***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 
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    ***EXAMPLES*** 
    Input: PURPOSE A r and omized , double-blind , dose finding , placebo controlled , parallel group clinical study was done to determine the incidence of prostate cancer in men with high grade prostatic intraepithelial neoplasia treated with toremifene .  MATERIAL S AND METHODS A total of 514 patients with high grade prostatic intraepithelial neoplasia and no evidence of prostate cancer on screening biopsy were r and omized to 20 , 40 or 60 mg toremifene , or placebo daily for 12 months . Patients underwent re-biopsy at 6 and 12 months . RESULTS The number of evaluable patients , that is those with 1 on study biopsy who were compliant , was 447 . The cumulative risk of prostate cancer was decreased in patients on 20 mg toremifene compared with placebo ( 24.4 % vs 31.2 % , p < 0.05 ) . The annualized rate of prevention was 6.8 cancers per 100 men treated . In patients with no biopsy evidence of cancer at baseline and 6 months , the 12-month incidence of prostate cancer was decreased by 48.2 % with 20 mg toremifene compared with placebo ( 9.1 % vs 17.4 % , p < 0.05 ) . The 20 mg dose was most effective but cumulative and 12-month incidences of prostate cancer were lower for each toremifene dose vs placebo with a cumulative risk of 29.2 % and 28.1 % , and a 12-month incidence of 14.3 % and 13.0 % for 40 and 60 mg , respectively . Gleason scores were similar across treatments . The overall incidence of drug related and serious adverse events did not differ between any of the toremifene groups and the placebo group . CONCLUSIONS Toremifene decreased the incidence of prostate cancer by 1 year and had a tolerability profile comparable to that of placebo in a high risk population The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention . High- grade prostatic intraepithelial neoplasia ( HGPIN ) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention . In vitro , in vivo , epidemiologic , and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here : a double-blind , r and omized ,  placebo-controlled  trial of selenium 200 ( μg/d ) as selenomethionine  in men with HGPIN . The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period . This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group ( SWOG ) . Of 619 enrolled patients , 423 r and omized men with HGPIN ( 212 selenium and 211 placebo ) were eligible ( by central pathology review ) and included in the primary analysis . Three-year cancer rates were 36.6 % ( placebo ) versus 35.6 % ( selenium ; P = 0.73 , adjusted ) . The majority of patients who developed cancer  on trial ( 70.8 % , selenium and 75.5 % , placebo ) had a Gleason score of 6 or less than 6 ; there were no differences in Gleason scores between the two arms . Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk ( relative risk = 0.82 ; 95 % CI : 0.40–1.69 ) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level ( < 106 ng/mL ) . Overall , and in all other subsets defined by baseline blood selenium levels , selenium supplementation had no effect on prostate cancer risk . The 36 % prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk . Future study in this setting should focus on selenium-deficient population s and selenium pharmacogenetics . Cancer Prev Res ; 4(11 ) ; 1761–9 . © 2011 AACR BACKGROUND We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer , as detected on biopsy , among men who are at increased risk for the disease . METHODS In this 4-year , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study , we compared dutasteride , at a dose of 0.5 mg daily , with placebo .  Men were eligible for inclusion in the study if they were 50 to 75 years of age , had a prostate-specific antigen ( PSA ) level of 2.5 to 10.0 ng per milliliter , and had had one negative prostate biopsy ( 6 to 12 cores ) within 6 months before enrollment . Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years . RESULTS Among 6729 men who underwent a biopsy or prostate surgery , cancer was detected in 659 of the 3305 men in the dutasteride group , as compared with 858 of the 3424 men in the placebo group , representing a relative risk reduction with dutasteride of 22.8 % ( 95 % confidence interval , 15.2 to 29.8 ) over the 4-year study period ( P<0.001 ) . Overall , in years 1 through 4 , among the 6706 men who underwent a needle biopsy , there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group ( P=0.81 ) . During years 3 and 4 , there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group , as compared with only 1 in the placebo group ( P=0.003 ) . Dutasteride therapy , as compared with placebo , result ed in a reduction in the rate of acute urinary retention ( 1.6 % vs. 6.7 % , a 77.3 % relative reduction ) . The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia , except that in our study , as compared with previous studies , the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group ( 0.7 % [ 30 men ] vs. 0.4 % [ 16 men ] , P=0.03 ) . CONCLUSIONS Over the course of the 4-year study period , dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia . ( Clinical Trials.gov number , NCT00056407 . Purpose High- grade prostatic intraepithelial neoplasia ( HGPIN ) is a potential precursor of prostate cancer ( PCa ) , and patients with HGPIN are at high risk for PCa development . Objective of our study was to evaluate the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated HGPIN on biopsy . Methods This prospect i ve , r and omized , phase III , open-label 3-year trial assessed dutasteride versus active surveillance in patients with HGPIN . Patients were r and omized to dutasteride 0.5 mg daily or active surveillance . Per- protocol prostate biopsies were performed at 6 , 12 , 24 , and 36 months until cancer detection or study end . The primary end point was cancer-free survival ( CFS ) . An intention-to-treat analysis was done for patients who underwent at least one per- protocol biopsy . An efficacy analysis was done for patients who completed the study . CFS was evaluated using Kaplan – Meier and log-rank analysis . Results In total , 220 men were r and omized ( dutasteride  , n = 107 ; surveillance , n = 113 ) . PCa was detected in 47.6 : 49.1 % in the surveillance group and 45.9 % in the treatment group ( p = 0.66 ) . The detected PCa differentiation by Gleason score ( GS ) was GS 6 in 76.9 % , GS 7 in 19.8 % , and GS ≥ 8 in 3.3 % , with no difference between groups . The 3-year PCa-free survival was 43.6 % in the surveillance and 49.6 % in the dutasteride group ( log rank p = 0.57 ) . Limitations include a relatively high non-adherence rate , open-label design , and baseline sextant biopsy scheme . Conclusions Dutasteride 0.5 mg for 3 years did not lower the PCa detection rate but did not worsen detected PCa characteristics in men with HGPIN OBJECTIVES To evaluate factors predicting cancer detection by extended repeat prostate biopsies in patients with an initial , isolated , monofocal or plurifocal , high- grade prostatic intraepithelial neoplasia ( HGPIN ) diagnosis . METHODS From 1995 to 2002 , after a first set of 10 to 12 systematic biopsy cores , 47 patients with an initial HGPIN diagnosis underwent repeat biopsy using the same technique ( mean repeat biopsy cores 11.5 ) after a median follow-up of 11.4 months ( range 3 to 24 ) . RESULTS Cancer was detected at the second biopsy in 21 patients ( 44.6 % ) . Cancer detection was significantly greater in patients with plurifocal HGPIN than in those with monofocal HGPIN ( 70 % vs. 10 % , respectively ; P < 0.005 ) and in patients who underwent repeat biopsy more than 6 months after the first biopsy set ( 65 % ) compared with patients who underwent repeat biopsy within 6 months ( 25 % ; P < 0.01 ; mean follow-up 15.5 and 3.8 months , respectively ) . Multivariate analysis showed that prostate-specific antigen , prostate-specific antigen density , digital rectal examination , and transrectal ultrasound findings were not statistically significant predictors of prostate cancer , and HGPIN multifocality and interval between biopsies ( more than a 6-month follow-up interval ) were independent prognostic factors ( odds ratio 4.65 and 2.65 , respectively ) . After radical prostatectomy ( 14 patients ) , no statistically significant differences were found in the pathologic stage between patient groups stratified by repeat biopsy interval ( within or after 6 months ) . CONCLUSIONS After a 10 to 12-core biopsy , patients with initial , isolated monofocal or plurifocal HGPIN diagnoses had an overall cancer detection rate of 45 % on repeat extended biopsies . Plurifocal HGPIN on the first biopsy set was the strongest independent predictive factor in cancer detection . A 12 to 18-month interval before repeat biopsy could permit a significantly greater cancer detection rate , with no apparent likelihood of clinical cancer progression CONTEXT Secondary analyses of 2 r and omized controlled trials and supportive epidemiologic and pre clinical data indicated the potential of selenium and vitamin E for preventing prostate cancer . OBJECTIVE To determine whether selenium , vitamin E , or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , placebo-controlled trial ( Selenium and Vitamin E Cancer Prevention Trial [ SELECT ] ) of 35,533 men from 427 participating sites in the United States , Canada , and Puerto Rico r and omly assigned to 4 groups ( selenium , vitamin E , selenium + vitamin E , and placebo ) in a double-blind fashion between August 22 , 2001 , and June 24 , 2004 . Baseline eligibility included age 50 years or older ( African American men ) or 55 years or older ( all other men ) , a serum prostate-specific antigen level of 4 ng/mL or less , and a digital rectal examination not suspicious for prostate cancer . INTERVENTIONS Oral selenium ( 200 microg/d from L-selenomethionine ) and matched vitamin E placebo , vitamin E ( 400 IU/d of all rac-alpha-tocopheryl acetate ) and matched selenium placebo , selenium + vitamin E , or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years . MAIN OUTCOME MEASURES Prostate cancer and prespecified secondary outcomes , including lung , colorectal , and overall primary cancer . RESULTS As of October 23 , 2008 , median overall follow-up was 5.46 years ( range , 4.17 - 7.33 years ) . Hazard ratios ( 99 % confidence intervals [ CIs ] ) for prostate cancer were 1.13 ( 99 % CI , 0.95 - 1.35 ; n = 473 ) for vitamin E , 1.04 ( 99 % CI , 0.87 - 1.24 ; n = 432 ) for selenium , and 1.05 ( 99 % CI , 0.88 - 1.25 ; n = 437 ) for selenium + vitamin E vs 1.00 ( n = 416 ) for placebo . There were no significant differences ( all P>.15 ) in any other prespecified 
    Output:
    
The overall efficacy of chemoprevention agents in HGPIN patients is limited .
But Green tea catechins showed the superiority to decrease prostate cancer in HGPIN patients