***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: OBJECTIVE Screening practice s for prostate cancer have result ed in an increasing incidence of prostate cancers . Our knowledge about which prostate cancers are life threatening and which are not is limited . Thus , for ethical , medical , and economic reasons we need to define which patients can be managed by active surveillance . METHODS From 1993 through 1999 , men from the Rotterdam section of the European R and omized study of Screening for Prostate Cancer ( ERSPC ) were screened by two strict protocol s , which were based on prostate-specific antigen ( PSA ) , digital rectal examination , and transrectal ultrasound . For this study , men with criteria that reflect current active surveillance studies were selected : those with a biopsy Gleason score < or = 3 + 3 in two or fewer cores , with a PSA density < 0.2 and a maximum PSA-level of 15 ng/ml . Clinical stage had to be T1C or T2 . RESULTS Of the 1,014 prostate cancers detected in the prevalence screen , 293 men ( 28.9 % ) met the criteria for active surveillance . Their mean age was 65.7 and the mean PSA level was 4.8 ng/ml .  Radical prostatectomy was elected by 136 men ( 46.4 % ) , radiotherapy by 91 ( 31.1 % ) , and watchful waiting by 64 ( 21.8 % ) . The mean follow-up was 80.8 months . The eight-year prostate cancer-specific survival was 99.2 % ; the overall survival was 85.4 % . Nineteen men who chose watchful waiting changed to definitive treatment during follow-up . CONCLUSION Only three men died of prostate cancer , none of whom were on watchful waiting . Our observations provide preliminary validation of the arbitrary selection criteria for active surveillance OBJECTIVES To compare the impact that the number of biopsy cores have on final pathologic findings when minimal disease is detected at biopsy . Discordance has been noted between transrectal ultrasound-guided biopsy results and tumor volume even when minimal amounts of tumor are found on biopsy . METHODS We identified patients who had undergone radical retropubic prostatectomy for a single microscopic focus of adenocarcinoma from a prospect ively maintained surgical data base . Patients were stratified into two groups : those with six biopsies or less and those with seven or more . The Gleason score , margin status , presence of extracapsular extension , and percentage of tumor volume were compared . RESULTS A total of 102 patients in our data base had a single microscopic focus of adenocarcinoma detected by needle biopsy . Of these patients , 65 underwent six or fewer biopsies and 37 underwent seven or more at transrectal ultrasonography . Of the 37 patients in group 2 , 27 ( 73 % ) had a final tumor volume of less than 5 % compared with 24 ( 37 % ) of 65 patients in group 1 ( P = 0.002 ) . Of the group 2 patients , 15 ( 75 % ) with Stage T1c had an estimated tumor volume of less than 5 % compared with only 11 ( 34 % ) in group 1 ( P = 0.01 ) . No statistically significant difference was noted between the two groups for margin status , presence of extracapsular extension , or Gleason score . CONCLUSIONS A single microscopic focus of cancer obtained after multiple cores predicts for a significantly lower tumor volume on final pathologic examination across clinical stages . In the context of greater tissue sampling , the minimal disease design ation may carry more predictive value and be a useful parameter in stratifying patients with Stage T1c and other good-risk factors with regard to surgical outcome 424 BMJ | 24 FEBRUARY 2007 | VOLUME 334 Almost all studies have some missing observations . Yet textbooks and software commonly assume that data are complete , and the topic of how to h and le missing data is not often discussed outside statistics journals . There are many types of missing data and different reasons for data being missing . Both issues affect the analysis . Some examples are : ( 1 ) In a postal question naire survey not all the selected individuals respond ; ( 2 ) In a r and omised trial some patients are lost to follow-up before the end of the study ; ( 3 ) In a multicentre study some centres do not measure a particular variable ; ( 4 ) In a study in which patients are assessed frequently some data are missing at some time points for unknown reasons ; ( 5 ) Occasional data values for a variable are missing because some equipment failed ; ( 6 ) Some laboratory sample s are lost in transit or technically unsatisfactory ; ( 7 ) In a magnetic resonance imaging study some very obese patients are excluded as they are too large for the machine ; ( 8) In a study assessing quality of life some patients die during the follow-up period 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 ) OBJECTIVES Evidence has been presented that biologic aggressiveness of prostate carcinoma increases with volume and that cancers less than 0.5 cc may be regarded as clinical ly insignificant for immediate treatment . We have analyzed the ability of core cancer length on needle biopsy to predict cancer volumes near the 0.5 cc threshold for distinction between incidental versus clinical carcinoma . METHODS  Systematic sextant transrectal ultrasound-guided prostate biopsies were performed on 110 men who then underwent radical prostatectomy for adenocarcinoma . The core cancer length within each biopsy was compared with the volumes of clinical and incidental carcinomas in the prostatectomy specimen . RESULTS Among incidental ( nonpalpable ) cancers , 14 % of those under 0.2 cc were detected , but 44 % at 0.2 to 0.5 cc and 92 % of those more than 0.5 cc were detected . Among clinical ly suspected carcinomas , 2 mm or longer core cancer length reliably predicted a cancer of 0.5 cc or larger , but among incidental cancers , it predicted a tumor of 0.2 cc or larger . A 3-mm core cancer length threshold predicted 0.5 cc for both groups . The high frequency of incidental cancers under 0.5 cc impaired the predictive value of multiple positive needle cores . Bilateral positive biopsy results indicated bilateral extension of clinical cancer in only 59 % of cases . CONCLUSIONS A core cancer length of 3 mm or more on one or two needle biopsies reliably predicts cancer of clinical ly significant volume ( 0.5 cc or larger ) . The high detection frequency of smaller incidental carcinomas on biopsy impairs the reliability of volume estimation from multiple positive needle cores and m and ates that treatment decisions be made with knowledge of core cancer length To compare a series of 121 sextant needle biopsy sets  with their corresponding  radical prostatectomy specimens  in screened participants in the European R and omized study of Screening for Prostate Cancer ( ERSPC ) , investigating the effect of screening for prostate cancer on disease‐specific mortality and quality of life , as the clinical significance of a small focus of well‐differentiated prostate cancer on biopsy is unclear OBJECTIVES To determine whether a very small focus of prostate cancer in a needle biopsy specimen correlates with organ-confined disease or with favorable disease parameters . METHODS Of 598 needle biopsies of the prostate performed from January 1990 through June 1994 , 49 specimens ( 8.2 % ) contained a microscopic focus ( less than 2 mm in length of the entire biopsy core specimen ) of adenocarcinoma . For these 49 patients , the clinical and pathologic features were correlated . RESULTS Of these 49 patients , 27 ( 55.1 % ) underwent either radical prostatectomy , with or without pelvic lymph node dissection ( 26 ) , or pelvic lymph node dissection alone ( 1 ) . Seven of these 27 patients ( 25.9 % ) had extraprostatic disease : lymph node involvement ( 1 ) , positive surgical margins ( 5 ) , or seminal vesicle invasion ( 1 ) . Ten of the 49 patients ( 20.4 % ) underwent radiotherapy , and 12 ( 24.5 % ) chose hormonal therapy . The pathologic stage for these 22 patients could not be ascertained . However , despite the limited amount of disease in the biopsy specimen , 2 patients treated with radiotherapy suffered a relapse ( mean interval to recurrence , 11.5 months ) , and 3 patients treated with hormonal therapy ( early or delayed ) had bony metastasis at the time of diagnosis . Overall , 12 of the 49 patients ( 24.5 % ) had unfavorable disease ( as defined by extraprostatic disease on pathologic specimen , relapse after radiotherapy , or bony metastasis at the time of diagnosis ) . CONCLUSIONS These findings suggest that a microscopic focus of prostatic adenocarcinoma in a needle biopsy specimen , per se , does not predict the pathologic stage or the biologic behavior of a tumor PURPOSE We evaluated the significance of focal prostate cancer found in sextant biopsies in men participating in a biennial prostate specific antigen ( PSA ) based screening program . MATERIAL S AND METHODS In 1995 , 10000 men 50 to 65 years old were r and omized to biennial screening with PSA testing . Sextant biopsies were recommended when total PSA was 3 ng/ml or greater at screening rounds 1 and 2 , and 2.54 ng/ml or greater at subsequent screening rounds . Focal cancer was defined as total a core cancer length of less than 3 mm in the biopsy specimen . Low volume cancer was defined as a total tumor volume of less than 0.5 cm in the radical retropubic prostatectomy specimen . RESULTS The number of men who underwent biopsy  and the number of cancers detected in the 5 possible sets of biopsies were 1725 and 402 , 706 and 124 , 307 and 36 , 103 and 9 , and 13 and 0 , respectively . The risk of detecting focal cancer was 7.9 % , 10.2 % , 7.5 % , 5.8 % and 0 % , respectively , but the relative ratio ( focal-to-all cancers ) increased 34 % , 58 % , 64 % , 67 % and , not applicable , respectively . In men with a total core cancer length of less than 10 mm there was no correlation between core cancer length and total tumor volume , as measured in the prostatectomy specimen . Two-thirds of men with a total core cancer length of less than 3 mm had a tumor volume of greater than 0.5 cm , while the risk of low volume cancer was less than 5 % only in men with a total core cancer length of greater than 10 mm . CONCLUSIONS In a repeat PSA based screening program sextant biopsies are of little or no value for predicting tumor volume OBJECTIVE To distinguish good c and i date s for watchful waiting from those who need immediate treatment in localized prostate cancer . METHODS Prostate specific antigen (PSA)-doubling time ( DT ) was calculated by a log-linear regression model for 78 patients with clinical ly localized prostate cancer ( T1c : 47 , T2a : 6 , T2b : 21 , and T3 : 4 ) under surveillance . Median observation period was 37.5 months . The first 1-year  PSA-DT  was compared with the overall PSA-DT  in 41 patients who had been under surveillance for more than 3 years . RESULTS There was significant difference in the PSA-DT distribution between a pooled group of T1c and T2a and a group of T2b and T3 patients ( median 58.8 versus 33.3 months , P = 0.0052 ) . A combination of three parameters consisting of initial PSA level less than 10 ng/ml , WHO grade 1 , one or two positive core per six to eight systematic biopsy cores with 50 % or less cancer involvement significantly correlated with PSA-DT distribution in the T1c plus T2a group ( P = 0.0034 ) . The first year assessment of PSA-DT was identical to the overall assessment in 48.8 % , 2 years or more in 36. 
    Output:
    
The results indicated that , despite differences in study design and reporting , a significant proportion of patients with microfocal cancer , regardless of how it was defined , had adverse pathologic findings and a significant risk of PSA recurrence after undergoing radical prostatectomy .
Biochemical and clinical recurrences also were observed after radiotherapy or watchful waiting .