2
[standard deviation (SD) 0.5]. We did not observe any differences in PSA and ALP values respectively among the two groups. None of patients of group A com- plained for serious adverse effects after injection of zoledronic acid. Conclusions: Administration of zoledronic acid once annual is a safe and effective method in order to prevent bone loss in men with nonmetastatic prostate cancer treated with LHRH agonist. MP-08.13 Does saturation biopsy reliably predict unilateral prostate cancer in patients with low-risk tumours? Pushkar D 1 , Govorov A 1 , Kosko J 2 , Kovylina M 1 , Kurjiev M 1 , Bormotin A 1 1 MSMSU, Department of Urology, Mos- cow, Russia; 2 Newman Regional Health, Emporia KS, United States Introduction: The interest in focal treat- ments of prostatic carcinoma has in- creased significantly with the advent of image-guided tissue ablative techniques. The patients that would benefit most from focal ablative therapies are those with uni- lateral cancer. Some studies have sug- gested that unifocality in prostate cancer is more prevalent than was previously reported. The aim of our study was to determine whether initial saturation bi- opsy can reliably predict unilateral pros- tate cancer in patients with low-risk tu- mours. Methods: We retrospectively identified 168 men with unilateral low-risk prostate cancer (clinical stage T1c, PSA 10 ng/ ml, biopsy Gleason score 6 and 1 posi- tive core) detected by means of 8 – 24 cores transrectal ultrasound-guided biop- sies who subsequently underwent radical retropubic prostatectomy (RP) between June 2001 and May 2006. All specimens were examined for laterality with respect to the side of positive biopsy and number of cores. Results: Overall, unilateral prostate cancer was identified in 16.6% (n28/168) of pa- tients. The probability of ultimately finding unilateral tumour was significantly higher (p0.01) in patients with low-risk prostatic carcinoma diagnosed by initial biopsy from 18 and 24 cores (27%; n16/59) comparing with those whose biopsy was taken from 8 – 12 cores (11%; n12/109). Conclusion: Our data suggest that an 8 – 12 cores biopsy scheme does not allow ruling out prostate cancer on the con- tralateral side even in low-risk patients. Saturation biopsy as an initial strategy sig- nificantly (up to 34.6%) improves the pre- diction of unilateral cancer in these pa- tients, although its ability to predict in which patients a focal ablative therapy would eradicate all cancer remains insuffi- cient. Indeed, our data shows that 65% of low risk patients predicted to have unilat- eral cancer on 24 core saturation biopsy actually had bilateral disease. MP-08.14 Eradication of osteoblastic and osteolytic skeletal metastases of hormone refractory prostate cancer (mHRPC) after treatment with pegylated trispecific disulfide linked Fv (sdFv) targeting epitopes of EGFR, PTHrP and RANKL conjugated covalently with SATA to vinorelbine tartrate Giannios J 1 , Alexandropulos N 2 , Michailakis E 3 1 Department.of Oncology, ACR; 2 Deptart- ment of Biopathology, IH; 3 Department of Oncology, Athens, Greece Introduction: HRPC related bone metas- tases are often osteoblastic on radio- graphs, yet osteolysis is seen microscopi- cally. Bone metastasis is a common complication of HRPC, and one for which only palliative treatment is available. We aim to inhibit the vicous cycle between tumor cells and the bone microenviron- ments, which results in enhanced tumor burden and bone destruction. Methods: HRPC cells obtained from a metastatic patient were inoculated into the left cardia ventricle of nude mice. Af- ter osteoclastic and osteoblastic metasta- ses were observed radiographicaly, the mice were treated with pegylated trispe- cific disulfide linked Fv(sdFv) targeting epitopes of PTHrP, RANKL and EGFR con- jugated covalently with SATA to vinorel- bine. Results: Post-treatment, we observed inhi- bition of HRPC cells, tumor associated endothelial cells and bone microvascular endothelial cells. Downregulation of EGFR led to inhibition of expression of AP1 blocking transcription of VEGF, and its receptors KDR and Flt-1 exerting an an- giocidal effect. EGFR downregulation led to reduced activity of osteoclasts, and in- hibition of PI3K,MAPK and MMP-9.Down- regulation of PTHrP and RANKL inhibited osteoclastogenesis , and proliferation of stromal/osteoblastic cells. Subsequently, release of growth factors TGF-a and IGF from the bone matrix was blocked. Vi- norelbine destabilised microtubule dynam- ics of tumor and endothelial cells block- ing cell cycle at G2/M.It also phosphorylated bcl-2 blocking uPAR and SP1 DNA binding activity through ERK signalling pathway. This led to inhibition of osteoblast proliferation by inhibiting hydrolysis of IGF-binding proteins, and downregulation of MMP-1,3,9.We ob- served antibody dependent cellular toxic- ity, and antibody mediated phagocytosis. In HRPC cells, tumor associated and bone derived endothelial cells, we observed inhibition of DNA synthesis, and meta- bolic activity by BrdU and MTT analysis. Transmission electron microscopy exhib- ited nuclear PCD type III with pyknosis, and zeiosis leading to secondary necrosis. Type I PCD which is caspase-3 depen- dent, and autophagic type II PCD led to a bystander killing effect of tumor and en- dothelial cells. Finally, there was not ra- diographic evidence of osteolytic and scle- rotic bone metastases of HRPC cells. Conclusion: This novel strategy may pro- vide a new therapeutic approach leading to the inhibition of the dominant molecu- lar processes involved in bone metastases caused by HRPC cells. MP-08.15 Low dose-rate brachytherapy with I125 in patients with local prostate cancer relapse after radical prostatectomy Veiga FG 1 , Ponce J 1 , Castelo LA 1 , Romero E 1 , Marin ˜o A 2 , Candal A 2 , Veiras C 2 , Janeiro J 1 , Lo ´pez D 1 , Gonza ´lez Martı ´n M 1 Urology Department, Juan Canalejo Hos- pital, Centro Oncolo ´gico de Galicia, La Corun ˜a, Spain Introduction & Objectives: Treatment for patients with biochemical progression after radical prostatectomy (RP) and suspi- cious of local relapse usually consists of external radiotherapy. This a valid option, Table 1. MP-08.13: The probability of unilateral prostate cancer after RP depending on scheme of initial biopsy No of biopsy cores 8 10 12 18 24 No of patients 28 42 39 33 26 Total n 109 Total n 59 Unilateral cancer after RP 2 5 5 7 9 No of patients 7.1% 11.9% 12.8% 21.2% 34.6% Total n 12 (11%) Total n 16 (27.1%) MODERATED POSTER SESSIONS UROLOGY 70 (Supplment 3A), September 2007 81

MP-08.15: Low dose-rate brachytherapy with I125 in patients with local prostate cancer relapse after radical prostatectomy

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[standard deviation (SD) �0.5]. We didnot observe any differences in PSA andALP values respectively among the twogroups. None of patients of group A com-plained for serious adverse effects afterinjection of zoledronic acid.Conclusions: Administration ofzoledronic acid once annual is a safe andeffective method in order to prevent boneloss in men with nonmetastatic prostatecancer treated with LHRH agonist.

MP-08.13Does saturation biopsy reliablypredict unilateral prostate cancer inpatients with low-risk tumours?Pushkar D1, Govorov A1, Kosko J2,Kovylina M1, Kurjiev M1, Bormotin A1

1MSMSU, Department of Urology, Mos-cow, Russia; 2Newman Regional Health,Emporia KS, United States

Introduction: The interest in focal treat-ments of prostatic carcinoma has in-creased significantly with the advent ofimage-guided tissue ablative techniques.The patients that would benefit most fromfocal ablative therapies are those with uni-lateral cancer. Some studies have sug-gested that unifocality in prostate canceris more prevalent than was previouslyreported. The aim of our study was todetermine whether initial saturation bi-opsy can reliably predict unilateral pros-tate cancer in patients with low-risk tu-mours.Methods: We retrospectively identified168 men with unilateral low-risk prostatecancer (clinical stage T1c, PSA � 10 ng/ml, biopsy Gleason score � 6 and 1 posi-tive core) detected by means of 8 – 24cores transrectal ultrasound-guided biop-sies who subsequently underwent radicalretropubic prostatectomy (RP) betweenJune 2001 and May 2006. All specimenswere examined for laterality with respectto the side of positive biopsy and numberof cores.Results: Overall, unilateral prostate cancerwas identified in 16.6% (n�28/168) of pa-tients. The probability of ultimately findingunilateral tumour was significantly higher(p�0.01) in patients with low-risk prostatic

carcinoma diagnosed by initial biopsy from18 and 24 cores (27%; n�16/59) comparingwith those whose biopsy was taken from 8– 12 cores (11%; n�12/109).Conclusion: Our data suggest that an 8 –12 cores biopsy scheme does not allowruling out prostate cancer on the con-tralateral side even in low-risk patients.Saturation biopsy as an initial strategy sig-nificantly (up to 34.6%) improves the pre-diction of unilateral cancer in these pa-tients, although its ability to predict inwhich patients a focal ablative therapywould eradicate all cancer remains insuffi-cient. Indeed, our data shows that 65% oflow risk patients predicted to have unilat-eral cancer on 24 core saturation biopsyactually had bilateral disease.

MP-08.14Eradication of osteoblastic andosteolytic skeletal metastases ofhormone refractory prostate cancer(mHRPC) after treatment withpegylated trispecific disulfide linkedFv (sdFv) targeting epitopes of EGFR,PTHrP and RANKL conjugatedcovalently with SATA to vinorelbinetartrateGiannios J1, Alexandropulos N2,Michailakis E3

1Department.of Oncology, ACR; 2Deptart-ment of Biopathology, IH; 3Departmentof Oncology, Athens, Greece

Introduction: HRPC related bone metas-tases are often osteoblastic on radio-graphs, yet osteolysis is seen microscopi-cally. Bone metastasis is a commoncomplication of HRPC, and one for whichonly palliative treatment is available. Weaim to inhibit the vicous cycle betweentumor cells and the bone microenviron-ments, which results in enhanced tumorburden and bone destruction.Methods: HRPC cells obtained from ametastatic patient were inoculated intothe left cardia ventricle of nude mice. Af-ter osteoclastic and osteoblastic metasta-ses were observed radiographicaly, themice were treated with pegylated trispe-cific disulfide linked Fv(sdFv) targetingepitopes of PTHrP, RANKL and EGFR con-

jugated covalently with SATA to vinorel-bine.Results: Post-treatment, we observed inhi-bition of HRPC cells, tumor associatedendothelial cells and bone microvascularendothelial cells. Downregulation of EGFRled to inhibition of expression of AP1blocking transcription of VEGF, and itsreceptors KDR and Flt-1 exerting an an-giocidal effect. EGFR downregulation ledto reduced activity of osteoclasts, and in-hibition of PI3K,MAPK and MMP-9.Down-regulation of PTHrP and RANKL inhibitedosteoclastogenesis , and proliferation ofstromal/osteoblastic cells. Subsequently,release of growth factors TGF-a and IGFfrom the bone matrix was blocked. Vi-norelbine destabilised microtubule dynam-ics of tumor and endothelial cells block-ing cell cycle at G2/M.It alsophosphorylated bcl-2 blocking uPAR andSP1 DNA binding activity through ERKsignalling pathway. This led to inhibitionof osteoblast proliferation by inhibitinghydrolysis of IGF-binding proteins, anddownregulation of MMP-1,3,9.We ob-served antibody dependent cellular toxic-ity, and antibody mediated phagocytosis.In HRPC cells, tumor associated and bonederived endothelial cells, we observedinhibition of DNA synthesis, and meta-bolic activity by BrdU and MTT analysis.Transmission electron microscopy exhib-ited nuclear PCD type III with pyknosis,and zeiosis leading to secondary necrosis.Type I PCD which is caspase-3 depen-dent, and autophagic type II PCD led to abystander killing effect of tumor and en-dothelial cells. Finally, there was not ra-diographic evidence of osteolytic and scle-rotic bone metastases of HRPC cells.Conclusion: This novel strategy may pro-vide a new therapeutic approach leadingto the inhibition of the dominant molecu-lar processes involved in bone metastasescaused by HRPC cells.

MP-08.15Low dose-rate brachytherapy withI125 in patients with local prostatecancer relapse after radicalprostatectomyVeiga FG1, Ponce J1, Castelo LA1, RomeroE1, Marino A2, Candal A2, Veiras C2,Janeiro J1, Lopez D1, Gonzalez Martın M1

Urology Department, Juan Canalejo Hos-pital, Centro Oncologico de Galicia, LaCoruna, Spain

Introduction & Objectives: Treatmentfor patients with biochemical progressionafter radical prostatectomy (RP) and suspi-cious of local relapse usually consists ofexternal radiotherapy. This a valid option,

Table 1. MP-08.13: The probability of unilateral prostate cancer after RP depending on schemeof initial biopsy

No of biopsy cores 8 10 12 18 24No of patients 28 42 39 33 26

Total n � 109 Total n � 59Unilateral cancer after RP 2 5 5 7 9No of patients 7.1% 11.9% 12.8% 21.2% 34.6%

Total n � 12 (11%) Total n � 16 (27.1%)

MODERATED POSTER SESSIONS

UROLOGY 70 (Supplment 3A), September 2007 81

but not exempt of complications, andhigher difficulty to adjust dose and treat-ment area. Low dose-rate prostatic brachy-therapy is actually an alternative optionfor patients with localized prostate can-cer. We present our experience with lowdose-rate brachytherapy for local prostatecancer relapse after RP.Material & Methods: Nineteen patientswere treated for local prostate cancer re-lapse from April 2004 to November 2006.Medium age is 67.8 years (54-74). All pa-tients were treated initially by RP with57.9% pT2a, 26.3% pT3a and 15.8% pT3b.Gleason ranged from 6-9. All of them under-went anastomosis area biopsy and confirmlocal relapse. Medium PSA before rescuetreatment was 2.2 ng/mL. (0.6-6.8). Realtime implant was realized using Vareseed�

7.2 and Rapid Strand� seeds were used.Treatment dose planning was for 140 Gy.Results: There were no major periopera-tive complications. Hospital stay was 21hin all of them. Continence worsened in 2(11%). Mild previous incontinence im-proved in 3 patients (15.8%). Two pa-tients had light gastrointestinal toxicity(grade 1). None of them had seed voidingin follow up after implant. Medium followup is 15.7 months (2-34). Medium PSAafter 1, 6 and 24 months is 2.2, 1.4 and0.34 ng/mL respectively. One patient (5%)had progression after 9 months, withoutevidence of metastasis.Conclusions: A longer follow up isneeded, but preliminary results with mini-mal morbidity and good biochemical re-sponse, make us think it is a valid optionfor patients with local relapse after radicalprostatectomy.

MP-08.16Docetaxel and oral estramustinephosphate in patients with hormonerefractory prostate cancerSegawa T, Masuda N, Shiraishi Y, NegoroH, Oka H, Iwamura H, Moroi S, Okubo K,Okada T, Kawakita M,Department of Urology, Kobe City Medi-cal Center General Hospital, Kobe, Japan

Introduction: Recently, Docetaxel hasbeen highlighted for the treatment of hor-mone refractory prostate cancer (HRPC),while Estramustine phosphate is an estab-lished oral drug for HRPC. To evaluate thesafety and efficacy of the combination, wehave conducted a clinical trial of Do-cetaxel and oral Estramustine phosphatein patients with HRPC.Methods: Patients with prostate cancer,which was progressing despite androgenablation therapy, were treated with i.v. Do-cetaxel, 35 mg/m2, on Day 2 with oral Es-

tramustine phosphate, 1260 mg, 840 mg,and 840 mg on Day 1, 2 and 3, respectively.Treatment cycles were adjusted for the pa-tients’ condition, with the basis of two cy-cles a month. Patients were evaluated forresponse every cycle, and the treatmentwas continued until the cancer progressed.Results: From April 2003, Twenty-sevenprogressive HRPC patients, with the me-dian age of 72.4 years (Range 55 to 82years) were treated for a median of 7 cy-cles (Range 1 to 46 cycles). Of 291 cycles,235 cycles (81%) were on an outpatientbasis. Median pretreatment PSA valueswere 37.6ng/ml (Range 1.8 to 1760ng/ml). Post-therapy decreases in serum PSAlevels of 50%, and 75% were seen in 52%,and 33% of the patients, respectively. Ofthe 16 patients with measurable disease,none (0%) had a complete response or apartial response. The overall median timeto PSA progression was 4 months (Range0 to 24 months. Major grade 3 or 4 ad-verse effects were anemia (11%), leukocy-topenia (33%). Mild anorexia / nauseawere observed in 56% of the patients.Conclusion: Docetaxel with oral Estra-mustine phosphate has significant anti-tumor activity and is well tolerated in pa-tients with progressive HRPC.

MP-08.17Correlation of clinical andpathological staging in patientsundergoing radical prostatectomyArumainayagam N1, McPhail S2, AyresB1, MacGrath J1, Fowler S3, Cottier B4,Verne J2, Gillatt DA3

1Bristol Urological Institute; 2South WestPublic Health Observatory; 3British Asso-ciation of Urological Surgeons; 4NationalCancer Surveillance and Analysis Team,Clatterbridge Centre for Oncology

Introduction: The aim of this retro-spective study was to compare the pre-operative clinical stage of patients un-dergoing radical prostatectomy (RP)with subsequent pathological stage.Methods: Patients undergoing radical pros-tatectomy from 1999 to 2005 were identi-fied using cancer registry databases and theclinical database of the British UrologicalSurgeons. This covers approximately 50% of

all RP’s performed in the UK in this periodwithin the NHS. The clinical T stage wascompared at the time of diagnosis with sub-sequent pathological stage after surgery.Results: The total number of patients was5339. Tumours were grouped as organ con-fined (T1 / T2), or locally advanced (T3).This was applied to both clinical and patho-logical staging.Conclusion: There is a significant dis-crepancy between clinical and actualpathological staging. Identifying risk fac-tors for up or down staging of tumoursmay aid clinical decision-making.

MP-08.18Robot-assisted laparoscopic radicalprostatectomy in locally advancedprostate cancer: results of a singlesurgeon experience in KoreaPark SY, Park SJ, Lee YH, Kim HJ, Lee SW,Han WK, Kim JH, Choi YD, Rha KH,Yang SCDepartment of Urology, College of Medi-cine, Urological Science Institute andBrain Korea 21 Project for Medical Sci-ence, Yonsei University, Seoul, Korea

Introduction: Radical prostatectomy stillremains controversial in the managementof locally advanced prostate cancer (LAP).The perception of an increased technicaldifficulty and a higher morbidity rate hasbeen a major cause of concern in propos-ing surgery for LAP. The purpose of thisstudy is to assess the feasibility and theoncologic outcome of robot-assisted lapa-roscopic radical prostatectomy (RLRP) inLAP.Methods: Between July 2005 and March2007, 29 RLRPs were performed by singlesurgeon in clinically LAP. LAPs were com-pared with 73 RLRPs performed duringthe same period by the same surgeon inclinically localized disease (LP).Results: The preoperative parameterswere comparable for both groups. Thetwo groups did not differ significantly insurgical morbidity except for estimatedblood loss and operative time, whichshowed a higher rate in patients withLAP. The mean estimated blood loss was367 mL for LAP and 320 mL for LP(P�0.03). The mean operating time was

Table 1. MP-08.17

CLINICAL STAGE T1 / T2 n � 5109 T3 n � 230

Pathological stage pT1-2 pT3 pT1-2 pT3Number 3915 1194 69 161Percentage 77 23 30 70

23 % of clinical T1-2 tumours are subsequently upstaged to pathological stage T3, and 30% of clinical T3 tumoursare subsequently downstaged to organ confined pathological stage T1-2.

MODERATED POSTER SESSIONS

82 UROLOGY 70 (Supplment 3A), September 2007