Prostate cancer: Localized (IV)

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METHODS: Tissue samples from 50 prostatectomy and 16 positive lymph node specimens were probed by immunohistochemistry with a panel of informative CD antibodies on serial frozen sections. Cancer cell type analysis was also done by flow cytornetry on single cells obtained by collagenase digestion of minced tissue. RESULTS: Compared to luminal secretory cells, prostate adenocarcinoma cells were negative for ectopeptidases CD 10 and CD 13, expressed increased amounts of the B cell activation molecule CD24, and decreased amounts of the apoptosis-associated multifunctional enzyme CD38. Expression of CD57, CD63, CDw75, COl07a, CDI07b, CD164, and CD166 in cancer cells was similar to that in secretory cells. Basal epithelial cells do not express the above CD antigens and the basal cell CD markers, CD29, CD44, CD49b, CD49f, CDI04, and NGFR were not expressed by cancer cells. The preferential expression of secretory cellassociated CD markers in prostate cancer cells suggested a closer lineage relationship between cancer and secretory than basal cells. Although the above CD phenotype was the most frequently seen, some prostate cancers contained CDIOor CD13-positive, and CD57-negative tumor cells. Furthermore, the cancer phenotype of metastasis was different from that of primary tumors, in that CD 1O-positive cancer cells were found in all the lymph nodes examined but fewer than 25% in primary tumors. Cancer-associated stromal mesenchyme cells were found to differ from those in benign tissue by an increased expression of the T cell activation molecule CD90 and endoglin CDI05. CONCLUSIONS: The CD marker expression profile of prostate cancer cells most closely resembles that of secretory prostate epithelial cells and that some prostate cancers consist of heterogeneous cell populations based on CD expression. Presence of CD IO-positive cancer cells indicates a likelihood of metastasis to lymph nodes (LNCaP and LuCaP 35, both established from nodes, are CDIOpositive). Sonrce of Funding: CaP CURE Foundation.

Prostate Cancer: Localized (IV) Discussed Poster Wednesday, April 30, 2003

8:00 AM·12:00 PM

THE JOURNAL OF UROLOGY®

1636 A PROSPECTIVE ASSESSMENT OF URINARY CONTINENCE AND LOWER URINARY TRACT SYMPTOMS (LUTS) FOLLOWING RADICAL RETROPUBIC PROSTATECTOMY (RRP) Herbert Lepor*, Ledia Kaci, New York, NY INTRODUCTION AND OBJECTIVE: To prospectively determine the effect of RRP on urinary continence and LUTS using validated self administered outcome indices. METHODS: Between October 2000 through August 2002, 500 consecutive men underwent RRP by a single surgeon. Continence and LUTS were evaluated preoperatively and at 3,6 and 12 months postoperatively using the UCLA Prostate Cancer Index and the AUA symptom index. 240 men were potentially evaluable at one year. Of these cases, 236 (98.3%), 233 (97.1%), and 226 (94.2%) completed the UCLA Prostate Cancer Index and the AUA symptom index at 3, 6, and 12 months, respectively. All responses to these questionnaires were self-reported. RESULTS: See Tables] and 2 below. CONCLUSIONS: If postoperative continence is defined as :5] pad over 24 hours or total control/occasional dribbling, 92.1 % and 95.2% of men regain urinary continence following RRP at 12 months. Longer follow up may yield even better continence outcomes. All of the individual LUTS captured by the AVA symptom index significantly improved in those men with significant baseline LUTS following RRP. TABLE 1 ContinenceOutcomes Pad Requiroment None 1

Katz, Erik T Golubojf, Peter J Puchner, Carl A Olsson, James M McKiernan, Mitchell C Benson, New York, NY INTRODUCTION AND OBJECTIVE: Clinical outcomes of surveillance or watchful waiting for localized prostate cancer (PC) are traditionally measured in terms of overall survival. If surveillance is considered a treatment option for PC, then intervention free survival (IFS) must be considered a relevant endpoint in outcomes research. Applying this definition of failure, we report our outcomes of surveillance for PC in a contemporary cohort of patients diagnosed and followed in the PSA era. METHODS: 72 patients with clinical stage TI-2 Gleason sum :5 7 PC were prospectively enrolled and followed in a surveillance database at our institution. Surveillance failure was defined as any intervention for prostate cancer for any indication including radiation, hormonal therapy, or surgery. These patients were evaluated for IFS and stratified by clinical stage, Gleason score, initial PSA, and indication for being placed on surveillance using univariate analysis. Indications for surveillance included either comorbid illness or presumed clinically insignificant prostate cancer. The Kaplan-Meier method and log-rank test were performed using SPSS-ll. RESULTS: The overall median PSA was 5, median stage TIc, and median Gleason sum 6. The median age at diagnosis was 72 years, median follow-up was 4 years, and overall and disease specific survivals were 94% and 100%, respectively. 48/72 (66.7%) patients remained free from intervention during the study, while 24/72 (33.3%) failed with a median time to intervention of 42 months. Indication for entering surveillance, clinical stage, and Gleason score, were not predictive of IFS in univariate analysis. Initial PSA alone was a significant predictor of IFS (p=0.014). CONCLUSIONS: In a contemporary cohort of patients electing surveillance for PC, no disease specific mortality was observed, but long term IFS occurred in only 2/3 of patients. Only pre-surveillance PSA was predictive of IFS in our experience. Moreover, patients placed on surveillance because of clinically insignificant cancers were as likely to receive treatment as patients whose poor overall health had prompted surveillance. The likelihood of IFS in the PSA era must be considered when counseling patients regarding therapy for localized PC. Source of Funding: None.

o o

33,7% 37.2% 14,6% 14,5%

63.5% 23.7% 7.6% 5.2%

76,2% 15.9% 4.4% 3,5%

85.8% 13.0% 0.4% 0,8%

23,7% 56,9% 15.4% 4.0%

40.2% 51.0% 7.2% 1,6%

48.7% 46.5% 3.5% 1.3%

100%

o

Frequency ofIncontinence Total Control Occasional Dribbling Frequent Dribbling NoControl TABLE 2 COMPONENTS OFAUASI

12 mos.

Baseline 3 mos. 6 mos.

2 ,3

# PTS. SCORE:!: 2 Baseline

1635 WATCHFUL WAITING FOR PROSTATE CANCER REEXAMINED: INTERVENTION FREE SURVIVAL WHILE ON SURVEILLANCE IN A CONTEMPORARY COHORT OF PATIENTS Young M Kang*, Todd V Cartee, Manlio A Goetzl, Aaron E

437

SYMPTOM SCORE

3 mos.

6 mos.

12mos.

% reduction at 12 mos.

Emptying bladder Urinary frequency Interrupted stream Postponing urination Weak stream Straining Nocturia

47 106 49 56 72

22 118

2.89 3.28 2,76 2,80 2.90 2.91 3,76

0,82 2.15 075 1,56 127 0.57 2.68

0.72 183 0.67 0,89 0.97 0,48 1,77

0,65 1,71 050 0.84 0.73 0.43 1,71

78 48 82 70 75 85 55

Source of Funding: None.

1637 IMPACT OF BACKDATING ON BIOCHEMICAL NED RATES USING THE ASTRO DEFINITION FOLLOWING 3-D CONFORMAL RADIATION FOR PROSTATE CANCER Robert G Uzzo*, Eric M Horwitz, Alexandra L Hanlon, Gerald E Hanks, Richard E Greenberg, Alan Pollack, Philadelphia, PA INTRODUCTION AND OBJECTIVE: Adoption of the ASTRO consensus definition has been critical in evaluating treatment efficacy following prostate radiation. Since its adoption, several points have remained controversial, namely backdating the date of failure (DOF) to the point midway between the posttreatment PSA nadir and the first PSA rise. We evaluate the impact of backdating on bNED control rates following 3D-conformal radiation and suggest changes to the definition. METHODS: Between April 1989 and January 1999, 1017 patients with non-metastatic prostate cancer were treated with 3D-conformal radiation therapy alone at our institution. Biochemical control was defined using the ASTRO consensus definition (midway between the post-treatment PSA nadir and the first of the three consecutive rises in PSA (DOF A)). To evaluate the impact of backdating on bNED rates, four alternate failure time-points were assessed including backdating to the date of the first rise in PSA after nadir, the date between the l st and 2nd rise, the date between the 2nd and 3rd rise, and the date of the third consecutive rise in PSA after nadir (DOF 1-4 respectively). Outcomes were stratified by prognosis based on stage, PSA and Gleason score (favorable, intermediate and unfavorable). A subset analysis of 480 patients treated prior to November 1994 was also performed. Kaplan-Meier estimates and hazard functions were performed. RESULTS: The l O-ycar actuarial bNED control rates were 64%, 52%, 47%, 42% and 38% using DOF A and 1-4, respectively (p
438

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persisted when stratified by prognostic group. Similar differences in bNED control were observed for the long-term follow-up subset where lO-year actuarial bNED control rates were 56%, 47%, 44%, 41% and 38% using the DOF A and 1-4, respectively (p < 0.001). Median follow-up was 53 months overall and 74 months for the subset treated prior to November 1994. Hazard functions demonstrated that earlier DOFs (i.e. ASTRO) are associated with the highest risk of failure in the first four years following radiotherapy but improved long-term bNED rates at 8 years in the entire cohort as well as the long term subset. CONCLUSIONS: Adoption of the ASTRO consensus definition has been crucial in standardizing outcomes following radiation. Modifications are necessary to improve the sensitivity and specificity of the ASTRO definition and may require changing the DOF to the point closer to the time that PSA failure is recognized. The inability to compare outcomes with surgery remains a key limitation. Source of Funding: None.

Neoadjuvant hormones were administered to 15 patients. The DFR were calculated using the Kaplan Meier method. For the overall population, the mean nadir PSA was 0.61 sd 1.17 ng/ml, and further follow up evidenced a 81% negative biopsy rate, and a 70.1% DFR at 60 months. CONCLUSIONS: The nadir PSA seems to be a valuable prognostic factor after HlFU treatment, moreover obtained within 3 months after the procedure. Control biopsies are nevertheless still needed to verify the local efficacy, and indicate if a HIFU retreatment should be considered. table1: results according to thePSA nadirlevel nadirPSA 0.5ng/ml

Patients nb 100 (73%) 16(12%) 21 (15%1

neg biopsiesrate 86% 75% 52%

DFR at 60months 77.9% 68.2% 39.0%

Source of Funding: None.

1638 NOMOGRAMS FOR LOCALIZED PROSTATE CANCER IN KOREAN MEN Hanjong Ahn, Cheryn Song*, Jun Hyuk Hong, Seoul, South Korea INTRODUCTION AND OBJECTIVE: With increasing incidence of prostate cancer in Korean men and the accumulation of data on its distinctive features, verification of applicability of the pretreatment nomograms to the Korean patients became inevitable as the necessity for the nomograms based on Korean data increased. We analyzed the Korean data to derive the pretreatment nomograms and compared the outcome with those from other studies. METHODS: A total of 255 Korean men with clinically localized prostate cancer who underwent radical retropubic prostatectomy at Asan Medical Center between June 1990 and April 2002 were included in this study. Using preoperative serum PSA, biopsy Gleason score and clinical stage as the clinical parameters, final pathological status was analyzed with respect to each variable. A multinomial log-linear regression was performed for the simultaneous prediction of organconfined disease (OC), seminal vesicle invasion (SVI) or lymph node metastasis (LN) and nomograms representing per cent probabilities were constructed and compared with the preexisting nomograms presented by Partin et al. and Egawa et al. RESULTS: Regarding OC we obtained higher probability than the Partin table especially with Gleason scores 7 and higher and similar results with the Egawa table though not with as much marked difference. As for SVI, we obtained generally higher probability than the Partin table especially with Gleason scores 8 and higher, but when compared to the Egawa table, we had lower probability when the clinical stages were higher than T2. For LN, we had markedly lower probability in the clinical stages Tla and b ranges while the other ranges revealed similar results compared to the Partin table. And by general linear repeated measures, all of these differences between each corresponding data were statistically significant when considered with respect to each clinical variables. When the ROC curves were constructed, using the Partin table, area under the curves (AUC) were 0.756, 0.761, and 0.762 for OC, SVI and LN respectively, and using the Egawa table, 0.586 and 0.671 for OC and SVI respectively. CONCLUSIONS: Comparison of the prediction tables revealed notable differences especially as to the OC and SVI, even between the Egawa table and ours, when the Asian population can easily be expected to harbor similar characteristics. Therefore it would be advisable to apply each table to its corresponding population. Source of Funding: None.

1639 TRANSRECTAL FOCUSED ULTRASOUND AND LOCALIZED PROSTATE CANCER: MAY THE NADIR PSA PREDICT THE TREATMENT SUCCESS? Gelet L Albert, Lyon, France INTRODUCTION AND OBJECTIVE: For radiation treatments, either external or interstitial, it was established that the nadir PSA has a strong predictive value for the long term patient outcome. Our purpose is to evaluate if the nadir PSA can also be considered as a predictive factor after High Intensity Focused Ultrasound (HIFU) therapy. METHODS: All our patients treated with HIFU as primary care for localized prostate cancer, with a baseline PSA level < 30 ng/ml, and with at least 1 year of follow up were included in this analysis. They were treated using the Ablatherm HIFU device (EDAP SA). Patients follow up included sextant biopsies and PSA level measurements. Any positive biopsy or 3 consecutive increases in the PSA level was considered as a failure for the disease free rate (DFR) calculation. RESULTS: 137 patients fulfilled these criteria and were all considered for analysis. The mean patients follow up was 33 sd 18 months (range: 12 to 96 months). The population description before HIFU was: mean age 72.0 sd 5.2 years, mean prostate volume 34.1 sd 17.4 cc, mean PSA level 8.8 sd 5.9 ng/rnl, and all had positive biopsies. The clinical stage was Tl for 65 patients, and T2 for 72 patients.These results were stratified according to the nadir PSA level(table 1). *Presenting author.

1640 POTENCY AFTER RADICAL RETROPUBIC PROSTATEC· TOMY (RRP): EVALUATION USING THE IIEF5 QUESTIONNAIRE (INDEX OF ERECTILE FUNCTION) Joachim Noldus*, Juri Palisaar, Uwe G Michl, Markus Graefen, Alexander Haese, Hartwig Huland, Hamburg, Germany INTRODUCTION AND OBJECTIVE: Aim of this study was to evaluate the postoperative potency of patients after nerve-sparing RRP (NSl=unilateral; NS2=bilateral) and non nerve-sparing RRP (NEO)using a validated questionnaire. METHODS: 691 consecutive patients were included in this retrospective study who underwent RRP between 3/1999 and 212001. All patients received the validated lIEF 5 questionnaire 12 months postoperatively. 515 (74.5%) returned their questionnaires. Additionally to the questionnaire, patients were asked of their preoperative erectile status, and whether postoperative erections were unassisted and sufficient for sexual intercourse (SI). 406 patients (78.8%) with good preoperative erections and unassisted sexual intercourse were evaluated. The degree of erectile dysfunction (ED) was classified*: severe (5-7), moderate to mild (8-21), and no ED (22-25). 'Rosen et al., Int J Impot Res 1999. RESULTS: 164/406 patients (40.4%; mean age 6lyrs.) received a NS2, 80 (19.7%; mean age 62yrs.) a NSI, and 162 (39.9%; mean age Myrs.) had non nerve-sparing RRP (NSO). Mean lIEF score for the 3 patient groups were statistically different: 13.7 (NS2), 9.5 (NSl), and 2.8 (NSO),respectively. The table shows the lIEF scores. 56.1% with NS2, 33.75% with NSl, and 0.6% with NSO(1 patient) had erections hard enough for unassisted S1. CONCLUSIONS: Using a validated questionnaire, evaluation of postoperative potency after RRP showed the highest lIEF score and SI rate after bilateral nerve-sparing. However, some patients with reduced lIEF score were able to perform unassisted S1.

NS2 NS1 NSO

25-22 31.2% 13.8%

o

liEF5 scores 21-8 34.1% 28.8% 4.9%

7-5 34.7% 57.4% 95.1%

Source of Funding: None.

1641 THE ROLE OF INTRA OPERATIVE BIOPSIES DURING RADICAL RETROPUBIC PROSTATECTOMY (RRP) Herbert Lepor*, Ledia Kaci, New York, NY INTRODUCTION AND OBJECTIVE: To determine the value of intraoperative biopsies of the apical margin (AM), bladder neck margin (BNM), and selected biopsies of the lateral pedicle/neurovascular bundle (LPINVB). METHODS: Between October 2000 and August 2002, 500 men underwent RRP by a single surgeon. Circumferential intraoperative biopsies were routinely obtained from the AM and BNM. Additional deeper biopsies of the AM were performed in 11 cases. Intraoperative biopsies of the LPINVB were obtained in selected cases. All of the tissue specimens were submitted for frozen section analysis. Overall, 468, 474, and 63 men underwent biopsy of the AM, BNM, and LPINVB. RESULTS: See Table 1 below. The AM from the surgical specimen showed no CaP in 9 (42.8%) of the cases with +ve AM biopsies. The AM was the only site of a positive margin in 17 (81%) of cases with a +ve AM biopsy. In case with a +ve AM biopsy, the final margin was assumed to be negative if the deepest AM biopsy showed < 5% CaP (J. Urol. 165:1943, 2001). Overall, frozen section biopsy was responsible for eradicating residual cancer in 15 of 468 (3.2%) of cases. CONCLUSIONS: Intraoperative biopsies and frozen section analysis of the BNM and LP/NVB have very low diagnostic yield and should not be routinely

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performed . The incidence of carcinoma at the AM is clinically significant and routine intr aoperative biopsy of AM provides the opportunity to achieve a negative surgical margin , thereb y increasing the likelihood of perfor ming a curat ive RRP. TABLE 1 Siteof Intraoperative Biopsy

# Biopsies

AM BNM

468 474

LPlNVB

63

#+ve CaP 21 (4.5%) 4(0.8%) 1(1.6%)

# Benign Tissue 162(34.6%) 155 (32-7%) 4(6.3%)

Source of Funding: None.

1642 PREDICTORS OF ACTIVE TREATMENT IN MEN WITH LOCALIZED PROSTATE CANCER WHO SELECT WATCHFUL WAITING: RESULTS FROM CAPSURE Susan L Rider", Eric P Elkin, Deborah P Lubeck, Maxwell V Meng, San Francisco, CA; Shilpa S Mehta, Lake Forest, IL; Peter R Carroll, San Francisco, CA INTRODUCTION AND OBJECTIVE : Watchful waiting (WW) is one of many options for men with clinically localized prostate cancer. Some individuals who initially choose WW may progress clinically and be treated at a later date. We wished to identify clinical and/or sociodemographic predictors of eventu al treatment in those who chose WW. METHODS: The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a national registry of patients with various stages and treatments of prostate cancer. Using this database, we identified 402 men diagnosed with localized prostate cancer between 1989-2000 and who elected WW as their initial management and had no active treatment for at least 6 months. Of these 402 men, 171 (43%) went on to have active treatment and 231 continued on surveillance (median follow-up 1.7 years). The groups were compared on baseline clinical and sociodemographic characteristics, follow-up PSA values, and changes in PSA using chi-square and t-tests. Analysis of PSA changes included 156 patients (69 with active treatment, 87 on WW) with both a baseline and follow-up PSA. Cox proportional hazards was used to determine factors related to time to active treatment. RESULTS: Compared to WW patients who continued on surveillance, a smaller percentage of those who went on to active treatment had baseline low risk clinical characteristics (45% vs. 63%, p= O.oo I) , TI disease (39% vs. 50%. p= 0.03), a PSA < 4 (13% vs. 21%, p < 0.000 1), and a biopsy without Gleason grade 4 or 5 (75% vs. 89%, p=0.002). Comparing follow-up PSA values, those who continued on to active treatment had a lower percentage with PSA < 4 and a higher percentage of PSA values > 20 (6% and 38% vs. 32% and 8%, respectively, p < 0.000 1). The mean PSA at baseline for WW with later active treatment was 11.1 and at follow-up was 19.0. For those who continued on WW, the values were 8.5 and 7.9, respectively. The mean PSA change was 8.0 vs. -0.6 (p <0.0001). PSA change was highly significant in a multivariable proportional hazards model: WW men with a PSA increase >5 were 3.90 times as likely, and those with an increase of 2-4.9 were 2.45 times as likely to receive active treatment as those with a PSA change < 2. Additional predictors of active treatment in this model were baseline T stage 3a, baseline Gleason score 4 or 5, higher income, and being in a relationship. CONCLUSIONS: For tho se who choose WW , baseline cl inical and sociodemographic variables predict eventual treatment. This information may help identify those most likely to benefit from this approach as initial treatment. Source of Funding: TAP Pharmaceutical Products, Inc.

1643 A COMPARISON OF POSITIVE SURGICAL MARGINS BETWEEN NERVE-SPARING AND NON NERVE-SPARING PROSTATECTOMY: INCIDENCE, LOCATION AND BIOCHEMICAL FAILURE Jiiri R Palisaar », Markus Graef en, Joachim Noldus, Peter Hammerer, Hartwig Huland, Hamburg, Germany INTRODUCTION AND OBJECTIVE: To determine impact of surgical procedure on the incidence and location of a positive surgical margin (+ SM) and impact on hiochemical failure. METHODS : We evaluated +SM, time to recurrence and recurrence in 620 and 123 consecutive patients who underwent non nerve-sparing and nerve-sparing (NS) prostatectomy (RP) for clinically localized prostate cancer between 1992 and 2000. Before 1996 almost all patients underwent non-NS RP. Since 1996 patient selection for NS based on preoperative PSA, Gleason grade and number of positive biopsy cores. We considered the incidence and location of a positive margin and whether NS was performed on that specific side or not for each prostate lobe among the same pathologic stages (pT2,pT3a,pT3b). Multivariate analysis was performed to evaluate association of clinical and histopathological parameters with biochemical failure.

439

RESULTS: For each prostate lobe the positive margin rate in pT2 cancers was 6.5% in NS vs. 5.1% in non NS. 10.3% vs. 17.3% in pT3a cancers and 15% vs. 25.1% in pT3b cancers. The positive margin in pT2 cancers was located apically/ laterally in 27.3/47.3% in NS vs. 61.8/11.8% in non NS, in pT3a cancers 33.4/44.4% vs. 48.9/22.7% and in pT3b 25/25% vs. 24.7/12.9%. Tumor recurrence was observed in n = 266 patients with a mean time to failure of I. 9 years (SD+ 1.6y). 2/3 (175/266) of all recurrences occurred within the first two years after surgery. Mean follow-up of patients who remained free from failure was 2.8 years. The 3- and 5 year recurrence free survival rate for patients with pT2,pT3a and pT3b cancers undergoing NS vs. non NS RP were 96.1194.9 vs. 94.9/90.8 (log rank p= O.768), 12.5m .1 vs. 67/54 (log rank p= 0.170) and 46/38 vs. 29/25 (log rank p =0.1( 2). In multi variate Cox' reg ress io n analysis ca psu lar penetra tio n( < 0. 000 1), lymph nod e statu s(< 0 .000 1), se mi na l vesic le invasion(< 0.0001), surgical margin status(O.O I) , Gleasonscorer-cu.Otju l ) and prepoperative PSA(0.005) were significantly associated with risk for failure, whereas NS itself was not (p= 0.798). Though a positive margin was an adverse prognostic factor, progression free survival in patients with a positive margin at the apex did not differ in comparison to patients with laterally located margins (log rank p =0.665). CONCLUSIONS: Though main location of +SM differed between NS and non NS RP, neither the positive margin rate nor recurrence free survival was adversely affected by NS. Source of Funding: None.

1644 THE EFFECT OF PUBO-PROSTATIC LIGAME NT (PPL) PRESERVATION ON THE EARLY RECOVERY OF CONTINENCE FOLLOWING RADICAL RETROPUBIC PROSTATECTOMY (RRP) Anna Smither", William A See, Milwaukee, WI INTRODUCTION AND OBJECTIVE: Incontinence is a major contributor to post operative morbidity in patients undergoing radical prostatectomy. Many techniques have been used in an attempt to facilitate the early return of postoperative continence and to lessen the degree of urine leakage. Preservation of the puboprostatic ligaments (PPL) at their condensation point with the pubic periostium has been reported to improve continence recovery following RRP. This study used quantitative measures of incontinence to compare early continence recovery in those patients with PPL preservation vs. patients undergoing standard PPL transection. METHODS: 132 consecutive patients undergoing a RRP by a single surgeon during a 24 month interval were reviewed. Patients underwent quantitative 1- hour pad testing, and questionnaire based assessment of quality of life. stress and urge incontinence 2 and 6 weeks following RRP. Only those patients with complete post-operative quantitative data sets were selected for comparison. Patients were divided according to the average volume leaked; tbose with minimal leak (less than or equal to I gram), mild (1.1 to 10 grams), moderate (10.1 to 50 grams) and those with severe leakage (greater than 50 grams). Final analysis compared 112 patients, 62 who had standard PPL transection, with the subsequent 50 patients having PPL preservation. RESULTS: Mean pad test leak volumes at 2 weeks (catheter removal) were 48.1 ml and 31.0 ml in the PPL transection and preservation groups respectively. At 6 weeks post operatively tbe PPL transection group had an average leak volume of 24.2 ml compared to the PPL preservation groups leak volume of 31.7 ml. There was no difference between groups in any of the subjec tive questionnaire scores. There was no statistical difference between the two groups when they were compared by average leak volume or by degree of incontinence. CONCLUSIONS: Contrary to prior reports, there was no difference in early continence recovery for patients with PPL preservation relative to those undergoing PPL transection. Longer follow up will be necessary to determine if the differences in technique result in long term differences in continence. Source of Funding: None.

1645 HIGH INTENSITY FOCUSED ULTRASOUND (HIF U) TREATMENT FOR LOCALIZED PROSTATE CANCER: FRENCH UROLOGICAL ASSOCIATION MULTICENTRIC STUDY - FIRST RESULTS ON 117 PATIENTS Pierre J Conort ", Paris, France; Pascal Rischmann, Toulouse. France; Daniel Chevallier, Nice, France; Christian Saussine, Strasbourg, France; Guy Val/ancien, Paris, France; Henri Bensadoun, Caen, France; Christian Pfister, Rouen, France; Albert Gelet, Lyon, France INTRODUCTION AND OBJECTIVE : to evaluate reproducibility , tolerance, safety, cost and efficacy of HIFU treatment for localized prostate cancer (PC) in a national independant prospective multicentric open study, supported by the French Urological Association (AFU); the aim was to include 100 patients in I year. METHODS: 8 departments of urology were involved in this study (after ethical committee' s approval) and have used Ablatherm® (HIFU delevering system from

440

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EDAP S.A.) from 25/0112001 to 25/0112002. Each urologist was trained to perform the same procedure. Inclusion criteria were: cancer Tl or T2, NO-MO, non treated before, PSA £ 15ng/ml, Gleason score (GS)
1646 ADJUVANT BICALUTAMIDE 150 MG SIGNIFICANTLY IMPROVES PROGRESSION-FREE SURVIVAL FOLLOWING RADIOTHERAPY FOR EARLY PROSTATE CANCER Christopher Tyrrell*, Plymouth, UK; William A See, Milwaukee, WI; David McLeod, Washington DC, WA; Manfred P Wirth, Dresden, Germany; Peter Iversen, Copenhagen, Denmark; Louise Garside, Macclesfield, UK INTRODUCTION AND OBJECTIVE: The non steroidal antiandrogen bicalutamide ('Casodex') 150 mg is being evaluated in the largest ever treatment trial in prostate cancer - the Early Prostate Cancer (EPC) program. At a median 3 years' follow-up, bicalutamide 150 mg in addition to standard care of radical prostatectomy, radiotherapy (RT) or watchful waiting reduced the risk of objective progression by 42% compared with standard care alone (See et al. J Urol 2002; 168: 429-435). In ensuing exploratory analyses, this overall effect was consistent across the 3 standard care options. A new analysis, the event time ratio (ETR) analysis, has now been conducted to estimate the relative progression-free survival (PFS) for the 1370 patients in the RT subgroup. METHODS: Hazard ratio (HR) and ETR values for objective progression and prostate-specific antigen (PSA) progression for bicalutamide 150 mg versus placebo in the treatment of the RT subgroup were calculated. An ETR > I indicated a benefit for bicalutamide 150 mg and 95% confidence intervals (CI) excluding I indicated statistical significance at the 2-sided 5% level. The model was used to determine the difference in time taken for 10% of patients to progress between the two treatment groups. RESULTS: After a median 3 years' follow-up, bicalutamide 150 mg as adjuvant to RT significantly reduced the risk of objective progression by 37% (HR 0.63; 95% CI 0.46, 0.85; p=0.0024), and, in doing so, significantly increased PFS by more than a third (ETR 1.36; 95% CI 1.11, 1.67). The estimated time taken for 10% of patients in the placebo group to progress was 2.2 years compared with 2.9 years in the bicalutamide 150 mg group, a difference at this point on the Kaplan-Meier curve of 8.4 months. Bicalutamide 150 mg as adjuvant to RT significantly reduced the risk of PSA progression by 58% (HR 0.42; 95% CI 0.33, 0.53; p< <0.0001), and, in doing so, almost doubled PSA PFS (ETR 1.99; 95% CI 1.65, 2.40). The estimated time taken for 10% of patients to experience PSA progression was longer for the bicalutamide 150 mg group (1.9 years) than the placebo group (1.0 years), a difference at this point on the Kaplan-Meier curve of 10.8 months. Analysis of the data by risk factor showed that treatment benefits were strongest in those patients with poor prognosis. CONCLUSIONS: Immediate bicalutamide 150 mg as adjuvant to RT significantly improves objective and PSA PFS in patients with localized or locally advanced prostate cancer. 'Casodex' is a trademark of the AstraZeneca group of companies. Source of Funding: AstraZeneca. 'Presenting author.

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1647 BIOCHEMICAL FAILURE DUE TO RESIDUAL BENIGN PROSTATE TISSUE AFTER RADICAL PROSTATECTOMY. IS THERE A NEED FOR AN ANASTOMOTIC BIOPSY Al"TER ALL? Theodore G Anagnostou, Athens, Greece; Mesut Remzi, Saeid Alavi, Vienna, Austria; Michael Lykourinas, Athens, Greece; Bob Djavan*, Vienna, Austria INTRODUCTION AND OBJECTIVE: Detectable PSA is almost always an indicator for a systemic or local recurrence, after radical prostatectomy. However few reports have assessed the incidence of benign residual prostate tissue as a finding from TRUS-guided anastomotic biopsy, in cases of biochemical failure, and the impact of this diagnosis in oncologic decision-making. METHODS: 64 cases of biochemical failure were assesed during post-radical prostatectomy follow-up, by abdominal CT-scan, bone scanning and a TRUSguided biopsy taken from cystourethral anastomosis in every case. Cases where adjuvant or neo-adjuvant therapy was administered, were not included in our study. Biopsies were taken by a 12-Gauge tru-cut needle, under continuous ultrasound guidance, through a steady biopsy channel on the transrectal probe (B-K medical). We have also performed a TRUS-guided biopsy, in 17 cases without biochemical failure (control group). We assessed the incidence of benign margin status, and correlated findings from prostate fossa biopsy to radical prostatectomy specimens. RESULTS: All patients underwent bundle and bladder neck preserving radical prostatectomy due to clinically localized prostate cancer (stage TIc or T2). PSA values were 1,6 ng/ml (O,7-2,4ng/ml) and median follow-up was 15,12 months (6-32 months), in biochemical recurrence cases group. Transrectal ultrasound guided biopsy has shown benign prostate tissue in 16 cases (25%), while prostate cancer was found in 18/64 cases (28%) with one time biopsy. In the control group, 2/17 cases (11%) with residual benign tissue, while 15/17 cases showed fibromuscular tissue. In our cohort of patients the incidence of a positive malignant margin was 42%, while a retrospective analysis of the specimens, revealed a strong correlation of residual benign tissue to benign margin status. CONCLUSIONS: Neurovascular bundle or bladder neck preserving techniques are performed as a measure to improve potency and incontinence rates in patients who are likely to develop these significant problems, due to this kind of operation. Local recurrence after radical prostatectomy is difficult to assess with one time biopsy. There are, though, a variety of pathological findings in TRUS-guided biopsies taken from vesicourethral anastomosis, and the incidence of benign tissue in cases of biochemical failure would justify a TRUS-biopsy procedure in these patients. Source of Funding: None.

1648 OUTCOME MODEL OF PROSTATE CANCER PROGRESSION FOLLOWING RADICAL PROSTATECTOMY Anthony Y Smith, Moben Mirza", Kevin Cahill, Albuquerque, NM; Judd W Moul, Washington, DC; Leon Sun, Rockville, MD INTRODUCTION AND OBJECTIVE: A new model of prostate cancer progression following radical prostatectomy (RP) has been developed in order to predict which men might derive life expectancy benefit from surgery. The program computes a tumor doubling time (DT) from prostate specific antigen (PSA) data and forecasts outcome based on the assumption of minimal retained disease. The model computes an expected time of death for watchful waiting (WW) and surgery which are compared to life expectancy (LE) to determine a net gain or loss of life years (NGLY). We then compared the theoretical NGLY to patients' actual NGLY. METHODS: The model was studied for patients selected from the Center for Prostate Disease Research (CPDR) database. From the CPDR database, 473 men who were followed to death after undergoing RPs were selected. Of the 473 patients, 116 patients had recurrent disease and adequate PSA data to calculate doubling times. Of these I J6 patients, 42 patients died of prostate cancer, 69 died from causes other than prostate cancer. Pathological data was missing on 3 patients, surgery date was missing on 1 patient, and 1 patient had no death date. RESULTS: Median DT in years was 0.24 for ages<60, 0.53 for ages 60-69, and 0.39 for ages>69. Median calculated NGLY was 0.76 for ages <60, U8 for ages 60-69, and 0.73 for ages>69. Median actual NGLY was 4.33 for ages<60, 1.63 for ages 60-69, and 1.71 for ages>69. Median DT in years was 0.66 for Gleason sum (GS)<7, 0.36 for GS 7, and 0.27 for GS >7. Median calculated NGLY was 0.88 for GS <7, 1.18 for OS 7, and 1.02 Icr GS >7. Median actual NGLY was -0.53 for GS <7,0.64 for GS 7, and 2.47 for GS >7. Predicted NGLY over WW for all causes of death showed sensitivity of 100% with a positive predictive value (PPV) of 82.5(r2=.57). For cancer deaths only, NGLY compared to WW had sensitivity of 99% with a PPV of 74.6 (r2= .77). Median time to death was only 7 years for all patients and not unexpectedly, there was no increase in NGLY over estimated LE. CONCLUSIONS: As expected, PSA doubling times were rapid for this early mortality group. The model proved useful to predict death as an outcome. Even in the face of minimal retained disease and aggressive cancer and in spite of positive

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margins or PSA recurrence, the study suggests that a majority of men should gain life years over WW after RP. Because of the assumption of minimal retained disease for all patients, the model predictions tend to be conservative. Source of Funding: Part of the project funded by Center for Prostate Disease Research (CPDR).

1649 SUCCESSFUL TRANSFER OF OPEN SURGICAL SKILLS TO A LAPAROSCOPIC ENVIRONMENT USING A ROBOTIC INTERFACE: INITIAL EXPERIENCE WITH LAPAROSCOPIC RADICAL PROSTATECTOMY Thomas E Ahlering*, Douglas W Skarecky, David Lee, Ralph V Clayman, Orange, CA INTRODUCTION AND OBJECTIVE: For a highly skilled laparoscopic surgeon, the learning curve for achieving proficiency with laparoscopic radical prostatectomy (LRP) is cited as 30-40 cases. For the laparoscopically naive surgeon, this learning curve could be as many as 80-100 cases, extending literally over years. It has been hypothesized that the development of robotic laparoscopic equipment with 6 degrees of freedom (i.e. da Vinci robot), can significantly shorten the LRP learning curve for the highly skilled open, albeit laparoscopically inexperienced surgeon. We report our initial experience with da Vinci robotic LRP by a fellowship trained, laparoscopically naive, urologic oncologist. METHODS: Following a one day da Vinci robotic laparoscopic training course(l cholecystectomy,! nephrectomy), an experienced urologic oncologist (TA) proceeded to obtain further training by performing two cadaveric robotic LRPs. No prior laparoscopic courses or clinical experience with laparoscopy preceded the three days of robotic training. Over a 4 month period (June-Oct., 2002), 12 consecutive robotic LRPs were performed (T.A.) using the technique described by Menon and colleagues. RESULTS: All 12 procedures were successfully completed laparoscopically. There were no conversions and no blood transfusions. While the initial 4 cases, averaged 7.3 hrs, the subsequent 8 cases averaged 4.9 hrs. The average time to perform the urethral vesical anastomsis was 51' (range 35-80). Instillation time for the robot averaged 29 '(range 15-40'). Five patients were discharged on postoperative day one; average LOS was 48 Hrs( range 24-168). There was one complication, anastomotic extravasation; successfully managed by ureteral stent placement. The final pathology showed: Gleason Score averaged 6.8, margin positive rate was 36% and average prostate volume was 50.5 grams (12.5-115). EBL averaged 167cc (25-350cc) Catheter indwelling time averaged 7 days; at 1 month following catheter removal 7 of 8 patients were continent (range 1-26 days), while 1 patient is wearing 1 pad per day. CONCLUSIONS: A laparoscopically naive, yet well-trained open surgeon can rapidly transfer open surgical skills to a laparoscopic environment using a robotic interface. Initial outcomes with this markedly truncated format have been highly favorable; indeed, these results are comparable to the reported literature experience of skilled laparoscopic surgeons after performing > 100 LRPs. Source of Funding: None.

1650 PRESERVATION OF THE NEUROVASCULAR BUNDLES (NVB) AT RADICAL PROSTATECTOMY (RRP) IN MEN WITH BIOPSY PERINEURAL INVASION (PNI) Glenn M Cannon*, Charles R Pound, Susan J Urda, Georgi Pirtskhalaishvili, Michael J Becich, Sheldon I Bastacky, Rajiv Dhir, Xiao C Mu, Joel B Nelson, Pittsburgh, PA INTRODUCTION AND OBJECTIVE: The finding of biopsy PNI has been associated with a high probability (up to 95%) of extracapsular extension (ECE) of prostate cancer at the time of RRP. Although some surgeons routinely perform wide excision of the NVB on the side of the biopsy PNI in an effort to gain negative surgical margins (SM), we feel that many times this is unnecessary. We investigated the significance of biopsy PNI in recent RRP patients at our institution. METHODS: The medical records of 433 patients undergoing RRP by a single surgeon in the last 34 months were reviewed. A GU pathologist at our institution evaluated all included patients' prostate biopsies preoperatively. 20 patients were excluded because their preoperative biopsies were reviewed elsewhere or they had received neoadjuvant hormonal ablation. Therefore, both the biopsy and the surgical specimen results of 413 patients were assessed. Operative reports and surgeon notes were reviewed to determine the extent of preservation of the NVB. RESULTS: 18% (741413) of men had evidence of biopsy PNI. 57% (42/74) of men with biopsy PNI had organ-confined disease at the time of surgery compared to an organ-confined rate of 80% in men without biopsy PNI (p
441

(p=0.027). In the 57 cases with biopsy PNI where both NVB were spared, there were only 5 +SM. In three of these cases the +SM was on the opposite side of the biopsy PNI. In one of these cases the +SM was at the distal urethreal margin, but all other margins were negative. In only one of these cases was the + SM on the same side as that of the biopsy PNI. CONCLUSIONS: Although biopsy PNI was associated with a higher probability of ECE and a lower likelihood of bilateral nerve-sparing technique, this finding alone is lacking in the prediction of significant extracapsular disease resulting in a positive surgical margin in an individual patient. The incidence of ECE in men with biopsy PNI in this series is less than previously reported. If the decision to preserve or resect the NVB is made intraoperatively by an experienced surgeon, we demonstrated that in the majority of men with biopsy PNI, both NVB may be spared without a significant increase in positive surgical margins. Source of Funding: None.

1651 PREDICTIVE FACTORS OF POTENCY RECOVERY AFTER NERVE-SPARING (NS) RADICAL RETROPUBIC PROSTATECTOMY (RRP) Chauveau Philippe», Barre Christian, Picard Herve, Saint Sebastien Sur Loire, France INTRODUCTION AND OBJECTIVE: Preservation of potency is a major concern for many patients, considering the choice of treatment for localized prostate cancer. We analyzed the potency rate and a variety of factors determined before and after NSRRP to identify those significantly associated with recovery of potency. METHODS: Between 1990 and 2000, 605 patients underwent RRP; of those, 200 consecutive potent patients were selected for NS : bilateral (87%), unilateral (13% ). Mean age was 61.7 (95% CI : 60.9 to 62.5 CI), mean P.S.A. 10.48 (95 % CI : 9.3 to 1.6), clinical stage: Tl (41%) T2 (59%), Gleason score: 2 to 6 (81%) 7 to 8 (19%). Erectile function (EF) was evaluated preoperatively: all patients were able to achieve intercourse, with normal erectile function (82%) or moderate erectile dysfunction (ED) (18%). Post operative erectile function was assessed every 3 months for 2 year. At 12, 18, 24 post operative months, patients available for assessment were respectively 195, 182, 157. Only patients who achieved unassisted intercourse were considered potent. Univariate and multivariate regression analysis was used to determine factors independently predictive of % potent 24 months after NSRRP. RESULTS: Mean duration of potency recovery was 13.3 (95% CI : 12.1 to 14.5) months: potency rates were respectively 38 % (95% CI: 31.3 to 45 ), 56 % (95% CI : 48.8 to 63.3), 70 % (95% CI : 62.9 to 77.2) at 12, 18, 24 months. Pre operative EF was independently predictive of potency recovery at 24 months : normal EF (n = 136) : 77 % potent vs moderate ED (n = 21) : 29 % potent (p < 0,001). Extent of NS was less significant: bilateral NS (n = 130) : 75 % potent vs unilateral NS (n = 27) : 48 % potent (p < 0,05). Gleason score (p = 0.08), age (p = 0.11), clinical and pathological stages (p = 0.22) and PSA level (p = 0.65) were not identified as independent prognostic factors. CONCLUSIONS: In this study, the most significant factors affecting post operative potency were pre-operative erectile function and extent of NS. As age was not significant, potent patients over 65 should be considered eligible for NSRRP if bilateral NS could be performed safely. Source of Funding: None.

1652 PROSTATE CANCER TUMOR VOLUME DOES CORRELATE WITH DIAGNOSTIC AND PSA RECURRENCE Judd W Moul*, Lionel Banez, Leon Sun, Hongyu Wu, David G McLeod, Bethesda, MD; Isabell A Sesterhenn, Fk Mostofi, Washington, DC; Michelle Zhao, Jack Chang, Bethesda, MD INTRODUCTION AND OBJECTIVE: In 2002, Stamey and colleagues reported that PSA at diagnosis was unrelated to prostate cancer volume in the common prostate cancer screening range of 2- 10 ng/m!. This was based on the large Stanford University whole-mounted prostatectomy study and was a damnation of the value of PSA test to screen and prognosticate for the disease in the now common range of clinical use. This study was mainly to confirm or refuse this finding using the DoD Center for Prostate Disease Research!Armed Forces Institute of Pathology whole mounted study ongoing since 1993. METHODS: 207 radical prostatectomy (RP) cases diagnosed between 1993 and 2000 were used. The specimens were step-sliced 2.25 mm thick and wholemounted. Sections at 5 fJ,ffi thickness were prepared from the slices. Tumor area and number in the sections were assessed. The sections were digitally scanned, and stacked up to form 3-dimensional reconstructed specimens. PSA recurrence was defined as post-treatment PSA > 0.4 ng/m!. Minimal follow-up was> 1.5 years. The association among tumor profile, race, diagnostic PSA, pathological Gleason sum and PSA recurrence were characterized.

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RESULTS: The median of total tumor volume, largest tumor volume and tumor number was 1.67 ern", 1.30 em" and 3, respectively. Tumor number ranged between 1-8 with 75% of specimens having 1-5 tumors. Significant correlation (p < 0.0001) were also found between tumor volume and diagnostic PSA level (1.43 ern" in PSA 4-10 ng/ml group, 2.55 crrr' in PSA 10.1 - 20 ng/ml group, and 3.28 ern" in PSA > 20 ng/ml). A significant correlation between tumor volume and PSA was found (p = 0.009), when PSA was defined as a continuous variable with range between 2 - 10 ng/ml. Tumor volume was significantly associated pathological Gleason sum (GS) (0.23 em" in GS < 5 group, 1.47 ern" in GS >5 and <=7, and 3.0 em:' in GS >7, P = 0.0008). Tumor volume in non-organ confined and organ confined disease was significantly different (2.02 crrr' vs 0.93 crrr', p < 0.0001). 3-and 5-year PSA recurrence free survival for groups of tumor volume < 1, 1-3 and> 3 ern" were 6.6 vs 13.6%, 11.0 vs 16.3% and 25.8 vs 36.2%, respectively (p=0.002). CONCLUSIONS: Unlike the Stamey et al experience, our data shows that diagnostic PSA is correlated with tumor volume. In addition, PSA recurrence is associated with tumor volume. The results indicate PSA' s clinical utility as a general surrogate for tumor volume. Source of Funding: U.S. Department of Defense and the Henry M. Jackson Foundation for the Advancement of Military Medicine.

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Kaplan·Meier 10·Yr Rates

Hazard Ratios Propensity Adjusted

WW

RT

RP

All Deaths

82%

75%

54%

CASpe· cific

65%

43%

25%

Covariate Adjusted

Propensity & Covariate Ad· justed

RT

RP

RT

RP

RT

RP

0.69 0.49, 096 0.60 0.36, 0.99

030 019, 0.48 0.27 0.14, 051

0.71 0.51, 099 0.62 0.37, 1.02

0.36 0.23, 0.56 0.41 0.22, 0.75

0.70 0.50, 0.99 0.63 0.38, 1.05

0.32 0.20, 051 0.32 017, 0.61

Source of Funding: None.

1655 PRESERVATION OF FECAL CONTINENCE AND BOWEL FUNCTION AFTER RADICAL PERINEAL AND RETROPUBIC PROSTATECTOMY: A QUESTIONNAIRE-BASED OUTCOMES STUDY Howard J Korman*, Timothy Mulholland, Ray R Huang, Royal Oak, MI

1653 RATE OF CONTINENCE RECOVERY OVER TIME AFTER LAPAROSCOPIC RADICAL PROSTATECTOMY Soroush A Ramin*, Mark H Kawachi, Laura E Crocitto, Timothy G Wilson, Duarte, CA INTRODUCTION AND OBJECTIVE: It has been reported that about 85% of men are continent at one year after laparoscopic radical prostatectomy. The rate of return of continence at three months (defined as zero to one pad usage per day) following open radical retropubic prostatectomy is 54%. This rate increases to 82% with Walsh's new technique of bladder neck intussusception. The rate of return of continence over time, after laparoscopic prostatectomy, has not been reported. We report this rate in men with at least 12 months of follow up after laparoscopic radical prostatectomy. METHODS: From October 1, 2001 to October I, 2002 III men with clinically confined prostate cancer, underwent laparoscopic radical prostatectomy, bilateral pelvic lymphadenectomy at a single U.S. institution. Age of patients ranged from 49 to 83. All procedures were performed through the same intra-peritoneal and bladder neck sparing technique by three surgeons. Number of pad usage per day was recorded at the one, three, six, nine, and 12 months follow up periods. Full return of continence was defined as zero pad usage. RESULTS: Follow up data was available for 98(88%) of patients. At One month after surgery, 36%, 28%, 20%, and 16% of patients were using zero, one, two to four, and five or greater pads respectively. At three months post-operatively, 64%, 11%, 14%, and 10% wore zero, one, two to four, and five or greater pads per day respectively. At the three month mark 75% of patients wore zero to one pad per day. At six months, 74%, 16%,9%,0% were using zero, one, two to four, and five or greater pads respectively. By the ninth month of follow up, 80%, 13%, 6%, and 0% of patients required zero, one, two to four, and five or greater pads per day. At the one year mark 95% wore no pads at all, while 4% required one pad, and one patient required 3 pads per day. CONCLUSIONS: Full recovery of continence (zero pads) after laparoscopic radical prostatectomy and bilateral pelvic lymphadenectomy should be expected in 75% of patients by the sixth month and 95% of patients by 12 months. Severe incontinence is very rare by the sixth month following laparoscopic prostatectomy. Complete return of continence following laparoscopic radical prostatectomy is very rapid and comparable to open radical retropubic prostatectomy. Source of Funding: None.

1654 DETERMINANTS OF LONG TERM SURVIVAL IN PATIENTS WITH CLINICALLY LOCALIZED HIGH GRADE CANCER: A PROPENSITY RISK APPROACH Ashutosh Tewari*, James Peabody, Mazen Hasan, Mani Menon, Detroit, MI INTRODUCTION AND OBJECTIVE: High grade cancers are very aggressive cancers and treatment is difficult. We wanted to study impact of various baseline factors on ultimate survival of the patients with high grade cancer. We took a propensity risk modeling approach and computed the impact of various factors on overall survival in 500 patients with high-grade cancer. METHODS: We established a cohort of 5000 patients who underwent treatment for prostate cancer at Henry Ford Hospital. Of these 500 had high-grade cancer. We captured data on confounding factors and long-term survival. The modeling results are as follows: RESULTS: As is seen in the table, the RP (radical Prostatectomy) patients had 30% reduction in overall survival and 37% reduction in cancer specific survival. CONCLUSIONS: Significant survival advantage can be obtained in patients with high grade cancer. *Presenting author.

INTRODUCTION AND OBJECTIVE: It has been suggested that the development of fecal incontinence and bowel dysfunction may be more common after radical perineal prostatectomy than retropubic prostatectomy. The objective was to compare the preservation of fecal continence and bowel function after radical perineal and retropubic prostatectomy using an age matched control group. METHODS: The bowel habits section of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire was sent to 150 consecutive radical prostatectomy patients: 79 perineal and 71 retropubic. Questionnaires were also sent to 75 age matched controls who were undergoing PSA screening for prostate cancer. All patients had the same surgeon (HK). Questionnaire issues included uncontrolled fecal leakage, character and quantity of bowel movements and bowel symptoms. The Exact test was used for statistical significance. RESULTS: For all three study groups 85% of questionnaires were returned: Perineal- 67/79, Retropubic 60/71, Control 63/75. Patient ages were not statistically different (p=0.16): Perineal 60.4(42-74), Retropubic 63.1(32-75), Control 60.9(39-75). There was no statistical difference in fecal incontinence rates (p=0.80): Perineal- 6%(4/67), Retropubic-6.7%(4/60), Control- 4.8%(3/63). The distribution of rectal urgency symptoms (p= 0.65) and overall degree of bowel problems (p=0.59) was also not statistically different for the 3 groups. CONCLUSIONS: In this same surgeon, questionnaire study, there was no statistical difference in preservation of fecal continence or bowel function for patients undergoing radical prostatectomy regardless of surgical approach. Furthermore there was no statistical difference between post-prostatectomy patients and age-matched controls in the study population. Prostatectomy patients should be counseled accordingly as to the likelihood of postoperative bowel problems. Rectal Urgency and Bowel Problems Perineal (N-67)

Retropubic (N=60)

Control (N=63)

Rectal Urgency (p=O.65) Never Weekly Daily

53(79%) 8(12%) 6(9%)

46(77%) 10(16%) 4(7%)

53(84%) 6(10%) 4(6%)

Bowel Problems(p=O.59) None Very Small Small Moderate/Large

49(73%) 12(18%) 5(8%) 1(1%)

40(67%) 11(18%) 7(12%) 2(3%)

45(71%) 11(17%) 6(10%) 1(2%)

Source of Funding: None.

1656 POSITIVE SURGICAL MARGINS IN LAPAROSCOPIC RADICAL PROSTATECTOMY: THE IMPACT OF APICAL DISSECTION, BLADDER NECK REMODELING AND NERVE PRESERVATION Ran Katz*, Jerusalem, Israel; Laurent Salomon, crteil, France; Andras Homek, Alexandre De La Taille, Patrick Antiphon, Claude C Abbou, Creteil, France INTRODUCTION AND OBJECTIVE: To assess the incidence and location of positive surgical margins in a consecutive series of patients who underwent laparoscopic radical prostatectomy. METHODS: Between May 1998 and September 2001,235 men underwent laparoscopic radical prostatectomy in our institution. During this period, modifications were made in the technique. Between 99 and 2000 we stopped

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preserving the puboprostatic ligaments. Between 2000 and 2001, we stopped preserving the bladder neck. Therefore, we have divided the patients to three groups: 1998 to 1999, 2000 and 2001. We have compared the incidence of apical and bladder neck margins before and after changing the surgical technique. Nerve sparing status was documented by the surgeon at the end of surgery and its' effect on the incidence of lateral positive margins was evaluated. In order to concentrate on the surgically induced margins, this study focused on pT2 patients. RESULTS: There were 169 pT2 patients and 32 (18.9%) positive margins locations. A constant decrease was noted in the overall incidence of positive margins, but while in 1998 apical margins were the most abundant, in 2001 posterolateral margins were the most abundant. Avoiding bladder neck preservation eliminated positive bladder neck margins in 2001. The overall incidence of positive lateral surgical margins in pT2 patients undergoing a nerve sparing procedure was 8.4%. CONCLUSIONS: The experience gained in this procedure led to a decrease in the incidence of positive margins. Wide resection of the bladder neck and cutting the puboprostatic ligaments decreased bladder neck and apical positive margins. Nerve preservation did not increase the incidence of positive margins. These technical modifications may improve the outcome of laparoscopic radical prostatectomy patients. Source of Funding: None.

1657 PATIENT REPORTED SEXUAL FUNCTION FOLLOWING LAPAROSCOPIC RADICAL PROSTATECTOMY Ran Katz*, Jerusalem, Israel; Laurent Salomon, Andras Hoznek, Alexandre De La Taille, Dimitrios Vordos, Antony Cicco, Claude C Abbou, Creteil, France INTRODUCTION AND OBJECTIVE: This study was aimed to evaluate the sexual function of patients who underwent laparoscopic radical prostatectomy. We assessed the effect of unilateral or bilateral preservation of the neurovascular bundle on their ability to achieve erections and have sexual intercourse post operatively. METHODS: Between May 1998 and September 2001, 232 men underwent laparoscopic radical prostatectomy for localized prostate cancer in our institution. Sexual function questionnaires were given to the patients preoperatively. The study included 143 patients who were potent pre operatively. After the procedure the operator noted whether he performed unilateral, bilateral or no nerve sparing. Sexual function questionnaires were collected at I, 3, 6, and 12 months after surgery. RESULTS: Out of 143 patients, 100,80,48 and 26 patients responded at 1, 3, 6 and 12 months respectively. In the non nerve sparing group, 1, 3, 6, and 12 months after surgery 11.7%, 11.1%, 16.6% and 30% of the patients respectively reported having erections. In the unilateral nerve sparing group, 20%, 35%, 41.6% and 50% respectively reported spontaneous erections. In the bilateral nerve sparing group, 32.5%, 41.1 %, 29.1 % and 87.5% respectively reported spontaneous erections. The overall incidence of positive lateral surgical margins in pT2 patients undergoing a nerve sparing procedure was 8.4%. CONCLUSIONS: The overall rate of patients who had erections preoperatively and maintained their erections after the surgery (53.8%) is comparable to the results in open surgery. Patients with bilateral preservation did better than patients with unilateral preservation. Our preliminary results show a promising rate of potency at one year after laparoscopic radical prostatectomy. Source of Funding: None.

1658 RADICAL PROSTATECTOMY: RETROPUBIC VS. LAPAROSCOPIC VS. PERINEAL Kapil Puri*, Gilberto Ruiz-Deya, Raju Thomas, Rodney Davis, New Orleans, LA INTRODUCTION AND OBJECTIVE: Radical Prostatectomy is the treatment of choice recommended by urologists for localized curative adenocarcinoma of the prostate. However, quality of life issues are increasingly a concern and dictate therapeutic choices. With three approaches now available for radical prostatectomy, there is often debate as to the advantages of each approach. METHODS: Twenty-five consecutive patients undergoing radical retropubic, laparoscopic and perineal prostatectomy were evaluated for technical factors, immediate postoperative outcomes, and long-term quality of life results. RESULTS: See table. CONCLUSIONS: RPP is favored when it comes to operative time, postoperative pain, back to work, hospital stay, etc. However, few residency programs teach this procedure. RLP, with its steep learning curve, may not be readily acceptable in mainstream practice. RRP will continue to be the workhorse.

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Retropubic (RRPI Laparoscoplc (RLPI Avg. Operative Time 129 minutes 282 minutes Avg. Hospital Stay 52 hours 47 hours Avg. Blood Loss 400cc 685cc Return to Normal Activity 18days 32days Catheter Duration 9 days 8 days Incontinence in 1yr 5% 12% Potency In1yr (Nerve 61% Sparing Age, Gleason scores and pathologic stages were comparable.

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Perineal (RPPI 106 minutes 16hours

350cc 16days 8 days

5.3% 41%

Source of Funding: None.

1659 INTRAOPERATIVE, PERIOPERATIVE, AND POSTOPERATIVE COMPLICATIONS FOLLOWING OPEN RADICAL RETROPUBIC PROSTATECTOMY (RRP) Herbert Lepor*, Ledia Kaci, New York, NY INTRODUCTION AND OBJECTIVE: To examine surgical outcomes following open RRP in a contemporary large series. METHODS: Between October 2000-August 2002, 500 men underwent RRP by a single surgeon (HL). Baseline characteristics, intraoperative, perioperative (in hospital), and postoperative (date of discharge through postoperative day (POD)#30) complications and surgical outcomes were prospectively recorded in real time and entered into a FileMaker database. The data was analyzed using JMP software program. Baseline outcomes and complications were evaluable for all 500 cases. RESULTS: The mean age was 58.8 years (range: 41 to 74). The percentage of men with preoperative clinical stages T l a/b> TIc, T2' and T3 was 0.6%, 86.2%, 13.0%, and 0.2%, respectively. The preoperative Gleason score was 2-4 in 0.4%, 5-6 in 74.6%,7 in 22.0% and 8-10 in 3.0%. The mean surgical time (ST) (incision to surgical dressing) for all cases was 143 minutes. In the 334 cases who underwent only a RRP, the mean ST was 119 minutes (range 63 to 180). 90.4% and 98.8% were discharged by POD #2 or POD #3, respectively. There were no deaths. The only intraoperative complication was a single urethral injury (0.2%). The perioperative complications included bleeding requiring reoperation(0.6%), myocardial infarction (0.2%), pneumonia (0.4%), prolonged ileus (0.4%), wound seroma (0.2%), and placement of a suprapubic tube after disoriented patient pulled out urinary catheter (0.2%). The postoperative complications included acute urinary retention (5.4%), clot urinary retention (1.2%), wound seroma/infection (1.0%), MI (0.4%), and DVT (0.4%). Positive surgical margins were observed in 7.8% of cases. 82.0% and 10.8% of men preoperatively received erythropoietin or donated autologous blood, respectively. The allogeneic transfusion rate was 5.6%. CONCLUSIONS: In the modern era, experienced surgeons can perform open RRP with no operative Or postoperative mortality. The surgical procedure can be performed quickly, with 99.8% and 98.6% of cases experiencing no intraoperative or perioperative complications, respectively. Postoperative complications are also sporadic and typically managed without sequelae. Open RRP is associated with a short hospital stay. The ultimate role of laparoscopic radical prostatectomy must be measured against contemporary experiences with open RRP. Source of Funding: None.

1660 EXTRAPERITONEAL ROBOTIC PROSTATECTOMY: COMPARISON OF TECHNIQUE AND RESULTS AT ONE INSTITUTION George Dakwar, Mutahar Ahmed*, Newark, NJ; Ihor Sawczuk, Jay Rosen, Vincient Lanteri, Micheal Esposito, Hackensack, NJ INTRODUCTION AND OBJECTIVE: This is an in-depth analysis of the robot-assisted prostatectomy (RAP) at our institution. We also make comparisons of our results of the transperitoneal approach versus the extraperitoneal approach to the prostate. METHODS: In a 14 month period, 45 RAP were performed at our institution, 36 of which were performed through the transperitoneal approach and 9 through the extraperitoneal approach. The mean age of the 45 patients was 58.1 years with an average PSA of 6.2 and Gleason score of 6. The parameters including time of surgery, complications, conversions, blood loss, surgical pathology, hospital length of stay, post-operative foley catheter removal and post-operative return to regular diet were analyzed retrospectively. Comparisons were made between the last 9 transperitoneal RAP and the last 9 extraperitoneal RAP. RESULTS: The average time for the 45 RAP, from first incision to final closure, was 413 minutes. The last 9 transperitoneal averaged 436 minutes and the last 9 extraperitoneal averaged 378 minutes. Average estimated blood loss for the 45 RAP was 476cc blood loss. The last 9 transperitoneal RAP averaged blood loss of 286cc and the extraperitoneal RAP 306cc. Of the 45 RAP, 7 (15.6%) had to be converted due to various reasons. Of the last 9 transperitoneal and the last 9 extraperitoneal RAP, none had to be converted. Of the 45 total RAP, 13 (29%) were found to have tumor positive margins according to the pathology reports. The

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last 9 extraperitoneal RAP found I (11.1 %) positive margin. The hospital stay was found to be an average of 3.11 days for the total group. For the last 9 transperitoneal, it was found to be an average of 2.6 days. For the last 9 extraperitoneal, hospital stay was an average of 1.7 days. For the 45 RAP, the average post-operative time for foley catheter removal had been 8.7 days. For the last 9 transperitoneal, the foley catheter was removed on average of 7.2 days after the RAP. For the last 9 extraperitoneal, the foley catheter was removed on average of 5.8 days after the RAP. For the 45 RAP, the post-operative regular diet was resumed on an average of 2.5 days. For the 9 transperitoneal, diet resumed on average by 2.1 days and for the extraperitoneal, by 1.3 days. CONCLUSIONS: Our data shows that the improving results are proportional with the increasing number of cases. Our data also strongly suggests that the extraperitoneal approach has a more favorable profile when compared to its transperitoneal counterpart. Source of Funding: None.

1661 VALIDATION OF THE KATTAN PRE-TREATMENT NOMOGRAM IN COMMUNITY PATIENTS UNDERGOING RADICAL PROSTATECTOMY: RESULTS FROM CAPSURE Gary D Grossfeld, Eric P Elkin, David J Pasta, Deborah P Lubeck, San Francisco, CA; Michael W Kattan, New York, NY; Shilpa S Mehta, Lake Forest, IL; Peter R Carroll*, San Francisco, CA INTRODUCTION AND OBJECTIVE: In 1998 Kattan and colleagues published a nomogram to predict recurrence in patients undergoing radical prostatectomy using pre-treatment disease characteristics. The nomogram has enjoyed widespread use and is accessible via the Internet. The purpose of this study was to determine performance of the nomogram in community patients undergoing prostatectomy, and to revise and potentially simplify the nomogram based on data from these patients. METHODS: Clinical data from 1,701 radical prostatectomy patients in the CaPSURE database (a longitudinal community-based disease registry of patients with prostate cancer) were used. Disease recurrence was defined as PSA 0.2 ng/ml or greater on 2 consecutive occasions following prostatectomy or a second cancer treatment at least 6 months after surgery. Nomogram predicted probabilities of disease recurrence were compared with actual outcomes using a concordance index. Cox proportional hazards analysis was performed to determine the optimal use of pre-treatment PSA, biopsy Gleason score, clinical tumor stage and percent positive prostate biopsies. RESULTS: Disease recurred in 24% of patients. The nomogram was accurate in CaPSURE patients with a concordance index of 0.68. The nomogram tended to overestimate recurrence in patients with a high predicted probability of recurrence. We considered several alternative transformations of PSA and concluded that a piecewise linear function, with changes in slope at 10 and 20 ng/ml, is a simple form that captures most of the information about survival. An investigation of Gleason score resulted in three categories: no pattern 4-5, Gleason 1-3/4-5, and Gleason 4-5/1-5. Clinical T-stage was not statistically significant and was replaced with percent positive biopsies using the following categories: less than 33%, 33-49% and 50% or greater. The concordance index for the final form of the model is 0.71. CONCLUSIONS: The Kattan preoperative nomogram performed well in CaPSURE patients undergoing radical prostatectomy. Changes in how PSA and Gleason are scored and the use of percent positive biopsies in place of clinical stage simplify the nomogram and appear to maintain or improve performance in community-based patients. Source of Funding: TAP Pharmaceutical Products, Inc.

1662 WEEKLY DOCETAXEL AND MITOXANTRONE PRIOR TO PROSTATECTOMY IN PATIENTS WITH HIGH RISK LOCALIZED PROSTATE CANCER Tomasz M Beer*, Mark Garzotto, Bruce A Lowe, Portland, OR; William J Ellis, Paul H Lange, Seattle, WA; Michelle A Montalto, Portland, OR; Celestia Higano, Seattle, WA INTRODUCTION AND OBJECTIVE: While combined modality therapy has improved survival in high-risk breast and colon cancer, this approach has been sparsely investigated in the management of prostate cancer. Docetaxel and mitoxantrone have substantial single-agent activity in advanced prostate cancer but have not been combined in this disease. We report the development of a new regimen that combines these drugs in high-risk patients undergoing prostatectomy. METHODS: Patients with high-risk localized prostate cancer (cT2b or T3a or PSA > 15 ng/ml or Gleason grade > 4+ 3) received four 28-day cycles of chemotherapy administered as 3 weekly doses followed by a I week break prior to prostatectomy. No prior or concurrent hormonal therapy was allowed. Docetaxel is given at 35 mg/m2 while mitoxantrone was escalated from a starting dose of 2 mg/m2 up to a planned ceiling dose of 6 mg/m2 in increments of I mg/m2. Dexamethasone 4 mg po is given 12 hr and I hr prior to and 12 hr after treatment. *Presenting author.

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RESULTS: 29 patients were enrolled to date. The MID of mitoxantrone in this combination was reached at 4 mg/m2 and phase II treatment continues at this dose level. 21 patients completed chemotherapy and surgery while 8 are currently on treatment. Grade 3/4 toxicity seen in more than I patient to date includes: abdominal pain - 2, hyperglycemia - 7, neutropenia - 20, diarrhea - 4. Efficacy data is reported for the 19 patients who received at least I cycle of chemotherapy before surgery. PSA changes observed were: reduction (median 40%, range 9% - 88%) in 18 patients and stable PSA in I patient. Negative surgical margins were achieved in 13 of 19 (68%) patients and a postoperative PSA was < 0.2 ng/ml in 12 of 17 (71%) of patients (post-surgery PSA is not yet available in 2). No change in testosterone was seen (p=0.34, n=19). CONCLUSIONS: Weekly docetaxel and mitoxantrone is a well-tolerated regimen in the treatment of high risk prostate cancer prior to prostatectomy. Direct anti-tumor activity of this regimen is suggested by PSA reductions in the absence of change in testosterone levels. Source of Funding: Amgen, 031.G0008; Aventis, GIA US16080.

1663 MAXIMUM TUMOR DIAMETER IS A SIMPLE AND VALUABLE INDEX OF DISEASE AGGRESSIVENESS IN LOCALIZED PROSTATE CANCER Ryuichi Mizuno*, Jun Nakashima, Makio Mukai, Ken Nakagawa, Mototsugu Oya, Ken Marumo, Masaru Murai, Tokyo, Japan INTRODUCTION AND OBJECTIVE: Tumor volume has been considered to reflect tumor aggressiveness in prostate cancer. It is, however, too difficult and time consuming to determine tumor volume in routine pathological practice. The present study was undertaken to investigate whether the maximum tumor diameter (MTD) and the maximum tumor area (MTA) correlate with total tumor volume (TTV) and pathological features of tumor aggressiveness and whether these simple estimates of tumor size can replace tumor volume to predict tumor aggressiveness in clinically localized prostate cancer. METHODS: Serial whole mount sections from 164 patients with clinically localized prostate cancer who underwent radical prostatectomy without neoadjuvant treatment were analyzed. RESULTS: Pathologically, 110 patients (67.1 %) had organ confined disease and 54 (32.9 %) demonstrated extraprostatic extension. The MID, MTA and TTY ranged from 0.46 to 4.83 em (2.04±0.07), from 0.10 to 10.92 cm2 (1.80 ±0.12) and from 0.05 to 33.30 cm3 (3.96 ±0.34), respectively. The MID, MTA and TTY significantly correlate with each other and with Gleason score. The MID, MTA and TTY of prostate cancers with microvascular invasion (2.41±O.l3 ern, 2.42 ±0.27 cm2, 5.62±0.82 cm3), with perineural invasion (2.25±0.08 em, 2.03 ±O.l4 cm2, 4.66±0.41 crn3) and with extraprostatic extension (2.53±0.11 em, 2.50 ±0.24 cm2, 5.94±0.74 cm3) were significantly greater than those without microvascular invasion (1.91 ±0.08 ern, 1.56 ±0.12 cm2, 3.33 ±0.33 cm3), without perineural invasion (1.49 ±O.ll em, 1.16 ±0.19 cm2, 2.35 ±0.54 cm3) and without extraprostatic extension (1.81 ±0.08 ern, 1.45 ±O.l2 cm2, 2.99 ±0.31 cm3), respectively. Multivariate stepwise logistic regression analysis demonstrated that MTD, Gleason score, microvascular invasion and perineural invasion (p=0.0217) were significant independent parameters associated with extraprostatic extension. CONCLUSIONS: The maximum tumor diameter of prostate cancer, which is a simple and readily obtainable estimate of tumor size, is a significant index of tumor aggressiveness and can replace tumor volume measurement. Source of Funding: None.

1664 PERCENT OF BIOPSY CORES WITH CANCER IS A SIGNIFICANT INDEPENDENT PREDICTOR OF PSA FAILURE AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE Stephen J Freedland*, William J Aronson, Los Angeles, CA; Martha K Terris, Augusta, GA; Christopher J Kane, San Franscisco, CA; Christopher LAmling, San Diego, CA; Frederick Dorey, Los Angeles, CA; Joseph C Presti, Palo Alto, CA INTRODUCTION AND OBJECTIVE: Prior studies suggested that the percent of prostate biopsy cores positive is a significant predictor of outcome among men undergoing radical prostatectomy (RP) or radiation therapy for prostate cancer. We sought to evaluate if either percent of cores with cancer or percent of cores positive from the most and least involved side of the biopsy was associated with a worse outcome after RP. METHODS: A retrospective survey of 1,094 men from the SEARCH Database treated with RP between 1988 and 2002 was performed. We used multivariate analysis to examine if total percent of cores with cancer, percent of cores positive from each side of the prostate, and other clinical variables were significant predictors of adverse pathology and PSA failure after RP. RESULTS: On multivariate analysis, PSA and percent of cores positive were significant predictors of positive margins, nonorgan-confined disease, and seminal vesicle invasion. Percent of cores positive (p
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Gleason score (p=0.014) were all significant independent predictors of PSA failure. On a separate multivariate analysis that included the variables of total percent of cores positive, percent of cores positive from the most involved side of the biopsy, percent of cores positive from the least involved side of the biopsy, and whether the biopsy was positive unilaterally or bilaterally, only the percent of cores positive from the most involved side of the biopsy was a significant independent predictor of PSA failure following RP. Percent of cores positive was used to separate patients into a low-risk «34%), intermediate-risk (34-50%), and highrisk (>50%) group, which provided significant pre-operative risk stratification for PSA failure after RP (p50% can be used to risk stratify patients prior to RP. The finding that percent of cores positive from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome. Source of Funding: Department of Veterans Affairs and a Center for Prostate Disease Research (CPDR) grant from the United States Army Medical Research and Material Command.

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improved treatment outcomes. However, limited data on the consequences of this shift are available from contemporary, parallel series. We have compared treatment outcomes with pretreatment tumor burden (in terms of clinical stage and prostatespecific antigen [PSA} level) in patients treated with curative intent (radical prostatectomy [RP} or radiotherapy [RTJ) in the 3 trials that comprise the bicalutamide ('Casodex') Early Prostate Cancer program. METHODS: A total of 5824 patients with T1-4NxMO prostate cancer were treated with curative intent (4454 RP, 1370 RT) in Trial 23 (North America), Trial 24 (Europe/South Africa/Israel/AustralialMexico) or Trial 25 (Scandinavia). RESULTS: Median pretreatment PSA levels were lowest and the percentage of patients with T1-2 disease was highest in the North American trial. Objective and PSA progression rates across all 3 trials were related to both the pretreatment disease stage and pretreatment PSA level (Table I). This relationship was independent of randomized therapy (bicalutarnide 150 mg or placebo), although in all 3 trials bicalutarnide 150 mg significantlyreduced the risk of objective and PSA progression. CONCLUSIONS: Results of this international, contemporary, comparative series re-confirm the disease stage shift occurring in North America. The lower clinical tumor burden in North American patients was associated with a marked reduction in the risk of disease recurrence following therapy of curative intent. However, therapy of curative intent alone may not be sufficient in patients with a higher tumor burden. 'Casodex' is a trademark of the AstraZeneca group of companies. Table 1

1665 RELATIONSHIP OF BIOCHEMICAL OUTCOME TO PERCENT POSITIVE PROSTATE BIOPSIES IN CLINICALLY LOCALIZED PROSTATE CANCER TREATED WITH PERMANENT INTERSTITIAL BRACHYTHERAPY Richard Lee, Brian M Levin", Yanlin Wang, Jesse Berlin, Richard Whittington, S Bruce Malkowicz; Philadelphia, PA INTRODUCTION AND OBJECTIVE: Recent studies have demonstrated that the percent of positive prostate needle biopsy cores can predict biochemical outcome after radical prostatectomy or external beam radiotherapy. Conclusive corresponding data for permanent interstitial brachytherapy however are lacking. We have conducted an analysis to determine the clinical utility of the percent of positive prostate biopsies (PPB) in predicting PSA outcome following interstitial brachytherapy for prostate cancer. METHODS: Of 360 patients, a total of 127 with clinical T1cff2cNXMO prostate adenocarcinoma underwent transperineal permanent prostate brachytherapy from January 1992 to November 2001. Percent of positive biopsies was recorded for each patient, as were age, PSA, Gleason score, and number of seeds. Patients were stratified into low, intermediate, and high risk groups based on percent of positive biopsies «34%, 34-50%, >50%). Followup was calculated from date of implant; biochemical disease-free survival was designated according to the ASTRO consensus definition. The relationship between risk of biochemical failure and biopsy category was calculated using logistic regression models. Time-to-failure was assessed by fitting Cox proportional hazards models and using Kaplan-Meier estimates. RESULTS: Percent of positive biopsies was positively but not significantly associated with risk of failure (p=0.64). Gleason score was strongly associated with risk of failure (p=0.002) as were clinical stage, age, and preimplant PSA (p=O.OI, 0.02, and 0.0002 respectively). Interestingly, the number of implanted seeds was inversely related to risk of failure (p=0.009). In time-to-failure models, age was positively but not significantly associated with outcome. PSA and Gleason score remained significantly associated with time to failure (hazard ratios 1.08 and 4.03, p=O.OOI and 0.01 respectively). CONCLUSIONS: Our results suggest that the percent of PPB is positively but not significantly associated with biochemical outcome for patients undergoing permanent interstitial brachytherapy. Gleason score, preimplant PSA, and age were significant predictors of biochemical failure; the first two were also significant in predicting time to failure. Our data suggest that the ability to aggressively treat and dose-escalate the periprostatic region with interstitial brachytherapy may obviate the clinical utility of percentage of PPB in predicting biochemical failure. Source of Funding: None.

1666 INTERNATIONAL DIFFERENCES IN PROSTATE CANCER TREATMENT OUTCOMES CORRELATE WITH CLINICAL STAGE AND PRETREATMENT PROSTATE-SPECIFIC ANTIGEN LEVEL: RESULTS OF AN ONGOING, PROSPECTIVE, INTERNATIONAL TRIAL PROGRAM William A See*, Milwaukee , WI; Manfred P Wirth, Dresden, Germany; David G McLeod, Washington DC, WA; Peter Iversen, Copenhagen, Denmark INTRODUCTION AND OBJECTIVE: Patients with prostate cancer are presenting at an earlier disease stage than in the past, particularly in North America. Relative to historical data, the shift in disease stage appears to be associated with

Trial 23(n=2647)

RP Trial 24(n=1648)

Trial 25(n=159)

Trial 23(n=645)

RT Trial 24{n=660)

Pretreatment tumorcharacterisUcs % with11-2 35.2 63.2 66.4 55.8 98.0 disease' Median PSA 10.4 14.4 8.1 16.2 69 level(nglml) Progression events (across bothrandomized!realment groups) % wRh objective 14.5 9.2 14.3 4.2 9.2 progression %wRh PSA 18.7 46.4 21.0 24.4 20.0 progression 'Disease stage was determined pathologically inthe RPgroup and clinically intheRTgroup

Trial 25(n=65)

36.9 29.4

40.4 61.6

Source of Funding: AstraZeneca.

1667 TRANSURETHRAL RESECTION COMBINED WITH HIGH INTENSITY FOCUSED ULTRASOUND (HIFU): INCREASED EFFECTIVITY AND DECREASED SIDE EFFECTS IN THE TREATMENT OF LOCALIZED PROSTATE CANCER Christian G Chaussy*, Stefan Thueroff, Hans-Juergen Kiel, Muenchen, Germany INTRODUCTION AND OBJECTIVE: Transrectal HIFU has shown its efficacy regarding negative follow up biopsy rate, PSA Nadir and stability.Postoperative necrotic debris of the coagulated adenoma caused frequently postoperative side effects as obstruction and infection inducing urgency and incontinence symptoms. In this study the impact of neoadjuvant TURP on patients postoperative morbidity is evaluated. METHODS: Inclusion criteria: patients with histological proven PCa, T1-2, Nx-NO,MO,not feasible for surgery, treated with HIFU at 3 MHz and 5 sec lesions were included. Prospective analysis of 289 patients, 51,6% (n= 149) only HIFU-, 48,4% (n= 140) treated with HIFU + neoadjuvant TURP of the adenoma as one treatment. Treatment strategies, -parameters and side effect rate were analysed. RESULTS: In patients with combined treatment,resection weight was 012gr (282gr, chips cancer free in 54%). In both groups, HIFU dose (median of 570 lesions (153-1072) ) and total treatment time (0165min/0168min) were similar. Urethral catheter were removed within 24 hours.Suprapubic catheter remained 035 days in HIFU and 08 days in HIFU +TURP cases. Incontinencesymptoms were reduced from 14,8%without TURP to 5,0% with TURP. Infectionrate decreased similar from 38,3% to 13,6%.IPSS (score: 0-35) after HIFU showed to be lower with the combined TURP (median score: 2/35) than without (median score: 5/35). CONCLUSIONS: HIFU +TURP as combination treatment in one session proved to be favourable. Arguments against this combination therapy as higher invasiveness or longer hospitalisation have to be balanced against better adaptation of every prostate size to HIFU penetration depth with identical overall treatment.Shorter suprapubic catheter time, lower infection-, incontinence- and morbidity rate are additive arguments for this high-tech urological treatment. Postoperative percourse of combined treated HIFU +TURP patients showed similar as after a classical TURP. Source of Funding: Funding by EDAP Technomed and Hospital.

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AN EVALUATION OF GENISTEINS ABILITY TO LOWER PSA IN PATIENTS WITH PROSTATE CANCER Ralph W Devere

TECHNIQUE FOR LAPAROSCOPIC RUNNING URETHRO· VESICAL ANASTOMOSIS: THE SINGLE KNOT METHOD

White*, Sacramento, CA; Robert M Hackman, Davis, CA; Stephanie E Soares, Sacramento, CA; Laurel A Beckett. Davis, CA

Thomas E Ahlering*, Orange, CA; Roland F Van Yelthoven, Brussels, Belgium; Douglas W Skarecky, Ralph V Clayman, Orange, CA

INTRODUCTION AND OBJECTIVE: To determine whether supplemental amounts of a polysaccharideloligosaccharide complex obtained from a soy extr act, Genistein Concentrated Polysacch aride (GCP), would lower PSA in patients with histologically proven prostate cancer (CaP). This extract has been widely used as part of complementary medical therapy for various cancers in Japan , Korea and other parts of Asia. This clinical trial was initiated based on studies performed in Japan and at the University of Californi a, Davis suggesting that GCP has anticancer properties such as increased apoptosis of cancer cells and anti-angi ogenic effects . METHODS : 62 men with hist ol o gi cally proven CaP who had 2 consec utively elevated PSA results and had not planned any additional therapy for 6 months were accrued to the study . As of July 2002, 49 men had completed their 6 months of study. These men were patients on either active surveillance or who had undergone radical prostatectom y, radiation therapy or hormonal therapy . The GCP was taken in capsular form at a dose of 5 gmlday. PSA were obtained at 0, 3, and 6 months. RESULT S: Interium analysis showed 49 of the 62 men accrued to study had completed their 6 month PSA as of July 2002. Of the 49 men, 45% (22149) increased their PSA greater than 50% over baseline . Ninete en men (39%) had a PSA increase from 1-25%. Two men (4%) had no change in their PSA. Of the 49 men, 9 were on active surveillance for their CaP. Six of the 9 active surveillance patients had a decrease in their 6 month PSA below baseline with the maximum decrease being 19%. CONCLUSIONS: I) Overall, the results were disappointing in the 49 patients tested. 2) Patients on active surveillance may do better due to stage of disease or distributi on of genistein within the prostate. 3) Based on the results of the patients on active surveillance, future study is warranted. Source of Funding: Amino Up Chemical Co., Ltd.

INTRODUCTION AND OBJECTIVE : Herein, we describe a technique for facilitating the urethrove sical anastomosis at the time of laparoscopic radical prostatectomy. METHODS : Two 6-inch polyglycolic acid sutures (one dyed, one white) are tied together at their tail ends and delivered into the operative field via a 12 mm port. A running suture is completed from 6:30 to 12:00 o'clock and from 5:30 to 12:00 o' cloc k, at the end of which a single intracorporeal tie is completed . The catheter is placed prior to complet ing the anterior row of sutures; the catheter is left in place for 5-7 days . RESULTS: This anastomoti c technique has been employed in 1221aparoscopic RP and 8 robot assisted LRPs. The average time for the anastomosis has been 35 minutes (range 14-67 minutes). All anastomoses were watertight. There have been no symptomatic postoperative urinary leaks. There have been no clinical bladder neck contractures. CONCLUSIONS: We describ e a simple watertight running laparosc opic technique for accomplishing the urethr ovesical anastomosis during a laparoscopic radical prostatectomy. Source of Funding: None .

1669 VISUAL ESTIMATE OF PROSTATE CANCER PREDICTS RECURRENCE AFTER RADICAL PROSTATECTOMY M Manoharan », Francisco Civantos, Sandy S Kim, Mark S Soloway, Miami, FL INTRODUCTION AND OBJECTIVE: Tum or volume is an important prognosti cator in predicting pro state cance r recurrence following radi cal prostatectomy (RP). Several methods have been described to calculate the tumor volume in the RP specimen. Visual estimate of percentage of carcinoma (VEPC) is an established method to describe the tumor volume. The purpose of the study is to assess the ability of VEPC to predict recurren ce. METHODS: 1048 men underwent radical pro statectomy by one surge on (M.S.S.) between 1992 and 2002. One path ologist (F. c.) using the diagram for prostate sectioning published by L. True reviewed 78% of the RP specimen s and est ima ted by camera lucida the percent of cut surface occupied by can cer. Step sections of 2 to 3 mm were per formed on the entire specimen. Pati ent s, who had less than 12 months foll ow up, salvage RRP and percent of carci noma not assessed o n the patholo gy specimen were excluded from the study . VEP C and other clinical variables including patient ' s age, PSA , clini cal stage , Gleason score, adj uva nt and neo adj uvant therapy, lymph node statu s, extra prostat ic extensio n (EPE), seminal vesicl e involvement and surgical margins were analyzed. Quartile cut- off points were produ ced for continuous vari ables such as age, initial PSA, and VEPC. We per formed Kaplan -Meier log-rank test to determ ine whether the above variable s can predi ct biochemical recurrence in univariate analysis. Multi vari ate analysis using Cox ' s proportional hazard s regression was perfo rmed. To accou nt for dif feren ces that might bia s the co mparison we adjus ted for the hazard- ratio estimates for all the variables used in the uni variate analysis. RES ULTS: 699 patients met the criteria for this analysis. Mean age of the patients was 61.4 ::':: 14.6 years. Mean follow up was 54.9 ::':: 29.4 months (range 12.0-123.4). 17.7% of the patients had a biochemical recurrence, PSA 2:0.4 . The mean VEPC was 25.6% in the recurren ce group and 12.5% in the non-recurrence group. All variables in univariate analysis were significant predictors for recurrence except for age. However, multivariate analysis using Cox's proportional hazard s regression model showed that, the only significant predictors of recurrence were EPE, Glea son score and VEPC. The hazard ratio for VEPC was 1.64, p=. 016, 95% C.I (1.10, 2.45). CONCLUSIONS: VEPC is a simple and inexpensive method, which provides important prognostic information by predict ing recurrence in patients who undergo RP. Source of Funding: None . *Prescnting author.

1671 ANALYSIS OF POSITIVE MARGINS DURING RADICAL PERINEAL PROSTATECTOMY Timothy L Mulholland *, Royal Oak, MI; Michael J Harris, Traverse City, MI INTRODUCTION AND OBJECTI VE: Tumor-free margins of resection and biochemi cal (PSA) free recurren ce are important parameters to compare the effectiveness of various methods of radical prostatectomy. Radical perineal prostatectomy (RPP) is a minimally invasive treatment of prostate cancer that provides excellent surgi cal exposure and relatively short recove ry. Assessment of margins during RPP and biochem ical recurrence after RPP is undertaken to determine its effectiveness as a surgical treatment of prostate cancer. METHODS: We have analyzed prospect ive data of 508 consecutive RPPs. The 92 cases of margin positivity are analyzed for location, focality, biochemical recurrence, tumor volume, pre-biop sy PSA, and pathologic Gleason score. All patients with clinically localized prostate cancer choosing surgery were treated with RPP and no patients undergoing RPP for clinically localized prostate cancer were excluded from this study. Location of a solitary positive margin was noted as apical, anterior , posteriorlposterol ateral , bladder base or bladder neck. Multiple sites are nonfocal. A solitary margin was considered focal if the pathologist estimates it to be 0.2. RESULTS: Eighty percent of margin positive cases were solitary, while 19.6% of margin positive cases were multiple . Average prostate size and tumor size are 49gms and 9.4gms, respectively. Margins positive by site: Apex-5 .1% (26; 19 focal,7 nonfocal) , Anterior-3 % (15; 14 focal, I nonfocal), Bladder neck-2.6 % (13; 5 focal, 8 nonfocal ), Bladder base-2.6% (7 focal, 6 nonfocal), Posterior-I.4% (7; 6 focal, I nonfocal), Multiple-3 .5% (18 nonfocal) and Total-18 .1% (92; 51 focal, 41 nonfocal). Biochemical evidence of disease is noted in 2 1% and 39% of the focal and nonfocal cases , respectively. CONCLUSIONS: A solitary apical margin is the most common source of a positi ve margin in our series of RPP , occurring in 5.1% of our patients . Multiple positive margins are next most common at 3.5%. Multiple sites, non-focal bladder neck and posterior bladder wall margin positive cases recurred at higher rates than focal margins positive . Focal margins positive are associated with much better biochemical freedom from disease than non-focal margins positi ve cases. Radical perineal prostatectom y is an effective method of removing prostate cancer . Source of Funding: None.

1672 INTRA OPERA TIVE PREPLANNING IMPROVES IMPLANT QUALITY AND BIOCHEMICAL DISEASE-FREE SURVIVAL IN PATIENTS TREATED WITH PERMANENT PROSTATE BRACHYTHERAPY Ronald D Ennis", Cheng-Shi Wuu, Darlene Vecchio, Tian Liu, Richard M Gewanter, Aaron E Katz, New York, NY INTRODUCTION AND OBJECTIVE: The classical "Seattle " permanent prostate brachytherapy approach is to perform a preplan prior to the implant using preprocedure ultrasound images. We have previously reported our change to an intraoperative preplanning technique in which the planning and implantation are performed in one OR session. In addition , we later adopted a dosimetric-driven urethral sparing technique to repl ace the modified uniform loading approach. In this study we analyze the impact of the se changes on implant quality, biochemical relapse and toxicity.

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METHODS: The first 103 patien ts to have undergone permanent pros tate brachytherapy without extern al beam RT at our institution were analyzed . Preplan 44 , inrraop plan 59. Modified uniform loading 58, urethral sparing 45. Stage cTlc 77, cT2a 14, cT2b 10, cT2c 1,1'21. PSA :s 10 94, > 10 9. Gleason 2-6, 94; 7, 4; 8, I , NOS I. Androgen deprivation 35. 1-125 5 1, Pd-10 3 52. Biochemi cal disease free survival (BDFS) as defined by ASTRO. Kaplan-M eier and Cox regression for univariate and multivariate survival analyses. Chi-square for ordinal factors. Median flu 25 mos. RESULTS: Overall 4- year BDFS is 89 (=3)%. Intr aoperative preplann ing resulted in improved 3-year BDFS compared with pre operati ve prepl annin g 98 (=2)% vs. 8 1 (=7) % (p =0.02) . Multivari ate analysis including clin ical stage, Gle ason , PS A, case number (as a surroga te for experien ce) and intra op plann ing techni que , only intraop planning was a sig nifica nt predictor of BDFS (p =0.02 5). Post- impl ant analys es revealed superior impl ants with the intraoperative plann ing techn ique . The percentage of the prescript ion dose delivered to 90% of the pro state as see n on the post-implant CT (% 090) increased to 85% fro m 75% (p <0.0 1). Th e per centage volume of the postimplant CT prostate cov ered by the prescription dose increased to 8 1% from 76% (p <0.05). Urethr al sparing resulted in non-sgnifican t trends toward decreased toxicity. For ex maple, chronic GU toxicity 2': grade 2 was decreased to 35% from 53% with modified uniform loading (p=O.I). Potency is preserved (with or wothout sildenafil) in 72 %. CONCLUSIONS: In our experience, intrao perative preplanning results in excellent 3-year biochmeical disease-free survival and is associated with superior result s when compared with standard pre operative planning. Source of Funding: Non e.

1673 PROSTATE CANCER GENE THERAPY: PRELIMINARY CLINICAL AND PRE-CLINICAL RESULTS Richard Rm Van der Linden s, Chris H Bangma, Robert Kraai}, Bart L Haagmans, Ab Dme Osterhaus, Rotterdam, Netherlands INTROD UCTION AND OBJECTIVE: Six patien ts with localised prostate cancer and at risk for capsular penetration were treated in an outpa tient setting with neoadjuv ant pre-radi cal pro st ate ct om y ge ne th er ap y . After intrap ro st at ic application of the aden oviru s vector AdS-RSV-tk, 1.10 9 or 1.10 10 IU, ganciclovir infusio n was given twice daily for two weeks and pati ent s had a radica l prostatectom y on day 21. Previous st udies have show n a predom inant T lymph ocytic infiltration at the site of vec tor administr ation. To further char acterise the syste mic and local immunological res ponse against the Ad5 vec tor, techniques were set up to detect adeno viru s speci fic T cells. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from healthy blood donors and patient s receiving gene therapy, at regular intervals during treatment. Antigen presenting cell s were generated using Epstein Barr virus transformation of B cells (BLCL) . T cell lines were generated from biopsy material obtained after the radical prostatectomy using allogeneic lymphocyte stimulation in the presence of IL-2 and mitogen. Interferon gamma (IPN -')') expression was analysed using ELISA , ELlS POT and intracellular FACS analysis. Paraffin embedded prostate sections of the gene therapy patients and a control prostate cancer patient, were stained for T -, B lymphocytes, Natural Killer cells and macrophages. RESULTS : PBMC from healthy don or s were infected with Ad5-CMV-EGFP virus . Expansion of adenovirus speci fic lymphocyte s wa s demonstrated by prol iferation, IPN- ')' ELISA and ELISPOT assay . Furth erm ore, using intracellular staining and FACS analysis, T cell lines generated from PBM C stimulated with Ad5-RSV-tk were shown to contain both CD 4 + and CD8+ T cell s able to produ ce IPN-')' upon stimulation with Ad5 -CM V-EGFP infec ted BLCL. Infe ction of these cells was co nfirmed by FACS anal ysis, sugges ting the reco gniti on of newly synthesis ed ade novi ral protei ns. T lymp hocyte infiltration increased in stained sections of the gene therapy pro stat es co mpared to the control prostate s. The infiltrated regions co ntained mor e B lymph ocytes and macrophages in gene thera py pati ent s co mpared to the controls. CONCLUSIONS: Adeno virus specific cytotoxic CD8+ T cells which recog nise AdS-CMV-EGFP infected cells can be detected in healthy subjects and T cell lines generated from patients using adenovirus infected BLCL. The presence of these cells and the increased T -, B lymphoc yte and macrophage infiltration may impede the efficacy of gene therapy in prostate cancer patients receiving Ad5-RSV-tk. Source of Funding: Dutch Can cer Society.

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METHODS: Ninety-four patient s with cli nica lly organ confined prostate ca ncer and a med ian age of 60.3 years under went RPP between 111 /01 and 02/3 1102 and were prospectively enrolled w ith follow -up data available for 84 subj ects at 6, and 72 at 9, and 50 pat ients at 12 month s. respe ctively. Using a valida ted assess ment tool, the ex panded prostate cance r index composite (EPIC), patient s were evaluated pre operati vely, and then pos toperatively using mailed surveys at I month and subseq uently 3 month s interval s. Th e results of the retu rned surveys were entered into a dedi cated database and analyzed using co mme rcia lly available softwa re. RES ULTS: The percen tage of pat ients repo rting any form of stoo l leakage (defi ned as other than rarely/ne ver ) prior to surgery was 12.2% and significantly increase d to 23.6% (p =0.04 7) by 4 wee ks after RPP . By 3 and 6 mo nths the percentages of pati ent s reporting stoo l leakage were 19.0% and 12.0%, whic h did not represent significant incre ase s co mpared to baseline (p>0.05) . Th e percent age of patients perce iving stoo l co ntrol as a problem was 2.2% at baseline and not sig nificantly increased at 5 .6%, 4 .8%, and 3.6% after I, 3, and 6 mon ths, respectively. Painful bowel movement s was the most prevalent and longest persisting symptom after RPP , with an incidence of 16.8% after I month (co mpared to 1.1% preoperatively) and 9.6% after 3 months (p=O.OOI). After 6 month s the percentage of patients complainin g of pain with defecation had returne d to baseline levels (1.1 %). The average health related quality of life summary score for the domain bowel wa s signi ficantly decreased 1 month after RPP (85.6:: 1.4) co mpare d to baseline (9 1.7= 1.0)(p =0.001), yet not significantly different after 3 mo nths or at any later po int in time (p >0.05) . CON CLUSIONS: RPP does not result in new onset fecal incontinence. While bowel related symptoms and complaints appear to be more frequent in the early postoperative phase, they are transien t and have a minor impact on the patients' perceived quality of life. A significant percent age of RPP candidates appear to have compromised fecal continence at baseline. Th is issue should be investiga ted further. So ur ce of Funding: No ne .

1675 BIOCHEMICAL RELAPSE FOLLOWING RADICAL PROSTATECTOMY ACCORDING TO MARGIN STATUS AND GLEASON SCORE Jean-Baptiste Lattouf* , Fred Saad, Montreal, QC, Canada INTRODUCTION Ai'lD OBJECTIVE : Ma ny studies report poo r prognosis related to positi ve mar gin s on radica l prostatectom y (RP) specimen s for prostate adenocarcinoma . However, few reports exam ine the progno stic va lue of uni- focal ver sus multi-focal positi ve margins. To co mpare biochemical relapse in uni -focal microsopicall y positi ve margins with relapse in negati ve and mult i-focal positive margins respectively. Al so, outcom e with respect to Gleason sco res in these categories was evaluated. METHODS: We reviewed radical prostatectomy cases done for pros tate ade nocarcinoma between October 1989 and February 2001 in one institutio n. Positive margins were defined as neopl astic tissue in contact with ink . Four hundred eleven patients (411) satis fied inclusio n crit eria. RESULTS: Of the 411 pati ent s, 287 had negative margins (70%), 54 had uni -focal positiv e margins (13%), and 70 had multifocal positive mar gin s (17%) . Patients with negati ve margins had bioche mical relap se at I , 5 and 10 years follow -up of 8,3% , 21,6% and 23,6% respectively. Uni-focal posi tive margins had a relapse rate of 22.2%, 40 ,7% and 46,3% at I , 5 and 10 years follow-up respecti vely. Finall y, multi-focal positive mar gins had a relapse rate of 20% , 54,3 % and 57 ,1% at I , 5 and 10 years follow-up respec tively . With respect to Gleason scores of 5-6, 7 and 8- 10, negative marg ins had a relapse rate of 23 ,8% , 25% and 80% respectively. Focal margins had a relapse rate of 36 %, 6 1,5 % an d 40 % respect ively and multi -focal margins had a relapse rate of 45 %, 82% and 50% respect ively. CONCLUSIONS: Our results suggest that micro scopi call y pos itive margins behave more like gross ly positive than negative margins. Gleason scores 5-6 have a relatively good pro gnosis regardl ess of ma rgin status . However, Gleason score 7 has a significantly higher risk of relapse in patie nts wi th positive margin s. Adj uvant therapy followin g rad ical pro stat ectom y sho uld be based on mar gin status and Gleason score combined. Source of Funding: None .

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1676

RADICAL PERINEAL PROSTATECTOMY DOES NOT RESULT IN FECAL INCONTINENCE Philipp Dahm*, Ari D Silverstein, Alon Z

RECRUITMENT STRATEGIES IN A LARGE RANDOMIZED CLINICAL TRIAL FOR PROST ATE CANCER- PIVOT Timothy J

Weizer, Matthew D Young, Johannes Vieweg, David M Albala, David F Paulson, Durham, NC

Wilt*, Debra McKeehen, Minneapolis, MN; Michael K Brawer, Seattle; Karen Jones, Joseph F Collins, Perry Point, MD; Ie Vernon Netto, Mary Dalton, Hampton, 1-'4.; Antonio Mataban, Gena Nelson, Clarksburg, WV; Parikshit Pandya, Bridget Wiley, Temple, TX

INTRODUCTION AND OBJECTIVE: Fecal incontinence has been suggested to rep resent a frequent complication of radical perineal prostatectomy (RPP) . We report the findings of a prospective study using a validated patient-administered questionn aire to evaluate the inciden ce of bowel related symptoms and relat ed qual ity of life follo wing RPP .

INTRODUCTION AND OBJECTI VE : The Prostate cancer Int ervent ion Versu s Observation Trial (PIVOT) is the largest randomized trial to study treatment with surgery ver sus watchful wa iting for the treatment of clinically

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localized prostate cancer, Recruitment began in November, 1994 and was finished in January, 2002. Several recruitment strategies were utilized to accomplish this goal. METHODS: Men were recruited to PIVOT from 44 VA Medical Centers and 8 National Cancer Institute sites. Patients with newly diagnosed clinically localized prostate cancer diagnosed within 12 months, a negative bone scan, who were <75 years old, and without serious co-morbidities were considered for enrollment. The core of recruitment was conducted by the participating investigators (PIs) one-onone with the patients. Initially, an educational and recruitment video was used by the PIs and study coordinators to assist with the informed consent process. This was later supplemented by a color brochure that patients could take home to discuss with their families. An informational website was also established to provide general information and referral contacts for the PIVOT stndy. RESULTS: A total of 12, 980 men were identified with newly diagnosed prostate cancer at the 52 recruitment sites. Of these, 4,279 men were eligible for enrollment. A total of 731 men ultimately consented to participate in PIVOT. Patients who declined enrollment were compared with men that enrolled were similar with respect to baseline patient and tumor characteristics, including age, race, co-morbid conditions, PSA, histologic grade, and their self-rated health status. Most men declined to enroll because they were not willing to participate in research (13%), not willing to leave decision for treatment to chance (68%), or faced family opposition to their participation (14%). CONCLUSIONS: Enhancing enrollment in randomized trials of prostate cancer treatment requires addressing concerns of patients about leaving cancer treatment decisions to chance. Different recruitment strategies and tools were necessary to accomplish successful recruitment in PIVOT. The greatest obstacle was that many men did not want to be randomized into one of two very different treatment modes, and often had pre-decided what their treatment preferences. Source of Funding: Department of Veterans Affairs/ National Cancer Institute/ Agency for Healthcare Research and Quality.

1677 VALIDITY OF REPEAT PROSTATIC BIOPSIES IN UNTREATED PATIENTS WITH LOCALIZED PROSTATE CANCER Phillip L Ross*, Andrew J Stephenson, Armen G Aprikian, Louis R Begin, Luis Souhami, Avrum I Jacobson, Simon Tanguay, Montreal, PQ, Canada INTRODUCTION AND OBJECTIVE: Early detection of prostate cancer has lead to a stage migration that may contribute to increased detection of insignificant prostate cancer. Many patients will consider watchful waiting as a way to delay treatment. The safety of observation is based mainly on clinical assessment of PSA measurements and digital rectal examination. The objective of this study was to evaluate the utility of PSA and repeat systematic prostate biopsy as reliable markers of prostate cancer progression in patients who elected for watchful waiting. METHODS: A prospective cohort of 104 patients with localized prostate cancer was followed expectantly with serial PSA measurements and digital rectal examination. Repeat systematic prostate biopsies were offered to all patients on a yearly basis to evaluate tumor progression. RESULTS: 94 patients had follow up greater than 12 months with a minimum of 3 distinct PSA values, median follow up was 33 months. Twenty-seven percent of patients had a short doubling time of less than 48 months. Progression on repeat prostate biopsies or the presence of clinically significant cancers correlated with PSA doubling time of less than 120 months. Despite relatively long PSA doubling times, 53% of the re-biopsied patients had evidence of pathologic progression based either on increased tumor volume or worsening in Gleason grade. CONCLUSIONS: PSA doubling time less than 120 months correlated with disease progression. Standardized criteria for expectant management of localized prostate cancer are yet to be defined. Repeat prostatic biopsies may be a useful tool to help determine disease progression in patients with stable PSA. Source of Funding: None.

1678 TIME FROM CLINICAL DIAGNOSIS TO SURGERY AND RISK OF EXTRACAPSULAR DISEASE IN MEN WITH CLINICALLY LOCALIZED PROSTATE CANCER Vincent L Freeman*, Kenneth Campbell, Katie Gallagher, Kwan Hur, Hines, IL; Robert C Flanigan, Maywood,IL INTRODUCTION AND OBJECTIVE: Diagnosis of prostate cancer at a clinically localized stage provides an opportunity to evaluate interventions that may increase the likelihood of surgical cure. However, the interval between clinical diagnosis and treatment varies considerably, and extracapsular disease is often present at the time of surgery. This study evaluated the relation between length of time from clinical diagnosis to surgery and risk of extracapsular disease. METHODS: Date of clinical diagnosis, pathologic confirmation, treatments, surgical findings and other relevant data were ascertained from the medical records *Presenting author.

of 288 consecutive cases of surgically treated clinically localized prostate cancer. Logistic regression compared time from clinical diagnosis to treatment for extracapsular cases to that for organ-confined controls adjusted for age, clinical stage, biopsy Gleason sum (GS), pre-operative PSA and race. RESULTS: PSA, GS and clinical stage were significantly associated with extracapsular disease at time of surgery (p=0.00l-0.016), but time from clinical diagnosis to surgery was not (vs. < 60 days, RR = 1.08 (0.49, 2.40), 1.27 (0.48, 3.38), 0.99 (0.41, 2.35) for 60-119, 120-179 and >=180 days (180 to 2381, mean=540)), respectively, p=0.64 to 0.97). CONCLUSIONS: The window of opportunity for curative interventions following a diagnosis of clinically localized prostate is wide. Also, the pathologic stage determined at the time of surgery is likely the pathologic stage at clinical presentation. Source of Funding: Robert Wood Johnson Foundation (MMFDP 0033363); Department of Veterans Affairs, Health Services Research & Development Service (ARCD 97-317).

1679 AN EVALUATION OF THE DECREASING INCIDENCE OF POSITIVE SURGICAL MARGINS IN A LARGE RADICAL RETROPUBIC PROSTATECTOMY SERIES Misop Han*, David Y Chan, Alan W Partin, Baltimore, MD INTRODUCTION AND OBJECTIVE: Positive surgical margins adversely affect recurrence-free survival outcome following radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. We retrospectively reviewed a large institutional series of men who underwent RRP to define the change in incidence of organ-confined (OC) diseases and positive surgical margins (SM+) for the past two decades. METHODS: Between 1982 and 2001, 8,730 men underwent RRP for clinically localized prostate cancer (T I to T3a) at our institution. We compared the incidences of OC and SM+ in the pT3 disease (extraprostatic extension and/or seminal vesicle involvement) and the overall RRP population by the years of surgery. RESULTS: An increasing proportion of men presented with OC disease over time. The incidence of SM + in the overall RRP population decreased dramatically over time. However, the proportion of men with SM + was stable and consistently elevated in the pT3 disease population. CONCLUSIONS: Wide spread early detection programs for prostate cancer resulted in a downward stage migration in men presenting with clinically localized prostate cancer at our institution over the past two decades. Decreasing incidence of SM+ from the overall RRP population is probably due to a better patient selection as well as downward stage migration. The high percentage of SM+ among men with pT3 diseases dictates the need for continued evaluation of surgical technique and the need for effective rational adjuvant therapy. Number ofmen ('!o) with SM+ and OCin RRP forpT3 disease and overall population Years OC/Overall SM+/Overall SM+/pT3diseases

1982·86 153/428 (35.8%) 169/428 (39.5%) 142/245 (58.0%)

1987·91 1992-96 1997·2001 33411110 1363/2817 2995/4375 (30.1%) (48.4%) (68.5%) 236/1110 490/2817 (17.4%) 424/4375 (9.7%) (21.3%) 181/675 (26.8%) 423/1335 (31.7%) 361/1319 (27.4%)

Source of Funding: None.

1680 DISEASE-FREE SURVIVAL IN MEN AGE 60 YEARS OR YOUNGER AFTER RADICAL PROSTATECTOMY FOR LOCALIZED PROSTATE CANCER Charles J Rosser*, Houston, TX INTRODUCTION AND OBJECTIVE: Widespread use of the prostate-specific antigen (PSA) assay has led to an increased incidence of prostate cancer in recent years. Herein we set out to determine disease-free survival rates in patients < 60 years of age treated with surgery for localized prostate cancer. METHODS: We reviewed the medical records of 596 patients 60 years of age or younger who underwent radical prostatectomy as the sole primary treatment modality for prostate cancer. Follow-up PSA levels were measured 4-8 weeks after surgery and semiannually thereafter. Disease progression was defined as a detectable PSA or radiologic evidence of disease progression in follow-up. Median follow-up of the entire study group was 53 months. RESULTS: Seventy-nine percent of the patients presented with a serum PSA <10 ng/ml and 52% had a Gleason score of <7 on prostate biopsy. On wholemount examination, 70% of patients had organ-confined disease and 87% of specimens had a Gleason score of7. The 1-,5- and 7-yearbiochemical disease-free survival rates were 96, 87%, and 83%, respectively. Multivariate regression demonstrated that initial PSA, Gleason score on biopsy, Gleason score on specimen, and pathologic stage were predictive of biochemical failure.

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CONCLUSIONS: In the PSA era, men with prostate cancer who are 60 years of age or younger and treated with surgery have a favorable disease-free outcome. Our data suggest screening and surgery may help improve disease-specific mortality of prostate cancer. Source of Funding: None.

1681 A PELVIC DRAIN MAYBE AVOIDED AFTER RADICAL RETROPUBIC PROSTATECTOMY Mark S Soloway", Marc Savoie, Sandy SKim, M Manoharan, Miami, FL INTRODUCTION AND OBJECTIVE: We reassess the role of routine drainage of the pelvic cavity in the prevention of complications after radical retropubic prostatectomy (RRP). METHODS: A radical retropubic prostatectomy was performed on 95 consecutive patients with clinically localized adenocarcinoma of the prostate. Clinical and pathological information was recorded for each patient. After the prostate was removed and the anastomotic sutures tied, the bladder was filled with 100 ml. of saline through the urethral catheter. If there was no leakage a drain was not placed. RESULTS: We did not place a drain in 72% (68/95) of the patients. There was one post-operative complication. One of the patients without a drain developed a urinoma that required percutaneous placement of a drain on the second postoperative day. None of the 95 patients had an infection, Iymphocele, or hematoma. Five patients had urinary retention after catheter removal on days 9-11 which required catheter reinsertion for an additional week. None developed an anastomotic stricture. CONCLUSIONS: The morbidity ofRRP is low when performed by those who regularly perform this procedure. If the bladder neck is preserved or meticulously reconstructed there may be little or no extravasation and thus routine drainage may be unnecessary. We tested this hypothesis by omitting a pelvic drain when there was no extravasation. In properly selected cases, morbidity is not increased by omitting a drain from the pelvic cavity after RRP. Source of Funding: None.

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1683 CLINICAL RELEVANCE OF SYNCHRONOUS BLADDER CARCINOMAS IN RADICAL PROSTATECTOMY PATIENTS (N = 1,536) Viktor Beck, Dieter R Echtle*, Elisabeth M Mueller, Detlef H Frohneberg, Karlsruhe, Germany INTRODUCTION AND OBJECTIVE: The probability of synchronous carcinoma of the bladder occurring before a radical prostatectomy (RPX) is given at 1.2% to 3.8%. The goal of this retrospective study was to evaluate the clinical relevance of the early detection of a synchronous bladder tumor. METHODS: Since 1990, radical prostatectomies have been performed on 1,536 patients with regionally confined prostate carcinomas. A preoperative urethrocystoscopy was conducted on all 1,536 patients. The mean patient age was 67.5 years (48 to 80). RESULTS: In 31/1,536 (2.0%) of the patients, a bladder tumor was discovered. 18/31 (58%) patients showed in frozen section a pTa tumor. These patients underwent transurethral resectioning of the bladder tumor which was repeated at 6 weeks. The RPX was performed later (after TURB and temporary androgen blocking). In13/31 patients higher tumor stages were found: pTl G3 in 6/13 cases, pT2 G2-3 in 2/13, and 2: pT3 G3 in 5/13 patients. All these patients with invasive bladder cancer underwent a cystoprostatovesiculectomy as well. CONCLUSIONS: A routine urethrocystoscopy before RPX reveals bladder carcinoma in 2.0% of patients. In nearly 60% of the cases, the planned treatment of the prostate carcinoma is not changed by these findings. Among the other 40% of this patient group, the radical operation is expanded to include both organs. The strategy for pTa tumors is maintenance therapy, but pTI tumors and higher receive radical surgical treatment. An immediate parallel radical operation permits the implantation of an orthotopic, continent neobladder, which is often no longer advisable in later cases of cystectomy post RPX. Thus endoscopy of the lower urinary tract allows for the early stage-relevant treatment of synchronous bladder tumors. Source of Funding: None.

1682

Infertility: Evaluation Moderated Poster

DECISION-MAKING STRATEGIES AND DISTRESS AMONG PATIENTS WITH LOCALIZED PROSTATE CANCER Michael A Diefenbach", Cheltenham, PA; Robert GUzzo, Richard E Greenberg, Philadelphia, PA; Jenevie Dorsey, Christy Vass, Cheltenham, PA INTRODUCTION AND OBJECTIVE: Receiving a prostate cancer diagnosis is one of the most stressful situations in a man's life. Yet, a patient not only has to cope with the emotional impact of the diagnosis, but also needs to understand complicated and probabilistic medical information to make an informed treatment decision. The purpose of this study was to examine the clinical, psychological and social factors that influence a patient's treatment decision for localized prostate cancer. METHODS: Patients (N = 654) were recruited into the study after a treatment consultation with a urologic surgeon or radiation oncologist. Patients were Caucasian (91%) or African American (7%), married (85%), retired (58%). Approximately 52% of patients decided on external beam radiation, followed by brachytherapy (25%), prostatectomy (17%), and watchful waiting (6%). Patients were asked to complete a mail questionnaire that assessed clinical and psychological variables, as well as data about information sources. Acceptance rate of the study was high (72%). RESULTS: Physicians were by far the most important source of information to make an informed decision and patients made liberal use of second opinions. In addition to the diagnosing physician, almost 75% of patients consulted with at least 2 additional physicians (of those 35% consulted with three physicians) before making a treatment choice. Spouses (68%), children (40%) and friends (55%) played a large role as additional information sources. The Internet was used by almost half of the sample (45%) to obtain information. Compared to patients who chose radiation treatment, those opting for surgery were significantly more distressed about their treatment decision (p < .001), thought that prostate cancer was more serious (p < .00I), and concerned that cancer might spread in the future (p < .005). Despite elevated distress levels, surgical patients were significantly more convinced that surgery would provide a cure, compared to those patients choosing radiation treatment (p < .005). CONCLUSIONS: A patient's treatment decision is influenced by a variety of unique factors that go beyond the considerations of clinical pros and cons. Often illness specific beliefs and emotional reactions play an important role in decisionmaking. The influence of non-medical information sources can be substantial and might lead to inaccurate perceptions about disease and treatment. A greater awareness of how patients process and react to information might positively influence the patient-physician consultation. Source of Funding: National Cancer Institute: Department of Health of the State of Pennsylvania.

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1685 SPERM RETRIEVAL IN INFERTILE MEN WITH AZF DELETION Carin V Hopps*, Anna Mielnik, Marc Goldstein, Gianpiero D Palermo, Zev Rosenwaks, Peter N Schlegel, New York, NY INTRODUCTION AND OBJECTIVE: AZF deletions of the Y chromosome are associated with severe male factor infertility. We evaluated the characteristics of men with deletions, including the frequency with which intratesticular spermatozoa were found for men with deletions of AZF regions a, b, or c. These data provided prognostic information on the benefit of sperm retrieval techniques for these patients based upon specific Y chromosome microdeletion. METHODS: AZF deletions were detected by polymerase chain reaction of 30 sequence tagged sites within the long arm of the Y chromosome emphasizing the AZFa, band c regions. For men found to have a deletion, average sperm concentration on semen analysis and findings on diagnostic testis biopsy or outcome of testicular sperm extraction (TESE) were recorded. The presence of elongating spermatids on diagnostic biopsy or the finding of spermatozoa on attempted TESE was correlated with the specific AZF region deleted. RESULTS: A total of 78 men with AZF deletion were evaluated. The number of patients in each deletion group and those patients within each group to undergo TESE, diagnostic testis biopsy or neither surgical procedure are shown in the table. All men with AZFa, AZFb, AZFb+c and Yq deletions were azoospermic and had complete absence of spermatozoa on both TESE and diagnostic biopsy. Of men with isolated AZFc deletion, sperm were found in 75% (9/12) of those who underwent TESE and in 45% (9120) of those who underwent biopsy (56% overall). 64% (27/42) of men with AZFc deletion were azoospermic, and 36% (15/42) had severe oligospermia. A total of 7 patients with the entire AZFa region deleted and 23 patients with deletions that involved at least the entire AZFb region had azoospermia and no spermatozoa identified with TESE or biopsy. CONCLUSIONS: Men with microdeletions that included the AZFa or AZFb regions were azoospermic and did not have sperm identified on diagnostic biopsy or with TESE. Patients with isolated AZFc deletion had a 56% chance of surgical sperm retrieval overall (75% by TESE, 45% on biopsy), and 36% had sperm found within the ejaculate. Microdeletion of either the AZFa or AZFb regions of the Y chromosome portends an exceptionally poor prognosis for sperm retrieval, whereas the majority of men with AZFc deletion have sperm retrieved successfully for use in in vitro fertilization with intracytoplasmic sperm injection.