***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: Study Type – Therapy ( prospect i ve cohort ) Level of Evidence 2b PURPOSE Active surveillance for favorable risk prostate cancer is an approach that may reduce the risk of overtreatment of clinical ly insignificant prostate cancer . In fact , some patients with favorable risk disease at diagnosis harbor more aggressive disease and may be at risk for prostate cancer mortality despite close monitoring . This is a detailed report of 5 of 453 patients on surveillance who died of prostate cancer . MATERIAL S AND METHODS A large phase 2 prospect i ve trial of active surveillance in patients with favorable risk prostate cancer was initiated in 1995 . Eligible patients had favorable risk prostate cancer ( prostate specific antigen 10 ng/ml or less , Gleason 6 or less , T1c/T2a ) . Epstein criteria for clinical ly insignificant prostate cancer ( a third or less of cores positive , 50 % or less involvement of any 1 core , and prostate specific antigen density less than 0.15 ) were used for men younger than 55 years . Patients were followed with serial prostate specific antigen determinations  every 3 months for 2 years and then every 6 months if stable . Biopsies were performed at 1 year and then every 3 to 4 years . Radical intervention was offered if prostate specific antigen doubling time was less than 3 years or Gleason 3 + 4 pattern disease was identified on repeat biopsy . For the first 5 years of the study patients older than 70 years were eligible if they had Gleason 3 + 4 or less , or prostate specific antigen less than 15 ng/ml . RESULTS The rate of intervention with radiation or surgery  was 38 % at 10 years ( actuarial ) . All 5 patients had a prostate specific antigen doubling time of 1.6 years or less triggering a recommendation of radical therapy . Radical intervention was performed in 3 of the 5 patients . Patients 1 and 4 received radiation and patient 3 underwent radical prostatectomy . Of the 2 patients who did not receive definitive treatment 1 was lost to followup ( patient 2 ) and was treated conservatively by his family doctor . Patient 5 elected and  rogen deprivation therapy  rather than  radical treatment . CONCLUSIONS The low prostate cancer mortality in our surveillance cohort provides support for an active surveillance approach to favorable risk prostate cancer . Only 1 of the 5 patients presented with favorable disease and experienced a theoretically preventable death . The absence of preventable deaths suggests that the basic approach is sound . Two patients had a trigger for intervention but did not receive it . This reinforces the importance of close monitoring and of definitive treatment for those in whom disease is reclassified as higher risk over time PURPOSE We analyzed competing active surveillance criteria in men who underwent radical prostatectomy  in relation to outcome data in a large , community based cohort . MATERIAL S AND METHODS We identified all men from the CaPSURE data base who underwent radical prostatectomy from 1999 to 2007 and met inclusion criteria for the stringent prospect i ve University of California-San Francisco and Johns Hopkins active surveillance protocol s. Rates of pathological upgrading , up staging and biochemical recurrence were compared . RESULTS We identified 2,837 men who underwent radical prostatectomy and had complete pathological and followup data available . Of these men 1,375 and 125 met University of California-San Francisco and Johns Hopkins criteria , respectively . When comparing men who met the 2 sets of criteria vs those who met University of California-San Francisco criteria only , there were no significant differences in the rate of upgrading ( 20 % vs 27 % , p = 0.07 ) and up staging ( 6 % vs 8 % , p = 0.39 ) at radical prostatectomy . At a median 36-month followup 5-year biochemical recurrence-free estimates were similar at 92 % in men who met the 2 sets of criteria and 90 % in those who met the University of California-San Francisco definition only . On multivariate analysis upgrading to 7 or greater ( HR 2.2 , 95 % CI 1.2 - 4.2 ) , up staging ( HR 3.5 , 95 % CI 1.3 - 9.3 ) , and upgrading plus up staging ( HR 6.9 , 95 % CI 3.3 - 14.5 ) were associated with a higher risk of biochemical recurrence in patients who met University of California-San Francisco criteria . CONCLUSIONS Men who met enrollment criteria for the 2 active surveillance protocol s had a similar rate of upgrading , up staging and 5-year biochemical recurrence-free rates after radical prostatectomy . Further comparison between current protocol s is warranted to establish universal inclusion criteria OBJECTIVES To study active surveillance as a management option for the important number of prostate cancer patients who would not have been diagnosed in the absence of screening . PATIENTS AND METHODS We analyzed baseline characteristics and outcome parameters of all men on active surveillance who were screen-detected in the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) . Recruitment and surveillance of men were not guided by a protocol but depended on individual decisions of patients and their physicians . RESULTS Active surveillance was applied in 278 men detected by screening from 1993 to 2006 . At diagnosis , their median age was 69.8 yr ( 25 - 75p ; 66.1 - 72.8 ) ; median PSA 3.6 ng/ml ( 25 - 75p ; 3.1 - 4.8 ) , and the clinical stage was T1c in 220 ( 79.1 % ) and T2 in 58 ( 20.9 % ) . During the follow-up of median 3.4 yr , 103 men ( 44.2 % ) had a PSA doubling time  that was negative ( ie , half-life ) or longer than 10 yr . Men detected at rescreening were significantly more likely to be on active surveillance , and they had more beneficial characteristics . Deferred treatment was elected in 82 cases ( 29.0 % ) . Overall survival was 89 % after 8 yr ; the cause-specific survival was 100 % . CONCLUSIONS This report shows a beneficial , although preliminary , outcome of screen-detected men managed on active surveillance . Men were more likely to be on active surveillance if the disease was detected at repeated screening . The report also shows that an important proportion of men have prolonged PSA doubling times , although the value of this parameter has not been established in untreated men BACKGROUND The incidence of small , localised , well-differentiated prostate cancer ( PCa ) is increasing , mainly as a result of screening . Many of these cancers will not progress , and radical therapy may lead to substantial overtreatment . Active surveillance ( AS ) has emerged as an alternative . OBJECTIVE To retrospectively vali date the currently used criteria for eligibility for AS . DESIGN , SETTING , AND PARTICIPANTS For this cohort study , data from 616 men who were diagnosed with PCa between 1994 and 2007 at a mean age of 66.3 yr in four centres of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) were combined . All patients fit the criteria for AS ( prostate-specific antigen [ PSA ] < or = 10.0 ng/ml , PSA-density < 0.2 ng/ml per ml , stage T1C/T2 , Gleason score < or = 3 + 3 = 6 , and < or = 2 positive biopsy cores ) , and initially they were managed expectantly . Median follow-up was 3.91 yr . MEASUREMENTS Disease specific- , overall- , and treatment-free survival were studied . Present PSA characteristics were assessed and also compared between men who were switching to deferred active therapy during follow-up and men remaining untreated . RESULTS AND LIMITATIONS The calculated ( Kaplan-Meier ) 10-yr PCa-specific survival ( 21 patients at risk ) was 100 % , which sharply contrasted with 77 % overall survival . Men still alive showed favourable PSA characteristics . Although the calculated 10-yr treatment-free survival was only 43 % , objective signs of progression often did not indicate the shift to radical treatment . The cohort consisted of men on AS and those on watchful waiting ( WW ) ; information on comorbidity or psychological distress was not available . CONCLUSIONS AS seems justified in selected men with screen-detected PCa . Prospect i ve protocol -based AS programs are necessary to optimise selection criteria and to find the appropriate trigger points for switching to active therapy . Possible negative psychological reactions with AS against improved quality of life by withholding side-effects from radical treatment should be considered Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early‐stage prostate cancer . In this article , the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance PURPOSE  Prostate specific antigen doubling time was used to stratify patients into groups at low and high risk for progression . The prostate specific antigen kinetics in these 2 groups were modeled . MATERIAL S AND METHODS In this prospect i ve , single-arm cohort study patients with favorable clinical parameters ( stage T1b-T2b N0M0 , Gleason score 7 or less , prostate specific antigen 15 ng/ml or less ) were conservatively treated with watchful waiting . Evolution of  serial prostate specific antigen measurements  over time was estimated from a general linear mixed model of the natural log of prostate specific antigen . The corresponding average and individual prostate specific antigen doubling times were also calculated . RESULTS Since November 1995 a total of 231 patients had at least 6 months of followup and at least 3 prostate specific antigen measurements . Based on prostate specific antigen doubling time and repeat biopsy , 93 patients fulfilled the criteria for high risk of disease progression and 138 were defined as low risk . Given the baseline status of these individuals , 2 reference average lines ( high risk and low risk ) were derived to model the evolution of prostate specific antigen levels and permit more rational decision making regarding the need for definitive intervention . The average prostate specific antigen doubling time was 2.97 years ( 95 % CI 2.2 - 4.4 ) in patients allocated to the high risk group and 6.54 years ( 95 % CI 4.8 - 12.3 ) in those at low risk . CONCLUSIONS By applying the dynamic prognostic rule in combination with serial biopsy , a rational decision for definitive intervention based on the risk of disease progression could be optimally recommended about 2.3 years after initiated surveillance OBJECTIVES Outcome data from a prospect i ve study of active surveillance of localised prostate cancer were analysed to identify factors , present at the time of diagnosis , that predict subsequent radical treatment . METHODS Eligible patients had clinical stage T1-T2a , N0-Nx , M0-Mx adenocarcinoma of the prostate with serum PSA<15 ng/ml , Gleason score < or= 7 , primary Gleason grade < or= 3 , and % positive biopsy cores ( pbc ) < or= 50 % . Monitoring included  serial PSA measurement and repeat prostate biopsies . Radical treatment was initiated in the event of biochemical progression ( PSA velocity > 1 ng/ml/yr ) or histological progression ( primary Gleason grade > or= 4 , or % pbc > 50 % ) . Multivariate Cox regression analysis of baseline variables was performed with respect to time to radical treatment . RESULTS The 326 men recruited from 2002 to 2006 have been followed for a median of 22 mo . Median age was 67 yr , and median initial PSA ( iPSA ) 6.4 ng/ml . Sixty-five patients ( 20 % ) had deferred radical treatment , 16 ( 5 % ) changed to watchful waiting because of increasing comorbidity , 7 ( 2 % ) died of other causes , and 238 ( 73 % ) remain on surveillance . On multivariate Cox regression analysis , the free/total PSA ratio ( p<0.001 ) and clinical T stage ( p=0.006 ) were independent determinants of time to radical treatment . CONCLUSIONS In addition to established prognostic factors , the free/total PSA ratio may predict time to radical treatment in patients with untreated , localised prostate cancer managed by active surveillance . This possibility warrants further study PURPOSE We assessed outcomes of men with prostate cancer enrolled in active surveillance .  PATIENTS AND METHODS Since 1995 , a total of 769 men diagnosed with prostate cancer have been followed prospect ively ( median follow-up , 2.7 years ; range , 0.01 to 15.0 years ) on active surveillance .  Enrollment criteria were for very-low-risk cancers , defined by clinical stage ( T1c ) , prostate-specific antigen density < 0.15 ng/mL , and prostate biopsy findings ( Gleason score ≤ 6 , two or fewer cores with cancer , and ≤ 50 % cancer involvement of any core ) .  Curative intervention was recommended on disease reclassification on the basis of biopsy criteria . The primary outcome was survival free of intervention , and secondary outcomes were rates of disease reclassification and exit from the program . Outcomes were compared between men who did and did not meet very-low-risk criteria . RESULTS The median survival free of intervention was 6.5 years ( range , 0.0 to 15.0 years ) after diagnosis , and the proportions of men remaining free of intervention after 2 , 5 , and 10 years of follow 
    Output:
    
Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time .
AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment .
This approach confers a low risk of disease-specific mortality in the short to intermediate term .