***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Study Type – Therapy ( prospect i ve cohort ) Level of Evidence 2b BACKGROUND Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance ( AS ) are needed . OBJECTIVE To examine the association between ERG expression at diagnosis and the risk of progression during AS . DESIGN , SETTING , AND PARTICIPANTS This study included 265 patients followed on AS with prostate-specific antigen ( PSA ) measurements , clinical examinations , and 10 - 12 core rebiopsies from 2002 to 2012 in a prospect ively maintained data base .  ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit ( anti-ERG , EPR3864 ) . Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Overall AS progression was defined as clinical progression : increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound , and /or histopathologic progression : up grade of Gleason score , more than three positive cores or bilateral positive cores , and /or PSA progression : PSA doubling time <3 yr . Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences ( Aalen-Johansen method ) . Curatively intended treatment , watchful waiting , and death without progression were treated as competing events . RESULTS AND LIMITATIONS A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information . In competing risk models , the ERG-positive group showed significantly higher incidences of overall AS progression ( p<0.0001 ) and of the subgroups PSA progression ( p<0.0001 ) and histopathologic progression ( p<0.0001 ) . The 2-yr cumulative incidence of overall AS progression was 21.7 % ( 95 % confidence interval [ CI ] , 14.3 - 29.1 ) in the ERG-negative group compared with 58.6 % ( 95 % CI , 48.7 - 68.5 ) in the ERG-positive group . ERG positivity was a significant predictor of overall AS progression in multiple Cox regression ( hazard ratio : 2.45 ; 95 % CI , 1.62 - 3.72 ; p<0.0001 ) . The main limitation of this study is its observational nature . CONCLUSIONS In our study , ERG positivity at diagnosis can be used to estimate the risk of progression during AS . If confirmed , ERG status can be used to individualise AS programmes . PATIENT SUMMARY The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression 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 . ) Purpose : We assessed the association of quantitative clinical and pathologic information , including serum and tissue pro – prostate-specific antigen ( proPSA ) measurements , with outcomes among men with prostate cancer in an expectant management ( active surveillance ) program .  Experimental Design : We identified 71 men enrolled in expectant management with frozen serum and tissue available from diagnosis : 39 subsequently developed unfavorable biopsies ( Gleason score ≥7 , ≥3 cores positive for cancer , > 50 % of any core involved with cancer ) , whereas 32 maintained favorable biopsies ( median follow-up , 3.93 years ) . Serum total PSA , free PSA ( fPSA ) , and [−2]proPSA  were measured by the Beckman Coulter immunoassay . [−5/−7]proPSA was evaluated in cancer and benign-adjacent areas ( BAA ) by quantitative immunohistochemistry . Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion . Results : The ratio [−2]proPSA/% fPSA in serum was significantly higher at diagnosis ( 0.87 ± 0.44 versus 0.65 ± 0.36 pg/mL ; P = 0.02 ) in men developing unfavorable biopsies . [−5/−7]proPSA tissue staining was more intense ( 4104.09 ± 3033.50 versus 2418.06 ± 1606.04 ; P = 0.03 ) and comprised a greater fractional area ( 11.58 ± 7.08 % versus 6.88 ± 5.20 % ; P = 0.01 ) in BAA of these men . Serum [−2]proPSA/% fPSA [ hazard ratio , 2.53 ( 1.18 - 5.41 ) ; P = 0.02 ] , BAA [−5/−7]proPSA % area [ hazard ratio , 1.06 ( 1.01 - 1.12 ) ; P = 0.02 ] and BAA [−5/−7]proPSA stain intensity [ hazard ratio , 1.000213 ( 1.000071 - 1.000354 ) ; P = 0.003 ] were significantly associated with unfavorable biopsy in Kaplan-Meier and Cox analyses . Serum [−2]proPSA/% fPSA significantly correlated with BAA [−5/−7]proPSA % area ( ρ = 0.40 ; P = 0.002 ) and BAA [−5/−7]proPSA stain intensity ( ρ = 0.33 ; P = 0.016 ) . Conclusions : In a prospect i ve cohort of men enrolled into expectant management for prostate cancer , serum and tissue levels of proPSA at diagnosis are associated with need for subsequent treatment . The increase in serum proPSA/% fPSA might be driven by increased proPSA production from “ premalignant ” cells in the prostate BAA . ( Clin Cancer Res 2009;15(23):7316–21 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 This article review s the data supporting an approach of active surveillance with selective delayed intervention for good risk localized prostate cancer . The challenge is to identify those patients who are not likely to experience significant progression , while offering radical therapy to those who are at risk . MATERIAL S AND METHODS A prospect i ve phase 2 study of active surveillance with selective delayed intervention was initiated in 1995 . Patients were treated initially with surveillance , while those who had a prostate specific antigen ( PSA ) doubling time ( DT ) of 2 years or less , or grade progression on re-biopsy were offered radical intervention . The remainder were closely monitored . RESULTS The cohort consisted of 299 patients with good risk prostate cancer or intermediate risk prostate cancer in men older than 70 years .  Median PSA DT was 7.0 years and 35 % of the men had a PSA DT of greater than 10 years . The majority of patients remain on surveillance . At 8 years overall actuarial survival was 85 % and disease specific survival was 99 % . CONCLUSIONS Most men with favorable risk prostate cancer will die of unrelated causes . The approach of active surveillance with selective delayed intervention based on PSA DT represents a practical compromise between radical therapy in all , which results in overtreatment in patients with indolent disease , and watchful waiting with palliative therapy only , which results in under treatment in those with aggressive disease . Results at 8 years are favorable . Longer followup will be required to confirm the safety of this approach in men with long ( greater than 15-year ) life expectancy BACKGROUND Prostate-specific antigen ( PSA ) based screening for prostate cancer ( PCa ) has been shown to reduce prostate specific mortality by 20 % in an intention to screen ( ITS ) analysis in a r and omised trial ( European R and omised Study of Screening for Prostate Cancer [ ERSPC ] ) . This effect may be diluted by nonattendance in men r and omised to the screening arm and contamination in men r and omised to the control arm . OBJECTIVE To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination . DESIGN , SETTING , AND PARTICIPANTS We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55 - 69 yr of age r and omised in seven participating centres of the ERSPC . Centres were also grouped according to the type of r and omisation ( ie , before or after informed written consent ) . INTERVENTION Nonattendance was defined as nonattending the initial screening round in ERSPC . The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam . MEASUREMENTS Relative risks ( RRs ) with 95 % confidence intervals ( CIs ) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose . RESULTS AND LIMITATIONS In the ITS analysis , the RR of PC 
    Output:
    
Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen ( PSA ) , a higher Prostate Health Index ( PHI ) , a higher PSA density ( PSAD ) , and greater biopsy core involvement at baseline predict a greater risk of progression .
During follow-up , serial measurements of PHI and PSAD , as well as repeat biopsy results , predict later biopsy progression .
No conclusive data support the use of genetic tests in AS .
PATIENT SUMMARY Several PSA-based tests ( free PSA , PHI , PSAD ) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance .