Pretreatment PSA Research Articles

MP62-13 PRIOR BLADDER OUTFLOW SURGERY OR LARGE PROSTATE VOLUME DOES NOT ADVERSELY AFFECT BIOCHEMICAL RECURRENCE-FREE SURVIVAL IN LOW DOSE RATE PROSTATE BRACHYTHERAPY: AN INTERMEDIATE TERM ANALYSIS

You have accessJournal of UrologyProstate Cancer: Localized V1 Apr 2015MP62-13 PRIOR BLADDER OUTFLOW SURGERY OR LARGE PROSTATE VOLUME DOES NOT ADVERSELY AFFECT BIOCHEMICAL RECURRENCE-FREE SURVIVAL IN LOW DOSE RATE PROSTATE BRACHYTHERAPY: AN INTERMEDIATE TERM ANALYSIS Áine Goggins, Hidekazu Yamamoto, Peter Acher, Stephen Morris, Ronald Beaney, Ben Challacombe, and Rick Popert Áine GogginsÁine Goggins More articles by this author , Hidekazu YamamotoHidekazu Yamamoto More articles by this author , Peter AcherPeter Acher More articles by this author , Stephen MorrisStephen Morris More articles by this author , Ronald BeaneyRonald Beaney More articles by this author , Ben ChallacombeBen Challacombe More articles by this author , and Rick PopertRick Popert More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2387AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The oncological outcomes of prostate brachytherapy remain uncertain in patients with large prostate volumes or previous bladder outflow obstruction surgery (PBOS). Here, the impact of PBOS and prostate size on intermediate term biochemical recurrence-free survival (BRFS) was investigated. METHODS Inclusion criteria were patients undergoing low dose rate prostate brachytherapy (LDRB) as monotherapy for localized prostate cancer between 2003-13, with or without PBOS. Data collected included PSA kinetics before and after LDRB, Gleason score, prostate volume, age, race, clinical and MRI stage, Charlson co-morbidity index, social deprivation status, & dosimetric parameters (D90 & V100). Primary outcome was biochemical recurrence-free survival, defined by a rise in PSA >2ng/ml above nadir. Secondary outcomes were the incidence of toxicity according to the Radiation Therapy Oncology Group toxicity grading, salvage therapy, PSA nadir, and time to nadir. Univariate Kaplan-Meier, and multivariate cox proportional hazards and logistic regression analyses were conducted. RESULTS A total of 407 patients with a median follow up of 43 months were included. 78 (19%) had PBOS, which consisted of TURP (n=72), HoLEP (n=4), HoLAP (n=1) and Millin's prostatectomy (n=1). Pathological grades were Gleason 6 or 7 for all cases. PBOS group contained a higher proportion Gleason 7 case (51%) compared to the Non-PBOS group (37%). Mean D90 and V100 were 171(±13)Gy and 96(±5%), respectively. Biochemical relapse occurred in 3/78 (4%) of PBOS and 20/329 (6%) of non-PBOS. By logrank analysis PBOS did not affect BRFS (p=0.52) however, a trend for favourable BRFS was observed in larger prostate volumes when analysed by size quartiles (p=0.02). Multivariate analysis of pre-treatment variables showed large prostate volume to be the only predictor of BRFS (HR=0.60 per 10mls increase in size, p=0.026). With the inclusion of post-treatment data (ie. PSA nadir, time to PSA, D90 and V100), independent predictors of BRFS were prostate volume (HR=0.50, p=0.024), PSA nadir (p=0.003) and time to nadir (p<0.001). History of bladder outflow surgery did not predict BRFS. A high pre-treatment PSA was the only pre-operative and post-operative predictor of grade III toxicity (HR=1.26, p=0.01). CONCLUSIONS Large prostate size is an independent predictor of favourable biochemical outcome after LDRB. PBOS did not affect BRFS nor increase the incidence of grade III toxicity and hence is not a reason to deny LDRB. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e785-e786 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Áine Goggins More articles by this author Hidekazu Yamamoto More articles by this author Peter Acher More articles by this author Stephen Morris More articles by this author Ronald Beaney More articles by this author Ben Challacombe More articles by this author Rick Popert More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP87-13 IMPACT OF PRE-TREATMENT PSA LEVEL ON CANCER CONTROL AFTER EARLY SALVAGE RADIATION THERAPY POST RADICAL PROSTATECTOMY: NEED FOR PATIENT STRATIFICATION ACCORDING TO PROSTATE CANCER FEATURES

You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2015MP87-13 IMPACT OF PRE-TREATMENT PSA LEVEL ON CANCER CONTROL AFTER EARLY SALVAGE RADIATION THERAPY POST RADICAL PROSTATECTOMY: NEED FOR PATIENT STRATIFICATION ACCORDING TO PROSTATE CANCER FEATURES Nicola Fossati, R. Jeffrey Karnes, Cesare Cozzarini, Claudio Fiorino, Steven Joniau, Wolfgang Hinkelbein, Karin Haustermans, Bertrand Tombal, Shahrokh F. Shariat, Pierre I. Karakiewicz, Gregor Goldner, Francesco Montorsi, Hein Van Poppel, Thomas Wiegel, and Alberto Briganti Nicola FossatiNicola Fossati More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Cesare CozzariniCesare Cozzarini More articles by this author , Claudio FiorinoClaudio Fiorino More articles by this author , Steven JoniauSteven Joniau More articles by this author , Wolfgang HinkelbeinWolfgang Hinkelbein More articles by this author , Karin HaustermansKarin Haustermans More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Gregor GoldnerGregor Goldner More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Hein Van PoppelHein Van Poppel More articles by this author , Thomas WiegelThomas Wiegel More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1958AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Early salvage radiotherapy (eSRT) represents an option for biochemical recurrence (BCR) after radical prostatectomy (RP). However, the optimal PSA level for eSRT initiation is still unclear. We hypothesized that the association between PSA at eSRT and cancer control is not linear and that it is significantly associated with prostate cancer features at RP. METHODS We evaluated a multi-institutional cohort of 716 node-negative patients with early undetectable postoperative PSA (<0.1 ng/ml), who experienced BCR after RP. All patients received eSRT, defined as local radiation to prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. BCR after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Multivariable Cox regression analyses tested the association between pre-eSRT PSA level and BCR. Covariates consisted of pathologic stage, pathologic Gleason score, and surgical margin status. Locally weighted scatter plot smoothing (lowess) methods were used to explore the relation between pre-eSRT PSA level and BCR-free survival rate at 5 years after eSRT according to cancer characteristics at RP. RESULTS Median follow-up after eSRT was 47 months. 5-year BCR-free survival rate was 81%. At multivariable analysis, pre-eSRT PSA level was associated with BCR after eSRT (hazard ratio [HR]: 4.89; p<0.0001). Moreover, pathologic stage ≥pT3b (HR: 2.07; p=0.007), pathologic Gleason score ≥8 (HR: 2.69; p=0.0002), and negative surgical margins (HR: 2.50; p<0.0001) were associated with BCR and were identified as risk factors. Overall, using lowess methods, we observed a decrease of 5-years BCR-free survival rate from 87% to 75% for pre-eSRT PSA level ranging from 0.1ng/ml to 0.5ng/ml. Overall, the 5-years BCR risk increased by 3% per 0.1ng/ml of PSA level. However, when patients were stratified according to the number of risk factors (≤1 vs. ≥2), the effect of increasing PSA at eSRT on cancer control was higher in men with more aggressive disease. Specifically, patients with ≥2 pathologic risk factors showed an increased risk of 5-years BCR equal to 10% per 0.1ng/ml of PSA level vs. 1.5% in patients with a single risk factor (p<0.001). CONCLUSIONS Cancer control after eSRT depends on pretreatment PSA level. This effect is highest in men with at least two of the following features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients eSRT should be administered at the very first sign of PSA increase in order to maximize cancer control. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1089 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicola Fossati More articles by this author R. Jeffrey Karnes More articles by this author Cesare Cozzarini More articles by this author Claudio Fiorino More articles by this author Steven Joniau More articles by this author Wolfgang Hinkelbein More articles by this author Karin Haustermans More articles by this author Bertrand Tombal More articles by this author Shahrokh F. Shariat More articles by this author Pierre I. Karakiewicz More articles by this author Gregor Goldner More articles by this author Francesco Montorsi More articles by this author Hein Van Poppel More articles by this author Thomas Wiegel More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP82-18 EFFECT OF NEOADJUVANT DOCETAXEL CHEMOTHERAPY COMBINED WITH ADJUVANT CHEMOTHERAPY COMPARED WITH RADICAL PROSTATECTOMY ALONE IN PATIENTS WITH HIGH RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2015MP82-18 EFFECT OF NEOADJUVANT DOCETAXEL CHEMOTHERAPY COMBINED WITH ADJUVANT CHEMOTHERAPY COMPARED WITH RADICAL PROSTATECTOMY ALONE IN PATIENTS WITH HIGH RISK PROSTATE CANCER Wansuk Kim, Cheryn Song, and Hanjong Ahn Wansuk KimWansuk Kim More articles by this author , Cheryn SongCheryn Song More articles by this author , and Hanjong AhnHanjong Ahn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.537AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Preoperative chemotherapy with androgen deprivation therapy is under investigation, some with promising results. However, the definitive value of preoperative and postoperative chemotherapy-only therapy remains unevaluated for high risk prostate cancer. We investigated the efficacy of docetaxel treatment before and after radical prostatectomy (RP) in patients with high risk prostate cancer. METHODS Patients with high risk prostate cancer according to D'Amico criteria were prospectively randomized to one of two treatment groups: neoadjuvant chemotherapy (three cycles) followed by RP (arm A, n=27); or RP alone (arm B, n=21). Patients in arm A were treated with 75 mg/m2 IV docetaxel every three weeks following premedication with 8 mg of dexamethasone; they then underwent RP two weeks later. After RP, 17 patients in group A were treated with docetaxel with same schedule. The median observation time was 50.74 months in both arms. RESULTS There were no differences in the age (66.6 and 64.2 years, p=0.080), pretreatment PSA levels (23.9 and 16.2 ng/mL, p=0.052), clinical stage and Gleason score between the patients in arm A and B, respectively. Grade 1-2 non-hematologic toxicities occurred in 13 patients (81.3%), none with grade 3-4 toxicities. The pathological stages were: T2 in 4(23.5%), T3a in 8(47.1%), and T3b in 5 (29.4%) in arm A; T2 in 5(23.8%), T3a in 8(38.1%), and T3b in 8(38.1%) in arm B (p=0.914). Positive margin rate was similar between the arms in pT2 patients while in pT3 patients it was lower in arm A (37.5% vs. 90.9%, p=0.008). PSA response (> 25% reduction) after chemotherapy was observed in 8 patients (50.0%), but pathological downstaging was noted in 2 (12.5%). After RP, 6 and 7 from each group failed to reach undetectable PSA. PSA failure rate was 27.3%, 50.0% in arm A and B respectively (p=0.414). CONCLUSIONS Docetaxel neoadjuvant chemotherapy lowers positive resection margin in patients with high risk prostate cancer. However, pathological downstaging or immediate oncological result was observed only in a limited number of patients who demonstrated substantial PSA response. But there was no difference in biochemical recurrence free survival. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1044 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wansuk Kim More articles by this author Cheryn Song More articles by this author Hanjong Ahn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

454 Impact of pre-treatment PSA level on cancer control after early salvage radiation therapy post-radical prostatectomy: Need for patient stratification according to prostate cancer features

454 Impact of pre-treatment PSA level on cancer control after early salvage radiation therapy post-radical prostatectomy: Need for patient stratification according to prostate cancer features

Young age to predict for transient elevation in PSA after definitive stereotactic body radiation therapy for prostate cancer.

118 Background: Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. There is a small body of literature characterizing a PSA bump after treatment with SBRT. Despite this, there is a paucity of data addressing rates of transient PSA increase immediately after SBRT treatment and what factors portend for this rare occurrence. This study reports outcomes on initial PSA after SBRT therapy for men who have received definitive SBRT for prostate cancer. Methods: Between May 2006 and February 2014, 921 patients with prostate cancer were treated with SBRT delivered via Cyberknife therapy. The mean age was 67 years old. 68.5% of patients were Caucasian, 17.4% African American, and 14.1% were another ethnicity. Patients were divided into prognostic risk groups with 44.7%, 43.5%, and 11.1% of patients falling in the low, intermediate, and high risk stratifications. Gleason scores were &lt; 6 in 44.4%, 7 in 41.3%, and 8-10 in 14.2%. 37 patients also received supplemental external beam radiation (median dose 4500cGy) and 8.9% of patients received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. Pre-treatment PSA was 0.8 – 205 ng/ml (median 6.1). Results: At 3 months’ follow-up, 2.8% of patients had a PSA elevated above their baseline value. 27.8% of patients age ≤50 (p&lt;.0001) and 8.4% of patients age ≤60 (p=.001) experienced an increased in baseline PSA. African Americans were more likely to experience a transient increase in PSA over Caucasians (7.8% vs. 3.0%, p=.06). Patients treated with fewer beams were also more likely have a temporary rise in PSA (p=.056). Gleason Score, Risk grouping, prostate volume, ADT, and EBRT did not predict for rise on Pearson Chi-Square analysis. On multivariate analysis, only age ≤50 (p&lt;.0001) portended for increased PSA at 3 months’ time. Conclusions: This represents the largest series evaluating elevation of PSA after definitive SBRT for prostate cancer. Temporary rise in baseline PSA after SBRT is rare. Despite that, a significant cohort of younger patients can experience transient elevation. Patient age ≤50 was found to be the only predictor of this otherwise rare occurrence.

Prognostic significance of perineural invasion in localized prostate cancer.

30 Background: While perineural invasion (PNI) has been associated with poorer clinical outcomes in prostate cancer patients, it is not well defined as a predictor of long-term endpoints in newly diagnosed prostate cancer. Therefore, we evaluated the role of PNI as a prognostic marker in patients with localized prostate cancer who underwent surgery or radiation. Methods: We analyzed a prospectively collected cohort of 5,034 consecutive patients with localized prostate cancer treated with surgery (n = 4,207) or radiation (n = 827) at University of Michigan from 1994-2013. The primary outcome measured was metastasis-free survival, with secondary outcomes of PSA-recurrence free survival and overall survival (OS). Covariates included age, treatment year, race, comorbidity index, pre-treatment PSA, Gleason score, and T-stage. Survival analysis was estimated using the Kaplan-Meir method, and multivariable analysis was performed using a Cox proportional hazards model. Results: 22.6% of surgery patients and 37.5% of radiation patients had PNI. 169 patients developed metastasis a median of 44 months (IQR 21-83 months) after primary therapy. In the combined cohort, PNI was a predictor of metastasis and PSA recurrence, but not OS (Table 1). For surgery, PNI was a predictor of metastasis, PSA recurrence, and OS. For radiation, PNI was a predictor of metastasis and PSA recurrence, but not OS. Conclusions: PNI is an independent predictor of long-term outcomes in newly diagnosed prostate cancer patients regardless of subsequent therapy. These data support the importance of PNI as a key factor denoting potentially aggressive prostate cancer and importing a significant increase in the likelihood of eventual metastatic progression. [Table: see text]

Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BackgroundKetoconazole is a well-known CYP-17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had prostate specific antigen (PSA) response rate (greater than 50% decline) of 21% to 62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state.MethodsMen with CRPC and performance status (PS) 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg PO three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (greater than 50% reduction from baseline) where a PSA response rate of 25% was to be considered promising for further study (versus a null rate of less than 5%); 25 patients were required. Secondary endpoints included PSA response greater than 30% from baseline, progression-free survival (PFS), duration of stable disease, and evaluation of adverse events (AEs).ResultsThirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng/ml (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the 2 grade 4 AEs was considered related to treatment.ConclusionsIn docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy.

Radical prostatectomy vs radiotherapy in high-risk prostate cancer patients: two centre experience

Background/objectiveThere are no randomized trials on the comparative effectiveness of radical prostatectomy (RP) and radiotherapy (RT) for high-risk prostate cancer. Our aim was to compare treatment outcomes of high-risk prostate cancer after RP and RT, including overall survival (OS), biochemical-progression-free survival (bPFS) and disease-progression-free survival (dPFS), using two cancer treatments centers’ patient data.MethodsData on high-risk prostate cancer patients between 2005 and 2009 were retrospectively reviewed in two cancer centers: National Cancer Institute, Vilnius, Lithuania and N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus; 210 patients were included in the study group treated with RP (n = 174) or RT (n = 36). The mean follow-up time was 5.6 and 6.6 years, respectively.ResultsLower T stage was an independent predictor of better OS (p = 0.01) and bPFS (p = 0.03). Only the highest Gleason score ≥8 was significantly predictive of a worse OS (p = 0.05), bPFS (p = 0.02) and dPFS (p = 0.001). A high PSA level was predictive of a worse bPFS (p = 0.007 for PSA ≥20) and dPFS (p = 0.008 for ≥20). The treatment modality in this study was insignificant after T stage, Gleason score and PSA level adjustment for OS, bPFS survival and dPFS survival (p = 0.17, p = 0.39, p = 0.20).ConclusionsThe T stage, Gleason score and pretreatment PSA level are significant factors for OS, bPFS survival, and dPFS survival of highrisk prostate cancer patients. Treatment option (RP or RT) was not an independent predictor of survival in this study.

Radical prostatectomy vs radiotherapy in high-risk prostate cancer patients: two centre experience

Background/objectiveThere are no randomized trials on the comparative effectiveness of radical prostatectomy (RP) and radiotherapy (RT) for high-risk prostate cancer. Our aim was to compare treatment outcomes of high-risk prostate cancer after RP and RT, including overall survival (OS), biochemical-progression-free survival (bPFS) and disease-progression-free survival (dPFS), using two cancer treatments centers’ patient data.MethodsData on high-risk prostate cancer patients between 2005 and 2009 were retrospectively reviewed in two cancer centers: National Cancer Institute, Vilnius, Lithuania and N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus; 210 patients were included in the study group treated with RP (n = 174) or RT (n = 36). The mean follow-up time was 5.6 and 6.6 years, respectively.ResultsLower T stage was an independent predictor of better OS (p = 0.01) and bPFS (p = 0.03). Only the highest Gleason score ≥8 was significantly predictive of a worse OS (p = 0.05), bPFS (p = 0.02) and dPFS (p = 0.001). A high PSA level was predictive of a worse bPFS (p = 0.007 for PSA ≥20) and dPFS (p = 0.008 for ≥20). The treatment modality in this study was insignificant after T stage, Gleason score and PSA level adjustment for OS, bPFS survival and dPFS survival (p = 0.17, p = 0.39, p = 0.20).ConclusionsThe T stage, Gleason score and pretreatment PSA level are significant factors for OS, bPFS survival, and dPFS survival of highrisk prostate cancer patients. Treatment option (RP or RT) was not an independent predictor of survival in this study.

SBRT for the Primary Treatment of Localized Prostate Cancer: The Effect of Gleason Score, Dose and Heterogeneity of Intermediate Risk on Outcome Utilizing 2.2014 NCCN Risk Stratification Guidelines.

Purpose: To report an update of our previous experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer, risk stratified by the updated National Comprehensive Cancer Network (NCCN) version 2.2014, reporting efficacy and toxicity in a community hospital setting.Methods: From 2007 to 2012, 142 localized prostate cancer patients were treated with SBRT using CyberKnife. NCCN guidelines Version 2.2014 risk groups analyzed included very low (20%), low (23%), intermediate (35%), and high (22%) risk. To further explore group heterogeneity and to comply with new guidelines, we separated our prior intermediate risk group into favorable intermediate and unfavorable intermediate groups depending on how many intermediate risk factors were present (one vs. > one). The unfavorable intermediate group was further analyzed in combination with the high risk group as per NCCN guidelines Version 2.2014. Various dose levels were used over the years of treatment, and have been categorized into low dose (35 Gy, n = 5 or 36.25 Gy, n = 107) and high dose (37.5 Gy, n = 30). All treatments were delivered in five fractions. Toxicity was assessed using radiation therapy oncology group criteria.Results: Five-year actuarial freedom from biochemical failure (FFBF) was 100, 91.7, 95.2, 90.0, and 86.7% for very low, low, intermediate and high risk patients, respectively. A significant difference in 5 year FFBF was noted for patients with Gleason score (GS) ≥8 vs. 7 vs. 5/6 (p = 0.03) and low vs. high dose (p = 0.05). T-stage, pretreatment PSA, age, risk stratification group, and use of ADT did not affect 5-year FFBF. Multivariate analysis revealed GS and dose to be the most predictive factors for 5-year FFBF.Conclusion: Our experience with SBRT for the primary treatment of localized prostate cancer demonstrates favorable efficacy and toxicity comparable to the results reported for IMRT in literature. GS remains the single most important pretreatment predictor of outcome.

S018: Current applications for pretreatment PSA doubling time in patients with prostate cancer

S018: Current applications for pretreatment PSA doubling time in patients with prostate cancer

Biochemical and Survival Outcomes in Patients With T3 Prostate Adenocarcinoma Treated With Brachytherapy

Purpose/Objective(s): To evaluate the freedom from biochemical failure (FFBF), prostate cancer-specific survival (PCSS), and overall survival (OS) in patients with cT3a-b prostate adenocarcinoma treated at a single institution. Materials/Methods: One hundred seven patients with cT3a-b, N0, M0 prostate adenocarcinoma underwent I-125 (72%) or Pd-103 (28%) low dose rate brachytherapy from 1998-2007. Seventy-five patients (70%) received supplemental external beam radiation therapy as part of combined modality therapy (CMT). Thirty-two patients (30%) underwent implant alone (MT). Ninety-two patients (86%) received androgen deprivation therapy (ADT). Median (range) age, pre-treatment PSA (iPSA), duration of ADT and follow-up were 69 years (47-93), 12.7 ng/ml (1.4-160), 4 months (2-36) and 73 months (9-160), respectively. Fifty-five men (51%) had Gleason sum (GS) 8-10. Eighty-nine patients (86%) had 50% of cores involved. Univariate analysis (UVA) was performed using the logrank test and Cox proportional hazards for continuous variables with the following covariates: age, T-stage (T3a vs. T3b), GS, iPSA, percent positive cores (PPC), ADT use, and implant setting (CMT vs. MT). Multivariable analysis (MVA) was performed using Cox proportional hazards modeling and included T-stage, GS, iPSA and all covariates with p-value <0.1 on UVA. Results: Kaplan-Meier estimates for FFBF, PCSS and OS are described in Table 1. On UVA, only CMT was associated with improved FFBF. CMT, younger age (p Z 0.09), and lower PSA (p<0.01) were associated with improved PCSS. CMT, younger age (p<0.01), higher GS (p Z 0.09), and lower iPSA (p Z 0.04) were associated with improved OS. ADT was not associated with FFBF, PCSS, or OS for the overall cohort or on subgroup analysis. MVA revealed CMTwas associated with improved FFBF (Hazard ratio [HR]: 0.28, 95% Confidence Interval [CI]: 0.14-0.59; p<0.01). Lower iPSA was associated with improved PCSS (HR: 0.98, 95% CI: .96-1.00; p Z 0.01), but CMTwas not (HR: 0.41, 95% CI: 0.1-1.73; pZ 0.23). Lower iPSA was associated with improved OS (HR: 0.98, 95% CI: 0.97-1.00; p<0.01). CMT had a trend towards improved OS (0.44, 95% CI: 0.171.12; p Z 0.09) and higher GS had a trend towards worse OS (HR: 1.35, 95% CI: 0.944-1.93; p<0.1). Conclusions: In patients with cT3a-b prostate adenocarcinoma, CMT is associated with improved biochemical control but may not be associated with PCSS or OS when controlling for other factors. The benefit of ADT in patients treated with brachytherapy is unclear.

Maximal Androgen Depletion with Abiraterone Acetate (Aa) Followed By Randomization of Maximal Androgen Ablation with Molecular Targeted Therapies Dasatinib or Sunitinib Malate in Metastatic Castrate Resistant Prostate Cancer (Mcrpc). Report on Candidate Predictive Androgen Signaling Signature

ABSTRACT Aim: Background: During the course of successful mCRPC drug development the unmet need for predictive markers has become pressing. We have previously (JCO 2012, EurUr 2014, ASCO 2014) identified a candidate androgen signaling signature associated with favorable outcome and lacking in patients with primary resistance to either abiraterone acetate or enzalutamide. Here we report on a prospective testing of the signature. Methods: This is a phase II study of AA in mCRPC patients randomized upon progression to combination with Dasatinib or Sunitinib. Patients underwent bone marrow biopsy sampling at baseline and upon progression with matched blood and bone marrow aspirate collection Endpoints included prespecified prospective assessment of tumor androgen signaling signature in pts with benefit vs primary resistance to AA (progression ≤ 4 months). Tumor Markers included, Androgen Receptor-N terminal (AR-N), AR-C terminal (AR-C), CYP17, Ki67, Glucocorticoid receptor (GR), ERG, Proliferation Index Ki67 (%), pSrc by IHC. Steroid metabolome assessed by LCMS. Results: Study (March 2011-April 2014) has completed accruing 170 mCRPC pts. Median Age is 67 years (range 49-88). All pts had bone metastases (100%). Diagnostic Gleason Score was ≥8 in 111/147 (76%) evaluable pts and median pretreatment PSA 21 (range 0.5-1655). Forty one pts completed study follow up and tissue and metabolome analyses at this time. The prespecified testing of the molecular signature comprising of tumor AR-N terminal overexpression the ratio of AR-C terminal expression/ AR-N terminal expression ≥ 0.8 and CYP17 expression exhibits a significant predictive value (p value Tumor Markers Primary Resistance (%) Benefit (%) P Value Fisher Test Ki67 >20% 5 (29) 2 (13) 0.4 ERG presence 8/21 (38) 1/19 (6) 0.023 GR presence 7/21(33) 0.723 ANDROGEN SIGNATURE AR-N overexpression + CYP17 expression AR-C/ AR-N ≥0.8 4/22 (18) 18 /19 (82) Conclusions: Conclusion and future direction: This initial prespecified testing of previously identified andogen signaling molecular signature, is highly supportive of its predictive value in maximal androgen deprivation strategies in mCRPC. These findings warrant validation in a study selecting for treatment based on signature presence. Disclosure: E. Efstathiou and C. Logothetis: Research funding, ad board, honoraria: JnJ, BMS, Pfizer, Bayer, Sanofi, Astellas, Takeda, Viamet; A. Aparicio: Research funding: JnJ, BMS, Pfizer, Bayer, Sanofi, Astellas, Takeda, Viamet. All other authors have declared no conflicts of interest.

Adjuvant radiotherapy after prostatectomy: have randomized clinical trials had any impact?

The objective was to evaluate if the release of randomized trials evaluating the impact of adjuvant radiotherapy after prostatectomy in high risk patients had any impact on national practice patterns in patients with at least two high risk features. The SEER database was used to extract data for patients with a diagnosis of prostate adenocarcinoma from the years 2004–2010, and who underwent prostatectomy with pathologic features of both extracapsular extension (ECE) and positive margins. Adjuvant radiotherapy (ART) utilization was calculated on a yearly basis, and odds ratios were calculated for the likelihood of ART use by year compared to 2004. Between 2004 and 2010, 5,231 patients were identified who underwent prostatectomy with both ECE and positive margins, of which only 19 % received ART. ART utilization was 21, 20, 22, 20, 18, 18, and 15 % for the years 2004–2010, respectively. Odds ratios demonstrated that the likelihood of ART to be used compared to 2004 demonstrated a statistical decrease from 0.97 (95 % C.I. 0.76–1.25, p = 0.85) in 2005 to 0.67 (95 % C.I. 0.51–0.90, p < 0.01) in 2010. At the end of the study time period, patients with higher risk disease were more likely to receive ART, with differences noted in clinical T stage, pretreatment PSA, Gleason score, Gleason patterns, and D’Amico risk classification (largest p = 0.02). The release of randomized controlled trials demonstrating clinical and survival benefits with ART use in high risk patients has failed to increase the utilization of ART, instead demonstrating decreased utilization. In light of recently published guidelines, future changes will be of interest.

Early closure of phase II prospective study on acute and late tolerance of hypofractionated radiotherapy in low-risk prostate cancer patients

AimTo assess acute and late toxicity of hypofractionated radiotherapy, its efficacy and impact on quality of life in patients with low-risk prostate cancer. Materials and methodsSince August 2006 to October 2007, 15 prostate cancer patients with favorable clinical features, aged 54–74 years (mean 67 years) entered the study. Tumor stage in the majority (73%) of patients was T2a, the mean pretreatment PSA value was 7.2ng/ml (range 5–10.9ng/ml). The study group was treated 3 times a week with 4Gy per fraction to the total dose of 60Gy within 5 weeks. 3D conformal treatment planning was used with no fiducial markers. Acute and late toxicity was evaluated using modified EORTC/RTOG/LENT scoring systems. Patients regularly filled the EORTC QLQ-PR25 questionnaires. ResultsAll patients completed radiotherapy according to the plan. During radiotherapy, 26% of patients had grade 1–2 rectal symptoms. The incidence of acute urinary toxicity score was 26%, 60%, and 14% for grade 0–1, 2 and 3, respectively. One year after RT, the incidence of grade 2 GI toxicity was 27%, which was the reason for an early closure of the accrual. Grade 2 late urinary toxicity was noted in 20% of patients. The mean PSA level was 0.61ng/ml after 24 months and 0.47ng/ml after 36 months (range: 0.06–1.54ng/ml). ConclusionsLow number of patients does not allow to determine the influence of hypofractionation on unsatisfactory tolerance of this regimen. Suboptimal (from the present day's perspective) target localization (no fiducial markers) could potentially explain higher than expected late GI reactions in our series.

233: Clinical and prognostic values of the pretreatment PSA doubling time in patients with prostate cancer

233: Clinical and prognostic values of the pretreatment PSA doubling time in patients with prostate cancer

B12 - Clinical and prognostic values of the pretreatment PSA doubling time in patients with prostate cancer

B12 - Clinical and prognostic values of the pretreatment PSA doubling time in patients with prostate cancer

MP46-12 FOURTEEN YEARS OF EXPERIENCE IN LOW DOSE RATE BRACHYTHERAPY FOR EARLY-STAGE PROSTATE CANCER IN ITALY: CHARACTERISTICS AND BIOCHEMICAL OUTCOMES IN A COHORT OF 2279 PATIENTS FROM NINE ITALIAN CENTRES

You have accessJournal of UrologyProstate Cancer: Localized IV1 Apr 2014MP46-12 FOURTEEN YEARS OF EXPERIENCE IN LOW DOSE RATE BRACHYTHERAPY FOR EARLY-STAGE PROSTATE CANCER IN ITALY: CHARACTERISTICS AND BIOCHEMICAL OUTCOMES IN A COHORT OF 2279 PATIENTS FROM NINE ITALIAN CENTRES Francesco Mistretta, Andrea Losa, Luciano Dante Nava, Paola Mangili, Giovanni Fellin, Francesco Pio Mangiacotti, Giovanni Ghiso, Vincesco Fusco, Marcello Mignogna, Beniamino La Face, Marco Stefanacci, Giovanni Silvano, and Maria Alessandra Mirri Francesco MistrettaFrancesco Mistretta More articles by this author , Andrea LosaAndrea Losa More articles by this author , Luciano Dante NavaLuciano Dante Nava More articles by this author , Paola MangiliPaola Mangili More articles by this author , Giovanni FellinGiovanni Fellin More articles by this author , Francesco Pio MangiacottiFrancesco Pio Mangiacotti More articles by this author , Giovanni GhisoGiovanni Ghiso More articles by this author , Vincesco FuscoVincesco Fusco More articles by this author , Marcello MignognaMarcello Mignogna More articles by this author , Beniamino La FaceBeniamino La Face More articles by this author , Marco StefanacciMarco Stefanacci More articles by this author , Giovanni SilvanoGiovanni Silvano More articles by this author , and Maria Alessandra MirriMaria Alessandra Mirri More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1445AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives To report the characteristics and biochemical outcomes of a cohort of 2279 localized prostate cancer (PCA) patients treated with low-dose rate brachytherapy ( LDR-BT) in 9 Italian centres (Trento, Milan S. Raffaele, Savona, Brescia, Lucca, Pistoia, Rionero in Vulture, Rome, Taranto). Methods From 1998 to 2012, 2279 patients with localized PCA were treated with iodine-125 (125I) or palladium-103 (103Pd) implants. Global data were collected and retrospectively analyzed. Patients were stratified into low (LR), intermediate (IR) and high (HR) risk groups through the D’Amico’s risk group classification. Freedom from biochemical failure (FFbF) and overall (OS) and disease specific (DSS) survival were calculated according to the Kaplan-Meier method. Biochemical failure was defined according to the Phoenix (PSA nadir plus 2 ng/mL) definition. Results Overall median follow-up was 44 months (3-143). Patients lost to follow up were 243/2279 (10,7%). Median age was 67 years (45-83), median pre-treatment PSA value was 6,66 ng/ml (0,64 -80) and the average pre-implant prostate volume was 35,7 cm3 (4-86,6). According to D’Amico’s risk group classification, 1603 (70,3%) patients has been defined as LR, 493 (21,6%) as IR, 59 ( 2,6%) as HR while 124 (5,4%) were not assessable because of the lack of completeness of data. Neo-adjuvant hormone therapy (OT) was prescribed to the 35,1 % (562/1603) of LR patients, to the 46,6% (230/493) of IR patients and to the 47,5% (28/59) of HR patients. 2197 (96,4%) patients received LDR-BT as a single curative modality and 82 (3,6%) as a boost with external beam RT. I125 and Pd 103 seeds were implanted in 2214 (97,1%) and 65 (2,8%) patients, respectively. The median D90 in patients implanted as monotherapy, was 150,8 Gy for I125 and 126,5 Gy for Pd103. The average V100 was 92% and median 94% for the group of I125 implants, and 88,7% and 90,3 for Pd 103 implants. The 5ys and10ys actuarial OS was 94% and 85%, and the same figures were 99% and 96% for DSS. The 3ys, 5ys,7ys and 10ys FFbF was overall 95%, 93%, 90% and 84%. The 5ys FFbF was 96%, 87% and 75% for LR, IR and HR group respectively. The 5ys FFbF was 95% and 90% if was achieved a D90 > or < 90% of prescribed dose. Conclusions This multi-institutional early report provides information on a large proportion of Italian patients. Our results indicate that a good biochemical outcome is achieved with permanent implant and that an implant of good quality, both for case selection and post implant dosimetric parameters, has been obtained. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e514 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Francesco Mistretta More articles by this author Andrea Losa More articles by this author Luciano Dante Nava More articles by this author Paola Mangili More articles by this author Giovanni Fellin More articles by this author Francesco Pio Mangiacotti More articles by this author Giovanni Ghiso More articles by this author Vincesco Fusco More articles by this author Marcello Mignogna More articles by this author Beniamino La Face More articles by this author Marco Stefanacci More articles by this author Giovanni Silvano More articles by this author Maria Alessandra Mirri More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Statin use is associated with decreased prostate cancer recurrence in men treated with brachytherapy

Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.

Type and dose of radiotherapy used for initial treatment of non-metastatic prostate cancer

BackgroundWe sought to describe patterns of initial radiotherapy among non-metastatic prostate cancer (PC) patients by recurrence risk groups.MethodsMedical records were abstracted for a sample of 9017 PC cases diagnosed in 2004 as a part of the Center for Disease Control and Prevention’s Prostate and Breast Patterns of Care Study in seven states. Non-metastatic PC cases are categorized as low-risk (LR), intermediate-risk (IR) or high-risk (HR) groups based on pretreatment PSA, tumor stage, and Gleason score per 2002 NCCN guidelines. Univariate and multivariate analyses were employed to determine factors associated with the type and dose of radiotherapy by the risk groups.ResultsOf the 9,017 patients, 3153 who received definitive radiotherapy either alone or in combination with hormone therapy (HT) were selected for in-depth analysis. Multivariate models showed that LR patients were more likely to receive seed implant brachytherapy (BT) than those in higher risk groups. Those in the IR group were most likely to receive external beam radiotherapy (EBRT) combined with BT or high-dose radiotherapy. Use of HT in combination with radiotherapy was more common in the IR and HR groups than for LR patients. Intensity modulated radiation treatment (IMRT) was used to treat 32.6% of PC patients treated with EBRT, with the majority (60.6%) treated with high-dose radiotherapy.ConclusionsRadiotherapy types and dosage utilization varied by PC risk groups. Patients in IR were more likely than those in LR or HR to receive high-dose radiotherapy. IMRT was used in about one third of patients to deliver high-dose radiotherapy.