***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: PURPOSE Patients who present with localized and locally advanced prostate cancer may be c and i date s for prostate brachytherapy . We evaluated the treatment outcomes in a diverse group of prostate cancer patients who presented with low , moderate and high risk features . MATERIAL S AND METHODS A total of 301 patients who presented with T1 to T3 prostate cancer were treated with brachytherapy alone or combined with hormonal therapy and /or external beam irradiation .  Of these patients 109 at low risk with prostate specific antigen ( PSA ) 10 ng./ml . or less , Gleason score 6 or less and clinical stage T2a or less were treated with 125iodine alone , 152 at moderate risk with PSA greater than 10 ng./ml . , Gleason score greater than 6 or stage T2b or greater were treated with 125iodine or 103palladium or combined implant alone with 5 months of hormonal therapy , and 40 at high risk with PSA greater than 15 ng./ml . , Gleason 8 or greater , clinical stage T2c to T3 or positive seminal vesicle biopsy ( 20 ) were treated with combination brachytherapy , external beam irradiation and 9 months of hormonal therapy .  Patients with a positive seminal vesicle biopsy ( T3c disease ) and negative pelvic lymph nodes were included in the high risk group , and the walls of the seminal vesicles were also treated with implantation . Followup was performed every 6 months with digital rectal examination and ultrasound evaluation . Prostate biopsy was routinely recommended 2 years after completion of the radiation . Failure was defined as PSA increase on 2 consecutive determinations above 1 ng./ml . or evidence of local recurrence on digital rectal examination , transrectal ultrasound or biopsy . Kaplan-Meier projections were used to calculate progression-free survival rates . RESULTS Of the 109 patients at low risk followed from 1 to 7 years ( median 18 months ) 91 % were free of PSA failure at 4 years . No patient experienced urinary incontinence following implantation , although grade 1 to 2 radiation proctitis occurred in 5 ( 4.5 % ) . Of the 152 patients at moderate risk 73 received implantation and 79 received implantation combined with hormonal therapy . The 4-year biochemical freedom from failure rate for the hormone group was 85 % versus 58 % for the no hormone group ( p = 0.08 ) . The difference was more significant for those with Gleason score 7 or greater ( 90 versus 43 % , p = 0.01 ) and for those with PSA greater than 10 ng./ml . ( 87 versus 59 % , p = 0.04 ) . Grade 1 to 2 radiation proctitis occurred in 1 of the 79 patients ( 1.3 % ) receiving hormonal therapy and in 3 ( 4 % ) treated with implantation only . There were no cases of urinary incontinence . Of the 40 patients at high risk 71 % were free of biochemical failure at 3 years . Of the 4 patients with failure ( 10 % ) 3 ( 75 % ) originally had positive seminal vesicle biopsies . Five patients experienced gastrointestinal complications , although none was grade 3 or 4 . The actuarial freedom from grade 2 proctitis was 82 % . No patient experienced urinary incontinence . Prostate biopsies were negative in 87 % of the low risk , 96.8 ( hormone group ) versus 68.6 % ( no hormone group ) of the moderate risk ( p = 0.0023 ) and 86 % of the high risk patients . CONCLUSIONS Brachytherapy appears to offer comparable results to external beam irradiation and radical prostatectomy when patients are stratified by disease extent . Adopting a strategy of implant alone , implant with hormonal therapy or implant with hormonal therapy and external beam irradiation in patients who present with low to high risk features can improve the overall results in the more advanced cases OBJECTIVES To evaluate the short- and long-term effects of neoadjuvant hormonal treatment in locally confined prostate cancer . METHODS We report the preliminary results of 354 patients ( 199 with a clinical T2 tumor and 155 with a clinical T3 tumor ) of whom 164 r and omly received neoadjuvant total and rogen deprivation using a luteinizing-hormone-releasing hormone ( LHRH ) analog ( goserelin ) plus flutamide for a period of 3 months . RESULTS Serum prostate-specific antigen ( PSA ) levels and prostatic volume decreased from a mean of 19.9 ng/mL and 37.7 cm3 to a mean of 0.8 ng/mL and 26.5 cm3 after 3 months of neoadjuvant therapy .  " Clinical down-staging " was seen in 32 % in the neoadjuvantly treated group . " Pathological downstaging " percentages were 6 % and 16 % in the direct radical prostatectomy group and neoadjuvantly-treated group , respectively ( P < 0.01 ) . In patients with clinical T2 tumors , a significant difference in number of positive margins was shown in favor of the neoadjuvantly treated group ( P < 0.01 ) . In patients with clinical T3 tumors , a significant difference could not be detected ( P = 0.14 ) . In 215 patients with a mean follow-up time of 15 months , the calculated 95 % confidence intervals of mean time of PSA progression-free survival were 26 to 35 months in the neoadjuvantly-treated group and 28 to 37 months in the direct radical prostatectomy group , indicating no significant differences between treatment groups . However , follow-up time is currently too short to draw definite conclusions . CONCLUSIONS These early data confirm high understaging percentages in clinical staging . The clinical relevance of the statistically significant smaller numbers of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor will have to be confirmed when further follow-up allows an accurate evaluation of time to PSA progression , local recurrence , and distant metastases . Presently , neoadjuvant therapy is not advisable outside clinical research setting A total of 161 patients diagnosed as having stage B ( 134 patients ) or C ( 27 patients ) prostate cancer were r and omly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the anti- and rogen flutamide and an LHRH agonist before radical prostatectomy . Neoadjuvant combination therapy before radical prostatectomy decreased cancer positive surgical margins from 33.8 % in the control group to only 7.8 % , thus leaving 92.2 % of patients with negative margins at surgery for a 39.2 % increase in specimen confined disease . Although on average the final stage determined at histopathological examination of the surgical specimen was more advanced than predicted at initial diagnosis in 33.8 % of control patients , an opposite observation was made in the group of men who received the 3 month neoadjuvant combination therapy where the final stage , instead of being more advanced , was less advanced than at diagnosis in an average of 21.1 % of men for a net 54.9 % improvement of staging in favour of combination therapy . On the other h and , organ confined disease increased from 49.3 % to 77.8 % of patients after 3 months of combination therapy , for a 57.9 % increase in the incidence of organ confined disease . Although long term follow up of these patients is required to determine the impact on survival , the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from 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 ( 66.6 % ) , which were mild to moderate in > 90 % of cases . CONCLUSIONS Bicalutamide 150 mg/day given as adjuvant to radiotherapy significantly improved PFS in patients with locally advanced prostate cancer . For patients with localised disease , the results at this stage from the radiotherapy subgroup and the overall EPC programme suggest that adjuvant hormonal therapy is currently not appropriate . There were no unexpected tolerability findings PURPOSE A prospect i ve phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen ( PSA ) recurrence rates after radical prostatectomy . Our interim analysis includes secondary end points of differences in biochemistry , pathology and adverse events between the 2 groups . MATERIAL S AND METHODS Men with clinical ly confined prostate cancer were r and omized to receive 7.5 mg . leuprolide intramuscularly monthly and 250 mg . flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy . Our study was powered to detect a 35 % decrease in PSA recurrence , assuming a 30 % recurrence rate in the 3-month arm after 3 years . RESULTS A total of 547 men were r and omized between August 1995 and April 1998 . Men in the 8 and 3-month groups were equally stratified for T stage ( 29 % T1c , 70 % T2 ) , Gleason grade ( 68 % less than 4 , 32 % 4 or greater ) and pretreatment PSA ( 63 % less than 10 , 27 % 10 to 20 and 10 % greater than 20 microg./l . ) . Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group ( 11.64 versus 9.95 microg./l . , respectively , p = 0.0539 ) . A total of 44 men withdrew from study before surgery and , therefore , were nonevaluable . Preoperative PSA nadir was less than 0.1 microg./l . in 43.3 % versus 75.1 % ( p < 0.0001 ) , and 0.3 microg./l . or greater in 21 % versus 9.2 % after 3 versus 8 months , respectively ( p < 0.0006 ) . Mean serum PSA decreased 98 % to 0.12 microg./l . after 3 months , with a further 57 % to 0.052 microg./l . from 3 to 8 months . Transrectal ultrasound determined that prostatic volume decreased 37 % from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy ( p = 0.0001 ) and a further 13 % to 22.2 cc after 8 months ( p = 0.03 ) . Mean hemoglobin decreased 15 % ( 148.2 to 125.4 gm./dl . ) after 3-month neoadjuvant hormonal therapy but stabilized thereafter . Radical prostatectomy was completed in 500 men , while surgery was aborted intraoperatively in 3 . Positive margin rates were significantly lower in the 8 than 3-month group ( 12 % versus 23 % , respectively , p = 0.0106 ) . There were no fatal adverse events and no differences between the 2 groups in the severity or causality ( p = 0.287 , 0.0564 ) of adverse events , or incidence of increased liver enzymes or diarrhea ( p = 0.691 , 0.288 , respectively ) . However , men in the 8-month group noticed a higher number of newly reported adverse events ( 4.5 versus 2.9 , p < 0.0001 ) and higher incidence of hot flushes than the 3-month group ( 87 % versus 72 % , respectively , p < 0 
    Output:
    
MAIN RESULTS Men with prostate cancer have different clinical outcomes based on their risk ( T1-T2 , T3-T4 , PSA levels and Gleason score ) .
Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer .
Significant local control may be achieved when given prior to prostatectomy or radiotherapy , which may improve patient 's quality of life .
When given adjuvant to these primary therapies , hormone therapy , not only provides a method for local control , but there is also evidence for a significant survival advantage .