments in patients with UC can be challenging. This study wasdesigned to determine if FISH can predict early recurrence of superficial UC (1997TNM; Ta, Tl , Tis) patients having a BCG course.

METHODS: Between 312001-812002.39 random patients about to undergo acourse of BCG were identified. All patients had pathologically confirmedsuperficial bladder Uc. A sterile catheterized urine specimen was obtained forFISH analysis just prior to the first BCG instillation and another specimen collectedbefore the last instillation. The urine was handled similar to a cytology specimen.FISH was recorded as negative (-) or positive (+ ) during each instillation. If (+ ),the % of non-inflammatory cells exhibiting aneusomy was determined. FISHresults were blinded to the urologist. The patients were then followed prospectivelythrough their UC surveillance and outcomes were recorded.

RESULTS: Follow-up was available on 37 patients for 38 courses of BCG. Aurine was missed at either the first or last BCG instillation in 13 patients. Twentyfive patients had FISH results for both time points (instillations). In the patients thathad two (+) FISH results during BCG (n=5), there was a decrease in aneusomy

observed from the first to the last; however, all developed an early recurrence and4 underwent cystectomy. Twenty nine patients had at least a FISH obtained justprior to the last BCG instillation. If this result was (+), all the patients recurred(8/8= 100%). If this result was (-). the majority (16121= 76%) were disease freeat last follow-up and recurrences did not demonstrate any progression.

CONCLUSIONS: BCG does not appear to affect the interpretability of FISH.There was evidence that a BCG course has an effect on the degree of sheddinganeusomic urinary cells. Monitoring of BCG treated patients with FISH may helpdetect earlier recurrences (or persistence) and impact management of Uc.

Source of Funding: None.

1006HEXYL AMINOLEVULINATE (HAL) FLUORESCENCE VERSUSSTANDARD CYSTOSCOPY FOR DETECTING CARCINOMA INSITU (CIS) OF THE BLADDER Michael Marberger", Vienna, Austria;Fred Witjes, Nijmegen, Netherlands; Nikolaus Schmeller, Salzburg, Austria;Ronald Donat, Dunfirmline, UK; Martin Susani, Vienna, Austria

INTRODUCTION AND OBJECTIVE: Fluorescence cystoscopy has beenreponed to improve the detection of CIS lesions but this has not been verified inlarge multicenter studies. In this study, recruiting patients from 19 centres in 8European countries, we compared the detection of CIS using hexyl aminolevulinate(HAL) fluorescence and standard white light cystoscopy.

METHODS: Patients suspected of having high risk bladder cancer had 50 mlHAL 8 mM (Hexvix®, Photocure ASA, Oslo, Norway) instilled one hour prior tocystoscopy. Cystoscopy was performed with D-Iight (Karl Storz, Germany)allowing for both white light and blue light (375-440 mm) inspection. Allsuspicious lesions were mapped. biopsied or resected by TUR and assessed by areference pathologist.

RESULTS: Of 211 evaluable patients 84 (40%) had CIS. Seventeen (20 %)CIS patients were detected by HAL only and in 54% of CIS patients HAL detectedadditional CIS lesions compared to standard cystoscopy. In 20 (22%) of 92 pTapatients HAL detected additional papillary lesions. Overall the lesion detectionrates for blue vs. white light cystoscopy were for CIS (174 lesions) 97% vs. 58%,Ta (376 lesions) 97% vs. 88%, Tl (82 lesions) 96% vs. 88% and T2 (29 lesions)100% vs. 97%, respectively. False detection rate of all lesions was low and similar(13% vs 10%) for Hexvix® and standard cystoscopy, respectively. There was nodifference in the positive predictive value of all lesions (93% vs 91%) for HAL andstandard cystoscopy, respectively. Only neglible side effects of HAL instillationswere reported including blood biochemistry an hematology.

CONCLUSIONS: HAL fluorescence cystoscopy improves the detection of CISsignificantly.

Source of Funding: Hexvix PCB301101 Study group.

Kidney and Ureteral Cancer: Evaluationand Treatment (III)

Moderated PosterMonday, April 28, 2003 3:30-5:30 PM

1007SPECIFIC GENETIC PATTERNS IN LUNG AND BONEMETASTASIS OF RENAL CARCINOMA AS DETECTED BYCGH Kerstin Junker", Jena. Germany; Joerg Saenger, Norbert Presselt,Bad Berka, Germany; Winfried Hindermann, Joerg Schubert. Jena, Germany

INTRODUCTION AND OBJECTIVE: Prognosis of patients with renal cellcarcinoma (RCC) is mainly determined by metastases. Generally, the cellular andmolecular biology of renal cancer metastases are not very well investigated. But theunderstanding of the metastatic process will give the basis for a differentialdiagnosis leading to an individual prognosis and to new therapeutical strategies. Inorder to define specific genetic alterations which are common in renal cancermetastases of lung and bone, we performed the Comparative GenomicHybridization (CGH) on metastases and in some cases on their related primaryrenal tumors.

METHODS: For CGH, DNA was isolated from 2 or 5 paraffin sections (5Mm).Tumor and normal (control) DNAs were amplified by DOP-PCR and labeled withbiotin-dUTP and digoxigenin-dUTP, respectively. Hybridization and detectionwere carried out according to standard protocols.

RESULTS: Genetic alterations were detected in 62 out of 70 metastases. Inlung metastases, most frequently the following genetic changes occurred: losses ofchromosomes 3p (74%), 8p (31%), 9 or 9q (34%). 14 (26), 18q (40%) and gainsof chromosome 5/5q 34%), 7 (31%) and 12 (26%). Bone metastases showed thefollowing alterations: losses of chromosomes 3p (73%), 6 (20%), 8p (20%), 9