***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: The objectives of the Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55 - 74 at entry whether screening with flexible sigmoidoscopy ( 60-cm sigmoidoscope ) can reduce mortality from colorectal cancer , whether screening with chest X-ray can reduce mortality from lung cancer , whether screening men with digital rectal examination ( DRE ) plus serum prostate-specific antigen ( PSA ) can reduce mortality from prostate cancer , and whether screening women with CA125 and transvaginal ultrasound ( TVU ) can reduce mortality from ovarian cancer . Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity , specificity , and positive predictive value ; to assess incidence , stage , and survival of cancer cases ; and to investigate biologic and /or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints . The design is a multicenter , two-armed , r and omized trial with 37,000 females and 37,000 males in each of the two arms . In the intervention arm , the  PSA and CA125 tests  are performed at entry , then annually for 5 years . The  DRE , TVU , and chest X-ray exams  are performed at entry and then annually for 3 years . Sigmoidoscopy is performed at entry and then at the 5-year point . Participants in the control arm follow their usual medical care practice s. Participants will be followed for at least 13 years from r and omization to ascertain all cancers of the prostate , lung , colorectum , and ovary , as well as deaths from all causes . A pilot phase was undertaken to assess the r and omization , screening , and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels . This paper describes eligibility , consent , and other design features of the trial , r and omization and screening procedures , and an outline of the follow-up procedures . Sample -size calculations are reported , and a data analysis plan is presented BACKGROUND Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world . One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen ( PSA ) ; however , the extent of benefit and harm with such screening is under continuous debate . METHODS In December , 1994 , 20,000 men born between 1930 and 1944 , r and omly sample d from the population register , were r and omised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years ( n=10,000 ) or to a control group not invited ( n=10,000 ) . Men in the screening group were invited up to the upper age limit ( median 69 , range 67 - 71 years ) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies . The primary endpoint was prostate-cancer specific mortality , analysed according to the intention-to-screen principle . The study is ongoing , with men who have not reached the upper age limit invited for PSA testing . This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31 , 2008 . This study is registered as an International St and ard R and omised Controlled Trial IS RCT N54449243 . FINDINGS In each group , 48 men were excluded from the analysis because of death or emigration before the r and omisation date , or prevalent prostate cancer . In men r and omised to screening , 7578 ( 76 % ) of 9952 attended at least once . During a median follow-up of 14 years , 1138 men in the screening group and 718 in the control group  were diagnosed with prostate cancer , result ing in a cumulative prostate-cancer incidence of 12.7 % in the screening group and 8.2 % in the  control  group ( hazard ratio 1.64 ; 95 % CI 1.50 - 1.80 ; p<0.0001 ) . The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40 % ( 95 % CI 0.17 - 0.64 ) , from 0.90 % in the control group to 0.50 % in the screening group . The rate ratio for death from prostate cancer was 0.56 ( 95 % CI 0.39 - 0.82 ; p=0.002 ) in the screening compared with the control group . The rate ratio of death from prostate cancer for attendees compared with the control group was 0.44 ( 95 % CI 0.28 - 0.68 ; p=0.0002 ) . Overall , 293 ( 95 % CI 177 - 799 ) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death . INTERPRETATION This study shows that prostate cancer mortality was reduced almost by half over 14 years . However , the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes . The benefit of prostate-cancer screening compares favourably to other cancer screening programs . FUNDING The Swedish Cancer Society , the Swedish Research Council , and the National Cancer Institute BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . BACKGROUND Screening for prostate cancer advances the time of diagnosis ( lead time ) and detects cancers that would not have been diagnosed in the absence of screening ( overdetection ) . Both consequences have considerable impact on the net benefits of screening . METHODS We developed simulation models based on results of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified , and on baseline prostate cancer incidence and stage distribution data . The models were used to predict mean lead times , overdetection rates , and ranges ( corresponding to approximate 95 % confidence intervals ) associated with different screening programs . RESULTS Mean lead times and rates of overdetection depended on a man 's age at screening . For a single screening test at age 55 , the estimated mean lead time was 12.3 years ( range = 11.6 - 14.1 years ) and the overdetection rate was 27 % ( range = 24%-37 % ) ; at age 75 , the estimates were 6.0 years ( range = 5.8 - 6.3 years ) and 56 % ( range = 53%-61 % ) , respectively . For a screening program with a 4-year screening interval from age 55 to 67 , the estimated mean lead time was 11.2 years ( range = 10.8 - 12.1 years ) , and the overdetection rate was 48 % ( range = 44%-55 % ) . This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4 % to 10.6 % , a relative increase of 65 % ( range = 56%-87 % ) . In annual screening from age 55 to 67 , the estimated overdetection rate was 50 % ( range = 46%-57 % ) and the lifetime prostate cancer risk was increased by 80 % ( range = 69%-116 % ) . Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinical ly relevant cancer detected . CONCLUSIONS These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy .  Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy  , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) PURPOSE This clinical trial is aim ed at evaluating the impact of prostate cancer screening on cancer-specific mortality . SUBJECTS AND METHODS Forty-six thous and four hundred and eighty-six ( 46,486 ) men aged 45 - 80 years registered in the electoral roll of the Quebec city area were r and omized in 1988 between screening and no screening . Screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and digital rectal examination ( DRE ) at first visit . At follow-up visits , serum PSA only was used . RESULTS Seventy-four ( 74 ) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following r and omization . Median follow-up of screened men was 7.93 years . A Cox proportional hazards model of the age at death from prostate cancer shows a 62 % reduction ( P < 0.002 , Fisher 's exact test ) of cause-specific mortality in the screened men ( P = 0.005 ) . These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America Of 9,026 males aged 50 - 69 years , 1,494 were r and omly selected and invited to participate in a programme including two screenings for carcinoma of the prostate by digital rectal examination performed in 19 
    Output:
    
Sub-group analyses indicated that prostate cancer-specific mortality was not affected by age at which participants were screened .
•Harms of screening included high rates of false-positive results for the PSA test , over-diagnosis and adverse events associated with transrectal ultrasonography guided biopsies such as infection , bleeding and pain .
•Any benefits from prostate cancer screening may take > 10 years to accrue ; therefore , men who have a life expectancy of < 10 - 15 years should be informed that screening for prostate cancer is not beneficial and has harms