RESULTS OF A PROSPECTIVE PILOT CLINICAL TRIAL ADMINISTERING ACUPUNCTURE FOR HOT FLASHES IN PATIENTS UNDERGOING HORMONAL THERAPY FOR PROSTATE CANCER

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treatment for pT3N0M0 prostate cancer, used after completion of radical prostatectomy, to decrease mortality, loco-regional / distant recurrence and PSA failure rates. 0(7+2'6$PHWDDQDO\VLVRIUDQGRPL]HGFRQWUROOHGWULDOV (RCT) was performed comparing adjuvant RT treatment for pT3N0MO prostate cancer to observation. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings were systematically searched for evidence. Relevant reports were reviewed and the references from these reports were searched for additional trials. 5(68/767KHUHYLHZLGHQWL¿HGWKUHH5&7V\LHOGLQJ patients. There were less locoregional failure after RT (112/717 = 15.6%) versus observation (195/713 = 27.3%, p<0.00001). The likelihood of PSA failure was 0.37-fold lower (95% CI 0.29 - 0.46, p<0.00001) in RT arms. The RCT quality scores were of 4 point in a 5 point scale. Pooled results IURPWKLVWKUHHUDQGRPL]HGWULDOVRIDGMXYDQW57GLGQRWVKRZDVLJQL¿FDQW reduction of mortality (p=0.26) and distant failure rates (p=0.27). CONCLUSIONS: This combination of randomised trial data suggest that there is an unequivocal capacity for adjuvant RT after radical prostatectomy to approximately halves the chance of having a future PSA-detectable and tumour recurrence in pT3 or margin positive patients. PSA relapse and disease recurrence may lead to adverse consequences, including the necessity of using adjuvant therapies, like hormonal therapy. This is associated to higher osteoporosis events, VH[XDOG\VIXQFWLRQKRWÀDVKHVDQGUHGXFHGTXDOLW\RIOLIH0RUHRYHU further follow-up is needed to assess the effect on overall survival and distant failure. The results of these trials should promote further randomised studies comparing adjuvant RT vs. early salvage RT using contemporary PSA assays. Source of Funding: None

525 SALVAGE CRYOTHERAPY FOR RECURRENT PROSTATE CANCER AFTER RADIATION FAILURE. THE UK EXPERIENCE Mohamed Ismail*, Marcia Hicks, Shwan Ahmed, John Davies. Guildford, United Kingdom. INTRODUCTION AND OBJECTIVE: In this study we report on the largest UK experience of salvage cryotherapy for recurrent prostate cancer after radiation failure, evaluating the biochemical outcome, complications and management and quality of life. METHODS: Between May 2000 and November 2005,100 patients underwent salvage targete cryoablation of the prostate (TCAP) for recurrent prostate cancer after radiotherapy. The mean follow-up was 33.5 months. All patients had biopsy proven recurrent prostate cancer. %LRFKHPLFDOUHFXUUHQFHIUHHVXUYLYDO%5)6 ZDVGH¿QHGXVLQJSURVWDWH VSHFL¿FDQWLJHQ36$ OHYHOQJPODQGE\DSSO\LQJWKH$PHULFDQ 6RFLHW\IRU7KHUDSHXWLF5DGLRORJ\DQG2QFRORJ\$6752 GH¿QLWLRQIRU ELRFKHPLFDOIDLOXUH3DWLHQWVZHUHVWUDWL¿HGLQWRULVNJURXSVKLJKULVN (n=68), intermediate-risk (n=20) and low-risk (n=12). RESULTS: There were no operative or cancer related deaths. 7KH¿YH\HDUVDFWXDULDOELRFKHPLFDOUHFXUUHQFHIUHHVXUYLYDOZDV 45% and 11% for the low, intermediate and high-risk groups respectively. Complications included incontinence (13%), erectile dysfunction (86%), lower urinary tract symptoms (16%), prolonged perineal pain (4%), XULQDU\UHWHQWLRQ DQGUHFWRXUHWKUDO¿VWXOD  CONCLUSIONS: Our series suggests that TCAP is safe, well tolerated, and an effective option for salvage treatment of prostate cancer. It is associated with low morbidity rate (except for erectile dysfunction) and for patients who failed their radiotherapy it offers additional hope of cure. High-risk patient showed the least favourable outcome hence, patient selection is essential prior to the treatment. Further research into long term survival and quality of life is recommended. Source of Funding: The Prostate Project Foundation.

526 OUTCOMES FROM A PHASE I TRIAL OF AN ADENOVIRUS/PSA VACCINE FOR PROSTATE CANCER David M Lubaroff*, Badrinath R Konety, Brian K Link, Timothy L Ratliff, Tammy Madsen, Richard D Williams. Iowa City, IA. INTRODUCTION AND OBJECTIVE: We have conducted a Phase I clinical trial of an adenovirus/PSA (Ad/PSA) vaccine for prostate

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cancer. Men with measurable metastatic disease were injected once with the vaccine. Toxicity, immune responses, changes in PSA doubling times, & patient survival have been assessed. METHODS: Thirty-two patients with stage D2 or D3 prostate cancer were treated with a single subcutaneous injection at 1 of 3 dose levels of the Ad/PSA (106, 107, or 108 pfu/ml). At each dose level, 3 patients were injected with the virus suspended in an aqueous solution and 3 patients received the virus suspended in Gelfoam® matrix that has previously been shown to potentiate the induction of immune responses E\$G36$ 7KH ¿QDO JURXS WKDW UHFHLYHG 8 pfu/ml contained 10 patients each, aqueous or Gelfoam®. All patients returned for physical and clinical chemistry examinations at 14 and 21 days, 2, 4, 8, and 12 months after injections. RESULTS: Patient median age was 71 years (52-89), median enrollment PSA was 128 ng/ml (1.31-3110), median follow-up was 12 months (2-12), and median survival was 18 months (2.5-71). The vaccine was deemed safe at all doses, whether administered as an aqueous suspension or in the Gelfoam® matrix with no vaccine-related adverse HYHQWV7KHPRVWSUHYDOHQW$(ZDVORFDOL]HGHU\WKHPDHFFK\PRVHVLQ SDWLHQWVZLWKFROGÀXOLNHV\PSWRPVLQIDWLJXHZLWKSURWHLQXUHDLQ and a transient decreased ANC in 1. Immune responses to PSA were PHDVXUHGDQGLGHQWL¿HGLQDWOHDVWRISDWLHQWV$QWL36$DQWLERGLHV were produced by 42% of patients and anti-PSA T cell responses, the responses documented to mediate tumor destruction, were produced by 71% of patients. The evaluation of effect the vaccination may have had on each patient’s prostate cancer was evaluated by: 1) changes in PSADT, 2) any change in survival different than that predicted by the Halabi nomogram. PSADT was increased in 48% of the patients in the trial while 57% of the vaccinated patients survived longer than predicted by the nomogram. The longest survival was 71 months, almost 6 years after the single vaccination. &21&/86,2167KH ¿QDO RXWFRPH RI WKH 3KDVH , FOLQLFDO trial of the Ad/PSA vaccine demonstrated its safety, its ability to induce anti-PSA antibody and T cell responses, and to seemingly affect the prostate cancer of 48% to 57% of the patients. Although the latter data are only derived from a small number of patients in this Phase I trial, they are encouraging enough to pursue further studies. A Phase II trial, GHVLJQHGWRH[SDQGRQRXULQLWLDO¿QGLQJVKDVUHFHQWO\EHHQDSSURYHG by the FDA. Source of Funding: Holden Comprehensive Cancer Center, VA Research Enhancement Award.

527 RESULTS OF A PROSPECTIVE PILOT CLINICAL TRIAL ADMINISTERING ACUPUNCTURE FOR HOT FLASHES IN PATIENTS UNDERGOING HORMONAL THERAPY FOR PROSTATE CANCER Jillian L Capodice*, Zhezhen Jin, Brian A Stone, James M McKiernan, Carl A Olsson, Aaron E Katz. New York, NY. INTRODUCTION AND OBJECTIVE: Androgen ablation XWLOL]LQJ OHXWLQL]LQJ KRUPRQH UHFHSWRU KRUPRQH /+5+  DJRQLVWV continues to be the main treatment for patients with advanced prostate cancer (CaP). Unfortunately the most common side effect in patients WUHDWHG ZLWK /+5+ DJRQLVWV LV KRW ÀDVKHV ZKLFK RIWHQ LQWHUIHUH ZLWK SDWLHQW TXDOLW\ RI OLIH 7R GDWH KRW ÀDVKHV KDYH QRW UHVSRQGHG ZHOO to conventional medications which often also cause undesirable side HIIHFWV:HUHSRUWWKHUHVXOWVRIWKH¿UVWSURVSHFWLYHFOLQLFDOWULDOWHVWLQJ WKH VDIHW\ DQG HI¿FDF\ RI DFXSXQFWXUH LQ UHGXFLQJ KRW ÀDVKHV LQ advanced CaP patients undergoing hormonal therapy. METHODS: An IRB approved, prospective pilot clinical trial was initiated in April 2006. The entry criteria included men >45 years, CaP Stage 3 or Stage 4 (no M1), receiving any LHRH agonist ± any DQWLDQGURJHQUHSRUWLQJ!ÀDVKHVGD\DVWDQGDUGL]HGYDOXHRQWKH Expanded Prostate Cancer Index (EPIC)-hormone questionnaire). )ROORZLQJFRQVHQWSDWLHQWVUHFHLYHGVWDQGDUGL]HGIXOOERG\DFXSXQFWXUH 1x/week (wk) for 14 wks. Patients were evaluated at 0, 7, 14 and a 14-wk follow-up (F/U) (28-wks). At 0 and 14 wks serum testosterone was measured. At the 0, 7, 14 and 28-wk evaluations EPIC and patient UHSRUWHGKRWÀDVKIUHTXHQF\ZHUHDGPLQLVWHUHG(QGSRLQWVDUHQXPEHURI ÀDVKHVDVGHWHUPLQHGE\WKH(3,&DQGSDWLHQWUHSRUWDQGWHVWRVWHURQH levels.

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RESULTS: As of 11/2007, all patients were enrolled (n=16) and 14 completed the trial. One patient was dropped due to presence of a second cancer. Of 14 evaluable patients, median age is 68 (range 53-76). Preliminary analysis shows no change in testosterone at baseline 11(ng/mL) (range 0-32) vs endpoint 18 (range 0-28) (p=0.237). No serious adverse events were reported. Preliminary analysis of the EPIC GHPRQVWUDWHVDWUHQGWRZDUGLPSURYHPHQWDIWHUZNVDQGDVLJQL¿FDQW improvement following 14 wks of acupuncture (p=0.01). Analysis of SDWLHQWUHSRUWHGIUHTXHQF\VKRZVDVLJQL¿FDQWUHGXFWLRQLQWKHQXPEHURI ÀDVKHVDWS S DQGZN)8S DVFRPSDUHG to baseline 20 (range 5-20). CONCLUSIONS: The administration of acupuncture in men with advanced CaP does not appear to be associated with any serious adverse events. Initial serum testosterones remain unchanged by the DGPLQLVWUDWLRQRIDFXSXQFWXUH%DVHGRQDVWDQGDUGL]HGTXHVWLRQQDLUH WKHHIIHFWRIDFXSXQFWXUHRQKRWÀDVKHVVXJJHVWVDPDUNHGGHFUHDVH LQWKHIUHTXHQF\RIKRWÀDVKHV Source of Funding: None

528 FACTORS PREDICTING DISEASE FREE SURVIVAL IN PATIENTS WITH NODE POSITIVE PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY AND EXTENDED PELVIC LYMPH NODE DISSECTION IN THE PSA ERA: ROLE OF ADJUVANT RADIOTHERAPY Luigi F Da Pozzo*, Alberto Briganti, Cesare Cozzarini, Andrea Salonia, Marco Bianchi, Felix K H Chun, Massimo Freschi, Nazareno Suardi, Pierre I Karakiewicz, Hartwig Huland, Ferruccio Fazio, Patrizio Rigatti, Francesco Montorsi. Milan, Italy, Hamburg, Germany, and Cancer Prognostics and Health Outcomes Unit, QC, Canada. INTRODUCTION AND OBJECTIVE: Good clinical outcome has been reported in patients with lymph node positive prostate cancer treated with radical prostatectomy (RP). However, only few reports have focused on factors predicting long term disease free survival in this FRKRUWRISDWLHQWV:HK\SRWKHVL]HGWKDWQRGHSRVLWLYHSURVWDWHFDQFHU is not always a systemic disease and patients might experience long term disease free survival when treated with extended pelvic lymph node dissection (ePLND), RP and adjuvant treatments METHODS: Between January 1986 and December 2007, 538 out of 5050 (10.6%) patients submitted to RP and ePLND had lymph node invasion. Of these, 285 patients were treated between 1988 and 2003 and represented the study cohort. All patients received adjuvant treatment: 144 (50.5%) were treated with a combination of radiotherapy (RT) and hormonal therapy (HT), while 141 (40.9%) received adjuvant HT alone. Kaplan-Meier curves assessed disease-free survival rates. Univariable and multivariable Cox regression models tested the association between predictors (baseline PSA, pathological stage, pathological Gleason score, number of number of nodes removed, number of positive nodes and adjuvant RT ) and biochemical recurrence (BCR) free survival. RESULTS: Mean PSA was 29.5 ng/ml (median 16 ng/ml). The mean number of nodes removed was 16.7 (range:7-52). The mean number of positive nodes was 2.7 (range:1-31). Median follow-up was 90 months (mean: 96, range 6-243). BCR free-survival rate at 5,8 and 10 years was 72, 61 and 53%, respectively. Except for number of nodes removed (p=0.4), all variables were univariate predictor of BCR-free VXUYLYDO DOO S”  ,Q PXOWLYDULDEOH &R[ UHJUHVVLRQ PRGHOV SUH operative PSA, number of positive nodes and adjuvant RT maintained DVLJQL¿FDQWDVVRFLDWLRQZLWK%&5IUHHVXUYLYDODOOS” &RQYHUVHO\ the number of nodes removed, pathological stage and pathological Gleason score were not indipendent predictors of BCR free survival DOS•  &21&/86,216 2XU VWXG\ FRQ¿UPV WKH H[FHOOHQW FOLQLFDO outcome of node positive patients treated with RP, ePLND and adjuvant treatments. More than 50% of patients were free of disease at 10-year follow-up. Moreover, this is the largest trial reporting a multivariate EHQH¿WRIDGMXYDQW57RQ%&5IUHHVXUYLYDOLQSDWLHQWVZLWKO\PSKQRGH invasion, suggesting the importance of a multidisciplinary approach in this high risk cohort of patients. Source of Funding: None

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529 PSA HALF LIFE AND PSA DOUBLING TIME AS A PREDICTOR OF RESPONSE TO ANDROGEN DEPRIVATION THERAPY FOR METASTATIC PROSTATE CANCER Yong Hyun Park*, Dong Soo Park, Chang Wook Jeong, Ja Hyun Ku, Cheol Kwak, Hyeon Hoe Kim. Seoul, Republic of Korea. INTRODUCTION AND OBJECTIVE: We determined the FOLQLFDOVLJQL¿FDQFHRISURVWDWHVSHFL¿FDQWLJHQ36$ KDOIOLIH36$71/2) and PSA doubling time after nadir (PSADTAN) as a predictor of response to hormone therapy for metastatic prostate cancer. METHODS: Between 1990 and 2004, 131 patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT) were included in this analysis. RESULTS: Median follow-up duration was 53.0 months. Mean PSA at baseline was 522.7 (±1013.9) ng/dL, mean biopsy Gleason score was 7.8 (±1.5), and mean nadir PSA was 23.6 (±146.2) ng/dL. Of 73 patients who had adequate data to evaluate, 49 (67.1%) had been developed hormone-refractory prostate cancer. Baseline PSA (445.3 vs 606.1ng/dL, p=0.367), nadir PSA (35.9 vs 10.3ng/dL, p=0.319) did not differ between the patients with short PSAT1/2 (1month or less) and long PSAT1/2 (longer than 1month). Patients with short PSAT1/2 had higher Gleason score (8.2 vs 7.3, p<0.001), shorter nadir duration (10 vs 24 PRQWKVS DQGVKRUWHUFDQFHUVSHFL¿FVXUYLYDOYVPRQWKV p<0.001). No differences were found between the patients with short PSADTAN (6 months or less) and long PSADTAN (longer than 6 months) in terms of baseline PSA (619.9 vs 697.5ng/dL, p=0.806), nadir PSA (13.0 vs 7.0, p=0.267), biopsy Gleason score (8.3 vs 8.1, p=0.578), and PSAT1/2 (1.8 vs 1.7 months, p=0.945). Short PSADTAN was associated with shorter nadir duration (13.2 vs 20.5 months, p=0.033) and poorer PHGLDQFDQFHUVSHFL¿FVXUYLYDOYVORQJHUWKDQPRQWKVS  2Q PXOWLYDULDWH DQDO\VLV *OHDVRQ VFRUH KD]DUG UDWLR >+5@   FRQ¿GHQFH LQWHUYDO >&,@  S   QDGLU 36$ +5 1.022, 95% CI 1.014-1.031, p<0.001) and PSAT1/2 (HR 2.316, 95% CI 1.476-3.632, p<0.001) remained as independent predictors of PSA rerising after ADT. Nadir PSA (HR 1.038, 95% CI 1.022-1.054, p<0.001), PSAT1/2 (HR 3.021, 95% CI 1.281-7.126, p=0.012) and PSADTAN (HR 2.919, 95% CI 1.093-7.797, p=0.033) were prognostic factors for cancerVSHFL¿FVXUYLYDO CONCLUSIONS: The results of present study suggest that PSAT1/2 and PSADTAN are independent prognostic indicators for PSA re-rising and cancer-related death in patients with metastatic prostate cancer treated with androgen deprivation therapy. Source of Funding: None

530 HIGH INCIDENCE OF PREVIOUSLY UNDIAGNOSED DIABETES MELLITUS IN PATIENTS ON ANDROGEN DEPRIVATION THERAPY COMPARED TO A CONTROL GROUP Selina L Liu*, Tamara Spaic, Stan H Van Uum, Stephen E Pautler, Linda Nott, Hassan Razvi. London, ON, Canada. INTRODUCTION AND OBJECTIVE: Androgen deprivation therapy (ADT) is the main therapeutic approach for men with locally invasive or metastatic prostate cancer. Epidemiological studies in patients on ADT suggest an increased prevalence of diabetes mellitus type 2 (DM2) and metabolic syndrome (MetS), however, very few studies have performed formal evaluation for DM2 and MetS. We evaluated patients on ADT for incidence of new DM2 and MetS, and compared with a control group. METHODS: We included patients receiving ADT and control subjects (CS) without prostate cancer. Patients had to be treatmentnaïve for hypercholesterolemia, and were excluded if they had DM2. All participants underwent a clinical assessment, including measurement of blood pressure and waist circumference, and a laboratory evaluation (fasting cholesterol profile and glucose tolerance test). DM2 was diagnosed based on a 75 gram oral glucose tolerance test (OGTT). In non-diabetic patients, the presence of MetS was diagnosed according to the revised NCEP/ATPIII criteria (2005). Data are presented as the mean and standard deviation. RESULTS: 82 patients receiving ADT and 53 CS were screened for enrolment. We excluded 45 ADT patients and 27 in CS. Reasons for exclusion were DM (18 and 14), statin use (18 and 10)