***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: This paper reports on results of the EORTC protocol 30892 , an open , prospect i ve , r and omized study of 310 patients with previously untreated metastatic prostate cancer with favourable prognostic factors who were treated by either flutamide ( FLU ) or cyproterone acetate ( CPA ) monotherapy .  The final analysis with regard to the main end points , time to progression and survival are still pending . Final results related to the evaluation of sexual functioning prior to and under treatment are reported here . Of 310 r and omized patients 294 were eligible for evaluation within this side study . The median age was 71 years ( range 48–85 ) . Potential risk factors related to age , general health and prostate cancer were evaluated . For evaluation of sexual functions a five-item question naire was used which was administered by the investigator . The protocol allowed time dependent observations at 3-monthly follow-up visits . Sexual functioning was dependent on age but not on prostate cancer-related parameters . Sexual functions at entry were similar within the two treatment groups , spontaneous ( nightly ) erections and sexual activity were seen in 43–51 % and 29–35 % of cases . Under treatment , sexual functions under FLU and CPA declined slowly with median times of 12.9 and 5.8 months versus 13.7 and 8.9 months respectively for spontaneous erections and sexual activity . Eventually , with an average observation time in excess of 2 years , loss of spontaneous erections and of sexual activity occurred in 80 % versus 92 % and in 78 % versus 88 % of men under FLU versus CPA treatment respectively . None of these differences reached statistical significance . Maintenance of potency under treatment with FLU as reported in the literature is not confirmed in this study . However , loss of sexual functions under monotherapy with both anti and rogens is slow and 10–20 % of men retain sexual activity after 2–6 years of treatment . This observation can be exploited in new treatment schemes and is likely to lead to improved quality of life . The advantage of FLU in time and total preservation of sexual functions is statistically not significant and must be balanced against the side effects of FLU and other pure anti and rogens , which may exceed those of CPA especially with respect to gynaecomastia . Hepatic toxicity may limit the long-term use of both drugs . © 2000 Cancer Research Background Subgroup analyses in r and omized trials examine whether effects of interventions differ between subgroups of study population s according to characteristics of patients or interventions . However , findings from subgroup analyses may be misleading , potentially result ing in suboptimal clinical and health decision making . Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered . The objectives of this study are : 1 ) to describe the reporting of subgroup analyses and cl aims of subgroup effects in r and omized controlled trials , 2 ) to assess study characteristics associated with reporting of subgroup analyses and with cl aims of subgroup effects , and 3 ) to examine the analysis , and interpretation of subgroup effects for each study 's primary outcome . Methods We will conduct a systematic review of 464 r and omized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine . We will r and omly select journal articles , stratified in a 1:1 ratio by higher impact versus lower impact journals . According to 2007 ISI total citations , we consider the New Engl and Journal of Medicine , JAMA , Lancet , Annals of Internal Medicine , and BMJ as higher impact journals . Teams of two review ers will independently screen full texts of reports for eligibility , and abstract data , using st and ardized , pilot-tested extraction forms . We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with cl aims of subgroup effects for the primary and any other outcomes . Discussion A clear underst and ing of subgroup analyses , as currently conducted and reported in published r and omized controlled trials , will reveal both strengths and weaknesses of this practice . Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses , and cl aim and interpretation of subgroup effects in r and omized trials But : Le programme EPC ( Early Prostate Cancer ) a ete concu pour evaluer l'efficacite et la tolerance d'une hormonotherapie par le bicalutamide a la dose de 150 mg en situation adjuvante ( a une prostatectomie totale ou a une radiotherapie ) ou en traitement seul chez des patients presentant un cancer de la prostate non metastase . Materiel : 8113 patients au stade localise ( T1-T2 , N0 , MO ) ou localement avance ( T1-T2 , N+ ou T3-T4 , Nx , MO ) ont ete inclus dans trois gr and es etudes internationales r and omisees comparant un traitement par le bicalutamide 150 mg ( n = 4052 ) a un placebo ( n = 4061 ) . Les objectifs primaires de ce programme sont la progression clinique objective ( determinee par scintigraphie osseuse , scanner , echographie ou IRM ) et la survie globale . La tolerance et la progression biologique sont des objectifs secondaires . Result ats : A 7,4 ans de suivi median , tous stades , toutes attitudes therapeutiques , toutes etudes confondues , le bicalutamide 150 mg reduit significativement le risque de progression de 21 % ( HR : 0,79 ; IC 95 % : 0,73 - 0,85 ; p < 0,001 ) . En analyse de sous-groupes , il n'y a pas de benefice a un traitement par bicalutamide 150 mg au stade localise . Au stade localement avance , le bicalutamide 150 mg en adjuvant a la radiotherapie externe reduit significativement le risque de deces de 35 % ( HR : 0,65 ; IC95 % : 0,44 - 0,95 ; p = 0,03 ) . En adjuvant a la prostatectomie radicale , il reduit significativement le risque de progression clinique de 25 % ( HR : 0,75 ; IC95 % : 0,61 - 0,91 ; p = 0,004 ) . Les effets secondaires les plus frequemment retrouves ( gynecomasties et/ou les douleurs mammaires : 73,6 % et 68,8 % ) sont en rapport avec l'activite pharmacologique du bicalutamide . Conclusion : La 3eme analyse du programme EPC a 7,4 ans de suivi median met en evidence un benefice significatif en survie globale en adjuvant a la radiotherapie et en survie sans progression clinique en adjuvant a la prostatectomie radicale au stade localement avance . Sur la base de ces result ats et d'une revue exhaustive de la litterature , trois avis d'experts explicitent les aspects pratiques de la prise en charge The efficacy of Casodex ( ICI 176,334 ; Zeneca Pharmaceuticals , Macclesfield , UK ) , a nonsteroidal anti and rogen , in the treatment of advanced prostate cancer has been compared in two trials with castration , either surgical ( bilateral orchitectomy ) or medical , with the gonadotropin-releasing hormone agonist Zoladex ( goserelin acetate ; Zeneca Pharmaceuticals ) . The half-life of Casodex is 7 to 10 days , and allows once-daily dosing . The first trial was a prospect i ve , r and omized study involving 150 patients receiving Casodex , 50 mg once daily p.o . , and 154 patients undergoing castration .  There were no significant differences between the two groups in subjective responses , time to treatment failure , or time to objective evidence of disease progression . The other study involved higher doses , the dose being selected after patients had received one of two doses of Casodex , 100 mg/day or 150 mg/day , in a double-blind study . On statistical analysis , it was clear that the higher dose was more effective , and thus most patients taking 100 mg/day were switched to 150 mg/day . Again , Casodex treatment was compared with medical or surgical castration  .  The higher dose of Casodex is well tolerated with a similar adverse event profile as the lower dose of 50 mg/day . Follow-up is as yet too short for an analysis of efficacy Purpose : Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer . Although many of the adverse effects of castration therapy are manageable , they can have a detrimental effect on quality of life . Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ( ‘ Casodex ’ ) 150 mg adjuvant to radiotherapy in patients with T1 - 4 , M0 , any n prostate cancer . Methods : The subset of patients within the early prostate cancer ( EPC ) program who received radiotherapy with curative intent ( n = 1,370 ) were included in the analysis . These patients were r and omized to receive oral bicalutamide 150 mg once daily ( n = 699 ) or placebo ( n = 671 ) . Results : The median follow-up for patients included in this analysis was 7.2 years . In patients with locally advanced disease ( n = 305 )  , bicalutamide adjuvant to radiotherapy significantly improved : progression-free survival ( PFS ) , reducing the risk of objective progression by 44 % compared with radiotherapy alone [ hazard ratio ( HR ) 0.56 ; 95 % confidence interval ( CI ) 0.40 , 0.78 ; P < 0.001 ) . Prostate-specific antigen (PSA)–PFS , reducing the risk of PSA progression by 59 % compared with radiotherapy alone ( HR 0.41 ; 95 % CI 0.30 , 0.55 ; P < 0.001 ) . Overall survival , reducing the risk of death by 35 % compared with radiotherapy alone ( HR 0.65 ; 95 % CI 0.44 , 0.95 ; P = 0.03 ) . This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths ( 16.1 vs 24.3 % , respectively ) . There was no significant difference in PFS or overall survival in patients with localized disease ( n = 1,065 ) . Conclusions : In patients with locally advanced disease  , bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival , PFS and PSA – PFS compared with radiotherapy alone . The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy ( Bolla et al. in Lancet 360:103–108 , 2002 ; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285–1290 , 2005 ) . In addition , the clinical benefit of bicalutamide 150 mg in locally advanced patients , but not in those with localized disease , is consistent with the overall results from the EPC program ( McLeod et al. BJU Int 97:247–254 , 2006 ) . Given the quality -of-life advantages of bicalutamide relative to castration , bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer BACKGROUND AND PURPOSE The ongoing Early Prostate Cancer ( EPC ) programme is assessing bicalutamide ( ' Casodex ' ) 150 mg , either alone or as adjuvant to treatment of curative intent , in patients with localised or locally advanced prostate cancer ( n=8113 ) . This paper presents an exploratory analysis of the subgroup of the EPC programme who received radiotherapy with curative intent ( n=1370 ) in order to determine the efficacy ( in terms of progression-free survival [ PFS ] ) and tolerability of bicalutamide 150 mg in this setting . PATIENTS AND METHODS 1370 patients with T1 - 4 , MO , any N prostate cancer received bicalutamide 150 mg or placebo adjuvant to radiotherapy of curative intent . This analysis was undertaken at median 5.3 years ' follow-up . RESULTS In patients with locally advanced disease ( n=305 ) , bicalutamide adjuvant to radiotherapy significantly increased PFS by 53 % ( event-time ratio 1.53 ; 95 % confidence intervals [ CI ] 1.16 , 2.02 ) compared with placebo and reduced the risk of disease progression by 42 % ( hazard ration [ HR ] 0.58 ; 95 % CI 0.41 , 0.84 ; P=0.00348 ) . In these patients , objective progression was experienced by 33.5 % of those r and omised to bicalutamide versus 48.6 % for those r and omised to placebo . The between-group difference in patients with localised disease ( n=1065 ) failed to reach statistical significance ( HR 0.80 ; 95 % CI 0.62 , 1.03 ; P=0.088 ) . The most common adverse events were breast pain ( 74.8 % ) and gynaecomastia ( 6 
    Output:
    
Predefined subgroup analyses showed that use of non-steroidal anti and rogens , compared with castration , was less favourable for overall survival , clinical progression ( at one year , 70 weeks , two years ) and treatment failure ( at one year , 70 weeks , two years ) in men with metastatic disease .
The effects of non-steroidal anti and rogens on cancer-specific survival and biochemical progression remained unclear .
Currently available evidence suggests that use of non-steroidal anti and rogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival , clinical progression , treatment failure and treatment discontinuation due to adverse events .