***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: BACKGROUND Cancer screening has been effective in detecting tumors early before symptoms appear . However , the effectiveness of the regular fecal occult blood test ( FOBT ) in colorectal cancer in the long term has not been quantified . METHODS We applied the statistical method developed by Wu and Rosner using data from the Minnesota Colon Cancer Control Study ( MCCCS ) . All initially asymptomatic participants were classified into four mutually exclusive groups : true-early-detection , no-early-detection , over-diagnosis , and symptom-free life ; human lifetime was treated as a r and om variable and is subject to competing risks . All participants in the screening program will eventually fall into one of the four outcomes above . Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data . RESULTS Depending on gender , screening frequency and age at the initial screening , for all participants the probability of " symptom-free-life " varies between 95.3 % and 96.6 % ; the probability of " true-early-detection " is 1.9 - 3.8 % ; the probability of no-early-detection is 0.3 - 2.0 % ; the probability of over-diagnosis is 0.16 - 0.3 % . Among those with colorectal cancer detected by regular FOBT , the probability of over-diagnosis is lower than expected and is between 6 % and 9 % , with 95 % CI ( 2.5 % , 21.3 % ) for females and ( 1.9 % , 44.7 % ) for males . The probability of true-early-detection increases as screening interval decreases . The probability of no-early-detection decreases as screening interval decreases . CONCLUSION The probability of over-diagnosis among the screen-detected cases is not as high as previously thought . We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in  mammographic screening for breast cancer at ages 50–69 years . Setting The Swedish Two-County r and omized trial of mammographic screening for breast cancer , and the UK Breast Screening Programme in Engl and , ages 50–69 years . Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group ( active study population ) of the Swedish Two-County Trial , by comparison with the control group ( passive study population ) . We estimated the same quantities for the mortality and incidence rates in Engl and ( 1974–2004 and 1974–2003 , respectively ) . We used Poisson regression for statistical inference . Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial ( P < 0.001 ) and the screening programme in Engl and ( P < 0.001 ) . The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in Engl and , respectively . The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were , respectively , 4.3 and 2.3 per 1000 . Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis . Between 2 and 2.5 lives are saved for every overdiagnosed case Introduction Overdiagnosis of breast cancer due to mammography screening , defined as thediagnosis of screen-detected cancers that would not have presented clinical ly in awomen 's lifetime in the absence of screening , has emerged as a highly contentiousissue , as harm caused may question the benefit of mammographic screening . Most studies included women over 50 years old and little information is available foryounger women . Methods We estimated the overdiagnosis of breast cancer due to screening in women aged 40to 49 years using data from a r and omised trial of annual mammographic screeningstarting at age 40 conducted in the UK . A six-state Markov model was constructedto estimate the sensitivity of mammography for invasive and insitu breast cancer and the screen-detectable mean sojourn time fornon-progressive in situ , progressive in situ , and invasivebreast cancer . Then , a 10-state simulation model of cancer progression , screening , and death , was developed to estimate overdiagnosis attributable to screening . Results The sensitivity of mammography  for invasive and in situ breast cancerswas 90 % ( 95 % CI , 72 to 99 ) and 82 % ( 43 to 99 ) , respectively . The screen-detectablemean sojourn time of pre clinical non-progressive and progressive in situ cancers was 1.3 ( 0.4 to 3.4 ) and 0.11 ( 0.05 to 0.19 ) years , respectively , and 0.8 years ( 0.6 to 1.2 ) for pre clinical invasive breast cancer . The proportion ofscreen-detected in situ cancers that were non-progressive was 55 % ( 25 to77 ) for the first and 40 % ( 22 to 60 ) for subsequent screens . In our main analysis , overdiagnosis was estimated as 0.7 % of screen-detected cancers . A sensitivity analysis , covering a wide range of alternative scenarios , yielded a range of 0.5%to 2.9 % . Conclusion Although a high proportion of screen-detected in situ cancers werenon-progressive , a majority of these would have presented clinical ly in theabsence of screening . The extent of overdiagnosis due to screening in women aged40 to 49 was small . Results also suggest annual screening is most suitable forwomen aged 40 to 49 in the United Kingdom due to short cancer sojourn times Background : Published lead time estimates in breast cancer  screening vary from 1 to 7 years and the percentages of overdiagnosis vary from 0 to 75 % . The differences are usually explained as r and om variations . We study how much can be explained by using different definitions and methods . Methods : We estimated the clinical ly relevant lead time based on the observed incidence reduction after attending the last screening round in the Norwegian mammography screening programme .  We compared this estimate with estimates based on models that do not take overdiagnosis into account ( model-based lead times ) , for varying levels of overdiagnosis . Finally , we calculated overdiagnosis adjusted for clinical and model-based lead times and compared results . Results : Clinical lead time was about one year based on the reduction in incidence in women previously offered screening . When overdiagnosed tumours were included , the estimates increased to 4–9 years , depending on the age at which screening begins and the level of overdiagnosis . Including all breast cancers detected in women long after the end of the screening programme dilutes the level of overdiagnosis by a factor of 2–3 . Conclusion : When overdiagnosis is not taken into account , lead time is substantially overestimated . Overdiagnosis adjusted for model-based lead time is a function tending to zero , with no simple interpretation . Furthermore , the estimates are not in general comparable , because they depend on both the duration of screening and duration of follow-up . In contrast , overdiagnosis adjusted for clinical ly relevant tumours is a point estimate ( and interpreted as percentage ) , which we find is the most reasonable method BACKGROUND No r and omized controlled trial of prostate cancer screening has been reported and none is likely to be completed in the near future . In the absence of direct evidence , the decision to screen must therefore be based on estimates of benefits and risks . The main risk of screening is overdetection -- the detection of cancer that , if left untreated , would not cause death . In this study the authors estimate the level of overdetection that might result from annual screening of men aged 50 - 70 . METHODS The annual rate of lethal screen-detectable cancer ( detectable cancer that would prove fatal before age 85 if left untreated ) was calculated from the observed prostate cancer mortality rate in Quebec ; the annual rate of all cases of screen-detectable prostate cancer was calculated from 2 recent screening studies . RESULTS The annual rate of lethal screen-detectable prostate cancer was estimated to be 1.3 per 1000 men . The annual rate of all cases of screen-detectable prostate cancer was estimated to be 8.0 per 1000 men . The estimated case-fatality rate among men up to 85 years of age was 16 % ( 1.3/8.0 ) ( sensitivity analysis 13 % to 22 % ) . INTERPRETATION Of every 100 men with screen-detected prostate cancer , only 16 on average ( 13 to 22 ) could have their lives extended by surgery , since the prostate cancer would not cause death before age 85 in the remaining 84 ( 78 to 87 ) It is currently not known whether most lung cancers detected by  computerized tomography ( CT ) screening  are aggressive and likely to be fatal if left untreated , or if a sizable fraction are indolent and unlikely to cause death during the natural lifetime of the individual . We developed a longitudinal biologically-based model of the relationship between individual smoking histories and the probability for lung cancer incidence , CT screen detection , lung cancer mortality , and other-cause mortality . The longitudinal model relates these different outcomes to an underlying lung cancer disease pathway and an effective other-cause mortality pathway , which are both influenced by the individual smoking history . The longitudinal analysis provides additional information over that available if these outcomes were analyzed separately , including testing if the number of CT detected and histologically-confirmed lung cancers is consistent with the expected number of lung cancers " in the pipeline " . We assume indolent nodules undergo Gompertz growth and are detectable by CT , but do not grow large enough to contribute significantly to symptom-based lung cancer incidence or mortality . Likelihood-based model calibration was done jointly to data from 6878 heavy smokers without asbestos exposure in the control ( placebo ) arm of the Carotene and Retinol Efficacy Trial ( CARET ) ; and to 3,642 heavy smokers with comparable smoking histories in the Pittsburgh Lung Screening Study ( PLuSS ) , a single-arm prospect i ve trial of low-dose spiral CT screening for diagnosis of lung cancer . Model calibration was checked using data from two other single-arm prospect i ve CT screening trials , the New York University Lung Cancer Biomarker Center ( NYU ) ( n=1,021 ) , and Moffitt Cancer Center ( Moffitt ) cohorts ( n=677 ) . In the PLuSS cohort , we estimate that at the end of year 2 , after the baseline and first annual CT exam , that 33.0 ( 26.9 , 36.9)% of diagnosed lung cancers among females and 7.0 (4.9,11.7)% among males were overdiagnosed due to being indolent cancers . At the end of the PLuSS study , with maximum follow-up of 5.8 years , we estimate that due to early detection by CT and limited follow-up , an additional 2.2 (2.0,2.4)% of all diagnosed cancers among females and 7.1 (6.7,8.0)% among males would not have been diagnosed in the absence of CT screening . We also find a higher apparent cure rate for lung cancer among CARET females than males , consistent with the larger indolent fraction of CT detected and histologically confirmed lung cancers among PLuSS females . This suggests that there are significant gender differences in the aggressiveness of lung cancer . Females may have an inherently higher proportion of indolent lung cancers than males , or aggressive lung cancers may be brought into check by the immune system more frequently among females than males OBJECTIVES To estimate overdiagnosis ( detection of latent carcinomas ) as a consequence of  screening for prostate cancer . DESIGN Based on actual screen ( first or repeat ) detected and interval prostate cancer rates observed in the Florence screening pilot study , a scenario was simulated where males aged 60 years ( or 65 ) had six biennal screens and were followed up for four years . Overdiagnosis was determined as the proportional excess of cancers detected by screening with respect to that expected in its absence . SETTING City of Florence , Italy , from 1992 through 1995 . POPULATION 2,740 resident males , aged 60 to 74 years . RESULTS Overdiagnosis was estimated to be 51 % ( 95 % confidence limits : 44%-55 % ) or 93 % ( 85%-101 % ) for age 60 or 65 at entry . Comparison with other screening experiences obtaining higher detection rates suggests that a more aggressive screening approach could be associated with overdiagnosis estimates as big as 200%-250 % . CONCLUSIONS Screening for prostate cancer is associated with a relevant risk of overdioagnosis . As latent carcinomas can not be presently identified , this would lead to overtreatment in most overdiagnosed cases . The negative consequences of overdiagnosis ( knowledge of having a cancer ) and of overtreatment ( impotence , incontinence , perioperatory death ) may be extremely serious . In absence of any scientific evidence of screening benefits ( if any ) screening should not be recommended as a current practice , but should be limited to prospect i ve controlled studies design ed to assess its cost-effectiveness As with wide-spread use of prostate cancer ( Pca ) screening with prostate-specific antigen testing , overdetection has increasingly gained attention . The authors aim ed to estimate absolute risk of overdetection ( RO ) in  Pca screening  with various interscreening intervals and ages at start of screening . We estimated age-specific pre clinical incidence rates ( per 100,000 person-years ) for progressive cancer ( from 128 for age group 55 - 58 years to 774 for age group 67 - 71 years ) and nonprogressive cancer 
    Output:
    
Well conducted ecological and cohort studies in multiple setting s are the most appropriate approach for quantifying and monitoring overdiagnosis in cancer screening programs .