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

Prostate Cancer: Advanced (II)Moderated Poster

METHODS: The stent was inserted under topical anesthesia in 25 patients withLUTS and 5 with AUR. Maximum flow rate (Qmax), voided volume (VV),post-void residual volume (PVR), and the International Prostate Symptom Score(IPSS) were assessed. Patient tolerance to the device was assessed with theauthor-developed Stent Performance Score. Patients were stratified into groupsaccording to baseline PVR as follows: PVR :s175 ml (Group 1), PVR >175ml and:s500ml (Group 2), and PVR 500ml (Group 3).

RESULTS: Stents remained in situ for a mean of 57 days (range 1 to 98 days;median, 63 days). Mean overall baseline and post-insertion Qmax were 8.2 and11.6 ml/sec, respectively, representing a 42% improvement from the baseline(p=.0002). Qmax improved after stenting among all three patient groups: Group 1:8.0 to 12.4 ml/sec; 55%; p=.002; Group 2: 9.5 to 11.2 ml/sec; 18%; p=NS; andGroup 3: 5.9 to 10.5 ml/sec; 78%; p=.007. Mean overall baseline and post­insertion VV were similar at 214.2 and 218.9 ml, respectively. Voided volumeincreased among Group 1 (17%) and Group 3 (39%) , but decreased among Group2 patients (22%) after stenting. Mean overall baseline and post-insertion PVRswere 312.1 and 109.4 ml, respectively, representing a 65% decrease (p=.004).Decreases were seen in all three patient groups (32%, 63%, and 72%, respectively).Mean overall pre- and post-treatment IPSS scores were 22.3 and 7.1, representinga 68% improvement (p<.OOl). All patients who completed the Stent PerformanceScore were highly satisfied with the device and 24 (86.6%) reported completecontinence, except for mild and transient urge incontinence in 6 (13.3%). Elevenpatients (36.6%) complained of mild perineal discomfort, especially when sitting.Other minor complications included: Infection of the urinary tract in 15 patients,intermittent hematuria (that resolved spontaneously) in 7 patients and transientstress incontinence in 5 patients.

CONCLUSIONS: The Spanner" effected symptomatic relief and urodynamicimprovement while preserving volitional voiding and continence. Post-insertionurodynamic variables indicate that the device ameliorates bladder outletobstruction.

Source of Funding: Abbeymoor Medical Inc., Miltona, MN.

1472ZOLEDRONIC ACID IS WELL TOLERATED FOR UP TO 24MONTHS AND SIGNIFICANTLY REDUCES SKELETALCOMPLICATIONS IN PATIENTS WITH ADVANCEDPROSTATE CANCER METASTATIC TO BONE Fred Saad*,Montreal, Quebec, Canada; Donald Gleason, Tucson, AZ; Robin Murray,East Melbourne, Victoria, Australia; Peter Venner, Edmonton, Alberta,Canada; Simon Tchekmedyian, Long Beach, CA; Louis Lacombe, Quebec,Canada; Joseph Chin, East London, Ontario, Canada; Jeferson Vinholes,Porto Alegre, Brazil; J Allen Goas, Bee-Lian Chen, John Seaman, EastHanover, NJ

INTRODUCTION AND OBJECTIVE: Patients with advanced prostate cancer(PC) often survive for several years after diagnosis of bone metastases and sufferfrom long-term skeletal morbidity that significantly impacts their quality of life. Amulticenter, randomized, placebo-controlled trial was conducted in patients withhormone-refractory PC and at least 1 bone metastasis to determine the efficacy andsafety of zoledronic acid for the prevention of skeletal complications.

METHODS: Patients were randomized to zoledronic acid (4 mg via 15-minuteinfusion) or placebo every 3 weeks for up to 24 months. Efficacy endpointsincluded the proportion of patients with a skeletal-related event (SRE), time to firstSRE, skeletal morbidity rate, and a multiple event analysis. An SRE was definedas a pathologic fracture, spinal cord compression, radiotherapy or surgery to bone,or a change in chemotherapy to treat bone pain.

RESULTS: Of 643 patients randomized, 208 patients completed the 15-monthcore phase and 186 patients continued to receive double-blind study medication onthe extension phase. After 24 months of therapy, significantly fewer patients treatedwith zoledronic acid had an SRE compared with placebo (38% vs 49%; P = .028),and this difference remained significant when asymptomatic fractures wereexcluded from the analysis (P = .019). The majority of SREs were fractures andradiation to bone. Zoledronic acid also significantly delayed the time to first SRE(median, 488 days vs 321 days for placebo; P = .009) and time to first pathologicfracture compared with placebo, and significantly reduced the skeletal morbidityrate (mean, 0.77 vs 1.47 events/year for placebo; P = .005). The multiple eventanalysis showed that zoledronic acid reduced the risk of developing an SRE by36% (hazard ratio = 0.64; 95% confidence interval, 0.49, 0.85; P = .002).Zoledronic acid also significantly reduced Brief Pain Inventory composite pain

Tuesday, April 29, 2003 3:30-5:30 PM

scores relative to placebo at 24 months (P = .024). Median survival was 546 daysin the zoledronic acid group and 469 days in the placebo group. Zoledronic acid (4mg via l5-minute infusion) demonstrated an overall safety profile similar to that ofother intravenous bisphosphonates and only a minor increase in the risk of elevatedserum creatinine compared with placebo (hazard ratio = 1.14; P = .752).

CONCLUSIONS: Zoledronic acid is safe and well tolerated for up to 24months and significantly reduces skeletal complications in patients with advancedPC and bone metastases.

Source of Funding: Novartis Pharmaceuticals Corporation has providedfunding for this study.

1473LONG-TERM REDUCTION OF BONE PAIN WITHZOLEDRONIC ACID IN PATIENTS WITH ADVANCEDPROSTATE CANCER METASTATIC TO BONE Fred Saad*,Montreal, Quebec, Canada; Donald Gleason, Tucson, AZ; Robin Murray,East Melbourne, Victoria, Australia; Peter Venner, Edmonton, Alberta,Canada; J Allen Goas, Bee-Lian Chen, John Seaman, East Hanover, NJ

INTRODUCTION AND OBJECTIVE: Patients with advanced prostate cancer(PC) are at high risk of developing bone metastases, which are often associatedwith severe bone pain. Although bisphosphonates have been shown to providetransient pain palliation in patients with PC, randomized, placebo-controlled trialswith etidronate, clodronate, and pamidronate have not demonstrated significantlong-term reductions in bone pain or skeletal complications. Zoledronic acid hasrecently been shown to significantly reduce skeletal complications after 15 monthscompared with placebo in patients with advanced PC metastatic to bone. Thelong-term effects on bone pain are reported here.

METHODS: Patients (N = 643) with advanced hormone-refractory PC and atleast 1 bone metastasis were randomized to zoledronic acid (4 mg via l5-minuteinfusion) or placebo every 3 weeks for 24 months. Bone pain was assessed usingthe Brief Pain Inventory (BPI) at baseline and at 6-week intervals.

RESULTS: At 24 months, 4 mg zoledronic acid significantly reduced theproportion of patients with a skeletal event (ie, pathologic fracture, spinal cordcompression, radiotherapy, or surgery to bone) and significantly delayed the timeto first skeletal event by more than 5 months. Zoledronic acid also consistentlyreduced bone pain over the entire 24 months on study. Mean baseline compositeBPI pain score was approximately 2 (on a scale of 0 to 10) in both treatmentgroups. All patients experienced a mean increase from baseline in composite BPIpain scores over time, but patients treated with 4 mg zoledronic acid experiencedless increase in pain compared with the placebo group. Between-group differencesin pain scores were statistically significant at 3 months (P = .003), 9 months (P =.03), 21 months (P = .014), and 24 months (P = .024). There were no significantdifferences in analgesic scores between treatment groups at any time point,suggesting that zoledronic acid achieved better pain control with the same level ofanalgesic use. Importantly, zoledronic acid was well tolerated, and there was nodeterioration in prospectively assessed FACT-G quality-of-life scores in patientstreated with zoledronic acid.

CONCLUSIONS: Patients receiving zoledronic acid experienced less increasein pain than those receiving placebo, and the differences reached significance atMonths 3, 9, 21, and 24. This is the first demonstration of durable palliation of bonepain achieved with bisphosphonate therapy in patients with PC metastatic to bone.

Source of Funding: Novartis Pharmaceuticals Corporation has providedfunding for this study.

1474USE OF BISPHOSPHONATES CAN DRAMATICALLYIMPROVE PAIN IN PATIENTS WITH ADVANCED PROSTATECANCER Paulo T Rodrigues", Alex Meller, Joao C Campagnari, FlaviaHering, Sao Paulo - SP, Brazil

INTRODUCTION AND OBJECTIVE: Prostatic adenocarcinomacomplications from osseous metastasis is a frequent event in progressing cancer.Fragility from osteolytic lesions may result in pain and fractures which worseprognosis. Historically prostatic metastasis was acknowledged as exclusiveosteoblastic lesion, but it has been shown it has a counterpart osteolytic componentwhich can explain fractures and pain. Bisphophonates are emerging approaches forthese conditions, since it can diminish osteclastic activity, improve the osseousrarefaction and restart bone strength in metastatic lesions.

METHODS: Thirty two patients (mean age: 69y) with metastatic lesions andon hormonal blockade were prospectively enrolled to receive clodronate 1600 mgevery 28 days in a open study. The patients were submitted to chemical or surgicalcastration for an average 35 months (range:19 to 47). All of them had bonescintigraphy to determine the extent of the disease as well as to verify the natureof the lesions. The Karnofsky index was applied for as a measure of general wellbeing with significant improvement if 5 or more points changed. A visual paingraded scale (0 to 10) were completed by the patients every 6 months. Newscintigraphy and plain x ray from the metastasis were obtained after 6 months for

*Presenting author.

Vo!' 169, No.4, Supplement, Tuesday, April 29, 2003 THEJOURNALOFUROLOGY® 395

comparisons. Metabolic, hormonal and PSA exams were requested periodically.Parametric, non parametric and t test were applied accordingly. Pre Tx PSA variedfrom 31 to 570 (avg:54).

RESULTS: Patients were followed by 13.7 months (6 to 28). Twenty five(78.1%) developed osteoblastic lesions while 7 (21.9%) showed exclusivelyosteolytic type. Lesions were widespread in 16 (50%) cases, followed by pelvis(28.1%), column (12.5%) and hip (9.4%). 90,6% of the patients showed significantclinical improvement in pain after 6 m on clodronate (pre Tx avg:7.7 (2 to 10) postTx avg: 2.1(1 to 5 ). Notwithstanding the radiologial aspect improved in 48% (12)of the osteoblastic lesions and in 48% (3) in the osteolytic type, approaching 46.8%of image aspect improvement. The Karnofsky index also improved from 42 (30 to45) pre Tx to 71 after Tx (50 to 80). After the initial 6 months pos Tx PSA variedfrom 54 to 157 with remarkable diminished doubling time. Minor drawbacks wereobserved in 2 patients which did not preclude further administration.

CONCLUSIONS: CONCLUSIONS: Clodronate was an effective and highlyefficient treatment for metastatic pain in advanced prostate carcinoma. Longerfollowup will determine if additional benefits on survival would be observed.

Source of Funding: None.

1475LAPAROSCOPIC RADICAL NEPHRECTOMY FOR RENALCELL CARCINOMA - INDICATION, TECHNIQUE ANDOUTCOME IN FIRST 100 CASES Andreas H Wille*, Jan Roigas,Serdar Deger, Ingolf Tuerk, Berlin, Germany

INTRODUCTION AND OBJECTIVE: Renal cell carcinoma is likely tobecome one of the most important indications for laparoscopic surgery worldwide.The laparoscopic technique combines the benefits of the minimal invasiveapproach with the established surgical principles. In our institution the laparoscopictransperitoneal approach with intact specimen extraction has become the standardtechnique for radical nephrectomies. We report the indications, techniques andoncological outcome in a single center experience.

METHODS: Between July 1999 and July 2002 we performed laparoscopicradical nephrectomies for renal cell cancer in 100 Patients.To date 60 patients wereavailable for follow up data and has been analyzed for initial staging,Complications, and oncological outcome. Patients with primary metastatic diseasewere excluded from this analysis.

RESULTS: The mean tumor size was 5.9 ern (range 2 to 14 em), the blood losswas 220 mL. the mean surgical time was 211 min, including the learning curves of5 surgeons. Histological findings were p'I'l in 66(66%), pT2 in 11 (II %) and pT3in 19 (19%) patients with an increasing tumor size according to the experience ofthe surgeons. In 4 cases (4 %) histology did not proof malignant disease. PositiveLymph nodes were detected in 3 cases (3%), surgical margins were negative fortumor in all patients. Follow up was between I and 30 month with an average of12.9 month. Progessive disease occurred in 2 cases, one patient with a multifocaltumor, the other one with positive lymph nodes. No cases of local recurrenceoccurred during observation.

CONCLUSIONS: Laparoscopic radical nephrectomy is a routine, effectivetreatment for patients with pTl and pT2 NOMO renal cell carcinoma. With a highergrade of experience a tumor size up to 12 ern can be managed safely giving all thebenefits of minimal surgery to these patients. Although no long term follow up isavailable our follow up data up to 30 month confirm the effectiveness oflaparoscopic radical nephrectomy in terms of surgical principles and oncologicaloutcome.

Source of Funding: None.

1476THE PREVENTIVE EFFECT OF GREEN TEA ON THE GAPJUNCTIONAL INTERCELLULAR COMMUNICATION INRENAL EPITHELIAL CELLS TREATED WITH A RENALCARCINOGEN Hajime Takahashi*, Koichiro Nomata, Manabu Matsuo,Taishi Miyaguchi, Mitsuru Noguchi, Hiroshi Kanetake, Nagasaki, Japan

INTRODUCTION AND OBJECTIVE: Clinical studies imply that epigallo­catechin gallate (EGCG), which is a main ingredient of green tea, has achemopreventive action against cancers and suppresses the proliferation of cancercells. However, there is no report about the chemopreventive effect for renalcancer. We determined that gap junctional intercellular communication (GJlC) wassuppressed by renal carcinogens. In this study we assessed the effect of EGCG onthe GJIC of renal epithelial cells which were treated with renal carcinogen.

METHODS: The canine renal tubular cell line MDCK was cultured in amodified Eagle's medium supplemented with 10% fetal calf serum. We studied theeffect of EGCG on MDCK treated with dimethylnitrosamine (DMN) that was oneof the renal carcinogens, concerning GJIC and connexin-43 (Cx-43) expression.The maximum adequate concentration of EGCG was determined by the lactatedehydrogenase (LDH) assay method. The GJIC of MDCK cells was observed byusing the scrape loading dye transfer method. The changes of connexin-43expression were observed using immunofluorescent staining.

RESULTS: The optimal concentration of EGCG was set up 10-2 mg/m!. Thelevel of GJIC and Cx-43 protein expression in MDCK cells pretreated with EGCGwere not different from non-treated MDCK cells. The level of GJIC and Cx-43protein expression were markedly decreased in MDCK cells treated with DMN.However, the level of GJIC and Cx-43 protein expression treated with DMN wasmaintained when pretreated with EGCG.

CONCLUSIONS: These results suggest that the preservation of GJIC might beone of potential action indicating the preventive effect of green tea on renalepithelial cells in vitro, when treated with a renal carcinogen.

Source of Funding: None.

1477ADENOVIRUS PSA (AD5-PSA) GENE THERAPY FORPROSTATE CANCER: A PHASE I CLINICAL TRIAL David MLubaroff, Badrinath R Konety*, Brian K Link, Tammy M Madsen, Mary EShannon, Dixie J Ecklund, Michael A O'Donnell, Timothy L Ratliff, RichardD Williams, Iowa City, IA

INTRODUCTION AND OBJECTIVE: We have previously demonstrated thatimmunization with PSA delivered in an adenoviral vector (Ad5-PSA) can elicit astrong anti-PSA immune response that results in the destruction of PSA-secretingtumors in mice. We are conducting a phase I clinical trial to determine the toxicityand immunologic modulation of a PSA-carrying adenovirus injectedsubcutaneously in patients with stage D2 or D3 prostate cancer.

METHODS: Twenty-one patients had measurable metastatic disease asdemonstrated on CT or bone scan and were treated with a single subcutaneousinjection at I of 3 dose levels of the Ad5-PSA (106 pfu/ml, 107 pfu/ml, 108pfu/ml). At each dose level, 3 patients were injected with the virus suspendedin an aqueous solution and 3 received the virus suspended in Gelfoam® matrixthat has previously been shown to potentiate the induction of immune responsesby Ad5-PSA. Toxicity was monitored along with dose escalation to assess formaximum tolerated dose defined as that causing dose-limiting toxicity in :2:33%of patients. Serum PSA, CT and bone scan were monitored up to I year aftertherapy to identify any treatment effects. Mean age of the patients enrolled todate is 69.7 (±8.3 yrs.), with a mean enrollment PSA of 267.7 (±500.4) ng/m!.All had failed androgen ablation therapy and evidence of bone and/or soft tissuemetastases.

RESULTS: At a median follow-up of 10.5 months (range 1-13.5), the onlyadverse events observed in these patients have been transient localized erythemalecchymoses at the injection site in 6 patients, flu/cold-like symptoms in 4,decreased neutrophil count (grade I) in 2, inguinal pain in I and fatigue withproteinuria in 1. No major toxicities have been observed. Transient serum PSAdeclines of <50% were noted in 3/21 patients shortly after injection. IncreasingPSA doubling times were noted in 3/21 patients. Mean PSA doubling time for allpatients declined from 4.5 (± 11.6) to -10.88 (±64.7). Three patients have died oftheir prostate cancer at 2, 3.5 and 5 months after injection.

CONCLUSIONS: Preliminary analysis reveals that adenovirus-based PSAgene therapy appears to be well tolerated in patients with advanced prostate cancer.Specifically there has been no dose-limiting toxicity observed and hence thehighest dose will be considered the maximum tolerated dose for future studies.Early indications suggest that even a single injection of Ad5-PSA produces a mildbut early effect on serum PSA. A prolongation of PSA doubling time may beobserved in some patients.

Source of Funding: None.

1478TARGETING METASTATIC PROSTATE CANCER WITHRADIOLABELED J591 MONOCLONAL ANTIBODY (MAB)SPECIFIC FOR THE EXTRACELLULAR DOMAIN OFPROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA E X T )

Edouard J Trabulsi*, Daniel Yao, Lale Kostakoglu, Shankar Vallabhajosula,Maureen A Joyce, Matthew Milowksy, David M Nanus, Stanley J Goldsmith,Neil H Bander, New York, NY

INTRODUCTION AND OBJECTIVE: J591 is a de-immunized mAb withspecificity to PSMAex t ' It is the 1st mAb capable of binding PSMA on viable cellsto enter clinical trials. Radioimmunoiscintigraphic (RIS) imaging of radiolabeledJ591 has demonstrated specific targeting of soft-tissue and bony metastatic lesionsin vivo. This study examines the targeting accuracy of llllndium(" 1ln) and177Lutetium ('77Lu) labeled J591 RIS in advanced prostate cancer (PCa) patients.

METHODS: Patients with progressing, metastatic, hormone-refractory PCawere enrolled into 2 phase I J591 radioimmunotherapy clinical trials with either90y or 177Lu. 177Lu emits both beta and gamma rays and can be imaged directly.90y is a pure beta emitter and requires use of II 'In for imaging. To date, 29 pts havereceived I' IlnpoY-J59I and 24 pts have received 177Lu-J591. RIS images wereobtained I hour after mAb injection and again at 3 separate points up to 2 weekspost-injection. RIS images were compared with conventional imaging to assesstargeting accuracy for metastatic prostate cancer lesions.

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

RESULTS: 38 pts had bony lesions on conventional imaging; of these, 35 pts(92%) had targeting of bony lesions with J591 RIS. No false positive bonetargeting was seen with J591. The accuracy, PPV and NPV for J591 RIS fortargeting bony lesions was 94%, 100% and 83%, respectively. 20 pts had extra­hepatic soft tissue lesions on conventional imaging; of these, 19 pts (95%)demonstrated lesion targeting with J591. Of the 33 pts with no extra-hepatic softtissue metastasis, there was I false positive J591 scan. The accuracy, PPV and NPVfor J591 targeting of extra-hepatic soft tissue metastasis was 96%, 95% and 97%,respectively. 3 pts had J591 RIS targeting in previously unknown sites which wereconfirmed to be new lesions on subsequent conventional imaging.

CONCLUSIONS: J591 RIS imaging of advanced PCa patients demonstratesvery sensitive and specific targeting of both bony and soft tissue lesions includingsome metastatic lesions that were previously undetected on conventional imaging.While currently being utilized in phase 1 therapeutic trials, this technique may, inthe future, prove useful as a diagnostic imaging modality and merits furtherevaluation.

Source of Funding: CapCure; Department of Defense; Cancer ResearchInstitute; Koch Foundation.

1479PHASE II TRIAL OF A GM-CSF GENE-TRANSDUCEDPROSTATE CANCER CELL LINE VACCINE IN HORMONEREFRACTORY PROSTATE CANCER Dale Ando*, Foster City, CA;Jonathan Simons, Atlanta, GA; William Nelson, Baltimore, MD; JohnNemunaitis, Dallas, TX; Arturo Centeno, San Antonio, TX; Eugene Dula, VanNuys, CA; Walter Urba, Portland, OR; Cathy Howard, Foster City, CA; EricSmall, San Francisco, CA

INTRODUCTION AND OBJECTIVE: A Phase II trial (G-9803) of a cell­based vaccine comprised of irradiated, allogeneic prostate carcinoma cell lines(PC-3 and LNCaP) genetically modified to secrete GM-CSF, was conducted in 34patients with hormone-refractory prostate cancer with disease metastatic to thebone.

METHODS: The patients were treated at two vaccine dose levels: 24 patientsreceived a 500 million cell prime dose followed by 12 booster doses of 100 millioncells at 2-week intervals, and 10 patients received the same prime dose and a higherbooster dose of 300 million cells.

RESULTS: At the 2.5-year follow up, seven of the 24 patients (29%) treatedwith the lower booster dose are alive and two have been lost to follow up (MedianDuration = 22m). In the 10 patients treated with the higher booster dose, there wasa trend toward increased overall survival with five patients (50%) alive at 2.5 yearfollow up (Median Duration = 31m). There was also a consistent trend towardlonger median time to disease progression as measured by bone scan in the patientswho received the higher dose of vaccine (140 days) compared to comparablepatients who received the lower dose (85 days). A covariate analysis of patientdemographics revealed no statistically significant difference between the two dosegroups. No dose limiting or autoimmune toxicities were seen, and the mostcommon treatment related toxicity was injection site reaction.

CONCLUSIONS: These studies suggest a dose response relationship fordelayed clinical progression and prolonged survival in patients treated with higherdoses of the allogeneic prostate cancer vaccine. New, irradiated, allogeneic prostatecarcinoma cell lines (PC-3 and LNCaP), modified to secrete GM-CSF at higherlevels, have been developed and a multicenter Phase IIII trial in patients withhormone refractory prostate cancer and metastatic bone disease at baseline is nowunder way. These studies are designed to optimize the dose and schedule ofadministration of the new higher potency allogeneic cell line product. Phase IIItrials are being planned.

Source of Funding: Cell Genesys funded clinical tria!'

1480IMMEDIATE HORMONAL THERAPY COMPARED WITHOBSERVATION AFTER RADICAL PROSTATECTOMY ANDPELVIC LYMPHADENECTOMY IN MEN WITH NODEPOSITIVE PROSTATE CANCER: RESULTS AT 10 YEARS OFEST 3886 Edward Messing*, Rochester" NY; Judith Manola, Boston;Michael Sarosdy, San Antonio; George Wilding, Madison; E DavidCrawford, Denver; Donald Trump, Buffalo

INTRODUCTION AND OBJECTIVE: We have previously reported 7 yearfollow-up of a study in which men with clinically localized prostate cancer, whounderwent radical prostatectomy (RP) and pelvic lymphadenectomy (PLD) andwere found to have nodal metastases (N+), had significantly improved survivaland disease-specific survival when they received immediate (within 3 months ofsurgery) and continuous androgen ablative monotherapy compared with those whohad this treatment withheld until distant metastases were identified (NEJM 341:1781,1999). To determine the durability of this effect, we now update results.

METHODS: 98 N+ men were randomized after RP+LND to receiveGoserelin acetate or bilateral orchiectomy (N=47) vs. observation (N=51) until

*Presenting author.

distant disease was documented. Patients were followed with semi-annual examsand laboratory tests, and annual bone scans.

RESULTS: Patients were well-matched for age (mean 65.9 yrs), prostate size,local extent, and Gleason score. Only 20% of men had detectable PSA's followingtheir surgery at the time of randomization. At median follow-up of 10 years, 13 of47 men who received immediate hormonal therapy died (6 of prostate cancer, 7 ofnon-prostate cancer causes with undetectable PSA's at the time of death) vs 26 inthe deferred arm (22 of prostate cancer, 4 of non-prostate cancer causes). Thedifferences in both overall (immediate 72.4%; vs deferred 49.0%, p = .025), andcause specific survival (immediate: 87.2%; deferred: 56.9%, p = .001) at 10 yearsbetween the two arms were highly significant. Toxicities of treatment weretolerable, and at last follow-up, no immediately treated man had experienced anosteoporotic fracture or had discontinued hormonal therapy.

CONCLUSIONS: At this time median survival in the deferred arm has beenreached, and early androgen ablative therapy in patients with N+ disease followingRP+PLD continues to be associated with highly significant improvements inoverall and disease-specific survival. The treatment has been generally welltolerated. Early androgen ablative therapy's role in other disease scenarios warrantstesting in prospective randomized studies.

Source of Funding: supported by CA23318 awarded by National CancerInstitute.

1481CAN INTERMITTENT ANDROGEN DEPRIVATION BE ANALTERNATIVE TO CONTINUOUS ANDROGEN WITH­DRAWAL IN PATIENTS WITH PSA-RELAPSE? FIRSTRESULTS OF THE RANDOMIZED PROSPECTIVE PHASE-IIICLINI-CAL TRIAL EC 507 Ulf W Tunn*, Oliver Eckart, Offenbach,DE, Germany; Erika F Kienle, Hiltrud Hillger, Aachen, DE, Germany

INTRODUCTION AND OBJECTIVE: This is the first randomizedprospective trial comparing intermittent (lAD) to continuous androgen deprivation(CAD) in patients with PSA-Relapse after radical prostatectomy (RP). Aim of thestudy was to evaluate efficacy and tolerability in both treatments.

METHODS: 184 patients with PSA-Relapse (PSA >= I ng/ml) wererecruited. Within 6 months post RP patients had PSA level reduction < 0.5 ng/ml.Patients were treated with the 3M-depot of leuprorelin acetate and received aflare-up prophylaxis with cyproterone ace-tate. Patients were randomized after 6months treatment under the condition that PSA levels decreased to less than 0.5ng/m!. In the lAD group treatment was stopped and recommenced when PSAlevels became > = 3 ng/ml. PSA and testosterone- (T) levels were determinedmonthly in all patients.

RESULTS: 150 patients (81.5%) received lAD (n = 82) or CAD (n = 68) atrandom. Mean follow-up is 24 months. The mean off-treatment times (OTT) in thelAD group were 9.9 months (62% in cycle 1) and 6.1 months (51% in cycle 2).Median PSA at baseline was 3.5 in the lAD-group. The median PSA-values in thelAD-group decreased to 0.3 ng/ml during the treatment period of 6 months. Themedian PSA-doubling time in the off-treatment period showed variations. MedianT level in the lAD-group at baseline was 3.9 and de-creased during treatment to 0.3ng/m!. In the off-treatment period median testosterone levels recovered to normalvalues of 3.2 ng/m!. These normal values were attained by more than 90 % ofpatients. Median Twas 2.1 and 3.3 ng/ml 3 and 4 months after ces-sation oftreatment respectively. There was a significant correlation between T at base-lineand T recovery in the off-treatment period. Concerning time to progression nosta-tistically significant difference between treatment arms could be seen.

CONCLUSIONS: These results of this first randomized phase III trialcomparing lAD to CAD in patients with PSA-relapse after RP suggest a benefit forlAD with regard to the quality of life during OTT. More than 90 % of patients inthe lAD-group regained normal T values. OTT were 62 % and 51 % in lAD cyclesI and 2 respectively. Time to progression showed no difference in either treatment.lAD would seem to be an attractive alternative in high risk patients who needandrogen deprivation after RP and PSA-relapse.

Source of Funding: Grant of Takeda Pharma GmbH, Germany.

1482PHASE I RADIOIMMUNOTHERAPY (RIT) TRIALS OFMONOCLONAL ANTIBODY (MAB) J591 TO THEEXTRACELLULAR DOMAIN OF PROSTATE SPECIFICMEMBRANE ANTIGEN (PSMAEXT ) RADIOLABELED WITH90YTTRIUM (90y ) OR 177LUTETIUM e77LU) IN ADVANCEDPROSTATE CANCER (PCA) Edouard J Trabulsi*, Daniel Yao,Maureen A Joyce, Matthew Milowksy, Lale Kostakoglu, ShankarVallabhajosula, David Nanus, Stanley Goldsmith, Neil H Bander, NewYork, NY

INTRODUCTION AND OBJECTIVE: J591 is a de-immunized mAb withspecificity to PSMA

eXlthat is capable of binding PSMA on viable cells. The

primary objectives of these two Phase I RIT trials are to assess the targeting,

Vol. 169, No.4, Supplement, Tuesday, April 29, 2003 THE JOURNAL OF UROLOGY® 397

tOXICIty, dosimetry, pharmacokinetics (PK), and immunogenicity of 90y- and177Lu_J591 in patients (pts) with advanced PCa. As a secondary endpoint in thesePhase I trials, anti-tumor responses were monitored.

METHODS: Pts having progressing, metastatic, hormone-refractory Pea wereeligible for study enrollment. To date, 29 pts have received 90Y_J591 and 24 ptshave received 177Lu-J591. While 177Lu can be imaged directly, 90Y_J591 ptsreceive an initial dose of 11'In_J591, I week earlier, for imaging purposes. Doselevels are escalated in cohorts of 3-7 pts with a 6-8 week observation periodbetween dose levels. Toxicity is evaluated and serum PK, dosimetry and humananti- humanized antibody (HAHA) reactivity are determined. Serum PSAs andmeasurable disease, when present, are followed.

RESULTS: 53 patients are evaluable. 36% of the pts had failed at least onechemotherapy regimen. 72% of pts had bony metastatic lesions, and 44% hadmeasurable soft tissue disease. Virtually every visible lesion was successfullytargeted. Toxicity was dose-related and limited to reversible myelosuppression(primarily thrombocytopenia). The maximal tolerated dose (MTD) of 90Y_J591 is17.5 mCi/m 2

• The MTD of 177Lu_J591 is not yet defined. The current dose level of177Lu is 70mCi/m 2

. No patient has developed HAHA. Dose-related anti-tumoreffects have been noted. Two patients receiving 90Y_J591 have had PSA declinesof 65-85%. One of these pts had measurable disease, whose disease volumereduced by 90%. Three patients receiving 177Lu_J591, who did not havemeasurable disease, had a >50% PSA decline. All responses are durable at 3+months.

CONCLUSIONS: J591 targets tumor sites with high sensitivity and specificity.The radiolabeled mAb is non-immunogenic. Toxicity has been limited to dose­related, reversible myelosuppression related to the radioactivity. J591 RIT inducesdose-related anti-tumor effects in pts with advanced PCa. MTD of 90y-J591 is 17.5mCi/m 2

; the MTD of 177Lu_J591 remains to be defined.Source of Funding: CapCure; Department of Defense; Cancer Research

Institute; Koch Foundation.

1483INTERMITTENT ANDROGEN SUPPRESSION FOR THETREATMENT OF ADVANCED PROSTATE CANCER EdithSchasfoort*, Hoevelaken, Netherlands; Peter Heathcote, Brisbane, Australia;Tycho Lock, Utrecht, Netherlands; Marc Zerbib, Paris, France; HeroDijkema, Almelo, Netherlands; Henk Vergunst, Nijmegen, Netherlands;Miguel Srougi, Sao Paulo, Brazil; Don Newling, Amsterdam, Netherlands

INTRODUCTION AND OBJECTIVE: An international, prospective,randomized clinical trial was initiated in 1998 to obtain more data on intermittentandrogen suppression (lAS). The primary objective of this study was evaluation oftime to clinical tumor progression and/or PSA escape (defined as PSAconcentrations over 50 mg/mL). The major secondary objective was evaluation ofpatients' quality of life.

METHODS: Study centers were located in 12 countries worldwide. In total290 histologically proven advanced prostate cancer patients were enrolled inthe study to receive the combination of buserelin depot and nilutamide. Patientsstill in the study after 6 months of maximal androgen blockade and showingnormalization of PSA (below 4 mg/mL) became eligible for randomization toeither lAS (97 patients) or continuous androgen suppression (CAS, 96patients). From the randomized patients 155 were classified as T2-4NxMI and38 classified as T2-4NI-3MO. Serum prostate specific antigen (PSA) andtestosterone levels were centrally analyzed at least every 2 months; radiologicalexaminations were done half yearly. For the patients randomized to lAS,therapy was started when the PSA level rose to 20 mg/mL or above (NO-3MI)or to 10 mg/mL or above (NI-3MO). Therapy was discontinued in case PSA fellto below 4 mg/mL. If the PSA persisted at high levels (above 50 mg/mL) or incase of clinical progression, androgen suppression remained continuous. Thefirst patient entered the study in March 1998, follow-up of the patients endedin August 2001.

RESULTS: Observation period of the patients was maximal 40 months,median time 24.5 months. The three treatment cycles in the intermittent grouplasted respectively 18,8; 9,4 and 5,0 months with a mean time off therapy 65%,31% and 16%. Preliminary withdrawals (before the observation period ended)were more frequently reported in the CAS arm and the main reasons forwithdrawal were patients' wish, adverse events, or lack of efficacy (in totallAS: 35 patients, CAS: 50 patients). This can indicate a difference in quality oflife. The primary objective, median time to clinical progression/PSA-escapewas 18,0 months in the lAS arm and 24,1 months in the CAS arm. Theevaluated safety profile showed a good tolerability. Median time to survival hasnot been reached yet.

CONCLUSIONS: This trial showed that both treatments were well tolerated,although quality of life may be higher in the lAS arm. The time to progressionlPSAescape was longer in the CAS arm, indicating that continuous therapy may be moreeffective than intermittent therapy.

Source of Funding: Aventis.

1484SALVAGE SURGERY FOR RADIORECURRENT PROSTATECANCER: OUTCOMES AND COMPLICAnONS FROM A 30­YEAR EXPERIENCE John F Ward*, Horst Zincke, Thomas J Sebo,Michael L Blute, Rochester, MN

INTRODUCTION AND OBJECTIVE: Radiotherapy with a curative intent hasbeen ever more utilized in the treatment of men with prostate cancer (PCA).Re-biopsy series demonstrate a sizable proportion of patients harboring locallypersistent cancer. An independent association between local persistence of PCAand the development of distant metastasis is now apparent. Radical extirpation ofthe prostate as a salvage therapy is increasingly offered to the young, healthy manwith localized, radioresistant (RR) PCA. We present the oncologic controlachieved and the complications encountered during the 30 years we have beenperforming these surgeries.

METHODS: A retrospective longitudinal cohort study using the a referral­based registry was conducted after obtaining local IRB approval. Patients withbiopsy proven RR PCA who underwent curative intent salvage surgery wereidentified (1967-2000). Perioperative and long term complications were assessedthrough a detailed chart review. All surgical specimens were evaluated by a singlepathologist for grade, stage, margins and DNA ploidy. Progression free, cancerspecific (CSS) and overall survival estimates were performed using the method ofKaplan and Meier. Differences between our early «1990) and late (2:1990)experience was assessed.

RESULTS: Of the 211 patients who underwent salvage surgery for, 199 (138retropubic prostatectomies (RP); 61 cystoprostatectomies (CP» have sufficientinformation for inclusion. Median follow-up time is 7.0 years. Rectal injury rates(5% RP; IO%CP) have remained stable over time while transfused units of bloodhave decreased. Urinary extravasation (15%) and bladder neck contracture (22%)are the most common post-operative complications. Continence(O pads) hasimproved from 43% to 56% (p=0.17) with an additional 20% of patients requiring:0;2 pads per day. Patients whose cancer is amenable to RP fair better than thosenecessitating a CP (median progression free survival 8.7 years vs. 4.4 years;p<O.OOI). Tumor ploidy is the strongest predictor of CSS (aneuploid risk ratio4.14, p<O.OOI). Hormonal therapy did not improve any survival endpoint.

CONCLUSIONS: Salvage surgery has defined and acceptable risks.Continence rates have improved over time. Patients with non-aneuploid tumorsamenable to RP can successfully achieve a long term disease free state. In thisseries of salvage surgery patients, hormonal therapy for RR PCA conferred nolong-term survival benefit.

Source of Funding: None.

1485PROGNOSIS OF PATIENTS WITH STAGE D1 PROSTATECANCER FOLLOWING RADICAL PROSTATECTOMY SiamakDaneshmand*, John P Stein, Gary Lieskovsky, Marcus L Quek, Jie Cai, SusanGroshen, Eila C Skinner, Donald G Skinner, Los Angeles, CA

INTRODUCTION AND OBJECTIVE: Lymph node metastasis in prostatecancer portends an unfavorable prognosis. The literature suggests that patients withlimited node positive disease have a survival advantage over those with largernodal tumor burden. A retrospective review was performed on all patients with DIprostate cancer at our institution to determine the prognostic factors that affectrecurrence and survival.

METHODS: Between 1972 and 1999, 1934 patients underwent radicalretropubic prostatectomy and staging pelvic lymph node dissection forclinically organ-confined prostate cancer. 235 patients (12.1%) were found tohave disease metastatic to the lymph nodes on final pathological analysis (stageDI). In an effort to identify factors that affect prognosis we reviewed the tumorstage (TNM), gleason grade, number and percentage of involved lymph nodes(lymph node density), pre-operative PSA (when available), and adjuvanttreatment. Overall survival and recurrence free survival were estimated usingKaplan-Meier plots.

RESULTS: Follow-up ranged from 1-24 years (median 8.5 years). Overallmedian survival was 12.4 years. Overall clinical recurrence free survival at 5 and10 years was 80% and 63%, respectively. In a stratified log rank test, only the Tstage of the prostate cancer and the number and percentatge of positive lymphnodes correlated with recurrence free survival and overall survival. Patients whohad I or 2 positive lymph nodes had clinical recurrence free survival of 89% and86% at 5 years versus 59% for those who had five or more involved nodes(p=0.0031). Patients with lymph node density of 20% were at higher risk ofclinical recurrence as compared to those with a density of 10% (relativerisk=2.31).

CONCLUSIONS: In our analysis local tumor bulk and the number of involvedlymph nodes significantly affected disease progression and survival rate. This datasuggests that radical prostatectomy may offer long term survival in patients whohave limited tumor bulk and nodal involvement.

Source of Funding: None.

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

1487EARLY VERSUS DELAYED ENDOCRINE TREATMENT INPN1·3 MO PROSTATE CANCER WITHOUT LOCALTREATMENT OF THE PRIMARY TUMOR - RESULTS OFEORTC 30846· A PHASE III STUDY Fritz H Schroder", Rotterdam,Netherlands; Karl H Kurth, Amsterdam, Netherlands; Sophie D Fossa, Oslo,Norway; Wytze J Hoekstra, Den Bosch, Netherlands; Herbert M Karthaus,Amsterdam, Netherlands; Muriel Dubois, Laurence Collette, Brussels,Belgium

INTRODUCTION AND OBJECTIVE: The timing of endocrine treatment ofprostate cancer remains controversial in spite of an increasing amount ofinformation from recent randomised studies. The issue is addressed in protocol30846 of the European Organisation for Research and Treatment of Cancer(EORTC) for patients with lymph node positive cancer without local treatment ofthe primary tumor.

METHODS: The study started in 1986 and was closed in 1998. 302 patientswith metastatic regional lymph nodes who had not received a local treatment forthe primary tumor were included in the trial: 234 have been randomised toimmediate versus delayed endocrine treatment. For the other 68 patients thetreatment was selected by the physician and the patient.. Endocrine treatmentconsisted of an LHRH agonist and 1 month anti-androgen treatment or surgicalcastration. Patients were followed by standard procedures. The main endpoint ofthe trial was overall survival. The analysis is limited to the randomised sample andfollows the intention to treat principle.

RESULTS: After a median follow-up of 8.7 years a total of 143/234 patients(61.1.9%) have died, 76.2 % of prostate cancer. The hazard ratio for survival ondelayed treatment versus immediate is 1.23 (95% Confidence interval: 0.88 - 1.71),

1486SALVAGE CRYOSURGERY USING 3RD GENERATION CRYO"NEEDLES" Ken-Ryu Han*, Allan J Pantuck, Danielo G Freitas, LosAngeles, CA; Carlos Cuevas, Boston, MA; Hyung L Kim, Los Angeles, CA;James Lugg, Stacy J Childs, Cheyenne, WY; Jeff K Cohen, Ralph J Miller,Pittsburgh, PA; Barry A Shuman, Albany, NY; Maury A Jason, Bayshore, NY;Neal D Shore, Myrtle Beach, SC; Yan Moore, Uniondale, NY; Amnon Zisman,Tracey L Krupski, Los Angeles, CA; Joe Y Lee, Minneapolis, MN; HorstZincke, Rochester, MN; Arie S Belldegrun, Los Angeles, CA

INTRODUCTION AND OBJECTIVE: Increasing numbers of patients arepresenting with rising PSA and local cancer recurrence following radiation therapy(XRT)- either brachytherapy and/or external beam radiation therapy (EBRT) forthe treatment of localized prostate cancer (CaP). Salvage prostatectomy in thesecases is associated with significant morbidities, leaving the patient with watchfulwaiting, hormone deprivation therapy, or cryosurgery as alternative therapeuticoptions. We reviewed the preliminary experience using 17-gauge (1.47mm), 3rdgeneration cryo "needles" in the treatment of recurrent CaP after XRT.

METHODS: One hundred twenty-two patients have undergone cryosurgeryusing the 3rd generation technique. Eighteen of these patients had previouslyundergone XRT and had biopsy-proven, recurrent CaP. Complication rates andpreliminary PSA data at 12 months are reported. Biochemical failure was definedas a PSA that does not nadir < 0.4 nglmL or rises >0.4 nglmL after reaching nadir.

RESULTS: The table below summarizes the complication rates of the 18patients at 12-month follow-up. Two of 18 patients required pads for incontinenceand 89% of patients were impotent after salvage cryosurgery. Three and 12-monthPSA values were available in 17 patients. Based on PSA failure rates, patients werestratified into low-risk (Gleason < 6, PSA < 10 ng/mL, and clinical T'I or T2) andhigh-risk (all others) groups. The biochemical recurrence-free survival at 3 monthswas 80% (8/10) and 86% (617)for low-risk and high-risk patients, respectively. At12-month follow-up, the rates were 70% (7110) and 86% (617) for low andhigh-risk groups, respectively.

CONCLUSIONS: Salvage cryosurgery using minimally invasive 17-gaugecryo "needles" can be performed through a brachytherapy template. It offers anattractive alternative to salvage prostatectomy for patients who fail XRT.Preliminary complications rates suggest decreased morbidity compared to earliergenerations of cryosurgery. Long-term follow-up of PSA values and survival isnecessary before any comment on efficacy can be made.

Complications rates aftersalvage cryosurgery

ComplicationUrinary retentionUrgeIncontinenceIncontinence (Pads)Penile paresthesiaImpotencePelvic painScrotal swelling

Source of Funding: Galil Medical.

2/18(11.1%)1/18 (5.6%)2/18(111%)1/17(5.9%)16/18 (89%)1/18(5.6%)2/18(11%)

indicating a 23% advantage for early treatment. The wide confidence intervalhowever shows that the results remain compatible with true effects ranging from12% benefit in favour of delayed treatment to a 71% detriment for the sametreatment approach.

CONCLUSIONS: This study, while it suggests an advantage for earlytreatment, does not show equivalence nor superiority for either the early or delayedapproach. Even if all patients had died the study would not reveal the 23%difference in favour of endocrine treatment as being statistically significant.

Source of Funding: National Cancer Institute: 2U1O CAl1488-16 through2UlO CA 11488-31.

1488SERIAL BIOPSY AND PROSTASTE SPECIFIC ANTIGEN (PSA)RESULTS ON SALVAGE CRYOABLATON FOR PROSTATECANCER: 5 YEAR RESULTS ON 142 PATIENTS (PTS) Joseph LChin*, Naji Touma, Madeleine Moussa, Karmdeep S Guram, Donal BDowney, London, ON, Canada

INTRODUCTION AND OBJECTIVE: Cryoablation (Cab) is now approvedfirst-line therapy in the U.S. in previously untreated prostate cancer. However,aside from short-term biopsy results, there has been a paucity of long-term resultson prostate primary Cab and no reports on histologic and prostate specific antigen(PSA) long-term results from salvage Cab. Serial biopsy and PSA results up to 5years (yrs) are reported herein on 142 pts who underwent salvage Cab afterradiation failure.

METHODS: 142 pts underwent 150 Cab procedures for biopsy- provenclinically localized radiation failure. Serum PSA was drawn every 6 months andTRUS-guided biopsy (usually> 4 cores) at 3,6,12,24 mos., and thereafter asindicated by PSA levels. Kaplan-Meier (K-M) analysis was performed withbiochemical failure or PSA relapse defined as 3 consecutive rises in PSA or PSA>0.5 ng/mL. Histologic findings including benign and malignant viable prostatetissue and cryo-induced changes were tabulated.

RESULTS: Out of 1,248 biopsy cores, 43 were positive from 24 pts (16.9 %).70% of the positive cores were found < 2 yrs post-Cab. However, 1 pt had his firstpositive biopsy 4 yrs post-Cab. Residual viable prostate glands and stroma werefound in up to 30% and 20% ofpts respectively, at different time points. The 5-yearactuarial biochemical relapse-free rate was 39%. The PSA relapse-free rate washighest (60%).in pts with Gleason score < 7, pre-radiotherapy PSA <lOng/mL andpre-cryo PSA< 5. Recto-urethral fistula occurred in 4% and severe incontinence in7% of pts.

CONCLUSIONS: Cab has a role in radiation-failure pts. who have fewremaining therapeutic options. Satisfactory long-term results with acceptablemorbidity can be achieved thereby obviating or deferring long-term endocrinetherapy, provided rigid selection criteria are used. Findings of residual viablebenign glandular and stromal tissue mandates vigilant long-term follow-up.

Source of Funding: None.

1489NATURAL HISTORY OF PROSTATE CANCER IN 3605 CPDRPATIENTS RECEIVING RADICAL PROSTATECTOMY ANDFACTORS AFFECTING POST·TREATMENT CLINICALMETASTASIS IN PSA ERA Leon Sun*, Judd W Moul, Hongyu Wu,David G Mcl.eod, Christopher Amling, Raymond Lance, John Foley, WadeSexton, Leo Kusuda, Andrew Chung, Douglas Soderdahl, Timothy Donahue,Michelle Xao, Jack Chang, Bethesda, MD

INTRODUCTION AND OBJECTIVE: This study was to characterize thenatural history of prostate cancer in patients receiving radical prostatectomy (RP)and the associations between clinical metastasis and prognostic variables.

METHODS: A total of 3605 patients receiving radical prostatectomy between1988 and 2001 were retrieved from the CPDR National Database. Patients whoreceived neoadjuvant and adjuvant treatment were excluded. PSA recurrence wasdefined as post-treatment PSA > 0.2 ng/m!. Minimal follow-up was> 0.5 years.Post-treatment PSA doubling time was calculated. The association among clinicalmetastasis, pathological stages, Gleason sum and interval between PR and PSArecurrence were characterized with nonparametric test, Kaplan-Meier survivalanalysis and Cox regression analysis.

RESULTS: Among 3605 RP patients, the percentage of diagnostic PSA groupsof > 4, 4 - 10, 10.1 - 20, and> 20 ng/ml were 20.5, 57.8, 15.9, and 5.8,respectively. 8.2% of patients had pathological Gleason sum> 7. Pathologicalstages of Tl , T2 and T3 were 1.2%, 57.8% and 41.0%, respectively. The rate ofPSA recurrence was 32.3% (1165). Of PSA recurrence cases, 7.6% (88) developedclinical metastatic disease. PSA recurrence-free and clinical metastasis-freesurvival were 85 vs 97.6% at year 1,64.8 vs 91.0% at year 5, and 56.2 vs 86.1%at year 8. Kaplan-Meier analysis showed that PSA doubling time <10 months andpathological Gleason sum > 7 were significantly associated with clinicalmetastasis (p < 0.01). Multivariate Cox regression model showed that hazard ratioof pathological Gleason sum, PSA doubling time « 10 months), and interval

*Presenting author.

Vol. 169, No.4, Supplement, Tuesday, April 29, 2003 THE JOURNAL OF UROLOGY® 399

between RP and PSA recurrence « 1 year) was 0.468 (p = 0.03), 2.235 (p =0.02), and 2.026 (p = 0.03), respectively.

CONCLUSIONS: In PSA era (since 1988), the natural history of prostatecancer after radical prostatectomy has been changed with significantly improvedclinical metastasis-free survival (83.5% at year 10). Variables of PSA doublingtime < 10 months, Gleason sum, and PSA recurrence time < I year affect clinicalmetastasis.

Source of Funding: U.S. Department of Defense and the Henry M. JacksonFoundation for the Advancement of Military Medicine, Inc.

1490AN ALGORITHM WITH PREOPERATIVE VARIABLES TOPREDICT PSA RECURRENCE IN PROSTATE CANCERPATIENTS RECEIVING RADICAL PROSTATECTOMY HongyuWu*, Leon Sun, Bethesda, MD; Judd W Moul, Rockville, MD; Hongyan Wu,Bethesda, MD; David G McLeod, Washington, DC; Christopher Amling,Raymond Lance, John Foley, Wade Sexton, Leo Kusuda, Andrew Chung,Douglas Soderdahl, Timothy Donahue, Lionel Banez, Bethesda, MD

INTRODUCTION AND OBJECTIVE: To characterize the relationshipbetween PSA recurrence and preoperative factors and construct a equation ofrelative risk of recurrence to predict PSA recurrence in patients post radicalprostatectomy.

METHODS: 1450 patients receiving radical prostatectomy (RP) from 1988 to2001 were retrieved from the CPDR National Database. Patients who receivedneoadjuvant and adjuvant treatment were excluded. The median follow-up was 3.1years (0.5-12.4). All the patients had complete information of diagnosis age, race,clinical stage, diagnosis PSA, biopsy Gleason sum, total number of biopsy coresand number of cancer positive cores. PSA recurrence was defined as post-treatmentPSA> 0.2 ng/ml. Effect of different ratio of cancer-positive biopsy cores over totalbiopsy cores «34%, 34-66%, >66%) on PSA recurrence was assessed withKaplan-Meier method. The multivariate Cox regression was used to identifypreoperative variables preclicting PSA recurrence.

RESULTS: In 1450 patients, 427 (29.4%) had PSA recurrence. The 3-year and8-year PSA recurrence-free survivals were 70.9% and 52.9% respectively.Univariate Log-rank test showed that the higher ratio of cancer-positive cores overtotal biopsy cores was, the worse PSA recurrence-free survival (p=0.033). Inmultivariate Cox model, race, diagnostic PSA and biopsy Gleason score were thethree most significant predictors of PSA recurrence, and the ratio of cancer-positivebiopsy cores over total biopsy cores was not an independent factor for predictingPSA recurrence. The relative risk of recurrence was calculated as exp(0.261*race]""k + 0.067PSA]ST + 0.130*biopsy Gleason sum), where PSAJST indicates asigmoidal transformation of PSA.

CONCLUSIONS: Race, diagnostic PSA and biopsy Gleason sum, rather thanthe ratio of positive biopsy cores over total biopsy cores, were prognostic variablesfor prediction of PSA recurrence in patients undergoing radical prostatectomy.

Source of Funding: U.S. Department of Defense and the Henry M. JacksonFoundation for the Advancement of Military Medicine, Inc..

1491DOCETAXEL AND MITOXANTRON IN THE MANAGEMENTOF HORMONE REFRACTORY PROSTATE CANCER:RESULTS OF A PROSPECTIVE PHASE·II TRIAL AxelHeidenreich*, Sebastian Wille, Carsten Ohlmann, Achim Elert, RainerHofmann, Marburg, Germany

INTRODUCTION AND OBJECTIVE: Taxanes are the most active cytotoxicdrugs in hormone refractory prostate cancer (HRPCA). The combination ofdocetaxel (DOC) and mitoxantron (MIT) has been shown to be highly active as firstor second line chemotherapy in metastatic breast cancer. It was the purpose of thistrial to determine the response rate of DOC/MIT in patients with asymptomaticHRPCA.

METHODS: 72 patients with HRPCA and asymptomatic PSA progressionwere recruited in the study protocol. HRPCA was defined as follows: PSA risedespite antiandrogen withdrawal, 3 consecutive PSA rises, castrate serumtestosterone serum levels. DOC and MIT were admintered at 60 mg/sqm and at 8mg/sqm, resp. every 3 weeks for 6 cycles; dose reduction was performed fortherapy associated toxicity grade 3/4. Quality of life (QoL) was assessed at eachcycle and 3-monthly thereafter (EORTC-QLQ 30 questionnaire). PSA levels werefollowed at each cycle and 3-monthly after completion of chemotherapy. Primaryendpoint of the study was prolongation of survival, secondary endpoints wereobjective PSA response, time to progression, time to the development of pain,safety of combination therapy and QoL.

RESULTS: The mean age of the patients was 65.9 (56-85) years; 68172(94.4%) pts are eligible for analysis. The mean PSA level at initiation of therapywas 182.1 (2.0-1680) ng/ml. 38172 (52.7%) pts demonstrated a > 50% PSAreduction, 14172 (25%) pts showed stable PSA serum levels and 10/72 (10.9%) ptsprogressed during therapy. We observed 3 (4.2%) therapy associated letal events:

1 Iisterial meningitis during grade 4 neutropenia, 2 pts myocardial infarctionsduring cycle I. The dosage of DOCfMIT had to be reduced in 8172 (11.1 %);hematotoxicty was limited with 2 (2.8%) pts developing neutropenic fever, 12172(16.7%) pts developed grade 3 leukopenia, there were no significantgastrointestinal side effects. After a median follow-up of 7.5 (2-14) months 3(4.2%) are DOD, 20% demonstrate PSA progression and 16% exhibit stable PSAserum levels. There was no significant correlation between initial PSA serum leveland objective response. QoL did not impair significantly during or followingDOCfMIT therapy.

CONCLUSIONS: Combination of DOC and MIT is well tolerated, has alimited spectrum of therapy associated side effects, does not interfere with QoL,and results in a high objective response rate in HRPCA with asymptomatic PSAprogression. DOC/MIT will serve as control arm for further prospectiverandomised phase-III-trials.

Source of Funding: None.

Urodynamic TestingModerated Poster

Tuesday, April 29, 2003 3:30-5:30 PM

1492PATIENT PERCEPTION OF VIDEOURODYNAMIC TESTING:A QUESTIONNAIRE-BASED STUDY Harriette M Scarpero*,Nashville, TN; Priya Padmanabhan, Xiaonan Xue, Victor W Nitti, NewYork, NY

INTRODUCTION AND OBJECTIVE: Urodynamics provide detailedinformation about lower urinary tract function. However, some perceive that itcauses significant physical and emotional discomfort. We sought to determinethe degree of anxiety, embarrassment and discomfort anticipated by patientsbefore videourodynamics (VUDS) and the actual degrees experienced. We alsocompared these variables between men and women and younger and olderpatients.

METHODS: All patients undergoing VUDS for the first time were given atwo-part questionnaire. Patients with neurological disease or requiring intermittentor indwelling catheter drainage were excluded. The first part, given immediatelyprior to VUDS, contained 5 questions regarding expected anxiety, pain,embarrassment, apprehension and preparedness. The second part, givenimmediately after VUDS, contained 7 questions comparing anticipated to actualoverall experience, pain and embarrassment as well as willingness to undergoVUDS again. Each question had a 5-point scale. Responses for each question werecombined into three categories: none or minimal, moderate, and severe orunbearable. Contingency table analysis was performed to evaluate the homogeneityof the distribution of the responses for each question at various age groups «=40,41-60, >60) and genders. Fisher's exact test was used to test for heterogeneityacross age groups or genders.

RESULTS: 166 patients completed the questionnaire, 78 men (mean age 65)and 88 women (mean age 59). Most patients (>95% for each question) expectedno to moderate anxiety, pain, and embarrassment. This did not vary with age,however more women anticipated a greater degree of embarrassment and moremen anticipated little or no embarrassment (p<O.OOl). Most patients (>90% foreach question) felt that VUDS was the same as or better than expected and wasassociated with the expected or less than expected level of pain and embarrassment.This did not vary between genders, but more younger people found the experienceworse than expected, more painful and more embarrassing than expected, whilemore elders found it better than expected, less painful and less embarrassing thanexpected (p-values = 0.01,0.02 and <0.001 respectively). 95% of patients wouldundergo VUDS again if medically indicated.

CONCLUSIONS: VUDS is well tolerated and associated with only minimal tomoderate anxiety, discomfort and embarrassment. The vast majority of patientswould undergo repeat testing. Suspected lack of tolerance should not be a barrierto performing medically indicated urodynamic testing.

Source of Funding: None.

1493IMPACT OF RECTAL DISTENSION ON THE EVALUATION OFLOWER URINARY TRACT SENSATION Stefan De Wachter*, Jean­Jacques Wyndaele, Wilrijk, Belgium

INTRODUCTION AND OBJECTIVE: Symptoms affecting bladder and bowelfunction often coexist. A relation between constipation and urinary incontinenceand between urinary tract problems and irritable bowel syndrome have beensuggested. However little is known on the interaction between bladder and rectal