EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. Efficacy and safety of different interventions in castration resistant prostate cancer progressing after docetaxel-based chemotherapy: Bayesian network analysis of randomized controlled trials Long-term follow-up of a phase II trial of chemotherapy plus hormone therapy for biochemical relapse after definitive local therapy for prostate cancer. Androgen suppression plus radiation versus radiation alone for patients with stage D1/pathologic node-positive adenocarcinoma of the prostate: updated results based on national prospective randomized trial Radiation Therapy Oncology Group 85-31. Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31. Radiation Therapy Oncology Group. Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). eRADicAte: A Prospective Evaluation Combining Radium‐223 Dichloride and Abiraterone Acetate Plus Prednisone in Patients With Castration‐Resistant Prostate Cancer Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. Combining carboplatin and etoposide in docetaxel-pretreated patients with castration-resistant prostate cancer: a prospective study evaluating also neuroendocrine features. Feasibility study of a randomized controlled trial comparing docetaxel chemotherapy and androgen deprivation therapy with sequential prostatic biopsies from patients with advanced non-castration-resistant prostate cancer. TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Defining a new testosterone threshold for medical castration: Results from a prospective cohort series. Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group. PTEN Protein Loss and Clinical Outcome from Castration-resistant Prostate Cancer Treated with Abiraterone Acetate Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer
CONTEXT The most recent summary of the European Association of Urology ( EAU ) guidelines on prostate cancer ( PCa ) was published in 2011 . OBJECTIVE To present a summary of the 2013 version of the EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined PCa . EVIDENCE ACQUISITION A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group . The guidelines have been up date d , and levels of evidence and grade s of recommendation have been added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS A full version of the guidelines is available at the EAU office or online ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy . A biopsy progression indicates the need for active intervention , whereas the role of PSA doubling time is controversial . In men with locally advanced PCa for whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) , with equivalent oncologic efficacy . Active treatment is recommended mostly for patients with localized disease and a long life expectancy , with radical prostatectomy ( RP ) shown to be superior to WW in prospect i ve r and omized trials . Nerve-sparing RP is the approach of choice in organ-confined disease , while neoadjuvant ADT provides no improvement in outcome variables . Radiation therapy should be performed with ≥ 74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa . For locally advanced disease , adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice . Follow-up after local therapy is largely based on PSA and a disease-specific history , with imaging indicated only when symptoms occur . CONCLUSIONS Knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice . PATIENT SUMMARY A summary is presented of the 2013 EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined prostate cancer ( PCa ) . Screening continues to be done on an individual basis , in consultation with a physician . Diagnosis is by prostate biopsy . Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to and rogen-deprivation therapy in locally advanced PCa not requiring immediate local treatment . Radical prostatectomy is the only surgical option . Radiation therapy can be external or delivered by way of prostate implants . Treatment follow-up is based on the PSA level OBJECTIVE Our aim was to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the screening , diagnosis , and treatment of clinical ly localised cancer of the prostate ( PCa ) . METHODS The working panel performed a literature review of the new data emerging from 2007 to 2010 . The guidelines were up date d , and level of evidence and grade of recommendation were added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. RESULTS A full version is available at the EAU office or Web site ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy .  PSA doubling time in <3 yr or a biopsy progression indicates the need for active intervention . In men with locally advanced PCa in whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) with equivalent oncologic efficacy . Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial . Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables . Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk PCa , respectively . For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice . Follow-up after local therapy is largely based on PSA , and a disease-specific history with imaging is indicated only when symptoms occur . CONCLUSIONS The knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice PURPOSE This was an exploratory analysis of a trial of intermittent and rogen deprivation ( IAD ) in men with biochemical relapse ( BR ) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer ( CRPC ) and death . PATIENTS AND METHODS Men with BR of prostate cancer after radical prostatectomy ( RP ) or radiation ( RT ) were treated with and rogen deprivation therapy ( ADT ) comprised of leuprolide and flutamide . After 9 months on treatment , ADT was stopped , and monthly prostate-specific antigen ( PSA ) levels were observed during the off-treatment interval . When the PSA reached a threshold value ( 1 ng/mL for RP , 4 ng/mL for RT ) , ADT was resumed in a new cycle . Patients were treated intermittently in this manner until CRPC , which was defined as > or = two consecutive increasing PSA values while on ADT with castrate testosterone levels . RESULTS Seventy-two of 100 patients enrolled onto the study met criteria for this analysis . The duration of the first off-treatment interval ( < or = v > 40 weeks ) was associated with shorter time to CRPC ( hazard ratio = 2.9 ; 95 % CI , 1.1 to 7.7 ; P = .03 ) and death ( hazard ratio = 3.8 ; 95 % CI , 1.1 to 13.6 ; P = .04 ) after adjusting for age , stage , grade , and PSA at diagnosis . CONCLUSION In patients who completed the first cycle of IAD , a duration of the first off-treatment interval of < or = 40 weeks defines a subset of patients at higher risk of CRPC and death . Conversely , patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis PURPOSE Persistence of lig and -mediated and rogen receptor signaling has been documented in castration-resistant prostate cancers ( CRPCs ) . Abiraterone acetate ( AA ) is a potent and selective inhibitor of CYP17 , which is required for and rogen bio synthesis in the testes , adrenal gl and s , and prostate tissue . This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy . PATIENTS AND METHODS Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA ( 1,000 mg daily ) with prednisone ( 5 mg twice daily ) . Twenty-seven ( 47 % ) patients had received prior ketoconazole . The primary outcome was > or = 50 % prostate-specific antigen ( PSA ) decline , with objective response by Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria , and changes in Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) and circulating tumor cell ( CTC ) numbers . Safety was also evaluated . RESULTS A > or = 50 % decline in PSA was confirmed in 22 ( 36 % ) patients , including 14 ( 45 % ) of 31 ketoconazole-naïve and seven ( 26 % ) of 27 ketoconazole-pretreated patients . Partial responses were seen in four ( 18 % ) of 22 patients with RECIST-evaluable target lesions . Improved ECOG PS was seen in 28 % of patients . Median time to PSA progression was 169 days ( 95 % CI , 82 to 200 days ) . CTC conversions with treatment from > or = 5 to < 5 were noted in 10 ( 34 % ) of 29 patients . The majority of  AA-related adverse events were grade 1 to 2 , and no AA-related grade 4 events were seen . CONCLUSION AA plus prednisone was well tolerated , with encouraging antitumor activity in heavily pretreated CRPC patients . The incidence of mineralocorticoid-related toxicities ( hypertension or hypokalemia ) was reduced by adding low-dose prednisone . The combination of AA plus prednisone is recommended for phase III investigations Background : Most patients receiving docetaxel-based chemotherapy for castration resistant prostate cancer ( CRPC ) will eventually progress , and the optimal interventions for these patients are controversial . The objective of our study is to evaluate the clinical efficacy and safety of pharmacological interventions for CRPC patients progressing after docetaxel-based chemotherapy .  Methods : A systematic review and Bayesian network meta- analysis of the literature was carried out according to st and ard methods . Major electronic data bases including PubMed , Web of Science and Embase were search ed until Jan 2017 . Hazard ratios ( HRs ) and odds ratios ( ORs ) with corresponding 95 % credible intervals ( CrIs ) were used to estimate the association . Results : 17 R and omized Controlled Trials ( RCTs ) comprising 14 different interventions with 12347 patients were enrolled . Compared with control arms , Abiraterone Acetate ( HR : 0.70 , 95%CrI : 0.63 - 0.79 ) , Cabazitaxel ( HR : 0.70 , 95%CrI : 0.51 - 0.95 ) and Enzalutamide ( HR : 0.63 , 95%CrI : 0.53 - 0.75 ) presented similar benefits in term of OS .  Enzalutamide showed superiority over PFS and PSA response with a highest probability to rank 1 . Moreover , sensitivity analysis showed that Abiraterone Acetate ( HR : 0.71 , 95%CrI : 0.63 - 0.78 ) exhibited the most efficacious intervention of being rank 1 in term of OS compared with control arms , followed by Cabazitaxel and Cetuximab . On the other h and , Abiraterone Acetate ( OR : 0.86 , 95%CrI : 0.35 - 2.03 ) presented no significant toxicities compared with control arms . Conclusions : Our results demonstrated that Abiraterone Acetate might be the optimal intervention for CRPC patients after docetaxel failure with acceptable tolerability . Future well- design ed RCTs and systematic review s are needed to vali date these findings OBJECTIVE To evaluate long-term follow-up of a phase II trial of chemohormonal therapy in 62 men with prostate cancer biochemical relapse ( BR ) . METHODS Treatment was 4 cycles of docetaxel ( 70 mg/m(2 ) ) every 3 weeks and estramustine 280 mg three times a day ( days 1 - 5 ) followed by 15 months of goserelin acetate/bicalutamide . The primary endpoint was the proportion with prostate-specific antigen ( PSA ) < 0.1 with recovered testosterone 5 years after completion of therapy . Secondary endpoints included time to progression ( TTP ) , time to reinitiate and rogen deprivation therapy ( ADT ) , the proportion with castration-resistant prostate cancer ( CRPC ) , and overall survival ( OS ) . RESULTS Median follow-up was 8.6 years ( range 1.3 - 11.1 years ) . At 5 year follow-up , 7 patients ( 11 % ) had PSA < 0.1 ( 5 undetectable ) ; 8 ( 13 % ) had PSA > 0.1 but without reinitiation of ADT ( median PSA 0.37 ) . Of the 15 ( 24 % ) men without reinitiation of ADT , and 14 have recovered testosterone to normal range . Median TTP for the complete cohort was 35.0 months ( 95 % confidence interval [ CI ] 31.7 - 39.2 ) . Baseline PSA < 3.0 ng/dL , no prior ADT , and prostatectomy ( vs radiation ) were associated with longer TTP ( P = .0001 , P = .0055 , and P = .0398 , respectively ) . At the time of analysis , 42 men ( 68 % ) had restarted ADT , 23 men had CRPC ( 37 % ) , and 11 ( 18 % ) had chemotherapy . Median time to reinitiation of ADT was 32.6 months ( range 0 - 107.6 months ) . Median OS has not been reached ; there were 15 deaths . CONCLUSION Chemotherapy plus ADT for BR result ed in durable ( > 5 years ) complete responses ( < 0.1 ng/mL ) in 7 men ( 11 % ) . Twenty-four percent of men have not re-initiated ADT 5 years from completion of protocol therapy PURPOSE To up date the effect of immediate and rogen suppression in conjunction with st and ard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate . MATERIAL S AND METHODS A national prospect i ve r and omized trial ( Radiation Therapy Oncology Group 85 - 31 ) of st and ard external-beam irradiation plus immediate and rogen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three patients in this trial had histologically involved lymph nodes . Ninety-eight patients received radiation plus immediate and rogen suppression ( luteinizing hormone-releasing hormone [ LHRH ] agonist ) , whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median follow-up of 6.5 years for all patients and 9.5 years for living patients , estimated progression-free survival with prostate-specific antigen ( PSA ) level less than 1.5 ng/mL at 5 and 9 years was 54 % and 33 % , respectively , for patients who received immediate LHRH agonist versus 10 % [ corrected ] and 4 % for patients who received radiation alone with hormonal manipulation instituted at time of relapse ( P < .0001 ) . Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed : absolute survival , disease-specific failure , metastatic failure , and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL. CONCLUSION Pending the results of r and omized trials , patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes ( pathologic node-positive or clinical stage D1 ) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse OBJECTIVES To evaluate the effect of immediate and rogen suppression in conjunction with st and ard external beam irradiation ( RT ) versus RT alone on a group of men after prostatectomy who had indications for adjuvant treatment . METHODS A national prospect i ve r and omized trial ( Radiation Therapy Oncology Group [ RTOG ] 85 - 31 ) comparing st and ard external beam RT plus immediate and rogen suppression versus external beam RT alone with delayed hormonal treatment at relapse was initiated for patients with locally advanced adenocarcinoma of the prostate . One hundred thirty-nine of the patients in this trial had indications for adjuvant treatment after prostatectomy ( eg , capsular penetration , seminal vesicle involvement ) . Seventy-one of the patients received RT with immediate and rogen suppression ( luteinizing hormone-releasing hormone [ LHRH ] agonist ) ;  68 patients received RT alone with hormonal manipulation instituted only at the time of relapse . RESULTS With a median follow-up of 5 years , the estimated progression-free survival rate ( failure defined as prostate-specific antigen [ PSA ] greater than 0.5 ng/mL ) was 65 % for the men who received combination therapy and 42 % for those treated by RT alone with hormones reserved for relapse ( P = 0.002 ) . Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL ( 71 % versus 46 % ; P = 0.008 ) and PSA greater than 4.0 ng/mL ( 76 % versus 55 % ; P = 0.05 ) , respectively . No differences were observed between the groups with respect to the end points of local control , distant failure , and overall survival . The use of immediate and rogen suppression ( ie , LHRH agonists ) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse by multivariate analysis . CONCLUSIONS Patients with prostate cancer and indications for postoperative RT should be considered for combined RT and hormonal manipulation . Because statistically significant advantages for this experimental approach could not be defined for all end points studied ( in particular , overall survival ) , efforts should be made to enroll these patients in the recently activated RTOG trial ( 96 - 01 ) comparing RT plus placebo to the combination of RT plus Casodex in the postoperative setting Background : Radical prostatectomy ( RP ) has limited cancer control potential for the patient with high-risk prostate cancer ( Pca ) . We prospect ively examined the efficacy and safety of neoadjuvant therapy with luteinizing hormone-releasing hormone ( LHRH ) agonist + low-dose estramustine phosphate ( EMP ) ( LHRH+EMP ) followed by RP . Methods : High-risk Pca was defined by the D’Amico stratification system . A total of 142 patients with high-risk Pca were enrolled in this trial from September 2005 to March 2011 . The LHRH+EMP therapy included administration of LHRH agonist and 280 mg day–1 EMP for 6 months before RP .  Pathological cancer-free ( pT0 ) rate on the surgical specimen was the primary end point . Secondary end points were PSA-free survival and toxicity . Results : The average patient age was 67.4 years ( interquartile range ( IQR ) 72 , 65 ) and the median initial PSA level was 14.80 ng ml–1 ( IQR 26.22 , 7.13 ) . The median Gleason score was 9 ( IQR 9 , 7 ) and 97 patients ( 68.3 % ) had clinical stage T2c or T3 . All patients completed 6 months of LHRH+EMP neoadjuvant therapy with no delays in RP . Seven patients ( 4.9 % ) achieved pT0 . Surgical margins were negative in 125 patients ( 87.0 % ) . At a median follow-up period of 34.9 months , PSA-free survival was 84.3 % . No serious adverse events were reported during the study and there were no toxicity-related deaths . Conclusions : Six months of LHRH+EMP neoadjuvant therapy followed by RP is safe and oncological outcomes are acceptable . Although this study was a single-arm trial with a relatively short follow-up , this treatment may have a potential to improve PSA-free survival in high-risk Pca patients . Further clinical trials are warranted BACKGROUND There is evidence linking metformin to improved prostate cancer (PCa)-related outcomes . OBJECTIVE To evaluate treatment with metformin in patients with castration-resistant PCa ( CRPC ) and the effect of the treatment on progression-free survival ( PFS ) and PSA doubling time ( PSA DT ) . DESIGN , SETTING , AND PARTICIPANTS Forty-four men with progressive metastatic CRPC from 10 Swiss centers were included in this single-arm phase 2 trial between December 2010 and December 2011 . INTERVENTION Patients received metformin 1000 mg twice daily until disease progression . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was the absence of disease progression at 12 wk . Simon two-stage optimal design was applied . With a 5 % significance level and 90 % power , 44 patients were required to test PFS at 12 wk ≤ 15 % ( H0 ) compared with ≥ 35 % ( H1 ) . RESULTS AND LIMITATIONS Thirty-six percent of patients were progression-free at 12 wk , 9.1 % were progression-free at 24 wk , and in two patients a confirmed ≥ 50 % prostate-specific antigen ( PSA ) decline was demonstrated . In 23 patients ( 52.3 % ) we observed a prolongation of PSA DT after starting metformin . The homeostatic model assessment index fell by 26 % from baseline to 12 wk , indicating an improvement in insulin sensitivity . There was a significant change in insulin-like growth factor-1 and insulin-like growth factor binding protein 3 from baseline to 12 wk . Sample size and lack of a control arm are the limitations of this trial ; analyses are therefore exploratory . CONCLUSIONS Treatment with metformin is safe in nondiabetic patients , and it yields objective PSA responses and may induce disease stabilization . The activity of metformin in PCa , along with its low cost , favorable toxicity profile , and positive effect on metabolic parameters , suggests that further investigation of metformin as therapy for patients with PCa is of interest . PATIENT SUMMARY In this trial we assessed the use of the diabetes mellitus drug metformin in patients with advanced prostate cancer . We found disease stabilization and prolongation of prostate-specific antigen doubling time in some patients as well as effects on metabolic parameters . TRIAL REGISTRATION This study is registered with Clinical Trials.gov with the identifier NCT01243385 . PREVIOUS PRESENTATION The study was presented at ESMO 2012 ( abstract 1460 ) Background Multiple castration‐resistant prostate cancer ( CRPC ) therapies are approved by the United States Food and Drug Administration . Radium‐223 dichloride ( Ra‐223 ) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off‐target side‐effect profiles . We prospect ively investigated their combined safety , tolerability , and patient‐reported outcome measures . Patients and Methods eRADicAte , an investigator‐initiated , phase II trial , studied 31 patients with metastatic CRPC , from 5 United States uro‐oncology research sites . Patients completed 6 cycles of Ra‐223 with concurrent abiraterone therapy .  Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy‐Prostate and the Brief Pain Inventory‐Short Form question naires and their subscales ; we reported the number of subjects meeting st and ardized criteria for clinical ly meaningful improvements on each scale . Safety assessment included Eastern Cooperative Oncology Group performance status , laboratory changes , opioid use , radiographic responses , and adverse events ( AEs ) . Results Twenty of 31 ( 65 % ) experienced positive clinical ly meaningful improvement changes on the Functional Assessment of Cancer Therapy‐Prostate , and 25 ( 81 % ) of 31 on the Prostate Cancer Subscale . Eighteen ( 58 % ) of 31 demonstrated reduced pain intensity and 12 ( 39 % ) of 31 demonstrated reduction of pain interference in their lives . At baseline , subjects averaged 11.6 ± 2.8 bone lesions ; at the end of treatment , subjects averaged 5.6 ± 2.4 bone lesions ( P = .0002 ) . The most frequent AEs were diarrhea ( 17 % ) , nausea ( 17 % ) , and fatigue ( 14 % ) . There were 6 serious AEs ; 1 led to study withdrawal . Conclusions Patients experienced clinical ly meaningful improvements in quality of life and pain , without unexpected adverse toxicities . Phase III combination trials of Ra‐223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit . Micro‐ Abstract This is the first study to prospect ively evaluate the combined use of radium‐223 dichloride and a novel oral hormonal therapy , abiraterone acetate , in men with metastatic castration‐resistant prostate cancer . The eRADicAte study showed that patients with metastatic castration‐resistant prostate cancer experienced clinical ly meaningful improvements in quality of life with decreased pain , reduction in bone lesions , and an acceptable safety and toxicity profile BACKGROUND Previous r and omised trials demonstrated that adjuvant radiation therapy ( aRT ) improves cancer control in patients with pT3 prostate cancer ( PCa ) . However , there is currently no evidence supporting early salvage radiation therapy ( eSRT ) as equivalent to aRT in improving freedom from biochemical recurrence ( BCR ) after radical prostatectomy ( RP ) . OBJECTIVE To evaluate BCR-free survival for aRT versus observation followed by eSRT in cases of relapse in patients undergoing RP for pT3pN0 , R0-R1 PCa . DESIGN , SETTING , AND PARTICIPANTS Using a European multi-institutional cohort , 890 men with pT3pN0 , R0-R1 PCa were identified . INTERVENTION All patients underwent RP . Subsequently , patients were stratified into two groups : aRT versus initial observation followed by eSRT in cases of relapse . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES : Propensity-matched analysis was employed , and patients were stratified into two groups : aRT versus observation and eventual eSRT , defined as RT given at a postoperative serum prostate-specific antigen ( PSA ) ≤ 0.5 ng/ml at least 6 mo after RP . BCR , defined as PSA > 0.20 ng/ml and rising after administration of RT , was compared between aRT and initial observation followed by eSRT in cases of relapse using Kaplan-Meier and Cox regression methods . RESULTS AND LIMITATIONS Overall , 390 ( 43.8 % ) and 500 ( 56.2 % ) patients were treated with aRT and initial observation , respectively . Within the latter group , 225 ( 45.0 % ) patients experienced BCR and underwent eSRT . In the postpropensity-matched cohort , the 2- and 5-yr BCR-free survival rates were 91.4 % and 78.4 % in aRT versus 92.8 % and 81.8 % in patients who underwent initial observation and eSRT in cases of relapse , respectively ( p=0.9 ) . No differences in the 2- and 5-yr BCR-free survival rates were found , even when patients were stratified according to pT3 substage and surgical margin status ( all p ≥ 0.4 ) . These findings were also confirmed in multivariable analyses ( p=0.6 ) . Similar results were achieved when the cut-off to define eSRT was set at 0.3 ng/ml ( all p ≥ 0.5 ) . CONCLUSIONS The current study suggests that timely administration of eSRT is comparable to aRT in improving BCR-free survival in the majority of pT3pN0 PCa patients .  Therefore , eSRT may not compromise cancer control but significantly reduces overtreatment associated with aRT PURPOSE Abiraterone acetate is a prodrug of abiraterone , a selective inhibitor of CYP17 , the enzyme catalyst for two essential steps in and rogen bio synthesis . In castration-resistant prostate cancers ( CRPCs ) , extragonadal and rogen sources may sustain tumor growth despite a castrate environment . This phase I dose-escalation study of abiraterone acetate evaluated safety , pharmacokinetics , and effects on steroidogenesis and prostate-specific antigen ( PSA ) levels in men with CPRC with or without prior ketoconazole therapy . PATIENTS AND METHODS Thirty-three men with chemotherapy-naïve progressive CRPC were enrolled . Nineteen patients ( 58 % ) had previously received ketoconazole for CRPC . Bone metastases were present in 70 % of patients , and visceral involvement was present in 18 % . Three patients ( 9 % ) had locally advanced disease without distant metastases . Fasted or fed cohorts received abiraterone acetate doses of 250 , 500 , 750 , or 1,000 mg daily . Single-dose pharmacokinetic analyses were performed before continuous daily dosing . RESULTS Adverse events were predominantly grade 1 or 2 . No dose-limiting toxicities were observed . Hypertension ( grade 3 , 12 % ) and hypokalemia ( grade 3 , 6 % ; grade 4 , 3 % ) were the most frequent serious toxicities and responded to medical management . Confirmed > or = 50 % PSA declines at week 12 were seen in 18 ( 55 % ) of 33 patients , including nine ( 47 % ) of 19 patients with prior ketoconazole therapy and nine ( 64 % ) of 14 patients without prior ketoconazole therapy . Substantial declines in circulating and rogens and increases in mineralocorticoids were seen with all doses . CONCLUSION Abiraterone acetate was well tolerated and demonstrated activity in CRPC , including in patients previously treated with ketoconazole . Continued clinical study is warranted Objectives : Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer ( CRPC ) . Methods : Thirty patients with progressing CRPC and a rising prostate-specific antigen ( PSA ) received docetaxel/prednisone in st and ard conditions for 6 cycles in combination with per os curcumin , 6,000 mg/day ( day -4 to day + 2 of docetaxel ) . The co- primary endpoint was the overall response rate determined by PSA and target assessment s. An ancillary study assessed the seric values of chromogranin A ( CgA ) and neuron-specific enolase ( NSE ) . Results : Twenty-six patients received the scheduled treatment , 2 progressed and 2 died before the end of treatment . A PSA response was observed in 59 % of patients ( 14 % of PSA normalization ) and achieved within the first three cycles for 88 % of responders . Partial response was reached for 40 % of evaluable patients . The regimen was well tolerated , and no adverse event was attributed to curcumin . Twenty patients were 100 % curcumin compliant . The PSA level and objective response rate were not correlated with the serum values of CgA and NSE . Conclusion : This study produced additional data on curcumin as a treatment for cancer , with a high response rate , good tolerability and patient acceptability , justifying the interest to conduct a r and omized trial PURPOSE It has been postulated that castration-resistant prostate cancer ( CRPC ) commonly remains hormone dependent . Abiraterone acetate is a potent , selective , and orally available inhibitor of CYP17 , the key enzyme in and rogen and estrogen bio synthesis . PATIENTS AND METHODS This was a phase I/II study of abiraterone acetate in castrate , chemotherapy-naive CRPC patients ( n = 54 ) with phase II expansion at 1,000 mg ( n = 42 ) using a two-stage design to reject the null hypothesis if more than seven patients had a prostate-specific antigen ( PSA ) decline of > or = 50 % ( null hypothesis = 0.1 ; alternative hypothesis = 0.3 ; alpha = .05 ; beta = .14 ) . Computed tomography scans every 12 weeks and circulating tumor cell ( CTC ) enumeration were performed . Prospect i ve reversal of resistance at progression by adding dexamethasone 0.5 mg/d to suppress adrenocorticotropic hormone and upstream steroids was pursued . RESULTS A decline in PSA of > or = 50 % was observed in 28 ( 67 % ) of 42 phase II patients , and declines of > or = 90 % were observed in eight ( 19 % ) of 42 patients . Independent radiologic evaluation reported partial responses ( Response Evaluation Criteria in Solid Tumors ) in nine ( 37.5 % ) of 24 phase II patients with measurable disease . Decreases in CTC counts were also documented . The median time to PSA progression ( TTPP ) on abiraterone acetate alone for all phase II patients was 225 days ( 95 % CI , 162 to 287 days ) . Exploratory analyses were performed on all 54 phase I/II patients ; the addition of dexamethasone at disease progression reversed resistance in 33 % of patients regardless of prior treatment with dexamethasone , and pretreatment serum and rogen and estradiol levels were associated with a probability of > or = 50 % PSA decline and TTPP on abiraterone acetate and dexamethasone . CONCLUSION CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses , confirming that CRPC commonly remains hormone driven BACKGROUND There is currently no st and ard treatment for patients with castration-resistant prostate cancer ( CRPC ) whose disease progresses after docetaxel-based chemotherapy .  The purpose of this study was to prospect ively assess the anticancer activity and tolerance of the carboplatin-etoposide combination in this setting while evaluating neuroendocrine ( NE ) features . PATIENTS AND METHODS Patients with CRPC and metastases who experienced failure after first-line docetaxel-based chemotherapy  were treated with carboplatin ( area under the curve 5 , day 1 ) and etoposide ( 80 mg/m(2)/day from days 1 to 3 ) , repeated every 3 weeks . The association between serum chromogranin A ( CgA ) , neuron-specific enolase ( NSE ) , prostate-specific antigen-doubling time ( PSADT ) , and treatment efficacy was studied . RESULTS Forty patients with CRPC who had received docetaxel with ( n = 20 ) or without ( n = 20 ) estramustine received the  carboplatin-etoposide combination  as second-line chemotherapy . A prostate-specific antigen ( PSA ) response defined as a PSA decline > or = 50 % was achieved in nine patients ( 23 % ) . Median progression-free survival ( PFS ) was 2.1 months ( range 0.6 - 9.6 ) and median overall survival was 19 months ( range 2.1 - 27.7 ) . Pain response was achieved in 15 ( 53 % ) of 28 assessable patients . Toxicity , including mainly grade s 3 - 4 anaemia ( 25 % ) and febrile neutropenia in only 2 % of patients , was manageable . Baseline CgA , NSE , or PSADT were not significant predictors for response or PFS . The PSA response rates were 18 % and 31 % in patients with normal and elevated serum CgA , respectively . It was 25 % and 20 % , respectively , in patients with normal and elevated serum NSE . CONCLUSIONS Combining carboplatin and etoposide as second-line chemotherapy in patients with CRPC is active and well tolerated in spite of a limited PFS . Activity was observed in CRPC with and without NE features BACKGROUND AND OBJECTIVE Sequential tissue biopsies taken during clinical trials of novel systemic anticancer therapies for advanced prostate cancer ( PCa ) may aid pharmacodynamic evaluation and biomarker discovery . We conducted a single institution phase-II open-labeled r and omized study to assess the safety , tolerability , and early efficacy of docetaxel chemotherapy plus and rogen deprivation therapy ( ADT ) vs. ADT alone for patients with advanced non-castration-resistant PCa with sequential prostatic biopsies . PATIENTS AND METHODS We r and omized 30 patients with newly diagnosed high- grade locally advanced or metastatic ( cT3 - 4/N0 - 1/M0 - 1 ) PCa to receive ADT with ( n = 15 ) or without ( n = 15 ) docetaxel . Transrectal ultrasound-guided prostatic biopsies were taken at r and omization and ~22 weeks after treatment initiation . Primary end point : biochemical response rate . Secondary end points : time to progression and tumor profiling . RESULTS Both treatments appear to be well tolerated , and there was no difference in mean nadir prostate-specific antigen and time to prostate-specific antigen relapse between treatment arms ( P>0.05 ) . No adverse effects of pre- and post-treatment prostatic biopsies were observed . The study was neither design ed nor sufficiently powered to demonstrate statistically significant differences in oncological outcomes or safety profiles between the 2 treatment arms . CONCLUSIONS Despite the lack of statistical power , our study suggests that docetaxel and ADT in combination may be well tolerated with apparently similar short-term efficacy compared with ADT alone for high- grade locally advanced or metastatic non-castration-resistant PCa , Sequential prostatic biopsies may provide tissue for tumor profiling to yield mechanistic or prognostic insights relating to novel systemic anticancer therapies BACKGROUND Abiraterone acetate ( AA ) is an and rogen bio synthesis inhibitor shown to prolong life in patients with castration-resistant prostate cancer ( CRPC ) already treated with chemotherapy .  AA treatment results in dramatic declines in prostate-specific antigen ( PSA ) in some patients and no declines in others , suggesting the presence of molecular determinants of sensitivity in tumors . OBJECTIVE To study the role of transmembrane protease , serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogene homolog ( ERG ) fusion , an and rogen-dependent growth factor , in circulating tumor cells ( CTCs ) as a biomarker of sensitivity to AA . DESIGN , SETTING , AND PARTICIPANTS The predictive value of TMPRSS2-ERG status was studied in 41 of 48 men with postchemotherapy-treated CRPC enrolled in sequential phase 2 AA trials . INTERVENTION Patients received AA 1000 mg daily and continuously . MEASUREMENTS TMPRSS2-ERG status was characterized by a sensitive , analytically valid reverse transcription polymerase chain reaction assay in CTCs enriched from ethylene-diaminetetraacetic acid anticoagulated blood obtained prior to AA treatment . Outcomes were measured by PSA Working Group 1 criteria . RESULTS AND LIMITATIONS St and ard procedures for specimen acquisition , processing , and testing using the vali date d TMPRSS2-ERG assay on a multiplex platform gave intra-assay and interassay coefficients of variation < 7 % . TMPRSS2-ERG fusion was present in 15 of 41 patients ( 37 % ) , who had a median baseline CTC count of 17 ( interquartile range : 7 - 103 cells per 7.5 ml ) . A PSA decline ≥50 % was observed in 7 of 15 patients ( 47 % ) with the fusion and in 10 of 26 patients ( 38 % ) without the fusion . Although limited by the low number of patients , a posttherapy CTC count of less than five per 7.5 ml was prognostic for longer survival relative to a CTC count five or more . TMPRSS2-ERG status did not predict a decline in PSA or other clinical outcomes . CONCLUSIONS Molecular profiles of CTCs with an analytically valid assay identified the presence of the prostate cancer-specific TMPRSS2-ERG fusion but did not predict for response to AA treatment . This finding demonstrates the role of CTCs as surrogate tissue that can be obtained in a routine practice setting . TRIAL REGISTRATION Clinical Trials.gov : NCT00474383 ( COU-AA-003 ) , NCT00485303 ( COU-AA-004 ) BACKGROUND We seek to determine if testosterone levels below the accepted castration threshold ( 50 ng/dL ) have an impact on time to progression to castrate-resistant prostate cancer ( CRPC ) . METHODS This is a prospect i ve cohort series of patients undergoing and rogen deprivation therapy ( ADT ) with luteinizing hormone-releasing hormone agonist or antagonist at a tertiary centre from 2006 to 2011 .  Serum testosterone level  was assessed every 3 months . Patients with any testosterone > 50 ng/dL were excluded . Patients were stratified into groups based on those achieving mean testosterone levels < 20 ng/dL and < 32 ng/dL. Progression to CRPC was assessed with the Kaplan-Meier method and compared with the log-rank test . RESULTS A total of 32 patients were included in this study . Mean patient follow-up was 25.7 months . Patients with a 9-month serum testosterone < 32 ng/dL had a significantly increased time to CRPC compared to patients with testosterone 32 to 50 ng/dL ( p = 0.001 , median progression-free survival ( PFS ) 33.1 months [ < 32 ng/dL ] vs. 12.5 months [ > 32 ng/dL ] ) . Patients with first year mean testosterone < 32 ng/dL also had a significantly increased time to CRPC compared to 32 to 50 ng/dL ( p = 0.05 , median PFS 33.1 months [ < 32 ng/dL ] vs. 12.5 months [ 32 - 50 ng/dL ] ) . A testosterone < 20 ng/dL compared to 20 to 50 ng/dL did not significantly predict with time to CRPC . CONCLUSION This study supports a lower testosterone threshold to define optimal medical castration ( T < 32 ng/dL ) than the previously accepted st and ard of 50 ng/dL. Testosterone levels during ADT serve as an early predictor of disease progression and thus should be measured in conjunction with prostate-specific antigen PURPOSE Cure rates for localized high-risk prostate cancers ( PCa ) and some intermediate-risk PCa are frequently suboptimal with local therapy . Outcomes are improved by concomitant and rogen-deprivation therapy ( ADT ) with radiation therapy , but not by concomitant ADT with surgery . Luteinizing hormone-releasing hormone agonist ( LHRHa ; leuprolide acetate ) does not reduce serum and rogens as effectively as abiraterone acetate ( AA ) , a prodrug of abiraterone , a CYP17 inhibitor that lowers serum testosterone ( < 1 ng/dL ) and improves survival in metastatic PCa . The possibility that greater and rogen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the re assessment of neoadjuvant ADT with more robust and rogen suppression . PATIENTS AND METHODS A neoadjuvant r and omized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa ( N = 58 ) . For the first 12 weeks , patients were r and omly assigned to LHRHa versus LHRHa plus AA . After a research prostate biopsy , all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy .  RESULTS The levels of intraprostatic and rogens from 12-week prostate biopsies , including the primary end point ( dihydrotestosterone/testosterone ) , were significantly lower ( dehydroepi and rosterone , Δ(4)- and rostene-3,17-dione , dihydrotestosterone , all P < .001 ; testosterone , P < .05 ) with LHRHa plus AA compared with LHRHa alone . Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease , with residual T3- or lymph node-positive disease in the majority . CONCLUSION LHRHa plus AA treatment suppresses tissue and rogens more effectively than LHRHa alone . Intensive intratumoral and rogen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden PURPOSE To evaluate the effect of immediate and rogen suppression in conjunction with st and ard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate . METHODS AND MATERIAL S A national prospect i ve r and omized trial ( RTOG 85 - 31 ) of st and ard external beam irradiation plus immediate and rogen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes . Ninety-eight of these patients received radiation plus the immediate and rogen suppression ( LHRH agonist ) , while 75 received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median followup of 4.9 years , estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55 % for the patients who received radiation plus immediate LHRH agonist vs. 11 % of the patients who received radiation alone with hormonal manipulation at relapse ( p = 0.0001 ) . Because all of these patients had locally advanced disease ( i.e. , pathologically positive lymph nodes ) , stage does not explain this difference in outcome , and Gleason grade was not statistically different between the two groups . Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65 % for the radiation alone group who received and rogen suppression at relapse . Estimated disease-specific survival at 5 years was 82 % for the radiation and immediate LHRH agonist group and 77 % for the radiation-alone group . CONCLUSION Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes ( pN+ or clinical stage D1 ) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse Background Loss of the tumor suppressor phosphatase and tensin homolog ( PTEN ) occurs frequently in prostate cancers . Pre clinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer . Objective To explore the antitumor activity of abiraterone acetate ( abiraterone ) in castration-resistant prostate cancer ( CRPC ) patients with and without loss of PTEN protein expression . Design , setting , and participants We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer ( HSPC ) and /or CRPC tissue available for PTEN immunohistochemical analysis . Outcome measurements and statistical analysis The primary end point was overall survival from initiation of abiraterone treatment . Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses . Results and limitations A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue . Overall , loss of PTEN expression was observed in 40 % of patients . Matched HSPC and CRPC tumor biopsies were available for 41 patients .  PTEN status in CRPC correlated with HSPC in 86 % of cases . Loss of PTEN expression was associated with shorter median overall survival ( 14 vs 21 mo ; hazard ratio [ HR ] : 1.75 ; 95 % confidence interval [ CI ] , 1.19–2.55 ; p = 0.004 ) and shorter median duration of abiraterone  treatment ( 24 vs 28 wk ; HR : 1.6 ; 95 % CI , 1.12–2.28 ; p = 0.009 ) . PTEN protein loss , high lactate dehydrogenase , and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis . Conclusions Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment . Further studies in larger and prospect i ve cohorts are warranted . Patient summary PTEN is a protein often lost in prostate cancer cells . In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate . We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression PURPOSE The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate , an oral , specific , irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer ( CRPC ) . PATIENTS AND METHODS In this multicenter , two-stage , phase II study , abiraterone acetate 1,000 mg was administered once daily continuously . The primary end point was achievement of a prostate-specific antigen ( PSA ) decline of > or = 50 % in at least seven of 35 patients . Per an attained phase II design , more than 35 patients could be enrolled if the primary end point was met . Secondary objectives included : PSA declines of > or = 30 % and > or = 90 % ; rate of RECIST ( Response Evaluation Criteria in Solid Tumors ) responses and duration on study ; time to PSA progression ; safety and tolerability ; and circulating tumor cell ( CTC ) enumeration . RESULTS Docetaxel-treated patients with CRPC ( N = 47 ) were enrolled .  PSA declines of > or = 30 % , > or = 50 % and > or = 90 % were seen in 68 % ( 32 of 47 ) , 51 % ( 24 of 47 ) , and 15 % ( seven of 47 ) of patients , respectively . Partial responses ( by RECIST ) were reported in eight ( 27 % ) of 30 patients with measurable disease . Median time to PSA progression was 169 days ( 95 % CI , 113 to 281 days ) . The median number of weeks on study was 24 , and 12 ( 25.5 % ) of 47 patients remained on study > or = 48 weeks . CTCs were enumerated in 34 patients ; 27 ( 79 % ) of 34 patients had at least five CTCs at baseline . Eleven ( 41 % ) of 27 patients had a decline from at least five to less than 5 CTCs , and 18 ( 67 % ) of 27 had a > or = 30 % decline in CTCs after starting treatment with abiraterone acetate . Abiraterone acetate was well tolerated . CONCLUSION Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC . R and omized , phase III trials of abiraterone acetate are underway to define the future role of this agent Background Radium-223 dichloride ( radium-223 ) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer ( CRPC ) with bone metastases . This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases . Methods In this open-label , multicenter , phase II study , patients with progressive , symptomatic CRPC and bone metastases were treated with radium-223 ( 55 kBq/kg , intravenously ) in a 4-week cycle for six cycles . The primary endpoint was the percent change in total alkaline phosphatase ( ALP ) from baseline at 12 weeks . Secondary endpoints included the percent ALP change from baseline to end of treatment ( EOT ) , ALP response rates , percent change in prostate-specific antigen ( PSA ) from baseline to 12 weeks and EOT , PSA response rates , overall survival ( OS ) , and time to symptomatic skeletal events ( SSEs ) . Adverse events were monitored throughout the study period . Results Of the 49 Japanese patients ( median age 74 years ) , 28 completed all infusions . Mean percent change in total ALP and PSA from baseline to 12 weeks was −19.3 and + 97.4 % , respectively . One-year OS and SSE-free rate at the end of active follow-up were 78 and 89 % , respectively . The ALP response rate was 31 % , while the PSA response rate was 6 % . Grade 3/4 treatment-emergent adverse events observed in ≥10 % of patients included decreased lymphocyte count ( 14 % ) , anemia ( 14 % ) , anorexia ( 10 % ) , and bone pain ( 10 % ) . Conclusions Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases . Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients ( ALSYMPCA ) trial . Clinical trial registration Clinical Trials.gov NCT01929655
LHRH antagonists decrease testosterone without any testosterone surge , and they may be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
LHRH antagonists decrease testosterone without any testosterone surge , and they might be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
OBJECTIVE To present a summary of the 2013 version of the European Association of Urology ( EAU ) guidelines on the treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) .
The guidelines were up date d , and levels of evidence and /or grade s of recommendation were added to the text based on a systematic review of the literature that included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) .
Treatment of CRPC includes sipuleucel-T , abiraterone acetate plus prednisone ( AA/P ) , or chemotherapy with docetaxel at 75mg/m(2 ) every 3 wk .
Cabazitaxel , AA/P , enzalutamide , and radium-223 are available for second-line treatment of CRPC following docetaxel .
CONCLUSIONS The knowledge in the field of advanced , metastatic , and castration-resistant PCa is rapidly changing .
PATIENT SUMMARY We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) .
Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) .
Relapse after local therapy is defined by prostate-specific antigen ( PSA ) values > 0.2 ng/ml following radical prostatectomy ( RP ) and > 2 ng/ml above the nadir and after radiation therapy .
Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels < 0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures .