***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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    Input: UNLABELLED PSA-driven screening has been applied to a large part of the male population in many countries . An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer . In such cases the yearly rate of increase of PSA ( PSA velocity [ PSAV ] ) may improve the test characteristics of PSA . MATERIAL S AND METHODS Data from the European R and omized Study of Screening for Prostate Cancer Rotterdam are used to study the issue . Relative sensitivity , relative specificity , and positive predictive value ( PPV ) are calculated . Logistic regression analysis is used to compare odds ratios for positive biopsies . The relationship between PSAV and parameters of tumour aggressiveness is investigated . RESULTS Five hundred eighty-eight consecutive participants were identified who presented at their first screening with PSA values < 4.0 and who progressed to PSA values > 4.0 ng/ml four years later . None were biopsied in round one , all were biopsied in round two . Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25 - 1.0 ng/ml/yr . The use of PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0 ng/ml , nor do any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer with respect to the cut-off value of 4.0 ng/ml . The rate of aggressive cancers seems to increase with increasing PSAV . CONCLUSIONS PSAV does not improve the detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening after four years BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) BACKGROUND The optimal upper limit of the normal range for prostate-specific antigen ( PSA ) is unknown . We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less . METHODS Of 18,882 men enrolled in the prevention trial , 9459 were r and omly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination . Among these 9459 men , 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination , had a final PSA determination , and underwent a prostate biopsy after being in the study for seven years . RESULTS Among the 2950 men ( age range , 62 to 91 years ) , prostate cancer was diagnosed in 449 ( 15.2 percent ) ; 67 of these 449 cancers ( 14.9 percent ) had a Gleason score of 7 or higher . The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter , 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter , 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter , 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter , and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter . The prevalence of high- grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter . CONCLUSIONS Biopsy-detected prostate cancer , including high- grade cancers , is not rare among men with PSA levels of 4.0 ng per milliliter or less -- levels generally thought to be in the normal range PURPOSE Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells . Prostate specific antigen doubling time , or the change in prostate specific antigen over time , has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer . It is important to agree on definitions and values for the calculation of prostate specific antigen doubling  time , and to develop a common approach to outcome analysis and reporting . MATERIAL S AND METHODS In September 2006 a conference was held at the National Cancer Institute in Bethesda , Maryl and to define these parameters and develop guidelines for their use . RESULTS The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time , evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials . CONCLUSIONS We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity . We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome . Furthermore , the use of common st and ards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to r and omized trials in which " hard " end points such as survival will be used Prostate-specific antigen velocity ( PSAV ) is one of the oldest concepts in PSA screening , yet today it is one of the most controversial . Publication of a wide range of studies with different design s , study population s , and results has fueled uncertainty about the best way to use PSAV and confused the issue of its utility in the early detection setting . Studies of disease prognosis suggest that PSAV is strongly associated with lethal cancers . However , prospect i ve screening trials find that PSAV is at best a weak predictor of high-risk disease . In this commentary , we synthesize and reconcile the evidence about the value of PSAV in the early detection setting . We review recent studies of PSAV and determine a set of statistical considerations that we believe to be critical in study evaluation and interpretation . We explain why the association between  PSAV  and disease-specific survival does not necessarily imply that PSAV will be a useful screening tool . In addition , we argue that the st and ard concept of PSAV  -- the absolute change in PSA per year -- confuses disease aggressiveness with the interval from disease onset to detection . We therefore recommend that other methods be explored to incorporate information about PSA kinetics that could ultimately improve-- and even transform -- how we detect and treat prostate cancer 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 The prostate component of the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen ( PSA ) testing and digital rectal examination ( DRE ) . Mortality after 7 - 10 years of follow-up has been reported previously . We report extended follow-up to 13 years after the trial . METHODS A total of 76 685 men , aged 55 - 74 years , were enrolled at 10 screening centers between November 1993 and July 2001 and r and omly assigned to the intervention  ( organized screening of annual PSA testing for 6 years and annual DRE for 4 years ; 38 340 men ) and control ( usual care , which sometimes included opportunistic screening ; 38 345 men ) arms . Screening was completed in October 2006 . All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31 , 2009 , were ascertained . Relative risks ( RRs ) were estimated as the ratio of observed rates in the intervention and control arms , and 95 % confidence intervals ( CIs ) were calculated assuming a Poisson distribution for the number of events . Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age , comorbidity status , and pretrial PSA testing . All statistical tests were two-sided . RESULTS Approximately 92 % of the study participants were followed to 10 years and 57 % to 13 years . At 13 years , 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm . Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years , respectively , result ing in a relative increase of 12 % in the intervention arm ( RR = 1.12 , 95 % CI = 1.07 to 1.17 ) . After 13 years of follow-up , the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years , respectively , result ing in a non-statistically significant difference between the two arms ( RR = 1.09 , 95 % CI = 0.87 to 1.36 ) . No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age ( P(interaction ) = .81 ) , pretrial PSA testing ( P(interaction ) = .52 ) , and comorbidity ( P(interaction ) = .68 ) . CONCLUSIONS After 13 years of follow-up , there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening , which forms part of usual care , and there was no apparent interaction with age , baseline comorbidity , or pretrial PSA testing PURPOSE Preoperative prostate-specific antigen ( PSA ) velocity ( PSAV ) , or the rate of PSA rise before diagnosis , predicts for risk of cancer death after 
    Output:
    
The preponderance of evidence suggests that there is high collinearity between PSA and PSAV and therefore the calculation of PSAV adds little to the measurement of PSA level .
PSAV calculation has been advocated by many investigators as a strategy to improve the screening and clinical management of patients with CaP. However , when PSAV definitions are rigorously applied , its calculation does not significantly enhance the clinical performance of PSA alone