2
659 PHASE 2 TRIAL OF NEOADJUVANT LHRH PLUS ESTRAMUSTINE FOR HIGH RISK PROSTATE CANCER FOLLOWED BY RADICAL PROSTATECTOMY Takuya Koie*, Teppei Okamoto, Kengo Imanishi, Naoki Sugiyama, Yuichiro Suzuki, Kazuyuki Mori, Shigemasa Kudoh, Takahiro Yoneyama, Yasuhiro Hashimoto, Noritaka Kamimura, Chikara Ohyama, Hirosaki, Japan INTRODUCTION AND OBJECTIVES: Effective treatment for high risk prostate cancer (PC) has not yet been established. We examined efficacy and safety of neo-adjuvant therapy with LHRH agonist estramustine (EMP) (LHRHEMP) followed by retropubic radical prostatectomy (RRP). METHODS: Risk stratification was performed according to the DfAmicofs method. Eighty seven patients with high risk PC were enrolled onto this trial from September 2005 and August 2009. The LHRH EMP therapy included administration of LHRH and 280 mg/day EMP for 6 months prior to the RRP. Post-therapy pathological evaluation to no residual disease at RRP (pT0), and PSA-free survival were endpoints of interest. RESULTS: The average age of the patients was 67.2 years (range 49 to 78 years), and mean initial PSA level was 22.5 ng/ml (range 4.2 to 95.6 ng/ml). The median Gleason sum score was 8 (range 6 to 9), and clinical stage T2c or greater was 76 patients (87.4%). Eighty-six (98.9%) completed 6 months of LHRHEMP neo-adjuvant therapy without delay for RP. The pT0 was achieved in 4 patients (4.6%). The negative surgical margin was 73 patients (83.9%). At a mean follow-up period of 22.2 months, the PSA-free survival was 75.1%. The 2-year PSA-free survival was 83.8% with negative surgical margin, and 35.9% with positive surgical margin (P 0.0001) (Figure). CONCLUSIONS: Six months of LHRHEMP neo-adjuvant ther- apy followed by RP is safe and effective. Although the present study is not randomized, this treatment may improve PSA-free survival in high-risk prostate cancer. A prospective randomized trial is warranted. Source of Funding: None 660 PREDICTING BIOCHEMICAL RECURRENCE FREE SURVIVAL IN PATIENTS WITH POSITIVE PELVIC LYMPH NODES AT RADICAL PROSTATECTOMY Christian von Bodman*, Guilherme Godoy, Daher C. Chade, Angel Cronin, Laura J. Tafe, Samson W. Fine, Vincent Laudone, Peter T. Scardino, James A. Eastham, New York, NY INTRODUCTION AND OBJECTIVES: We evaluated clinical and pathological predictors of freedom from biochemical recurrence (BCR) in patients with pelvic lymph node metastasis (LN) at radical prostatectomy (RP). METHODS: We identified 207 patients with LN metastasis treated with laparoscopic or open RP and bilateral pelvic lymph node dissection (BPLND) between 2000 and 2008. Patients who received any neoadjuvant therapy or adjuvant radio- or chemotherapy were excluded. 45 patients received adjuvant androgen deprivation therapy (ADT) and 162 did not. BCR was defined as prostate-specific antigen (PSA) 0.1ng/mL with one confirmatory rise. Univariate and multi- variable Cox proportional hazards regression models were used to investigate predictors of BCR. Recurrence probabilities were estimated using Kaplan-Meier methods. RESULTS: In the cohort of LN patients (n207) a median of 13 (IQR, 9-19) nodes were removed. Stratifying this cohort into patients who did not receive adjuvant ADT (n162) and patients who received adjuvant ADT (n45) a median of 14 (IQR, 9-20) and a median of 11 (IQR, 8-17) nodes were removed, respectively. Of the 207 patients, 59% (n122) had only 1 LN, 21% (n44) had 2 and 20% (n41) had 3 or more LNs. In the cohort of 162 patients not receiving ADT, 64% (n103) had one, 22% (n35) had 2, and 15% (n24) had 3 or more LNs. In this subgroup 69 patients experienced BCR, with a median follow-up for BCR-free patients of 19 months. The median time to recurrence in patients with 1, 2, and 3 or more LNs was 59, 13 and 3 months, respectively. Only specimen Gleason score (hazard ratio [HR], 2.04 for 8 vs 7; 95% CI, 1.15-3.64) and number of LNs (HR, 1.16 for 2 vs 1 LN; 95% CI, 0.57-2.35; HR, 3.11 for 3 vs 1 LN; 95% CI, 1.57-6.16) were independent predictors of BCR on multivariable anal- ysis. The recurrence free probability 2 years after RP for patients not receiving ADT with 1 LN and a RP Gleason score 7 was 79% (95% CI, 65%-87%) versus 29% (95% CI, 14%-45%) for patients with a RP Gleason score 8 and 2 LNs. CONCLUSIONS: The prognosis of patients with LN metastasis depends on the number of positive nodes removed and the Gleason grade of the primary tumor. Despite a median of 13 (IQR 9-19) LNs removed 80% of all patients with LN metastasis had only 1 or 2 positive nodes. A surprisingly large subset of lymph node positive patients with and a RP Gleason score 7 and a single LN have a favorable prognosis. Full BPLND should be performed in patients with interme- diate and high risk cancers to optimally identify those with minimal nodal burden who may benefit the most from removal of metastatic nodes. Source of Funding: None 661 RACE AND LONG-TERM OUTCOMES AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE. Stephen Freedland*, Durham, NC; Martha Terris, Augusta, GA; Joseph Presti, Jr., Palo Alto, CA; Christopher Kane, San Diego, CA; Christopher Amling, Portland, OR; William Aronson, Los Angeles, CA INTRODUCTION AND OBJECTIVES: Black race is a risk fac- tor for prostate cancer diagnosis and poor outcome. In a prior study of men treated with radical prostatectomy within an equal access setting, we found black race was associated with increased risk of recurrence, but recurrences were equally aggressive regardless of race. Herein, we sought to examine the association between race and long-term out- comes including prostate-cancer specific mortality (PCSM) and overall survival (OS) after radical prostatectomy. METHODS: Retrospective analysis of 762 (45%) black and 934 (55%) white subjects treated with radical prostatectomy from the SEARCH database treated between 1989 and 2009 (total n1,696). We used a Cox analysis to examine the association between race and biochemical recurrence (BCR), BCR with a PSADT 9 months (ag- gressive BCR), metastases, PCSM, and OS. Analyses were adjusted for multiple demographic and clinical pre-operative features. RESULTS: Among men alive at last follow-up, mean and me- dian follow-up was 60 and 50 months, respectively. During this time, 272 men died of which 21 were due to prostate cancer. On univariate analysis, black race was associated with BCR (HR 1.30, p0.003) but no other outcomes. On multivariate analysis, black race was not e258 THE JOURNAL OF UROLOGY Vol. 183, No. 4, Supplement, Monday, May 31, 2010

661 RACE AND LONG-TERM OUTCOMES AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE

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Page 1: 661 RACE AND LONG-TERM OUTCOMES AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE

659PHASE 2 TRIAL OF NEOADJUVANT LHRH PLUSESTRAMUSTINE FOR HIGH RISK PROSTATE CANCERFOLLOWED BY RADICAL PROSTATECTOMY

Takuya Koie*, Teppei Okamoto, Kengo Imanishi, Naoki Sugiyama,Yuichiro Suzuki, Kazuyuki Mori, Shigemasa Kudoh, TakahiroYoneyama, Yasuhiro Hashimoto, Noritaka Kamimura, ChikaraOhyama, Hirosaki, Japan

INTRODUCTION AND OBJECTIVES: Effective treatment forhigh risk prostate cancer (PC) has not yet been established. Weexamined efficacy and safety of neo-adjuvant therapy with LHRHagonist � estramustine (EMP) (LHRH�EMP) followed by retropubicradical prostatectomy (RRP).

METHODS: Risk stratification was performed according to theD�fAmico�fs method. Eighty seven patients with high risk PC wereenrolled onto this trial from September 2005 and August 2009. TheLHRH � EMP therapy included administration of LHRH and 280mg/day EMP for 6 months prior to the RRP. Post-therapy pathologicalevaluation to no residual disease at RRP (pT0), and PSA-free survivalwere endpoints of interest.

RESULTS: The average age of the patients was 67.2 years(range 49 to 78 years), and mean initial PSA level was 22.5 ng/ml(range 4.2 to 95.6 ng/ml). The median Gleason sum score was 8 (range6 to 9), and clinical stage T2c or greater was 76 patients (87.4%).Eighty-six (98.9%) completed 6 months of LHRH�EMP neo-adjuvanttherapy without delay for RP. The pT0 was achieved in 4 patients(4.6%). The negative surgical margin was 73 patients (83.9%). At amean follow-up period of 22.2 months, the PSA-free survival was75.1%. The 2-year PSA-free survival was 83.8% with negative surgicalmargin, and 35.9% with positive surgical margin (P �0.0001) (Figure).

CONCLUSIONS: Six months of LHRH�EMP neo-adjuvant ther-apy followed by RP is safe and effective. Although the present study is notrandomized, this treatment may improve PSA-free survival in high-riskprostate cancer. A prospective randomized trial is warranted.

Source of Funding: None

660PREDICTING BIOCHEMICAL RECURRENCE FREE SURVIVAL INPATIENTS WITH POSITIVE PELVIC LYMPH NODES AT RADICALPROSTATECTOMY

Christian von Bodman*, Guilherme Godoy, Daher C. Chade, AngelCronin, Laura J. Tafe, Samson W. Fine, Vincent Laudone, Peter T.Scardino, James A. Eastham, New York, NY

INTRODUCTION AND OBJECTIVES: We evaluated clinicaland pathological predictors of freedom from biochemical recurrence(BCR) in patients with pelvic lymph node metastasis (�LN) at radicalprostatectomy (RP).

METHODS: We identified 207 patients with LN metastasistreated with laparoscopic or open RP and bilateral pelvic lymph nodedissection (BPLND) between 2000 and 2008. Patients who receivedany neoadjuvant therapy or adjuvant radio- or chemotherapy wereexcluded. 45 patients received adjuvant androgen deprivation therapy(ADT) and 162 did not. BCR was defined as prostate-specific antigen(PSA) � 0.1ng/mL with one confirmatory rise. Univariate and multi-variable Cox proportional hazards regression models were used toinvestigate predictors of BCR. Recurrence probabilities were estimatedusing Kaplan-Meier methods.

RESULTS: In the cohort of �LN patients (n�207) a median of13 (IQR, 9-19) nodes were removed. Stratifying this cohort into patientswho did not receive adjuvant ADT (n�162) and patients who receivedadjuvant ADT (n�45) a median of 14 (IQR, 9-20) and a median of 11(IQR, 8-17) nodes were removed, respectively. Of the 207 patients,59% (n�122) had only 1 �LN, 21% (n�44) had 2 and 20% (n�41) had3 or more �LNs. In the cohort of 162 patients not receiving ADT, 64%(n�103) had one, 22% (n�35) had 2, and 15% (n�24) had 3 or more�LNs. In this subgroup 69 patients experienced BCR, with a medianfollow-up for BCR-free patients of 19 months. The median time torecurrence in patients with 1, 2, and 3 or more �LNs was 59, 13 and 3months, respectively. Only specimen Gleason score (hazard ratio [HR],2.04 for � 8 vs � 7; 95% CI, 1.15-3.64) and number of �LNs (HR, 1.16for 2 vs 1 �LN; 95% CI, 0.57-2.35; HR, 3.11 for � 3 vs 1 �LN; 95% CI,1.57-6.16) were independent predictors of BCR on multivariable anal-ysis. The recurrence free probability 2 years after RP for patients notreceiving ADT with 1 �LN and a RP Gleason score � 7 was 79% (95%CI, 65%-87%) versus 29% (95% CI, 14%-45%) for patients with a RPGleason score � 8 and � 2 �LNs.

CONCLUSIONS: The prognosis of patients with LN metastasisdepends on the number of positive nodes removed and the Gleasongrade of the primary tumor. Despite a median of 13 (IQR 9-19) LNsremoved 80% of all patients with LN metastasis had only 1 or 2 positivenodes. A surprisingly large subset of lymph node positive patients withand a RP Gleason score � 7 and a single �LN have a favorableprognosis. Full BPLND should be performed in patients with interme-diate and high risk cancers to optimally identify those with minimalnodal burden who may benefit the most from removal of metastaticnodes.

Source of Funding: None

661RACE AND LONG-TERM OUTCOMES AFTER RADICALPROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE.

Stephen Freedland*, Durham, NC; Martha Terris, Augusta, GA;Joseph Presti, Jr., Palo Alto, CA; Christopher Kane, San Diego, CA;Christopher Amling, Portland, OR; William Aronson, Los Angeles, CA

INTRODUCTION AND OBJECTIVES: Black race is a risk fac-tor for prostate cancer diagnosis and poor outcome. In a prior study ofmen treated with radical prostatectomy within an equal access setting,we found black race was associated with increased risk of recurrence,but recurrences were equally aggressive regardless of race. Herein, wesought to examine the association between race and long-term out-comes including prostate-cancer specific mortality (PCSM) and overallsurvival (OS) after radical prostatectomy.

METHODS: Retrospective analysis of 762 (45%) black and 934(55%) white subjects treated with radical prostatectomy from theSEARCH database treated between 1989 and 2009 (total n�1,696).We used a Cox analysis to examine the association between race andbiochemical recurrence (BCR), BCR with a PSADT �9 months (ag-gressive BCR), metastases, PCSM, and OS. Analyses were adjustedfor multiple demographic and clinical pre-operative features.

RESULTS: Among men alive at last follow-up, mean and me-dian follow-up was 60 and 50 months, respectively. During this time,272 men died of which 21 were due to prostate cancer. On univariateanalysis, black race was associated with BCR (HR 1.30, p�0.003) butno other outcomes. On multivariate analysis, black race was not

e258 THE JOURNAL OF UROLOGY� Vol. 183, No. 4, Supplement, Monday, May 31, 2010

Page 2: 661 RACE AND LONG-TERM OUTCOMES AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE

associated with BCR (HR 1.07, p�0.44), aggressive BCR (HR 0.88,p�0.61), metastasis (HR 1.23, p�0.62), PCSM (HR 1.19, p�0.72), orOS (HR 0.94, p�0.65). Further adjustment for pathological diseasefeatures from the surgical specimen had no effect on these results.

CONCLUSIONS: Among black and white men undergoing rad-ical prostatectomy at multiple equal access centers, black men are notat increased risk of aggressive biochemical recurrence, metastasis, orprostate cancer specific mortality as compared to white men. Whethersimilar results are seen at non-equal access centers remains to bedetermined.

Source of Funding: DOD, NIH, AUA Foundation, GeorgiaCancer Coalition, VA, Duke University

662THE SURVIVAL BENEFIT OF PRIOR DEFINITIVE LOCALTHERAPY IN MEN WITH ADVANCED/METASTATIC PROSTATECANCER: RESULTS FROM A PHASE III PROSPECTIVERANDOMIZED TRIAL.

Michael Williams*, Randall Millikan, Xuemei Wang, Curtis Pettaway,Houston, TX

INTRODUCTION AND OBJECTIVES: Among patients with ad-vanced (104/286 [36.4%]) and metastatic (182/286 [63.6%]) prostatecancer treated on a phase III randomized trial of chemotherapy andandrogen ablation (AA) versus AA alone, we found that prior localcontrol was independently associated with survival (Millikan et al. JCO2008; 26:5936-42). Further, disease volume in bone, nadir PSA, PSAat study entry, and PSA doubling time (PSADT) were also predictive ofsurvival. In this study, we evaluated the associations between priorlocal therapy and the other prognostic factors to examine the origin ofthis effect.

METHODS: The records of all 286-study patients were re-viewed to define the relationship between having prior local therapy(LT) and prognostic factors, including high volume metastases, age,treatment arm, PSADT, PSA nadir, and PSA at study entry usingFisher’s exact test. For each factor, we examined the presence orabsence of having prior LT to determine its impact on overall (OS) anddisease specific survival (DSS) using the log-rank test.

RESULTS: One-hundred and twenty-six of 286 patients in thestudy had prior LT (44.0%). The median survival among all patients inthe study was 64.5 months. The proportion of patients with a PSA atstudy entry �20ng/mL was significantly more in patients with prior localtherapy as compared to those without (65.1% v. 17.5%, p�0.0001).Likewise, the proportion of patients with high volume metastases werehigher in those without prior LT than in those with LT (59.4% v. 24.6%,p�0.0001). In this study cohort, PSA at study entry and the presenceor absence of LT were highly correlated (p�0.0001). PSA nadir wasundetectable in more patients with prior LT than in those without(71.4% v. 46.8%, p�0.001). Of note PSADT, Age, & treatment armwere not associated with prior LT.

CONCLUSIONS: Patients with prior local therapy in this ran-domized prospective study exhibited more favorable disease charac-teristics at study entry as shown by response to therapy and enhancedsurvival. We hypothesize that close follow-up post LT may have beenresponsible for improvements in survival (i.e., when compared to pa-tients with de novo metastases and an uncontrolled prostate) byfacilitating treatment at lower tumor volumes, as disease biology(based on PSADT) was similar between both cohorts. The role of LTamong prostate cancer patients with metastases at presentation re-mains to be defined and will require prospective evaluation.

Source of Funding: None

663ADJUVANT VERSUS SALVAGE RADIATION THERAPY FORPROSTATE CANCER AND THE RISK OF DEATH

Anthony D’Amico*, Boston, MA; Ming-Hui Chen, Storrs, CT; LeonSun, W. Robert Lee, Vladimir Mouraviev, Cary Robertson, PhilipWalther, Thomas Polascik, David Albala, Judd Moul, Durham, NC

INTRODUCTION AND OBJECTIVES: Adjuvant radiation ther-apy (RT) for men with positive margins (R1), extracapsular or seminalvesicle extension (pT3) decreases the risk of all cause mortality (ACM).Whether salvage RT for PSA failure can provide the same result asadjuvant was investigated.

METHODS: We studied 1638 men at Duke University whounderwent radical prostatectomy for unfavorable-risk prostate cancerand who’s postoperative PSA was undetectable. Cox regression wasused to evaluate whether salvage versus adjuvant RT in men with arapid (� 10 months) or slow (at least 10 months) PSA doubling time(DT) was associated with the risk of ACM adjusting for adverse features(pT3, R1, pGleason score 8 to 10), age, preoperative PSA level,comorbidity and hormonal therapy use.

RESULTS: Despite less men with at least 2 adverse features(61% versus 82%; p � 0.016), salvage for a rapid PSADT versusadjuvant RT increased the risk of ACM (Adjusted Hazard Ratio (AHR):3.42, 95% Confidence Interval (CI): [1.27 to 9.20]; p � 0.015). Therewas no difference (AHR: 1.39, 95% CI: [0.50 to 3.90]; p � 0.53) in therisk of ACM among men who received salvage for a slow PSADT oradjuvant RT. Nearly all (90%) men with a slow PSA DT had pGleasonscore 7 or less and the majority (59%) had at most pT3 or R1 disease.

CONCLUSIONS: Only in men with pGleason score 7 or less andpT3R0 or pT2R1 disease, RT following PSA failure was not associatedwith an increased risk of ACM when compared to adjuvant RT

Clinical Characteristic

Number ofObserved

Men

Number ofObserved

Events

Multivariable AnalysisAdjusted HR

95% CI p-valueAdjuvant RT 65 6 1.0 (Ref) -

Salvage RT (t) andslow PSA DT 49 10 1.39 (0.50, 3.90) 0.532

Salvage RT (t) andrapid PSA DT 46 13 3.42 (1.27, 9.20) 0.015

No RT (t) 1478 185 2.49 (1.07, 5.76) 0.034

No HT (t) 1538 191 1.0 (Ref) -

Adjuvant HT 18 1 0.72 (0.10, 5.24) 0.103

Salvage HT (t) for initialPSA failure 14 1 0.15 (0.02, 1.12) 0.064

Salvage HT (t) followingSalvage RT 68 21 0.79 (0.49, 1.29) 0.347

Preoperative PSA levelin ng/ml 1638 214 0.94 (0.77, 1.15) 0.554

pGleason score

6 or less 275 54 1.0 (Ref) -

7 1154 123 1.46 (1.03, 2.07) 0.033

8 116 17 1.80 (1.01,3.20) 0.046

9 or 10 93 20 2.40 (1.40, 4.14) 0.002

Age in years at RP 1638 214 1.03 (1.01, 1.05) 0.007

Prostatectomy Stage

pT2 1441 177 1.0 (Ref) -

pT3 197 37 1.26 (0.91, 1.76) 0.170

Margin Status

Negative 881 110 1.0 (Ref) -

Positive 757 104 1.28 (0.97, 1.69) 0.087

No Comorbidity (t) 817 131 1.0 (Ref) -

Comorbidity Present atBaseline 577 27 2.02 (1.28, 3.18) 0.002

Comorbidity acquired(t) following RP 244 56 1.31 (0.95, 1.81) 0.097

(t) Signifies a time dependent covariate

Source of Funding: None

Vol. 183, No. 4, Supplement, Monday, May 31, 2010 THE JOURNAL OF UROLOGY� e259