High-risk PCa Research Articles

Abstract 1099: Testosterone abolishes cabazitaxel efficacy in an in vivo model of prostate cancer and affects intratumoral concentrations

Abstract Introduction Docetaxel combined with castration provides a major survival benefit in newly diagnosed metastatic PCa. Conversely, docetaxel without castration in high-risk localized PCa is not active. Cabazitaxel is a new taxane retaining its activity in tumors resistant to docetaxel and new hormonal therapies. We aimed at better characterizing in vivo the relationship between cabazitaxel and circulating androgens in a preclinical human-derived xenograft model of castration-resistant prostate cancer (CRPC). Material and methods Athymic nude mice were inoculated with the androgen receptor wt, PSA secreting CRPC cell line PC346C-DCC-K. Mice were surgically castrated when tumors were established (tumor volume (TV) of 150 mm3). After 7 days, mice were randomized to receive testosterone (40 mg) or empty pellet. The following day mice were injected with one bolus injection of cabazitaxel (33 mg/kg) or NaCl intraperitoneally. Mice were sacrificed when tumors exceeded a volume of 1,500 mm3 or the maximum follow-up of 90 days after cabazitaxel treatment. Blood was sampled biweekly for PSA and testosterone and analyzed by an immunoassay. In a second in vivo experiment intratumoral uptake of cabazitaxel was determined in the presence and absence of testosterone using a similar experimental set-up, with the exception that mice were sacrificed 7 days after cabazitaxel treatment. Here, intratumoral cabazitaxel concentrations were determined in snap frozen tumors by LC/MS-MS and corrected for tumor weight. Results Cabazitaxel treatment of castrated male mice bearing PC346C-DCC-K tumors resulted in a complete or near-complete antitumor response. In contrast, in mice supplemented with testosterone the anti-tumor effect of cabazitaxel was not significantly different from placebo (median time till TV 1,500 mm3 48 and 45 days resp.). Importantly, testosterone supplementation alone did not significantly affect tumor growth, confirming the CRPC nature of the (PC346C-DCC-K) xenograft. Interestingly, in tumors of testosterone supplemented castrated mice the intratumoral cabazitaxel concentrations were significantly decreased compared to mice that did not receive testosterone (0.39 ng cabazitaxel per mg tumor tissue vs. 1.36 ng/mg, t-test p=0.0032). Conclusions These findings indicate that circulating testosterone significantly impairs the efficacy of cabazitaxel. Testosterone supplementation may alter the metabolism of cabazitaxel, or may interfere with uptake and/or accumulation of cabazitaxel in PCa cells. We will further investigate the relationship between circulating androgens and intratumoral cabazitaxel accumulation as well as anti-tumor efficacy. The study was supported by a research grant from Sanofi Citation Format: Lisanne Mout, Corrina de Ridder, Debra Stuurman, Peter Bruijn, Ron H. Mathijssen, Ronald de Wit, Martijn P. Lolkema, Wytske M. Weerden. Testosterone abolishes cabazitaxel efficacy in an in vivo model of prostate cancer and affects intratumoral concentrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1099. doi:10.1158/1538-7445.AM2017-1099

Adjuvant androgen deprivation (AD) +/- mitoxantrone + prednisone (MP) in patients with high-risk prostate cancer (PC) post radical prostatectomy (RP): Phase III intergroup trial S9921.

5019 Background: Patients (pts) with high-risk PC post RP are at risk of systemic relapse with related morbidity/mortality. Adjuvant AD can reduce this risk. In 1999, based on available data, we hypothesized that adjuvant MP + 2 years (ys) of AD can further reduce mortality. Methods: Eligible pts had cT1-T3, N0 PC with post RP > = 1 high risk factors defined as Gleason sum (GS) ≥ 8, pT3b, pT4, pN+, GS 7 + positive margin or any of these preoperative findings (in pts with neoadjuvant AD): preoperative PSA of > 15 ng/ml, bx GS score > 7, or PSA of > 10 ng/ml + bx GS > 6. Pts had to have post RP PSA = < 0.2 ng/ml, were stratified by T, N, GS, and adjuvant radiation plan and randomized: Arm 1 AD (bicalutamide + goserelin for 2 ys) or Arm 2 AD + 6 cycles m 12 mg/m2 + P 5mg BID. Primary endpoint: overall survival (OS). Median OS was estimated to be 10 ys in AD arm requiring 680 pts/arm to detect a hazard ratio (HR) of 1.30 with 92% power and one-sided α = 0.05. Results: 983 pts (961 eligible intent to treat) with median age 60 ys and median PSA 7.6 ng/ml were randomized to AD or AD + MP from 10/99 -1/07 when the DSMC recommended stopping accrual due to higher leukemia rate in Arm 2. 16% had N1 (Group “Gr” 1), 61% GS ≥8 or pT3b (Gr 2),23% other risk factors (Gr 3). Median time to testosterone recovery was 9.5 months. Median follow-up (f/u) 11.2 ys. Conclusions: OS was higher than anticipated in both arms; MP did not improve OS and increased other malignancy risk. These data illustrate that systemic therapy benefit cannot be extrapolated from different disease stages and the importance of adequate f/u in adjuvant PCa trials. The remarkable DFS and 10 y OS, irrespective of risk extent, may be result of risk definition, and/or 2 ys AD. Pending definitive data 2 ys adjuvant AD for high-risk PCa post RP is a reasonable option to consider. Clinical trial information: NCT00004124. [Table: see text]

Efficacy and adverse effects of hypofractionated radiotherapy versus conventionally fractionated radiotherapy in patients with intermediate-to high-risk localized prostate cancer: a meta-analysis

Objective To compare the efficacy and adverse effects of hypofractionated radiotherapy versus conventionally fractionated radiotherapy for intermediate-to high-risk localized prostate cancer . Methods A literature search was performed in PubMed, Embase, Web of Science, CNKI, VIP database, and Wanfang Data to collect the controlled clinical trials of hypofractionated radiotherapy versus conventionally fractionated radiotherapy in patients with intermediate-to high-risk localized PCa published up to August 31, 2016. Stata 12.0 was used for meta-analysis. The difference between two groups was estimated by calculating the hazard ratio (HR) or risk ratio (RR) with 95% confidence interval (CI). Results According to the inclusion and exclusion criteria, a total of 5 controlled clinical trials involving 1621 patients with PCa were included in this meta-analysis. The meta-analysis showed that overall survival (HR=1.00, 95%CI: 0.85-1.17, P=0.980) and biochemical failure (RR=0.87, 95%CI: 0.68-1.12, P=0.274) were comparable between the two groups. Compared with the conventionally fractionated radiotherapy, the incidence of acute gastrointestinal adverse events (grade≥2) was significantly higher in the hypofractionated radiotherapy (RR=1.94, 95%CI: 1.23-3.06, P=0.004). However, there were no significant differences in the incidence of acute genitourinary adverse events (grade≥2)(RR=1.03, 95%CI: 0.92-1.14, P=0.626), late gastrointestinal adverse events (grade≥2)(RR=1.17, 95%CI: 0.90-1.51, P=0.238), and late genitourinary adverse events (grade≥2)(RR=1.11, 95%CI: 0.94-1.30, P=0.228) between the two groups. Conclusions Conventionally fractionated radiotherapy and hypofractionated radiotherapy have comparable therapeutic effects in patients with intermediate-to high-risk localized PCa. Although the patients treated with hypofractionated radiotherapy have a higher incidence of acute gastrointestinal adverse events than those treated with conventionally fractionated radiotherapy, the incidence of late gastrointestinal and genitourinary adverse events is comparable between the two groups of patients and the adverse effects are tolerable. Key words: Prostate neoplasms/radiotherapy; Radiotherapy, hypofractionated; Radiotherapy, conventional; Meta-analysis

MP53-13 FREEDOM FROM ANDROGEN DEPRIVATION AND RADIOTHERAPY THERAPY AFTER UPFRONT MINIMALLY INVASIVE SURGERY FOR HIGH-RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III1 Apr 2017MP53-13 FREEDOM FROM ANDROGEN DEPRIVATION AND RADIOTHERAPY THERAPY AFTER UPFRONT MINIMALLY INVASIVE SURGERY FOR HIGH-RISK PROSTATE CANCER Pol Servian Vives, Amit Patel, David Eldred-Evans, Declan Cahill, Christian Brown, Ben Challacombe, and Mathias Winkler Pol Servian VivesPol Servian Vives More articles by this author , Amit PatelAmit Patel More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Declan CahillDeclan Cahill More articles by this author , Christian BrownChristian Brown More articles by this author , Ben ChallacombeBen Challacombe More articles by this author , and Mathias WinklerMathias Winkler More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1664AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Up front tailor-made wide excision surgery is sometimes offered to men as part of combined modality treatment with adjuvant radiotherapy +/- androgen deprivation therapy (ADT) for high risk and non-metastatic prostate cancer. Particularly young men want to avoid long periods of ADT which is required for primary radiotherapy treatment. Upfront surgery is therefore seen as a reasonable alternative to achieve cure without ADT. We prospectively assessed short term PSA recurrence rates, the need for adjuvant radiotherapy and ADT. METHODS 278 patients with high risk PCa (47.5% were locally advanced), underwent laparoscopic or robotic radical prostatectomy with pelvic lymphadenectomy from July 2007 to July 2016 at three inner London tertiary referral centres. D′Amico criteria (cT2c, PSA>20, Gleason grade 8-10) were used to define high risk. Supersensitive PSA measurements were used. PSA recurrence was defined as two tests results above 0.02. Kaplan-Meier survival estimates were generated. A small number of patients were offered radiotherapy +/- ADT for undetectable PSA nadir based on the presence of pathological risk factors. Some patients were randomised to the RADICALS study(CRUK/07/008). Uni and multivariate analysis was performed on all available variables. Kaplan-Meier estimates were calculated. Cox multivariate regression analysis was computed to identify pre- and post-operative factors associated with PSA recurrence. RESULTS Median follow up was 34 months (range 0.9-98 months). Of all patients 55.4% did not have PSA recurrence, 38.1% required radiotherapy and 25.2% ADT. Positive margins (p=0.014)and tumour volume (p=0.041) were independently predictive of PSA recurrence. Tumour volume >4cm3 may be predictive of almost certain biochemical recurrence with supersensitive PSA. 5 year free recurrence survival was 51% globally and 50.3% and 18.4% for tumour volume <4cm3 and >4cm3 respectively. CONCLUSIONS Young men may have a high chance to avoid ADT (75% in three years) if treated with surgery alone or in combination with radiotherapy. Tumour volume in addition to margin status is a strong predictor of biochemical recurrence in high risk prostate cancer. Since tumour volume can now be obtained pre-operatively with later generation CAD (computer-aided design) software it could be a meaningful pre-operative risk stratification tool for treatment selection and new study designs. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e718 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Pol Servian Vives More articles by this author Amit Patel More articles by this author David Eldred-Evans More articles by this author Declan Cahill More articles by this author Christian Brown More articles by this author Ben Challacombe More articles by this author Mathias Winkler More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Efficacy of a neoadjuvant gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate in high-risk prostate cancer: A single-center study.

e542 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone agonist plus low-dose estramustine (LHRH agonist + EMP) prior to radical prostatectomy (RP). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate (GnRH antagonist + EMP) in patients with high-risk Pca. Methods: Between September 2005 and March 2016, we identified 406 high-risk Pca patients of whom 136 received neoadjuvant GnRH antagonist + EMP and 270 received LHRH agonist + EMP before RP. We retrospectively evaluated the clinical and pathological covariates between the two groups. The primary endpoint was the rate of pathological ≤ T2 status, and the secondary endpoint was BRFS. Results: The rates of pathological ≤ T2 status were 80.2% and 61.5% in the GnRH antagonist + EMP and LHRH agonist + EMP groups, respectively ( P &lt; 0.001). The 3-year BRFS rates were 97.8% and 85.2% in the GnRH antagonist + EMP and LHRH agonist + EMP groups, respectively ( P = 0.021). Multivariate analysis revealed that biopsy Gleason score, GnRH antagonist + EMP, and clinical T stage were independent predictors of pathological ≤ T2 status in surgical specimens. Conclusions: Our findings suggest that neoadjuvant GnRH antagonist + EMP followed by RP may improve the pathological outcomes and reduce the risk of biochemical recurrence in patients with high-risk Pca. Further prospective studies to confirm these findings are warranted.

The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: A multi-institutional analysis.

e543 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low-dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). The aim of this study was to assess whether neoadjuvant LHRH+EMP confers an oncological benefit for high-risk Pca compared to extended lymph node dissection (e-PLND). Methods: The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at 4 institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The neoadjuvant LHRH+EMP therapy included the administration of 280 mg/day of LHRH and EMP for 6 months before RP. The outcome measure was BRFS. Results: The 5-year BRFS rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9% and 54.7%, respectively ( P &lt; 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Conclusions: Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP might reduce the risk of biochemical recurrence.

Efficacy of a neoadjuvant gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate in high-risk prostate cancer: a single-center study.

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone agonist plus low-dose estramustine (LHRH+EMP) prior to radical prostatectomy (RP). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate (GnRH+EMP) in patients with high-risk Pca. Between September 2005 and March 2016, we identified 406 high-risk Pca patients of whom 136 received neoadjuvant GnRH+EMP (GnRH group) and 270 received LHRH+EMP (LHRH group) before RP. We retrospectively evaluated the clinical and pathological covariates between the two groups. The endpoint was the rate of pathological T0 status. The rates of pathological T0 status were 11.0 and 8.9% in the GnRH group and LHRH group, respectively (P=0.490). The 2-year BRFS rates were 97.8% in the GnRH group and 87.8% in the LHRH group (P=0.027). Our findings suggest that neoadjuvant GnRH antagonist+EMP followed by RP may improve the pathological outcomes and reduce the risk of biochemical recurrence in patients with high-risk Pca. Further prospective studies to confirm these findings are warranted.

Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection.

To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2-6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8-10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: a multi-institutional analysis.

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH+EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P<0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP might reduce the risk of biochemical recurrence.

V4-10 18 F-CHOLINE PET/CT GUIDED SUPEREXTENDED PLND FOR VERY HIGH RISK PCA. FEASIBILITY AND SURGICAL TECHNIQUE

You have accessJournal of UrologyRobotics – Prostate/Novel Imaging1 Apr 2016V4-10 18 F-CHOLINE PET/CT GUIDED SUPEREXTENDED PLND FOR VERY HIGH RISK PCA. FEASIBILITY AND SURGICAL TECHNIQUE Giuseppe Simone, Riccardo Mastroianni, Rocco Papalia, Mariaconsiglia Ferriero, Francesco Minisola, Leonardo Misuraca, Gabriele Tuderti, Salvatore Guaglianone, Giovanni Muto, and Michele Gallucci Giuseppe SimoneGiuseppe Simone More articles by this author , Riccardo MastroianniRiccardo Mastroianni More articles by this author , Rocco PapaliaRocco Papalia More articles by this author , Mariaconsiglia FerrieroMariaconsiglia Ferriero More articles by this author , Francesco MinisolaFrancesco Minisola More articles by this author , Leonardo MisuracaLeonardo Misuraca More articles by this author , Gabriele TudertiGabriele Tuderti More articles by this author , Salvatore GuaglianoneSalvatore Guaglianone More articles by this author , Giovanni MutoGiovanni Muto More articles by this author , and Michele GallucciMichele Gallucci More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1814AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent evidences have highlighted the potential benefits of surgical treatment for very high risk and oligometastatic prostate cancer (PCa) patients. In this video we highlight the surgical steps of a 18 fluoro-choline PET-CT guided superextended pelvic lymph node dissection (PLND) during robot assisted radical prostatectomy (RARP) in a 56 yr-old patient with a cT3/N1 Gleason 8 PCa. METHODS The patient was placed in a steep trendelemburg position and a 6 trocar access, as for a robot assisted radical cystectomy, was performed. Separate package PLND was performed to assess PET-CT accuracy. Surgical steps were: identification of inferior mesenteric artery and dissection of nodes around the IMA according to PET-CT; paraaortic and left common iliac node dissection; presacral node dissection; right PLND starting from the common iliac nodes towards the obturator fossa, dissecting the fossa of Marcille; external iliac, internaliliac and obturator node dissection; deflection of the sigma on the right side, and left PLND as described for the right side; extrafascial radical prostatectomy (not shown in the video). RESULTS Operative time was 190 minutes. Estimated blood loss was 130 mL. Postoperative course was uneventful and the patient was discharged on 3th postopeative day. Pathologist reported a pT3b Gleason score 9 PCa with extraprostatic extension, negative surgical margins and 24 positive nodes out of 40 dissected, confirming nodal metastases in the 4 nodal packages highlighted by the PET-CT scan (paraaortic/left common, distal right common, bilateral obturator). Postoperative 1-mo PSA level was 0.3 ng/mL. Patient started maximum androgen block and 9 mo postoperatively has undetectable PSA levels. CONCLUSIONS RARP demosntrated to be a feasible and safe procedure for locally advanced PCa. The use of 18-F-choline PET-CT is a rational guide to perform an imaging guided PLND for clinically node positive patients. Reduced invasiveness of this surgery and optimal nodal clearance may contribute to expand indication for surgery in this setting of patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e519-e520 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Giuseppe Simone More articles by this author Riccardo Mastroianni More articles by this author Rocco Papalia More articles by this author Mariaconsiglia Ferriero More articles by this author Francesco Minisola More articles by this author Leonardo Misuraca More articles by this author Gabriele Tuderti More articles by this author Salvatore Guaglianone More articles by this author Giovanni Muto More articles by this author Michele Gallucci More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP09-12 FREEDOM FROM BIOCHEMICAL RECURRENCE AND METASTASIS IN MEN WITH VERY HIGH RISK PROSTATE CANCER TREATED AT A TERTIARY CENTER: VALIDATION OF A NEW RISK STRATUM

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2016MP09-12 FREEDOM FROM BIOCHEMICAL RECURRENCE AND METASTASIS IN MEN WITH VERY HIGH RISK PROSTATE CANCER TREATED AT A TERTIARY CENTER: VALIDATION OF A NEW RISK STRATUM Debasish Sundi, Jeffrey Tosoian, Mary Achim, John Davis, Curtis Pettaway, John Ward, Surena Matin, Louis Pisters, Edward Schaeffer, Ashley Ross, and Brian Chapin Debasish SundiDebasish Sundi More articles by this author , Jeffrey TosoianJeffrey Tosoian More articles by this author , Mary AchimMary Achim More articles by this author , John DavisJohn Davis More articles by this author , Curtis PettawayCurtis Pettaway More articles by this author , John WardJohn Ward More articles by this author , Surena MatinSurena Matin More articles by this author , Louis PistersLouis Pisters More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Ashley RossAshley Ross More articles by this author , and Brian ChapinBrian Chapin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2299AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Oncologic outcomes of men with high risk prostate cancer (HR PCa) are known to be quite divergent based on the severity of their pre-treatment tumor characteristics. Very high risk (VHR) PCa was originally defined at Johns Hopkins in 2013 and adapted by the NCCN in 2015. In a cohort of men with high risk PCa treated by radical prostatectomy (RP) at MD Anderson Cancer Center (MDACC, 2005-2015), we evaluated the association of VHR PCa with oncologic outcomes. METHODS After institutional review board approval, medical records of HR men treated by RP were abstracted. VHR was defined as 1) presence of primary pattern 5 on biopsy OR 2) presence of more than 4 biopsy cores containing Gleason sum 8-10 OR 3) presence of multiple HR features OR 4) clinical stage T3b-T4, effectively combining previously described Hopkins and NCCN VHR criteria. Hazards for biochemical recurrence (BCR) and metastasis were modeled with Cox proportional hazards models (Stata 13.1). Multivariable analyses adjusted for patient age, treatment year, and receipt of neoadjuvant androgen deprivation therapy. RESULTS Of 658 men with HR PCa treated by RP, 203 were VHR (30.9%). The most common VHR qualification criterion was presence of multiple HR features (152/203, 74.9%). Compared to HR men, VHR patients were more likely to have a positive surgical margin (63.4% vs 30.6%, p<0.001) and pN1 disease (77.2% vs 29.4%, p<0.001). In multivariable models, VHR men were 2-3 fold more likely to sustain biochemical recurrence or metastasis after surgery (Table). CONCLUSIONS In a contemporary cohort of men with HR PCa undergoing RP at a tertiary center, VHR PCa was associated with adverse pathologic and oncologic outcomes, particularly pN1 disease and subsequent metastasis. The distinct clinical outcomes of VHR men may warrant more aggressive or combined modality treatment approaches to maximize cancer free survival. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e98 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Debasish Sundi More articles by this author Jeffrey Tosoian More articles by this author Mary Achim More articles by this author John Davis More articles by this author Curtis Pettaway More articles by this author John Ward More articles by this author Surena Matin More articles by this author Louis Pisters More articles by this author Edward Schaeffer More articles by this author Ashley Ross More articles by this author Brian Chapin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP57-18 EXPRESSION OF STEROID HORMONE RECEPTORS IN RESIDUAL CANCER AND STROMAL CELLS AFTER NEOADJUVANT CHEMOHORMONAL THERAPY WITH DOCETAXAL FOR HIGH-RISK LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III1 Apr 2016MP57-18 EXPRESSION OF STEROID HORMONE RECEPTORS IN RESIDUAL CANCER AND STROMAL CELLS AFTER NEOADJUVANT CHEMOHORMONAL THERAPY WITH DOCETAXAL FOR HIGH-RISK LOCALIZED PROSTATE CANCER Shintaro Narita, Taketoshi Nara, Mingguo Huang, Koichiro Takayama, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Hiroshi Nanjo, Shigeru Satoh, and Tomonori Habuchi Shintaro NaritaShintaro Narita More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Koichiro TakayamaKoichiro Takayama More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Atsushi MaenoAtsushi Maeno More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , Hiroshi NanjoHiroshi Nanjo More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.672AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies suggest that activation of steroid hormone receptors (SHRs) is associated with PCa progression and resistance to chemohormonal therapy. In this study, we investigated SHR expressions in human PCa tissues in patients who underwent radical prostatectomy (RP) with and without neoadjuvant chemohormonal therapy. METHODS A tissue microarray with 210 cores from 70 high-risk localized PCa patients who underwent RP without neoadjuvant therapy (NNA), with neoadjuvant hormonal therapy (NHT), or with neoadjuvant chemohormonal therapy with docetaxel (CHT) was used to assess the epithelial and stromal expressions of four SHRs including androgen receptor (AR), glucocorticoid receptor (GR), estrogen receptor (ER) alpha, and progesterone receptor (PR). Expression levels of SHRs between the three groups were statistically assessed. Multivariate analyses were performed to investigate the prognostic factors of BCR in patients who underwent surgery with CHT. RESULTS AR and GR were expressed in both residual cancer and stromal cells, whereas ER alpha and PR were mainly expressed in stromal cells. The mean nuclear AR immunoreactivity score in residual cancer cells was significantly higher in the NNA group than in the NHT and CHT groups. The mean nuclear GR immunoreactivity score in residual cancer cells and mean nuclear ER alpha and PR in stromal cells were significantly higher in the CHT group than in the NNA and NHT groups. The patients with a low PR immunoreactivity score in stromal cells had a significantly higher BCR rate than those with a high nuclear immunoreactivity score (p = 0.011). In multivariate analysis, the number of risk factors constituting the classification of high-risk, a preoperative PSA level, pathological chemotherapy effect, and low nuclear PR immunoreactivity score in stromal cells were independent prognostic factors for BCR. CONCLUSIONS Stromal PR expression may be a potential prognostic marker for BCR in high-risk PCa patients who underwent radical prostatectomy after neoadjuvant chemohormonal therapy. The expression of SHRs in both residual cancer and stromal cells may play an important role in PCa resistance to chemohormonal therapy. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e759-e760 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Shintaro Narita More articles by this author Taketoshi Nara More articles by this author Mingguo Huang More articles by this author Koichiro Takayama More articles by this author Kazuyuki Numakura More articles by this author Hiroshi Tsuruta More articles by this author Atsushi Maeno More articles by this author Mitsuru Saito More articles by this author Takamitsu Inoue More articles by this author Norihiko Tsuchiya More articles by this author Hiroshi Nanjo More articles by this author Shigeru Satoh More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP07-09 ALDO-KETO-REDUCTASE 1C3 EXPRESSION IS AN INDEPENDENT RISK FACTOR FOR OCCURRENCE OF CASTRATION RESISTANT PROSTATE CANCER IN HIGH RISK PROSTATE CANCER TREATED WITH NEOADJUVANT THERAPY AND PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2016MP07-09 ALDO-KETO-REDUCTASE 1C3 EXPRESSION IS AN INDEPENDENT RISK FACTOR FOR OCCURRENCE OF CASTRATION RESISTANT PROSTATE CANCER IN HIGH RISK PROSTATE CANCER TREATED WITH NEOADJUVANT THERAPY AND PROSTATECTOMY Yasuhiro Hashimoto, Hiromichi Iwamura, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Takuya Koie, and Chikara Ohyama Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Hiromichi IwamuraHiromichi Iwamura More articles by this author , Atsushi ImaiAtsushi Imai More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Takuya KoieTakuya Koie More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2212AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is implicated in the development of castration-resistant prostate cancer (CRPC). In this study, we examined AKR1C3 expression in surgical specimens of high risk prostate cancer treated with neoadjuvant LHRH + EMP, and we investigate the correlation between the expression level of AKR1C3 and the occurrence of CRPC. METHODS High-risk Pca was defined by the D'Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study from July 2005 to August 2010. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone (< 50 ng/dL). Along with the routine pathological assessment, AKR1C3 expression was evaluated in tissue microarray analysis (TMA) in all patients. A multivariable Cox proportional hazards model was used to evaluate the association between CRPC and clinical data. RESULTS The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2-95.6). At a median follow-up period of 79.5 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). In TMA, overexpression of AKR1C3 was seemed in 14 patients (13.6%). 5-year CRPC free survival rate of AKR1C3(+) patients (64.2%) was significantly lower than that of AKR1C3(-) patients (97.6%). (Log-rank test: p < 0.001) On multivariable analysis, AKR1C3 expression is an independent risk factor for occurrence of CRPC in this study. (p=0.044) CONCLUSIONS Although the present study was small and preliminary, overexpression of AKR1C3 is an independent risk factor for occurrence of CRPC in the high risk prostate cancer treated with neoadjuvant LHRH + EMP and prostatectomy. Further study is warranted to elucidate its clinical significance. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e79-e80 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yasuhiro Hashimoto More articles by this author Hiromichi Iwamura More articles by this author Atsushi Imai More articles by this author Shingo Hatakeyama More articles by this author Takahiro Yoneyama More articles by this author Takuya Koie More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP18-20 THE NANOKNIFE ELECTROPORATION ABLATION TRIAL (NEAT): A PROSPECTIVE DEVELOPMENT STUDY

effects of combined “TURP+HIFU” for local radical ablation of high risk Prostate Cancer (hrPCa). METHODS: 480 hrPCa patients (T3-4 or initial PSA >20 or Gleason 8-10, N0, M0) were treated with TURP and consecutive transrectal complete HIFU Ablation with Ablatherm Integrated Imaging (EDAP-TMS, Lyon-France) and followed prospectively up to 17 years. “Disease progression” (failure) was defined as: Last PSA>initial PSA (PSAi) or M +/or onset of Salvage Therapy. RESULTS: In a high risk PCa patient cohort with a median follow up of 7 years (0.6-17.8) over all survival was 71.7%, metastasis free survival 91%, cancer specific survival 92.9% and progression free survival 63%. 30% needed adjuvant salvage ADT and 7% other salvage therapies in follow up after median 1.5 (0.1-12.5) years. Therapy induced side effects were: Stress Incontinence 7.9%, Obstruction: 3.7%, Fistula/Osteitis os pubis: 1.5%; UTI: 21.4%. CONCLUSIONS: Local radical prostate cancer ablation through transurethral resection (TURP) and transrectal complete High Intensity Focused Ultrasound (HIFU) with Ablatherm integrated imaging is a valid therapy even in high risk prostate cancer patients.

MP69-08 AN ANALYSIS OF THE MORBIDITY OF LIMITED, EXTENDED, AND SUPER-EXTENDED PELVIC LYMPHADENECTOMY TEMPLATES DURING RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V1 Apr 2016MP69-08 AN ANALYSIS OF THE MORBIDITY OF LIMITED, EXTENDED, AND SUPER-EXTENDED PELVIC LYMPHADENECTOMY TEMPLATES DURING RADICAL PROSTATECTOMY Vidit Sharma, Alessandro Morlacco, Jason E Joseph, Avinash K Nehra, Matthew K Tollefson, R. Houston Thompson, Stephen A Boorjian, Igor Frank, Matthew T Gettman, and R. Jeffrey Karnes Vidit SharmaVidit Sharma More articles by this author , Alessandro MorlaccoAlessandro Morlacco More articles by this author , Jason E JosephJason E Joseph More articles by this author , Avinash K NehraAvinash K Nehra More articles by this author , Matthew K TollefsonMatthew K Tollefson More articles by this author , R. Houston ThompsonR. Houston Thompson More articles by this author , Stephen A BoorjianStephen A Boorjian More articles by this author , Igor FrankIgor Frank More articles by this author , Matthew T GettmanMatthew T Gettman More articles by this author , and R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1386AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The impact of pelvic lymphadenectomy (PLND) templates on operative complications and functional outcomes during radical prostatectomy (RP) remains understudied. Here we analyze a large single institution series to determine the relationship between PLND templates, complications and functional outcomes after RP. METHODS Years 2001 to 2013 of a prospectively maintained single institution RP registry were queried for NCCN intermediate and high risk PCa patients undergoing PLND. Patients received 1 of 4 possible PLND templates: 1) obturator alone; 2) obturator + external iliac; 3) obturator + external iliac + hypogastric (ePLND); and 4) common iliac + ePLND (super-ePLND). Descriptive statistics and multivariate logistic regression models were used to compare rates of complications, 1-yr potency (erections with our without medications) and 1-yr incontinence (1 or more pads per day) across PLND templates. RESULTS Out of 2,962 RPs, there were 735 (24.8%) obturator PLNDs, 574 (19.4%) obturator + external PLNDs, 1501 (50.7%) ePLNDs, and 152 (5.1%) super-ePLNDs. The overall complication rates were 20.6%, 26.5%, 24.5%, and 38.3%, respectively (p<0.001). The incidences of lymphedema (0.3%, 0.2%, 0.5%, 2.7% p=0.001) and lymphocele (1.6%, 1.7%, 2.7%, 6.3%, p=0.005) were significantly higher in the super-ePLND cohort. The groups did not differ significantly in terms of intra-operative complications (1.0%, 2.1%, 0.9%, 2.0%, p=0.089). Rates of venous thromboembolism also did not vary significantly (2.5%, 2.4%, 2.2%, 3.5% p=0.796). On multivariate logistic regression analysis (after adjusting for Age, BMI, pT stage, open vs robotic), only super-ePLND (OR 2.120, p<0.001) remained significantly associated with increased overall complications. At 1 year, potency (61.5%, 48.5%, 45.4%, and 44.8%, p<0.001) was lower and incontinence higher (5.6%, 11.6%, 10.5%, 12.3%, p<0.001) with wider PLND templates. After adjusting for nerve sparing status, age, BMI, open vs robotic, pT stage, adjuvant hormonal therapy, and adjuvant radiation: potency was no longer associated with PLND template (all p>0.05), however incontinence continued to be associated with wider PLND template (Odds ratio range 1.896-2.103, p<0.053). CONCLUSIONS A super-extended PLND was associated with increased overall complications, lymphedema and lymphoceles. An ePLND alone was not independently associated with these complications. Further investigation into the relationship between PLND template and incontinence is warranted. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e900 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Vidit Sharma More articles by this author Alessandro Morlacco More articles by this author Jason E Joseph More articles by this author Avinash K Nehra More articles by this author Matthew K Tollefson More articles by this author R. Houston Thompson More articles by this author Stephen A Boorjian More articles by this author Igor Frank More articles by this author Matthew T Gettman More articles by this author R. Jeffrey Karnes More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract C32: Native American genetic ancestry is protective against prostate cancer in African Americans and European Americans

Abstract Prostate cancer (PCa) incidence and mortality varies by racial/ethnic groups in the U.S. African American (AA) men have a 60% higher incidence and twice the mortality rate of European America (EA) men, while Hispanic Americans and Native Americans have lower incidence rates than EA men. Several genetic admixture studies have examined the role of west African ancestry on prostate cancer risk in AA men, however the influence of Native American ancestry on PCa risk has not been explored. Here we evaluated the relationship between individual genetic ancestry proportions and the likelihood of PCa diagnosis and aggressiveness. Methods: We recruited 40-79 year old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for genotyping of 105 ancestry informative markers. West African, European, and Native American genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the likelihood of having high-risk PCa relative to controls, adjusting for age and family history of PCa. Results: In AAs, NAA ranged from 0.4% to 28.8%. Mean NAA was 4.6% in AA cases, while controls had mean NAA of 6.6%. NAA ranged from 0.5% to 17.4% in EAs. Mean NAA was 5.1% in cases and 6.8% in controls. NAA was negatively associated with PCa diagnosis. AA men in the highest quartile of NAA had significantly reduced odds of PCa diagnosis compared to men in the lowest quartile of NAA (OR 0.47, 95% C.I.: 0.29-0.77). Similarly, EA men in the highest quartile of NAA had significantly reduced odds of PCa diagnosis compared men in the lowest NAA quartile (OR 0.36, 95% C.I.: 0.21-0.61). Additional adjustment of body mass index, education, smoking, alcohol use, and marital status did not change the results. NAA was also negatively associated with diagnosis of high risk PCa in EAs (P=0.04) and also trending in the same direction in AAs however not significant. Conclusions: Our study reveals that NAA is protective against PCa diagnosis and high-risk PCa. Hispanic Americans and Native Americans have lower PCa incidence rates than AAs and EAs, and the identification of inherited genetic or environmental factors that are associated with high NAA may improve PCa risk prediction and/or help to develop prevention strategies. Citation Format: Adam Murphy, Ken Batai, Ebony Shah, Rick A. Kittles. Native American genetic ancestry is protective against prostate cancer in African Americans and European Americans. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C32.

Aldo-keto-reductase 1C3 expression as an independent risk factor for occurrence of castration resistant prostate cancer in high risk prostate cancer treated with neoadjuvant therapy and prostatectomy.

172 Background: Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is implicated in the development of castration-resistant prostate cancer (CRPC). In this study, we examined AKR1C3 expression in surgical specimens of high risk prostate cancer treated with neoadjuvant LHRH + EMP, and we investigate the correlation between the expression level of AKR1C3 and the occurrence of CRPC. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone ( &lt; 50 ng/dL). Along with the routine pathological assessment, AKR1C3 expression was evaluated in tissue microarray analysis (TMA) in all patients. A multivariable Cox proportional hazards model was used to evaluate the association between CRPC and clinical data. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). At a median follow-up period of 79.5 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). In TMA, overexpression of AKR1C3 was seemed in 14 patients (13.6%). 5-year CRPC free survival rate of AKR1C3(+) patients (64.2%) was significantly lower than that of AKR1C3(-) patients (97.6%). (Log-rank test: p &lt; 0.001) On multivariable analysis, AKR1C3 expression is an independent risk factor for occurrence of CRPC in this study. (p = 0.044). Conclusions: Although the present study was small and preliminary, overexpression of AKR1C3 is an independent risk factor for occurrence of CRPC in the high risk prostate cancer treated with neoadjuvant LHRH + EMP and prostatectomy. Further study is warranted to elucidate its clinical significance.

Genetic ancestry and odds of prostate cancer diagnosis in African American and European American men.

86 Background: Although ethnic differences in disease incidence among African American (AA) men may reflect differences in screening behaviors and behavioral and socioeconomic factors, genetic ancestry may be a factor. This study will investigate the association between West African and Native American genetic ancestry and PCa diagnosis. Methods: We enrolled 40-79 year-old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for the genotyping of 105 ancestry informative markers. West African (WAA), European (EA), and Native American (NAA) genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Univariate analysis was performed by Wilcoxon rank-sum test for continuous variables. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the odds of having high-risk PCa relative to controls, adjusting for age, body mass index (BMI), alcohol-use, and family history of PCa. Results: 857 men were enrolled; 34.5 % were diagnosed with PCa, 50.9 % were controls and 14.6 % were men with negative prostate biopsies. AAs comprised 27% of the sample. The median was 63 years (IQR 57 – 68). Among AA men, the median genetic WAA proportion was 0.78 (IQR 0.69 – 0.83) and NAA was 0.04 (IQR 0.02 – 0.09). There was no significant difference in genetic WAA among AA men with and without PCa diagnosis (p = 0.54); however, genetic NAA was significantly lower among PCa cases (median 0.034 vs 0.057,p = 0.03) compared to controls. Among EA men, the media NAA was 0.067 (IQR (0.03 – 0.10). Similarly among EA men, genetic NAA was significantly lower among cancer cases (0.04 vs. 0.08, p &lt; 0.001). On logistic regression, WAA ≥ 88% was associated with increased odds of PCa in AA men (OR 2.6 95% CI 1.1 – 6.7). In both AAs (OR 0.5, 95% CI 0.2 – 1.1) and EAs (OR 0.3, 95 % 0.2 – 0.6), men in the highest genetic NAA quintile had a decreased risk of PCa on logistic regression compared to men in the lowest quintile. Conclusions: Our study reveals that NAA is protective against PCa diagnosis among all men. Additionally, AA men with a high degree of WAA demonstrate an increased risk of PCa. Future work will focus on determining the association of known prostate cancer risk SNPs such as the 8q24 regions and genetic ancestry.

Évaluation préthérapeutique du patient candidat à la chirurgie du cancer de la prostate

To determine the tools of therapeutic decision that push towards surgical treatment in non metastatic prostate cancer eligible to local treatment. The optimized assessment of the disease and eventual comorbidities improves the selection of patients. Patient's files will be presented in the uro-oncological multidisciplinary discussions to validate the customized therapeutic approach proposed. Literature review using Medline (National library of medicine, Pubmed) and Med Science databases based on the scientific pertinence. Research was focused on the diagnosis of prostate cancer, the evaluation of the disease and patient's characteristics, and finally the elements that are with a surgical treatment (past medical history, past surgical history, functional status, patient's comorbidities, and life expectancy). The pretherapeutic oncologic evaluation allows to estimate the risks associated with prostate cancer; it is an essential aspect of therapeutic decision. Several clinical, biological, imaging and pathological criteria allow to guide decision-making according to tumor aggressiveness and risk of recurrence, estimating the results of the different treatments proposed. On the other hand, the evaluation of lower urinary tract symptoms, urinary continence and sexual function, the integration of anatomical data, past medical and past surgical history are all essential for the therapeutic decision, in addition to the comorbidities (Charlson, ASA, ICD). These elements should be taken all together in order to decide for a radical or conservative management of PCa, they guide decision-making in patients candidate for surgery. For example, age plays a key role in the choice of treatment, even in older men at risk of developing high-risk PCa that can affect overall survival. The combined evaluation of the patient and disease characteristics is of utmost importance in oncology, and especially in the treatment of non-metastatic PCa. The role of the anesthesiologist in the analysis and interpretation of comorbidities remains primordial and it is essential for the selection of the right candidates for surgery after being well informed, and orienting them toward surgery in agreement with the prerogatives programs of customized care.

A Novel Technology for Noninvasive Detection of Prostate Cancer DNA in the Blood and Urine of Men With High-Risk PCA Receiving Radiation Therapy and Androgen Suppression

A Novel Technology for Noninvasive Detection of Prostate Cancer DNA in the Blood and Urine of Men With High-Risk PCA Receiving Radiation Therapy and Androgen Suppression