EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion. Prostate-specific antigen-based early detection of prostate cancer--validation of screening without rectal examination. Prostate cancer detection in the "grey area" of prostate-specific antigen below 10 ng/ml: head-to-head comparison of the updated PCPT calculator and Chun's nomogram, two risk estimators incorporating prostate cancer antigen 3. Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer patients for active surveillance. Outcomes of men with screen-detected prostate cancer eligible for active surveillance who were managed expectantly. Identification of pathologically insignificant prostate cancer is not accurate in unscreened men Prostate-specific antigen change in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Whole-gland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic outcomes and morbidity in 1002 patients. Multicentric oncologic outcomes of high-intensity focused ultrasound for localized prostate cancer in 803 patients. Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Prostate cancer mortality in screen and clinically detected prostate cancer: estimating the screening benefit. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden PCA3: a molecular urine assay for predicting prostate biopsy outcome. Predictors of pathologic progression on biopsy among men on active surveillance for localized prostate cancer: the value of the pattern of surveillance biopsies.
OBJECTIVE Our aim was to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the screening , diagnosis , and treatment of clinical ly localised cancer of the prostate ( PCa ) . METHODS The working panel performed a literature review of the new data emerging from 2007 to 2010 . The guidelines were up date d , and level of evidence and grade of recommendation were added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. RESULTS A full version is available at the EAU office or Web site ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy .  PSA doubling time in <3 yr or a biopsy progression indicates the need for active intervention . In men with locally advanced PCa in whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) with equivalent oncologic efficacy . Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial . Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables . Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk PCa , respectively . For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice . Follow-up after local therapy is largely based on PSA , and a disease-specific history with imaging is indicated only when symptoms occur . CONCLUSIONS The knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice CONTEXT The most recent summary of the European Association of Urology ( EAU ) guidelines on prostate cancer ( PCa ) was published in 2011 . OBJECTIVE To present a summary of the 2013 version of the EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined PCa . EVIDENCE ACQUISITION A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group . The guidelines have been up date d , and levels of evidence and grade s of recommendation have been added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS A full version of the guidelines is available at the EAU office or online ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy . A biopsy progression indicates the need for active intervention , whereas the role of PSA doubling time is controversial . In men with locally advanced PCa for whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) , with equivalent oncologic efficacy . Active treatment is recommended mostly for patients with localized disease and a long life expectancy , with radical prostatectomy ( RP ) shown to be superior to WW in prospect i ve r and omized trials . Nerve-sparing RP is the approach of choice in organ-confined disease , while neoadjuvant ADT provides no improvement in outcome variables . Radiation therapy should be performed with ≥ 74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa . For locally advanced disease , adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice . Follow-up after local therapy is largely based on PSA and a disease-specific history , with imaging indicated only when symptoms occur . CONCLUSIONS Knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice . PATIENT SUMMARY A summary is presented of the 2013 EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined prostate cancer ( PCa ) . Screening continues to be done on an individual basis , in consultation with a physician . Diagnosis is by prostate biopsy . Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to and rogen-deprivation therapy in locally advanced PCa not requiring immediate local treatment . Radical prostatectomy is the only surgical option . Radiation therapy can be external or delivered by way of prostate implants . Treatment follow-up is based on the PSA level PURPOSE An American Society of Clinical Oncology ( ASCO ) provisional clinical opinion ( PCO ) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice -changing data from major studies . This PCO addresses the role of prostate-specific antigen ( PSA ) testing in the screening of men for prostate cancer . CLINICAL CONTEXT Prostate cancer is the second leading cause of cancer deaths among men in the United States . The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection . RECENT DATA Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening . An up date search was conducted to March 16 , 2012 , for additional evidence related to the topic . RESULTS In one r and omized trial ,  PSA testing in men who would not otherwise have been screened result ed in reduced death rates from prostate cancer , but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment . Although there are limitations to the existing data , there is evidence to suggest that men with longer life expectancy may benefit from PSA testing . Adverse events associated with prostate biopsy are low for the majority of men ; however , several population -based studies have shown increasing rates of infectious complications after prostate biopsy , which is a concern OBJECTIVES The evaluation of the screening procedures for prostate cancer ( PCa ) was a part of the protocol of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , section Rotterdam , The Netherl and s. We sought to establish an improved strategy for the early detection of PCa using a prostate-specific antigen ( PSA ) cutoff of 3.0 ng/mL or greater as the only indication for prostate biopsy with omission of the digital rectal examination ( DRE ) . METHODS In June 1996 , 8612 men , 55 to 74 years old , were r and omized to screening and were screened within the ERSPC Rotterdam by a PSA level of 4.0 ng/mL or greater or positive DRE or transrectal ultrasound findings as the indication for biopsy .  Four hundred thirty men had PCa . Those treated by radical prostatectomy provided the tumor characteristics considered essential for a change in the screening strategies . Various options were evaluated and predictions made by logistic regression analyses . The protocol change was implemented in February 1997 . Another 7943 men were screened according to the new protocol ( PSA 3.0 ng/mL or greater ) . The result ing data were used to compare the two protocol s. RESULTS The detection rate ( proportion of PCa in those screened ) turned out to be very similar , with rates of 5.0 and 4.7 at a PSA cutoff of 4.0 ng/mL or greater and 3.0 ng/mL or greater , respectively . This was due to a much larger number of cases of PCa per biopsy in the PSA range of 3 to 3.9 ng/mL than expected . The positive predictive value of the PSA range 3.0 to 3.9 ng/mL in the two protocol s was 18.0 % and 6.4 % , respectively . Tumor characteristics were studied on radical prostatectomy specimens from the original protocol . PCa detected with the new screening regimen had a similar distribution of Gleason scores but a larger proportion of confined disease . Tumor volumes were smaller in patients with PSA levels of less than 2.9 ng/mL ; the proportion of " minimal disease " in that group was 50 % compared with 28 % in the group with a PSA level between 3.0 and 3.9 ng/mL. CONCLUSIONS Lowering the biopsy indication to a PSA cutoff of 3.0 ng/mL or greater without a DRE improved the positive predictive value from 18.2 % to 24.3 % . The number of biopsies necessary to detect 1 case of PCa accordingly changed from 5.2 to 3.4 . The overall characteristics of the cases detected at that PSA cutoff differed very little from those detected with the regimen based on PSA , DRE , and transrectal ultrasound BACKGROUND Prostate cancer antigen 3 ( PCA3 ) holds promise in diagnosing prostate cancer ( PCa ) , but no consensus has been reached on its clinical use . Multivariable predictive models have shown increased accuracy over individual risk factors . OBJECTIVE To compare the performance of the two available risk estimators incorporating PCA3 in the detection of PCa in the " grey area " of prostate-specific antigen ( PSA ) < 10 ng/ml : the up date d Prostate Cancer Prevention Trial ( PCPT ) calculator and Chun 's nomogram . DESIGN , SETTING , AND PARTICIPANTS Two hundred eighteen patients presenting with an abnormal PSA ( excluding those with PSA > 10 ng/ml ) and /or abnormal digital rectal examination were prospect ively enrolled in a multicentre Italian study between October 2008 and October 2009 . All patients underwent ≥12-core prostate biopsy .  MEASUREMENTS PCA3 scores were assessed using the Progensa assay ( Gen-Probe , San Diego , CA , USA ) . Comparisons between the two models were performed using tests of accuracy ( area under the receiver operating characteristic curve [ AUC-ROC ] ) , calibration plots , and decision curve analysis . Biopsy predictors were identified by univariable and multivariable logistic regression . In addition , performance of PCA3 was analysed through AUC-ROC and predictive values . RESULTS AND LIMITATIONS PCa was detected in 73 patients ( 33.5 % ) . Among predictors included in the models , only PCA3 , PSA , and prostate volume retained significant predictive value . AUC-ROC was higher for the up date d PCPT calculator compared to Chun 's nomogram ( 79.6 % vs 71.5 % ; p=0.043 ) ; however , Chun 's nomogram displayed better overall calibration and a higher net benefit on decision curve analysis . Using a probability threshold of 25 % , no high- grade cancers would be missed ; the PCPT calculator would save 11 % of biopsies , missing no cancer , whereas Chun 's nomogram would save 22 % of avoidable biopsies , although missing 4.1 % non-high- grade cancers . The small number of patients may account for the lack of statistical significance in the predictive value of individual variables or model comparison . CONCLUSIONS Both Chun 's nomogram and the PCPT calculator , by incorporating PCA3 , can assist in the decision to biopsy by assignment of an individual risk of PCa , specifically in the PSA levels < 10 ng/ml BACKGROUND The optimal selection of prostate cancer ( PCa ) patients for active surveillance ( AS ) is currently being debated . OBJECTIVE To assess the impact of urinary prostate cancer antigen 3 ( PCA3 ) score as an AS criterion instead of and in addition to the current criteria . DESIGN , SETTING , AND PARTICIPANTS We prospect ively studied 106 consecutive low-risk PCa patients ( prostate-specific antigen [ PSA ] ≤10 ng/ml , clinical stage T1c-T2a , and biopsy Gleason score 6 ) who underwent a PCA3 urine test before radical prostatectomy ( RP ) .  MEASUREMENTS Performance of AS criteria ( biopsy criteria , PCA3 score , PSA density , and magnetic resonance imaging [ MRI ] findings ) was tested in predicting four prognostic pathologic findings in RP specimens : ( 1 ) pT3 - 4 disease ; ( 2 ) overall unfavourable disease ( OUD ) defined by pT3 - 4 disease and /or pathologic primary Gleason pattern 4 ; ( 3 ) tumour volume < 0.5 cm(3 ) ; and ( 4 ) insignificant PCa . RESULTS AND LIMITATIONS The PCA3 score was strongly correlated with the tumour volume in a linear regression analysis ( p<0.001 , r=0.409 ) . The risk of having a cancer ≥0.5 cm(3 ) and a significant PCa was increased three-fold in men with a PCA3 score of ≥25 compared with men with a PCA3 score of < 25 with most AS biopsy criteria used . There was a trend towards higher PCA3 scores in patients with unfavourable and non-organ-confined disease and Gleason > 6 cancers . In a multivariate analysis taking into account each AS criterion , a high PCA3 score ( ≥25 ) was an important predictive factor for tumour volume ≥0.5 cm(3 ) ( odds ratio [ OR ] : 5.4 ; p=0.010 ) and significant PCa ( OR : 12.7 ; p=0.003 ) . Biopsy criteria and MRI findings were significantly associated with OUD ( OR : 3.9 and 5.0 , respectively ; p=0.030 and p=0.025 , respectively ) . CONCLUSIONS PCA3 score may be a useful marker to improve the selection for AS in addition to the current AS criteria . With a predictive cut-off of 25 , PCA3 score is strongly indicative for tumour volume and insignificant PCa 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 Background : Identification of men harbouring insignificant prostate cancer ( PC ) is important in selecting patients for active surveillance . Tools have been developed in PSA-screened population s to identify such men based on clinical and biopsy parameters . Methods : Prospect ively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre .  Tumour volume was assessed by pathological examination . For each tool , receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared . Comparison of accuracy in screened and unscreened population s was performed . Results : Of 848 patients , 415 had Gleason 3 + 3 disease on biopsy . Of these , 32.0 % had extra-prostatic extension and 50.2 % were up grade d. One had positive lymph nodes . Two hundred and six ( 24 % of cohort ) were D’Amico low risk . Of these , 143 had more than two biopsy cores involved . None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden . Accuracy is low in PSA-screened and -unscreened population s. Conclusions : In our unscreened population , tools design ed to identify insignificant PC are inaccurate . Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy OBJECTIVES To determine the prostate-specific antigen ( PSA ) velocity , PSA slope , and PSA doubling time ( PSADT ) in men with positive biopsies , negative biopsies , and no biopsy indications 4 years after an initial screening ;  and to use this information to improve the test characteristics in the early detection of prostate cancer and provide normal values for these parameters in screened men with and without evidence of prostate cancer . METHODS Within the European R and omized Study of Screening for Prostate Cancer , section Rotterdam , we identified 9575 men with a second determination of PSA 4 years after the initial screening . These men were divided into three groups : men with positive biopsies , negative biopsies , and no biopsy  indications in the  second  round ( PSA less than 3.0 ng/mL ) . The predictive values of PSA dynamics for detection of prostate cancer were calculated . RESULTS The mean PSA velocity of men with prostate cancer was 0.62 ng/mL/yr versus 0.46 ng/mL/yr for men with a negative biopsy ( P = 0.001 ) . The mean PSADT for men with prostate cancer was 5.1 years and for those with a negative biopsy it was 6.1 years ( P = 0.002 ) . The PSADT for men with no indication for biopsy was 25.1 years . However , receiver operating characteristic analyses revealed only a moderate value for these test parameters in predicting biopsy outcome . CONCLUSIONS The mean values of PSA velocity , PSA slope , and PSADT in a rescreened population differed significantly between men with and without prostate cancer . However , in predicting the biopsy outcome , the PSA dynamics were of limited value BACKGROUND The Prostate CAncer gene 3 ( PCA3 ) assay has shown promise as an aid in prostate cancer ( pCA ) diagnosis in identifying men with a high probability of a positive ( repeat ) biopsy . OBJECTIVE This study evaluated the clinical utility of the PROGENSA PCA3 assay . DESIGN , SETTING , AND PARTICIPANTS This European prospect i ve , multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy . MEASUREMENTS After digital rectal examination ( DRE ) , first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score . The PCA3 score was compared to biopsy outcome . The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen ( % fPSA ) . RESULTS AND LIMITATIONS In 463 men , the positive repeat biopsy rate was 28 % . The higher the PCA3 score , the greater the probability of a positive repeat biopsy . The PCA3 score ( cut-off of 35 ) had a greater diagnostic accuracy than % fPSA ( cut-off of 25 % ) . The PCA3 score was independent of the number of previous biopsies , age , prostate volume , and total prostate-specific antigen ( PSA ) level . Moreover , the PCA3 score was significantly higher in men with high- grade prostate intraepithelial neoplasia ( HGPIN ) versus those without HGPIN , clinical stage T2 versus T1 , Gleason score > or=7 versus < 7 , and " significant " versus " indolent " ( clinical stage T1c , PSA density [ PSAD ] < 0.15ng/ml , Gleason score in biopsy < or=6 , and percent positive cores < or=33 % ) pCA . CONCLUSIONS The probability of a positive repeat biopsy increases with rising PCA3 scores . The PCA3 score was superior to % fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa BACKGROUND High-intensity focused ultrasound ( HIFU ) is a nonsurgical therapy for selected patients with localized prostate cancer ( PCa ) . OBJECTIVE The long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospect i ve , single-arm , single-institution cohort study . DESIGN , SETTING , AND PARTICIPANTS Participants were patients treated with HIFU for localized PCa from 1997 to 2009 . Excluded were patients with local recurrence following radiotherapy .  A second HIFU session was systematic ally performed in patients with biopsy-proven local recurrence . INTERVENTION Whole-gl and prostate ablation with transrectal HIFU . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Incontinence was assessed using the Ingelman-Sundberg score , and potency was assessed using the five-item version of the International Index of Erectile Function ( IIEF-5 ) scores . Primary outcomes were survival rates ( biochemical-free , cancer-specific , metastasis-free , and overall survival ) . Secondary outcomes were morbidity rates . Median follow-up was 6.4 yr ( range : 0.2 - 13.9 ) . The Kaplan-Meier method was used to determine survival estimates , and multivariate analysis was used to determine predictive factors of biochemical progression . RESULTS AND LIMITATIONS A total of 1002 patients were included . The median nadir prostate-specific antigen ( PSA ) was 0.14 ng/ml , with 63 % of patients reaching a nadir PSA ≤0.3 ng/ml . Sixty percent of patients received one HIFU session , 38 % received two sessions , and 2 % received three sessions . The 8-yr biochemical-free survival rates ( Phoenix definition ) were 76 % , 63 % , and 57 % for low- , intermediate- , and high-risk patients , respectively ( p < 0.001 ) . At 10 yr , the PCa-specific survival rate and metastasis-free survival rate ( MFSR ) were 97 % and 94 % , respectively . Salvage therapies included external-beam radiation therapy ( EBRT ) ( 13.8 % ) , EBRT plus and rogen-deprivation therapy ( ADT ) ( 9.7 % ) , and ADT alone ( 12.1 % ) . Severe incontinence and bladder outlet obstruction decreased with refinement in the technology , from 6.4 % and 34.9 % to 3.1 % and 5.9 % , respectively . Limitations included the fact that the study was a single-arm study without a comparison group , technological improvements , changes in surgical protocol during the study , and the use of ADT to downsize the prostate in 39 % of patients . CONCLUSIONS HIFU is a potentially effective treatment of localized PCa , with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity BACKGROUND High-intensity focused ultrasound ( HIFU ) is an emerging treatment for select patients with localized prostate cancer ( PCa ) . OBJECTIVES To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter data base . DESIGN , SETTING , AND PARTICIPANTS Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study . Previously irradiated patients were excluded from this analysis . In case of any residual or recurrent PCa , patients were systematic ally offered a second session . Kaplan-Meier analysis was performed to determine disease-free survival rates ( DFSR ) . MEASUREMENTS Prostate-specific antigen ( PSA ) , clinical stage , and pathologic results were measured pre- and post-HIFU . RESULTS AND LIMITATIONS A total of 803 patients from six urologic departments met the inclusion criteria . Stratification according to d'Amico 's risk group was low , intermediate , and high in 40.2 % , 46.3 % , and 13.5 % of patients , respectively . Mean follow-up was 42+/-33 mo . Mean PSA nadir was 1.0+/-2.8 ng/ml with 54.3 % reaching a nadir of < or = 0.3 ng/ml . Control biopsies were negative in 85 % of cases . The overall and cancer-specific survival rates at 8 yr were 89 % and 99 % , respectively . The metastasis-free survival rate at 8 yr was 97 % . Initial PSA value and Gleason score value significantly influence the DFSR . The 5- and 7-yr biochemical-free survival rates ( Phoenix criteria ) were 83 - 75 % , 72 - 63 % , and 68 - 62 % ( p=0.03 ) and the additional treatment-free survival rates were 84 - 79 % , 68 - 61 % , and 52 - 54 % ( p<0.001 ) for low- , intermediate- , and high-risk patients , respectively . PSA nadir was a major predictive factor for HIFU success : negative biopsies , stable PSA , and no additional therapy . CONCLUSIONS Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy ( EBRT ) . The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT 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 PCa death in men allocated to the intervention arm relative to the control arm was 0.80 ( 95 % CI , 0.68 - 0.96 ) . Adjustment for nonattendance result ed in a RR of 0.73 ( 95 % CI , 0.58 - 0.93 ) , and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 ( 95 % CI , 0.51 - 0.92 ) to 0.71 ( 95 % CI , 0.55 - 0.93 ) , respectively . Contamination data were obtained through extrapolation of single-centre data . No heterogeneity was found between the groups of centres . CONCLUSIONS PSA screening reduces the risk of dying of PCa by up to 31 % in men actually screened . This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening BACKGROUND To estimate the benefits of prostate-specific antigen ( PSA ) screening on prostate cancer ( Pca ) metastasis and Pca-specific mortality , we compared two population s with a well-defined difference in intensity of screening . METHODS Between 1997 and 1999 , a total of 11,970 men , aged 55 - 74 years , were included in the intervention arm of the European R and omised Study of Screening for Prostate Cancer ( ERSPC ) section Rotterdam . Control population consisted of 133,287 men , aged 55 - 74 years , between 1998 and 1999 in Northern Irel and ( NI ) . Men were followed for Pca incidence , Pca metastasis and cause of death until 31st December 2006 . RESULTS Median age in both groups was 63 years at study entry ( p=0.184 ) . In Rotterdam 94.2 % of men and in NI 6 % of men underwent PSA testing . In Rotterdam , 1153 men ( 9.6 % ) were diagnosed with Pca with median baseline PSA of 5.1 ng/ml . In NI , 3962 men ( 3.0 % , p<0.001 ) were diagnosed with Pca with median baseline PSA of 18.0 ng/ml ( p<0.001 ) . The relative risk of Pca metastasis during observation in the intervention population compared to control population was 0.47 ( 95 % confidence interval ( CI ) , 0.35 - 0.63 ; p<0.001 ) . The relative risk of Pca-specific mortality was also lower in the intervention population compared to the control population after a median follow-up of 8.5 years : 0.63 ( 95 % CI , 0.45 - 0.88 ; p=0.008 ) ; absolute mortality reduction was 1.8 deaths per 1000 men . CONCLUSIONS A relative reduction in Pca metastasis of 53 % and Pca mortality of 37 % was observed in the intervention population after 8.5 years of observation . The impact of overdiagnosis , quality of life benefits and cost-effectiveness need to be assessed before population -based PSA screening can be recommended Background Prostate-specific antigen ( PSA ) is widely used to detect prostate cancer . The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies . We set out to determine whether a multivariable model including four kallikrein forms ( total , free , and intact PSA , and human kallikrein 2 ( hK2 ) ) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA . Methods The study cohort comprised 740 men in Göteborg , Sweden , undergoing biopsy during the first round of the European R and omized study of Screening for Prostate Cancer . We calculated the area-under-the-curve ( AUC ) for predicting prostate cancer at biopsy . AUCs for a model including age and PSA ( the ' laboratory ' model ) and age , PSA and digital rectal exam ( the ' clinical ' model ) were compared with those for models that also included additional kallikreins . Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84 , for the laboratory and clinical models respectively . Using a 20 % risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 ( 57 % ) and missed only 31 out of 152 low- grade and 3 out of 40 high- grade cancers . Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA . A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening , but defer biopsy until there was stronger evidence of malignancy PURPOSE A urinary assay for PCA3 , an mRNA that is highly over expressed in prostate cancer cells , has shown usefulness as a diagnostic test for this common malignancy . We further characterized PCA3 performance in different groups of men and determined whether the PCA3 score could synergize with other clinical information to predict biopsy outcome . MATERIAL S AND METHODS Prospect ively urine was collected following st and ardized digital rectal examination  in 570 men immediately before prostate biopsy .  Urinary PCA3 mRNA levels were quantified and then normalized to the amount of prostate derived RNA to generate a PCA3 score . RESULTS The percent of biopsy positive men identified increased directly with the PCA3 score . PCA3 assay performance was equivalent in the first vs previous negative biopsy groups with an area under the ROC curve of 0.70 and 0.68 , respectively . Unlike serum prostate specific antigen the PCA3 score did not increase with prostate volume . PCA3 assay sensitivity and specificity were equivalent at serum prostate specific antigen less than 4 , 4 to 10 and more than 10 ng/ml . A logistic regression algorithm using PCA3 , serum prostate specific antigen , prostate volume and digital rectal examination result increased the AUC from 0.69 for PCA3 alone to 0.75 ( p = 0.0002 ) . CONCLUSIONS PCA3 is independent of prostate volume , serum prostate specific antigen level and the number of prior biopsies . The quantitative PCA3 score correlated with the probability of positive biopsy . Logistic regression results suggest that the PCA3 score could be incorporated into a nomogram for improved prediction of biopsy outcome . The results of this study provide further evidence that PCA3 is a useful adjunct to current methods for prostate cancer diagnosis BACKGROUND A better underst and ing of the independent predictors of disease progression for prostate cancer ( PCa ) patients is needed to improve the selection of ideal c and i date s for active surveillance ( AS ) and refine the surveillance regimen . OBJECTIVE To examine the association of clinical and pathologic characteristics , as well as patterns of  surveillance biopsy results , with the risk of progression in men on AS . DESIGN , SETTING , AND PARTICIPANTS The retrospective study consisted of men with PCa who were on AS in the prospect ively maintained University of California , San Francisco , institutional data base from 1996 to 2011 . Strict criteria for AS were prostate-specific antigen ( PSA ) ≤10 ng/ml , clinical stage T1 or T2 , biopsy Gleason grade 6 , <33 % positive cores , and < 50 % tumor in any single core . Men were then categorized based on results of their confirmatory surveillance biopsy . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Disease progression was defined as an increase in Gleason grade and /or biopsy volume beyond prespecified cut points . Serial biopsy patterns over the course of surveillance were stratified by confirmatory biopsy findings : negative , positive without progression , and positive with progression . Multivariable logistic regression models were used to evaluate predictors of progression during AS . RESULTS AND LIMITATIONS A total of 465 men met inclusion criteria ( median follow-up : 51 mo ) . Of these men , 23 % had negative confirmatory biopsies . Only 3 % of the men ( 1 of 30 ) progressed by the fourth surveillance biopsy following a biopsy pattern of negative confirmatory and negative third biopsy findings . Negative confirmatory biopsy and lower PSA density ( both p<0.01 ) were independently associated with decreased odds of biopsy progression at 3 yr . The main limitation of this study is its observational nature . CONCLUSIONS The patterns of surveillance biopsy results yield additional important information in AS . Negative confirmatory biopsy and PSA density are important independent predictors of progression on AS and may be used to better counsel men opting for AS
Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy .
PSA doubling time in < 3 yr or a biopsy progression indicates the need for active intervention .
In men with locally advanced PCa in whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) with equivalent oncologic efficacy .
Active treatment is mostly recommended for patients with localised disease and a long life expectancy  with  radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial .
Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables .
For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice .
OBJECTIVE Our aim was to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the screening , diagnosis , and treatment of clinical ly localised cancer of the prostate ( PCa ) .
Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa .
A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method .