eRADicAte: A Prospective Evaluation Combining Radium‐223 Dichloride and Abiraterone Acetate Plus Prednisone in Patients With Castration‐Resistant Prostate Cancer Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. 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. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. 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. 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. Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer Chemotherapy following radium‐223 dichloride treatment in ALSYMPCA Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies 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. 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 Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223 Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol Phase 3 randomized trial evaluating second-line hormonal therapy versus docetaxel-estramustine combination chemotherapy on progression-free survival in asymptomatic patients with a rising prostate-specific antigen level after hormonal therapy for prostate cancer: an Eastern Cooperative Oncology Grou Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven.
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 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 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 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 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 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 : 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 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 BACKGROUND Radium‐223 prolongs overall survival in patients with castration‐resistant prostate cancer ( CRPC ) and symptomatic bone metastases , regardless of prior docetaxel . Whether or not chemotherapy can be safely administered following radium‐223 treatment is of clinical importance . An exploratory analysis of prospect ively collected data , from the ALSYMPCA ( ALpharadin in SYMptomatic Prostate CAncer ) patient subgroup who received chemotherapy after radium‐223 or placebo treatment , was conducted to evaluate the safety and efficacy of chemotherapy following radium‐223 . METHODS In ALSYMPCA , CRPC patients with symptomatic bone metastases and no visceral metastases were r and omized 2:1 to receive six injections of radium‐223 ( 50 kBq/kg IV ) or placebo plus best st and ard of care , stratified by prior docetaxel , baseline alkaline phosphatase , and current bisphosphonate use . In this exploratory analysis , chemotherapy agents administered following study treatment were identified ; timing and duration were calculated . Hematologic safety was review ed , and overall survival analyzed . RESULTS Overall , 142 radium‐223 and 64 placebo patients received subsequent chemotherapy ; most common were docetaxel ( 70 % radium‐223 , 72 % placebo ) and mitoxantrone ( 16 % radium‐223 , 20 % placebo ) . The majority of patients ( 61 % radium‐223 , 58 % placebo ) had received prior docetaxel . Radium‐223 patients started subsequent chemotherapy later than placebo patients ; chemotherapy duration was similar between groups . In radium‐223 and placebo patients receiving subsequent chemotherapy  , median hematologic values ( hemoglobin , neutrophils , and platelets ) remained nearly constant up to 18 months following start of chemotherapy , regardless of prior docetaxel treatment . A low percentage of patients in both groups had grade s 3–4 hematologic values ( < 10 % ) . Platelet count decline , from last measurement before chemotherapy , was numerically greater in radium‐223 versus placebo patients . Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium‐223 and placebo , respectively . CONCLUSIONS Chemotherapy following radium‐223 , regardless of prior docetaxel , is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases . Prostate 76:905–916 , 2016 . © 2016 The Authors . The Prostate published by Wiley Periodicals , Purpose / Objectives : Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases . Initial studies investigating Radium-223 primarily used nonsteroidal first-generation anti and rogens . Since that time , newer anti and rogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer . It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes . Currently , there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals . Here , we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation anti and rogen therapies with either enzalutamide or abiraterone . Material s/ Methods : In a retrospective study , we analyzed patients who received Radium-223 as part of an early-access trial , and following FDA approval in May 2013 , patients receiving Radium-223 as part of st and ard care . Radium-223 was given at st and ard dosing of 50 kBq/kg each month for 6 total cycles . Complete blood counts were performed before treatment monthly and following each injection . Blood counts from patients receiving Radium alone and concurrently with next-generation anti and rogens were compared . To date , 25 total patients were analyzed , with a median of 5 monthly doses received per patient . Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide ( n=8 ) or abiraterone ( n=6 ) . Results : Six patients expired due to disease progression . Two patients discontinued treatment due to grade 3 myelosuppression . For patients receiving either Radium alone and with concurrent next-generation anti and rogen therapy , there did not appear to be any statistically significant differences between initial and nadir blood counts . Mean change from initial neutrophil count to nadir was 1.9 × 106/L in patients receiving Radium alone , versus 2.3 × 106/L in patients receiving concurrent therapy ( P=0.77 ) . Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone , versus 1.8 g/L in patients receiving concurrent therapy ( P=0.31 ) . Mean change from initial platelet count to nadir was 52.3 × 109 cells/L in patients receiving Radium alone versus 70.6 × 109 cells/L in patients receiving concurrent therapy ( P=0.39 ) . Individual blood counts for each measured laboratory are included in the supplemental data . PSA was stable or decreased in 22 % of patients receiving Radium alone versus 35 % of patients receiving combination treatment ( P=0.24 ) . Conclusions : Concurrent administration of Radium-223 and next-generation anti and rogen therapies appears to be well tolerated with similar toxicities to st and ard administration of Radium-223 alone . This particular cohort of patients represents a high-risk , heavily pretreated group of patients with advanced metastatic disease and significant marrow burden . Despite these risk factors , hematologic toxicity was modest and was in the range expected for this risk group based on previous trials . To date , this is the first study investigating the toxicity of combination treatment . Further studies investigating the safety and efficacy of combination treatments are warranted 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 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 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 Baseline clinical variables are prognostic for overall survival ( OS ) in patients with castration-resistant prostate cancer ( CRPC ) . Their prognostic and predictive value with agents targeting bone metastases , such as radium-223 , is not established . Patients and methods The radium-223 ALSYMPCA trial enrolled patients with CRPC and symptomatic bone metastases . Prognostic potential of baseline variables was assessed using Cox models . Percentage changes in biomarker levels from baseline were evaluated during the trial period ; changes from baseline to week 12 were evaluated for association with OS and surrogacy . Results Eastern Cooperative Oncology Group performance status , total alkaline phosphatase ( tALP ) , lactate dehydrogenase ( LDH ) , and prostate-specific antigen ( PSA ) at baseline were associated with OS ( P ≤ 0.0003 ) in the intent-to-treat population ( radium-223 , N = 614 ; placebo , N = 307 ) . tALP declined from baseline within 4 weeks after beginning radium-223 , by week 12 declining in 87 % of radium-223 and 23 % of placebo patients ( P < 0.001 ) . LDH declined in 51 % and 34 % ( P = 0.003 ) , whereas PSA declined in 27 % and 14 % ( P = 0.160 ) . Mean tALP change from baseline was 32.2 % decrease with radium-223 and 37.2 % increase with placebo . Radium-223 patients with tALP decline from baseline to week 12 ( confirmed ≥3 weeks from week 12 ) had 55 % lower risk of death ( hazard ratio = 0.45 ; 95 % CI 0.34–0.61 ) versus those with no confirmed tALP decline . Proportional treatment effect ( PTE ) values for tALP , LDH , and PSA changes from baseline at week 12 as OS surrogate markers were 0.34 ( 95 % CI : 0–0.746 ) , 0.07 ( 95 % CI : 0–0.211 ) , and 0 ( 95 % CI : 0–0.082 ) , respectively . Conclusions Significant tALP declines ( versus placebo ) occurred as early as 4 weeks after beginning radium-223 therapy . tALP or LDH declines at 12 weeks correlated with longer OS , but did not meet statistical surrogacy requirements . Dynamic changes in tALP and LDH during radium-223 treatments may be useful to monitor , but do not serve as surrogates for survival Purpose REASSURE is a global , prospect i ve , non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer . Here we report an interim analysis of patients according to previous use of chemotherapy .  Methods Radium-223 was administered in routine clinical practice . Interim safety analysis was planned after enrolment of the first 600 patients . Patient characteristics and safety data by previous administration of chemotherapy ( docetaxel and /or cabazitaxel ) were investigated . Results This interim analysis included 583 patients . Median duration of observation was 7 months ( range , 0–20 ) . Nineteen patients treated with concomitant chemotherapy were excluded , 564 ( 97 % ) were eligible for exploratory analysis according to prior use of chemotherapy ;  190 ( 34 % ) had previously received and completed chemotherapy , and 374 ( 66 % ) had not . In the prior versus no prior chemotherapy group , a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 ( 22 % vs 11 % ) and > 20 metastatic lesions ( 26 % vs 15 % ) , median alkaline phosphatase ( 162.0 vs 115.0 U/L ) and prostate-specific antigen ( 132.0 vs 40.2 ng/mL ) levels were higher , and a lower proportion completed 6 radium-223 injections ( 45 % vs 63 % ) . Drug-related treatment-emergent adverse events ( TEAEs ) occurred in 63 and 48 % , and haematological drug-related TEAEs in 21 and 9 % of patients who had or had not previously received chemotherapy . Four drug-related deaths were reported , all in the prior chemotherapy group . Conclusions The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies , irrespective of prior chemotherapy use . Haematological TEAEs occurred more frequently in the prior chemotherapy group , presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy . Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline , and a lower proportion discontinued radium-223 treatment PURPOSE Persistent and rogen signaling is implicated in castrate-resistant prostate cancer ( CRPC ) progression . This study aim ed to evaluate and rogen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations . PATIENTS AND METHODS This was an open-label , observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010 . Patients received oral abiraterone acetate ( 1 g ) once daily and prednisone ( 5 mg ) twice daily . And rogen receptor ( AR ) and CYP17 expression were assessed by immunohistochemistry , testosterone concentration by mass spectrometry , AR copy number by polymerase chain reaction , and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues . RESULTS Median overall survival was 555 days ( 95 % CI , 440 to 965 + days ) . Maximal prostate-specific antigen decline ≥ 50 % occurred in 28 ( 50 % ) of 56 patients . Homogeneous , intense nuclear expression of AR , combined with ≥ 10 % CYP17 tumor expression , was correlated with longer time to treatment discontinuation ( > 4 months ) in 25 patients with tumor-infiltrated bone marrow sample s. Pretreatment CYP17 tumor expression ≥ 10 % was correlated with increased bone marrow aspirate testosterone . Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression . CONCLUSION The observed pretreatment and rogen-signaling signature is consistent with persistent and rogen signaling in CRPC bone metastases . This is the first evidence that abiraterone acetate  achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels . Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone 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 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 ) Abstract Background Adding abiraterone acetate with prednisolone ( AAP ) or docetaxel with prednisolone ( DocP ) to st and ard-of-care ( SOC ) each improved survival in systemic therapy for advanced or metastatic prostate cancer : evaluation of drug efficacy : a multi-arm multi-stage platform r and omised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term and rogen deprivation therapy ( ADT ) . The protocol provides the only direct , r and omised comparative data of SOC + AAP versus SOC + DocP. Method Recruitment to SOC + DocP  and SOC + AAP overlapped November 2011 to March 2013 . SOC was long-term ADT or , for most non-metastatic cases , ADT for ≥2 years and RT to the primary tumour . Stratified r and omisation allocated pts 2 : 1 : 2 to SOC ; SOC + docetaxel 75 mg/m2 3-weekly × 6 + prednisolone 10 mg daily ; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily . AAP duration depended on stage and intent to give radical RT . The primary outcome measure was death from any cause . Analyses used Cox proportional hazards and flexible parametric models , adjusted for stratification factors . This was not a formally powered comparison . A hazard ratio ( HR ) < 1 favours SOC + AAP , and HR > 1 favours SOC + DocP. Results A total of 566 consenting patients were contemporaneously r and omised : 189 SOC + DocP and 377 SOC + AAP . The patients , balanced by allocated treatment were : 342 ( 60 % ) M1 ; 429 ( 76 % ) Gleason 8–10 ; 449 ( 79 % ) WHO performance status 0 ; median age 66 years and median PSA 56 ng/ml . With median follow-up 4 years , 149 deaths were reported . For overall survival , HR = 1.16 ( 95 % CI 0.82–1.65 ) ; failure-free survival HR = 0.51 ( 95 % CI 0.39–0.67 ) ; progression-free survival HR = 0.65 ( 95 % CI 0.48–0.88 ) ; metastasis-free survival HR = 0.77 ( 95 % CI 0.57–1.03 ) ; prostate cancer-specific survival HR = 1.02 ( 0.70–1.49 ) ; and symptomatic skeletal events HR = 0.83 ( 95 % CI 0.55–1.25 ) . In the safety population , the proportion reporting ≥1 grade 3 , 4 or 5 adverse events ever was 36 % , 13 % and 1 % SOC + DocP , and 40 % , 7 % and 1 % SOC + AAP ; prevalence 11 % at 1 and 2 years on both arms . Relapse treatment patterns varied by arm . Conclusions This direct , r and omised comparative analysis of two new treatment st and ards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival , nor in other important outcomes such as symptomatic skeletal events . Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs . Trial registration Clinical trials.gov : NCT00268476 Despite improvements in early detection of prostate cancer when it is clinical ly localized-- and therefore most amenable to curative local therapies-- approximately 33 % of men with early prostate cancer will develop biochemical failure with a rising prostate-specific antigen ( PSA ) during follow-up . The early use of and rogen suppression in this group of men has changed the clinical picture of and rogen-independent disease . Now , there are men on and rogen suppression who will develop biochemical failure and remain free of clinical or radiographic evidence of metastatic disease for a period of time . There is no st and ard approach to this group of men , who have a rising PSA on and rogen deprivation , because there are little or no data about strategies that may improve survival , delay time to progression , or improve quality of life . Therefore , current management of this population remains controversial . In an effort to determine which of these 2 approaches -- second-line hormone therapy or chemotherapy -- is optimal in delaying the time to progression , the Eastern Cooperative Oncology Group ( ECOG ) developed protocol E1899 . Although both approaches offer the potential for response ( reduction in PSA and prolonging the time to clinical progression ) , they have very different toxicity profiles , making impact on quality of life another important end point . This r and omized trial evaluating second-line hormonal therapy using ketoconazole and hydrocortisone versus docetaxel and estramustine combination chemotherapy on progression-free survival in asymptomatic men with a rising PSA on and rogen ablation for prostate cancer is the subject of this article PURPOSE Studies indicate that castration-resistant prostate cancer ( CRPC ) remains driven by lig and -dependent and rogen receptor ( AR ) signaling . To evaluate this , a trial of abiraterone acetate-a potent , selective , small-molecule inhibitor of cytochrome P ( CYP ) 17 , a key enzyme in and rogen synthesis -was pursued . PATIENTS AND METHODS Chemotherapy-naïve men ( n = 21 ) who had prostate cancer that was resistant to multiple hormonal therapies were treated in this phase I study of once-daily , continuous abiraterone acetate , which escalated through five doses ( 250 to 2,000 mg ) in three-patient cohorts . RESULTS Abiraterone acetate was well tolerated . The anticipated toxicities attributable to a syndrome of secondary mineralocorticoid excess-namely hypertension , hypokalemia , and lower-limb edema-were successfully managed with a mineralocorticoid receptor antagonist . Antitumor activity was observed at all doses ; however , because of a plateau in pharmacodynamic effect , 1,000 mg was selected for cohort expansion ( n = 9 ) . Abiraterone acetate administration was associated with increased levels of adrenocorticotropic hormone and steroids upstream of CYP17 and with suppression of serum testosterone , downstream and rogenic steroids , and estradiol in all patients . Declines in prostate-specific antigen > or= 30 % , 50 % , and 90 % were observed in 14 ( 66 % ) , 12 ( 57 % ) , and 6 ( 29 % ) patients , respectively , and lasted between 69 to > or= 578 days . Radiologic regression , normalization of lactate dehydrogenase , and improved symptoms with a reduction in analgesic use were documented . CONCLUSION CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC . These data confirm that CRPC commonly remains dependent on lig and -activated AR signaling
Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications .
PATIENT SUMMARY In men with a rise in their PSA levels after prior local treatment for prostate cancer only , it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients .
OBJECTIVE To present a summary of the 2016 version of the European Association of Urology ( EAU ) - European Society for Radiotherapy & Oncology ( ESTRO ) - International Society of Geriatric Oncology ( SIOG ) Guidelines on the treatment of relapsing , metastatic , and castration-resistant prostate cancer ( CRPC ) .
EVIDENCE SYNTHESIS Relapse after local therapy is defined by a rising prostate-specific antigen ( PSA ) level > 0.2ng/ml following radical prostatectomy ( RP ) and > 2ng/ml above the nadir after radiation therapy ( RT ) .
And rogen deprivation therapy ( ADT ) remains the basis for treatment of men with metastatic prostate cancer ( PCa ) .
Level 1 evidence for the treatment of metastatic CRPC ( mCRPC ) includes , abiraterone acetate plus prednisone ( AA/P ) , enzalutamide , radium 223 ( Ra 223 ) , docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel , AA/P , enzalutamide , and radium are approved for second-line treatment of CRPC following docetaxel .
CONCLUSIONS The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly .