***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction : We investigated the health-related quality of life ( HRQoL ) of long-term prostate cancer patients who received leuprorelin acetate in microcapsules ( LAM ) for and rogen-deprivation therapy ( ADT ) . Methods : The observational study was carried out by 30 office-based German urologists in 536 prostate cancer ( PCa ) patients treated for ≥5 years with LAM and in 116 patients of an age-matched control group ( CG ) . Data on HRQoL and health status was collected prospect ively using vali date d question naires QLQ-C30 , QLQ-PR25 and Karnofsky Index . Data on effectiveness ( clinical response , prostate specific antigen [ PSA ] , testosterone ) and safety was collected retrospectively from patients ' health records . We used descriptive statistics to analyze the data . Results : The mean treatment duration was 8.6 years ( range 4.5 - 19.8 years ) . General health status ( QLQ-C30 ) was comparable for both groups . Differences were observed regarding physical - and role functioning . ADT patients rated single items slightly worse than CG . Karnofsky-Index showed comparable high values ( median of 90 % ) . QLQ-PR25 revealed more PCa-related symptoms for ADT patients . Within 6 months , median PSA level declined > 90 % and median testosterone levels declined below castration level from 4.0 to 0.2 ng/mL. Clinical response ( European Organisation for Research and Treatment of Cancer criteria ) was observed in at least 90 % of ADT patients . Conclusions : Long-term ADT with LAM is a well-accepted , tolerated , effective , and low-burden treatment option for patients with advanced , hormone-sensitive PCa BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) 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 Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy .  We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy  , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing  long-term hormone  therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research Background : Bicalutamide is a widely used , relatively non-toxic anti- and rogen , particularly when used in combination with and rogen deprivation . In men on combined and rogen blockade ( CAB ) , the typical dose is 50 mg per day . For men receiving monotherapy with bicalutamide anti- and rogen  , the dose is 150 mg per day . The objective was to determine the PSA response rate to increasing bicalutamide to 150 mg per day in men who develop castrate-resistant prostate cancer ( CRPC ) on CAB with goserelin acetate and bicalutamide 50 mg per day . Methods : A national , multicentre , phase 2 , open-label study in men on CAB with a rising PSA>2.0 . The primary end point of the trial was PSA response at 12 months , defined as a decline by 50 % or more compared with baseline value . Partial response was defined as a PSA decline of 10–49 % . Secondary end points were duration of PSA response , change in slope of serum PSA , change in ratio of free PSA : total PSA at 3 months , 6 months and 12 months as compared with baseline ; duration of the bicalutamide withdrawal response after discontinuation ; the rate of cardiovascular events ; and toxicity . The study was initially planned to accrue 100 patients , but was closed early due to diminishing accrual . Results : Sixty-four patients were accrued ; 61 patients received trial treatment and constituted the intention-to-treat ( ITT ) cohort . 70 % were M0 . Among 59 evaluable ITT patients , 13 ( 22 % ) patients had a > 50 % PSA decline , 5 ( 8 % ) had a decline between 10 and 50 % , 4 ( 7 % ) had stabilization and 37 ( 63 % ) had PSA progression . The median duration was 3.7 months ( 95 % confidence interval of 0.92–6.21 months ) . Conclusion : In patients with early biochemical failure on CAB with bicalutamide 50 mg , an increase in dose to 150 mg of bicalutamide result ed in a 
    Output:
    
Conclusions Early st and ard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival .
Early st and ard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits .
Combined treatment at the time of development of castration-resistant disease is well established