title: Predicting High-Grade Cancer at Ten-Core Prostate Biopsy Using Four Kallikrein Markers Measured in Blood in the ProtecT Study 70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial. Radiotherapy and short-term androgen deprivation for localized prostate cancer. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Opportunistic testing versus organized prostate-specific antigen screening: outcome after 18 years in the Göteborg randomized population-based prostate cancer screening trial. Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial. Radical prostatectomy or watchful waiting in early prostate cancer. Radical prostatectomy versus observation for localized prostate cancer. Long-term results of the Dutch randomized prostate cancer trial: impact of dose-escalation on local, biochemical, clinical failure, and survival. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911) Optimal approach for prostate cancer detection as initial biopsy: prospective randomized study comparing transperineal versus transrectal systematic 12-core biopsy. Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: a randomized study. A prospective randomized comparison of diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer. Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from proton radiation oncology group/american college of radiology 95-09. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Long-term failure patterns and survival in a randomized dose-escalation trial for prostate cancer. Who dies of disease? Familial risk and familial survival in prostate cancer A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy. Characterization of prostate lesions as benign or malignant at multiparametric MR imaging: comparison of three scoring systems in patients treated with radical prostatectomy. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Magnetic resonance imaging-ultrasound fusion biopsy for prediction of final prostate pathology. Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median followup of 3 registries. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. Prostate Needle Biopsy Outcomes in the Era of the U.S. Preventive Services Task Force Recommendation against Prostate Specific Antigen Based Screening. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions.
abstract: Background : Many men with elevated prostate-specific antigen ( PSA ) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy . Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome . Methods : Free , intact and total PSA , and kallikrein-related peptidase 2  were measured in cryopreserved blood from 6129 men with elevated PSA ( ≥3.0ng/mL ) participating in the prospect i ve , r and omized trial Prostate Testing for Cancer and Treatment . Marker levels from 4765 men providing anticoagulated plasma  were incorporated into statistical models to predict any- grade and high- grade ( Gleason score ≥7 ) prostate cancer at 10-core biopsy . The models were corrected for optimism by 10-fold cross validation and independently vali date d using markers measured in serum from 1364 men . All statistical tests were two-sided . Results : The four kallikreins enhanced prostate cancer detection compared with PSA and age alone . Area under the curve ( AUC ) for the four kallikreins was 0.719 ( 95 % confidence interval [ CI ] = 0.704 to 0.734 ) vs 0.634 ( 95 % CI = 0.617 to 0.651 , P < .001 ) for PSA and age alone for any- grade cancer , and 0.820 ( 95 % CI = 0.802 to 0.838 ) vs 0.738 ( 95 % CI = 0.716 to 0.761 ) for high- grade cancer . Using a 6 % risk of high- grade cancer as an illustrative cutoff , for 1000 biopsied men with PSA levels of 3.0ng/mL or higher , the model would reduce the need for biopsy in 428 men , detect 119 high- grade cancers , and delay diagnosis of 14 of 133 high- grade cancers . Models exhibited excellent discrimination on independent validation among men with only serum sample s available for analysis . Conclusions : A statistical model based on kallikrein markers was vali date d in a large prospect i ve study and reduces unnecessary biopsies while delaying diagnosis of high- grade cancers in few men PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question  naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity BACKGROUND It is not known whether short-term and rogen-deprivation therapy ( ADT ) before and during radiotherapy improves cancer control and overall survival among patients with early , localized prostate adenocarcinoma . METHODS From 1994 through 2001 , we r and omly assigned 1979 eligible patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a prostate-specific antigen ( PSA ) level of 20 ng per milliliter or less to radiotherapy alone ( 992 patients ) or radiotherapy with 4 months of total and rogen suppression starting 2 months before radiotherapy ( radiotherapy plus short-term ADT , 987 patients ) . The primary end point was overall survival . Secondary end points included disease-specific mortality , distant metastases , biochemical failure ( an increasing level of PSA ) , and the rate of positive findings on repeat prostate biopsy at 2 years . RESULTS The median follow-up period was 9.1 years . The 10-year rate of overall survival was 62 % among patients receiving radiotherapy plus short-term ADT ( the combined-therapy group ) , as compared with 57 % among patients receiving radiotherapy alone ( hazard ratio for death with radiotherapy alone , 1.17 ; P=0.03 ) . The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8 % to 4 % ( hazard ratio for radiotherapy alone , 1.87 ; P=0.001 ) . Biochemical failure , distant metastases , and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT . Acute and late radiation-induced toxic effects were similar in the two groups . The incidence of grade 3 or higher hormone-related toxic effects was less than 5 % . Re analysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients , with no significant reductions among low-risk patients . CONCLUSIONS Among patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less , the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival . According to post hoc risk analysis , the benefit was mainly seen in intermediate-risk , but not low-risk , men . ( Funded by the National Cancer Institute ; RTOG 94 - 08 Clinical Trials.gov number , NCT00002597 . ) BACKGROUND The European R and omised study of Screening for Prostate Cancer ( ERSPC ) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up , but screening is controversial because of adverse events such as overdiagnosis . We provide up date d results of mortality from prostate cancer with follow-up to 2010 , with analyses truncated at 9 , 11 , and 13 years . METHODS ERSPC is a multicentre , r and omised trial with a predefined central ised data base , analysis plan , and core age group ( 55 - 69 years ) , which assesses prostate-specific antigen ( PSA ) testing in eight European countries . Eligible men aged 50 - 74 years were identified from population registries and r and omly assigned by computer generated r and om numbers to screening or no intervention ( control ) . Investigators were masked to group allocation . The primary outcome was prostate cancer mortality in the core age group . Analysis was by intention to treat . We did a secondary analysis that corrected for selection bias due to non-participation . Only incidence and no mortality data at 9 years ' follow-up are reported for the French centres . This study is registered with Current Controlled Trials , number IS RCT N49127736 . FINDINGS With data truncated at 13 years of follow-up , 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group .  The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 ( 95 % CI 1·83 - 1·99 ) after 9 years ( 1·64 [ 1·58 - 1·69 ] including France ) , 1·66 ( 1·60 - 1·73 ) after 11 years , and 1·57 ( 1·51 - 1·62 ) after 13 years . The rate ratio of prostate cancer mortality was 0·85 ( 0·70 - 1·03 ) after 9 years , 0·78 ( 0·66 - 0·91 ) after 11 years , and 0·79 ( 0·69 - 0·91 ) at 13 years . The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men r and omised , which is equivalent to one prostate cancer death averted per 781 ( 95 % CI 490 - 1929 ) men invited for screening or one per 27 ( 17 - 66 ) additional prostate cancer detected . After adjustment for non-participation , the rate ratio of prostate cancer mortality in men screened was 0·73 ( 95 % CI 0·61 - 0·88 ) . INTERPRETATION In this up date the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA , with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years . Despite our findings , further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening . FUNDING Each centre had its own funding responsibility Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment . We present a pre-planned analysis of the efficacy and side-effects of a r and omised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up . Methods CHHiP is a r and omised , phase 3 , non-inferiority trial that recruited men with localised prostate cancer ( pT1b – T3aN0M0 ) . Patients were r and omly assigned ( 1:1:1 ) to conventional ( 74 Gy delivered in 37 fractions over 7·4 weeks ) or one of two hypofractionated schedules ( 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks ) all delivered with intensity-modulated techniques . Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent and rogen suppression . R and omisation was by computer-generated r and om permuted blocks , stratified by National Comprehensive Cancer Network ( NCCN ) risk group and radiotherapy treatment centre , and treatment allocation was not masked . The primary endpoint was time to biochemical or clinical failure ; the critical hazard ratio ( HR ) for non-inferiority was 1·208 . Analysis was by intention to treat . Long-term follow-up continues . The CHHiP trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N97182923 . Findings Between Oct 18 , 2002 , and June 17 , 2011 , 3216 men were enrolled from 71 centres and r and omly assigned ( 74 Gy group , 1065 patients ; 60 Gy group , 1074 patients ; 57 Gy group , 1077 patients ) . Median follow-up was 62·4 months ( IQR 53·9–77·0 ) . The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3 % ( 95 % CI 86·0–90·2 ) in the 74 Gy group , 90·6 % ( 88·5–92·3 ) in the 60 Gy group , and 85·9 % ( 83·4–88·0 ) in the 57 Gy group . 60 Gy was non-inferior to 74 Gy ( HR 0·84 [ 90 % CI 0·68–1·03 ] , pNI=0·0018 ) but non-inferiority could not be cl aim ed for 57 Gy compared with 74 Gy ( HR 1·20 [ 0·99–1·46 ] , pNI=0·48 ) . Long-term side-effects were similar in the hypofractionated groups compared with the conventional group . There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures . The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group ( RTOG ) grade 2 or worse bowel and bladder adverse events was 13·7 % ( 111 events ) and 9·1 % ( 66 events ) in the 74 Gy group , 11·9 % ( 105 events ) and 11·7 % ( 88 events ) in the 60 Gy group , 11·3 % ( 95 events ) and 6·6 % ( 57 events ) in the 57 Gy group , respectively . No treatment-related deaths were reported . Interpretation Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new st and ard of care for external-beam radiotherapy of localised prostate cancer . Funding Cancer Research UK , Department of Health , and the National Institute for Health Research Cancer Research Network BACKGROUND Studies have reported a low α/β ratio for prostate cancer , suggesting that hypofractionation could enhance the biological tumour dose without increasing genitourinary and gastrointestinal toxicity . In the multicentre phase 3 , HYpofractionated irradiation for PROstate cancer ( HYPRO ) trial , hypofractionated radiotherapy was compared with conventionally fractionated radiotherapy for treatment of prostate cancer . We have previously reported acute and late incidence of genitourinary and gastrointestinal toxicity ; here we report protocol -defined 5-year relapse-free survival outcomes . METHODS We did an open-label , r and omised , phase 3 trial at seven Dutch radiotherapy centres . We enrolled patients with intermediate-risk to high-risk T1b-T4NX-N0MX-M0 localised prostate cancer , a prostate-specific antigen concentration of 60 μg/L or less , and a WHO performance status of 0 - 2 . We used a web-based application to r and omly assign ( 1:1 ) patients to either hypofractionated radiotherapy of 64·6 Gy ( 19 fractions of 3·4 Gy , three fractions per week ) or conventionally fractionated radiotherapy of 78·0 Gy ( 39 fractions of 2·0 Gy , five fractions per week ) . Based on an estimated α/β ratio for prostate cancer of 1·5 Gy , the equivalent total dose in fractions of 2·0 Gy was 90·4 Gy for hypofractionation compared with 78·0 Gy for conventional fractionation . The primary endpoint was relapse-free survival . All analyses were done on an intention-to-treat basis in all eligible patients . The HYPRO trial completed recruitment in 2010 and follow-up is ongoing . This trial is registered with IS RCT N , number IS RCT N85138529 . FINDINGS Between March 19 , 2007 , and Dec 3 , 2010 , 820 patients were enrolled , of whom 804 were eligible and assessable for intention-to-treat analyses . Of these , 407 were assigned hypofractionated radiotherapy and 397 were allocated conventionally fractionated radiotherapy . 537 ( 67 % ) of 804 patients received concomitant and rogen deprivation therapy for a median duration of 32 months ( IQR 10 - 44 ) . Median follow-up was 60 months ( IQR 51 - 69 ) . Treatment failure was reported in 169 ( 21 % ) of 804 patients , 80 ( 20 % ) in the hypofractionation group and 89 ( 22 % ) in the conventional fractionation group . 5-year relapse-free survival was 80·5 % ( 95 % CI 75·7 - 84·4 ) for patients assigned hypofractionation and 77·1 % ( 71·9 - 81·5 ) for those allocated conventional fractionation ( adjusted hazard radio 0·86 , 95 % CI 0·63 - 1·16 ; log-rank p=0·36 ) . There were no treatment-related deaths . INTERPRETATION Hypofractionated radiotherapy was not superior  to conventional radiotherapy with respect to 5-year relapse-free survival . Our hypofractionated radiotherapy regimen can not be regarded as the new st and ard of care for patients with intermediate-risk or high-risk prostate cancer . FUNDING Dutch Cancer Society BACKGROUND It has been shown that organized screening decreases  prostate cancer ( PC ) mortality , but the effect of opportunistic screening is largely unknown . OBJECTIVE To compare the ability to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening . DESIGN , SETTING , AND PARTICIPANTS The Göteborg screening study invited 10 000 r and omly selected men for prostate-specific antigen ( PSA ) testing every 2 yr since 1995 , with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml . The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing . Both groups were followed until December 31 , 2012 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Observed cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method . Using historical data from 1990 - 1994 ( pre-PSA era ) , we calculated expected PC incidence and mortality rates in the absence of any PSA testing . The number needed to invite ( NNI ) and the number needed to diagnose ( NND ) were calculated by comparing the expected versus observed incidence and mortality rates . RESULTS AND LIMITATIONS At 18 yr , 1396 men were diagnosed with PC and 79 men died of PC in the screening group , compared to 962 and 122 , respectively , in the control group . In the screening group , the observed cumulative PC incidence/mortality was 16%/0.98 % compared to expected values of 6.8%/1.7 % . The corresponding values for the control group were 11%/1.5 % and 6.9%/1.7 % . Organized screening was associated with an absolute PC-specific mortality reduction of 0.72 % ( 95 % confidence interval [ CI ] 0.50 - 0.94 % ) and relative risk reduction of 42 % ( 95 % CI 28 - 54 % ) . There was an absolute reduction in PC deaths of 0.20 % ( 95 % CI -0.06 % to 0.47 % ) and a relative risk reduction of 12 % ( 95 % CI -5 to 26 % ) associated with opportunistic PSA testing . NNI and NND were 139 ( 95 % CI 107 - 200 ) and 13 for organized biennial screening and 493 ( 95 % CI 213- -1563 ) and 23 for opportunistic screening . The extent of opportunistic screening could not be measured ; incidence trends were used as a proxy . CONCLUSIONS Organized screening  reduces PC mortality but is associated with overdiagnosis . Opportunistic PSA testing had little if any effect on PC mortality and result ed in more overdiagnosis , with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program . PATIENT SUMMARY Prostate-specific antigen ( PSA ) screening within the framework of an organized program seems more effective than unorganized screening BACKGROUND Robot-assisted laparoscopic radical prostatectomy ( RALP ) has become widely used without high- grade evidence of superiority regarding long-term clinical outcomes compared with open retropubic radical prostatectomy ( RRP ) , the gold st and ard . OBJECTIVE To compare patient-reported urinary incontinence and erectile dysfunction 12 mo after RALP or RRP .  DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , controlled , nonr and omised trial of patients undergoing prostatectomy in 14 centres using RALP or RRP .  Clinical -record forms and vali date d patient question naires at baseline and 12 mo after surgery were collected . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Odds ratios ( ORs ) were calculated with logistic regression and adjusted for possible confounders . The primary end point was urinary incontinence ( change of pad less than once in 24h vs one time or more per 24h ) at 12 mo . Secondary end points were erectile dysfunction at 12 mo and positive surgical margins . RESULTS AND LIMITATIONS At 12 mo after RALP , 366 men ( 21.3 % ) were  incontinent  , as were 144 ( 20.2 % ) after RRP . The unadjusted OR was 1.08 ( 95 % confidence interval [ CI ] , 0.87–1.34 ) . Erectile dysfunction was observed in 1200 men ( 70.4 % ) 12 mo after RALP and 531 ( 74.7 % ) after RRP . The unadjusted OR was 0.81 ( 95 % CI , 0.66–0.98 ) . CONCLUSIONS In a Swedish setting , RALP for prostate cancer was modestly beneficial in preserving erectile function compared with RRP , without a statistically significant difference regarding urinary incontinence or surgical margins . PATIENT SUMMARY We compared patient-reported urinary incontinence after prostatectomy with two types of surgical technique . There was no statistically significant improvement in the rate of urinary leakage , but there was a small improvement regarding erectile function after robot-assisted operation BACKGROUND Radical prostatectomy reduces mortality among men with localized prostate cancer ; however , important questions regarding long-term benefit remain . METHODS Between 1989 and 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012 . The primary end points in the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) were death from any cause , death from prostate cancer , and the risk of metastases . Secondary end points included the initiation of and rogen-deprivation therapy . RESULTS During 23.2 years of follow-up , 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died . Of the deaths , 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer ; the relative risk was 0.56 ( 95 % confidence interval [ CI ] , 0.41 to 0.77 ; P=0.001 ) , and the absolute difference was 11.0 percentage points ( 95 % CI , 4.5 to 17.5 ) . The number needed to treat to prevent one death was 8 . One man died after surgery in the radical-prostatectomy group . And rogen-deprivation therapy was used in fewer patients who underwent prostatectomy ( a difference of 25.0 percentage points ; 95 % CI , 17.7 to 32.3 ) . The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age ( relative risk , 0.45 ) and in those with intermediate-risk prostate cancer ( relative risk , 0.38 ) . However , radical prostatectomy was associated with a reduced risk of metastases among older men ( relative risk , 0.68 ; P=0.04 ) . CONCLUSIONS Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy ; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk . A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment . ( Funded by the Swedish Cancer Society and others . ) BACKGROUND The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen ( PSA ) testing is not known . METHODS From November 1994 through January 2002 , we r and omly assigned 731 men with localized prostate cancer ( mean age , 67 years ; median PSA value , 7.8 ng per milliliter ) to radical prostatectomy or observation  and followed them through January 2010 . The primary outcome was all-cause mortality ; the secondary outcome was prostate-cancer mortality . RESULTS During the median follow-up of 10.0 years , 171 of 364 men ( 47.0 % ) assigned to radical prostatectomy  died , as compared with 183 of 367 ( 49.9 % ) assigned to observation ( hazard ratio , 0.88 ; 95 % confidence interval [ CI ] , 0.71 to 1.08 ; P=0.22 ; absolute risk reduction , 2.9 percentage points ) . Among men assigned to radical prostatectomy , 21 ( 5.8 % ) died from prostate cancer or treatment , as compared with 31 men ( 8.4 % ) assigned to observation ( hazard ratio , 0.63 ; 95 % CI , 0.36 to 1.09 ; P=0.09 ; absolute risk reduction , 2.6 percentage points ) . The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age , race , coexisting conditions , self-reported performance status , or histologic features of the tumor . Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter ( P=0.04 for interaction ) and possibly among those with intermediate-risk or high-risk tumors ( P=0.07 for interaction ) . Adverse events within 30 days after surgery occurred in 21.4 % of men , including one death . CONCLUSIONS Among men with localized prostate cancer detected during the early era of PSA testing  , radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality , as compared with observation , through at least 12 years of follow-up . Absolute differences were less than 3 percentage points . ( Funded by the Department of Veterans Affairs Cooperative Studies Program and others ; PIVOT Clinical Trials.gov number , NCT00007644 . ) PURPOSE Nowadays , advanced irradiation techniques make it possible to escalate safely the dose in prostate cancer . We studied the effect of a higher dose on tumor control in a r and omized trial with a median follow-up of 110 months . PATIENTS AND METHODS Patients with T1b-T4N0 prostate cancer ( n=664 ) were r and omized between 78 Gy and 68 Gy . Primary endpoint was biochemical and /or clinical failure ( BCF ) according to the American Society for Therapeutic Radiology and Oncology ( ASTRO ) guidelines ( 3 consecutive rises ) , and to Phoenix ( nadir plus 2 μg/L ) . Secondary endpoints were clinical failure ( CF ) , local failure ( LF ) , prostate cancer death ( PCD ) , and overall survival ( OS ) . Explorative subgroup analyses were performed . RESULTS BCF rate ( HR=0.8 ; 20 % less events ) and LF rate ( HR=0.5 ; 50 % less events ) were significantly lower in the 78 Gy arm ( p<0.05 ) . CF , PCD and OS were similar in both arms . A significant heterogeneity of treatment effect was found for PSA cutoffs between 7 and 10 μg/L. CONCLUSION We observed significantly less BCF and LF in the high-dose arm . This suggests improvement of the therapeutic ratio . However , we observed similar rates of CF and PCD at the current up date . More follow-up is needed to investigate which patients benefit in terms of prolonged OS IMPORTANCE Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer . The implication s of targeted biopsy alone vs st and ard extended-sextant biopsy or the 2 modalities combined are not well understood . OBJECTIVE To assess targeted vs st and ard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1003 men undergoing both targeted and st and ard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States . Patients were referred for elevated level of prostate-specific antigen ( PSA ) or abnormal digital rectal examination results , often with prior negative biopsy results . Risk categorization was compared among targeted and st and ard biopsy and , when available , whole-gl and pathology after prostatectomy as the " gold st and ard . " INTERVENTIONS Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent st and ard biopsy . MAIN OUTCOMES AND MEASURES The primary objective was to compare targeted and st and ard biopsy approaches for detection of high-risk prostate cancer ( Gleason score ≥ 4 + 3 ) ; secondary end points focused on detection of low-risk prostate cancer ( Gleason score 3 + 3 or low-volume 3 + 4 ) and the biopsy ability to predict whole-gl and pathology at prostatectomy . RESULTS Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases , and st and ard biopsy diagnosed 469 cases . There was exact agreement between targeted and st and ard biopsy in 690 men ( 69 % ) undergoing biopsy . Targeted biopsy diagnosed 30 % more high-risk cancers  vs st and ard biopsy ( 173 vs 122 cases , P < .001 ) and 17 % fewer low-risk cancers ( 213 vs 258 cases , P < .001 ) . When st and ard biopsy cores were combined with the targeted approach , an additional 103 cases ( 22 % ) of mostly low-risk prostate cancer were diagnosed ( 83 % low risk , 12 % intermediate risk , and 5 % high risk ) . The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gl and pathology after prostatectomy was greater than that of st and ard biopsy or the 2 approaches combined ( area under the curve , 0.73 , 0.59 , and 0.67 , respectively ; P < .05 for all comparisons ) . CONCLUSIONS AND RELEVANCE Among men undergoing biopsy for suspected prostate cancer , targeted MR/ultrasound fusion biopsy , compared with st and ard extended-sextant ultrasound-guided biopsy , was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer . Future studies will be needed to assess the ultimate clinical implication s of targeted biopsy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00102544 Purpose We have previously reported that radiotherapy ( RT ) added to and rogen-deprivation therapy ( ADT ) improves survival in men with locally advanced prostate cancer . Here , we report the prespecified final analysis of this r and omized trial . Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94 - 0110 was a r and omized controlled trial of patients with locally advanced prostate cancer . Patients with T3 - 4 , N0/Nx , M0 prostate cancer or T1 - 2 disease with either prostate-specific antigen ( PSA ) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were r and omly assigned to lifelong ADT alone or to ADT+RT . The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone . Overall survival was compared using a log-rank test stratified for prespecified variables . Results One thous and two hundred five patients were r and omly assigned between 1995 and 2005 , 602 to ADT alone and 603 to ADT+RT . At a median follow-up time of 8 years , 465 patients had died , including 199 patients from prostate cancer . Overall survival was significantly improved in the patients allocated to ADT+RT ( hazard ratio [ HR ] , 0.70 ; 95 % CI , 0.57 to 0.85 ; P < .001 ) . Deaths from prostate cancer were significantly reduced by the addition of RT to ADT ( HR , 0.46 ; 95 % CI , 0.34 to 0.61 ; P < .001 ) . Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity , but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT . Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer BACKGROUND We report the long-term results of a trial of immediate postoperative irradiation versus a wait- and -see policy in patients with prostate cancer extending beyond the prostate , to confirm whether previously reported progression-free survival was sustained . METHODS This r and omised , phase 3 , controlled trial recruited patients aged 75 years or younger with untreated cT0 - 3 prostate cancer ( WHO performance status 0 or 1 ) from 37 institutions across Europe . Eligible patients were r and omly assigned central ly ( 1:1 ) to postoperative irradiation ( 60 Gy of conventional irradiation to the surgical bed for 6 weeks ) or to a wait- and -see policy until biochemical progression ( increase in prostate-specific antigen > 0·2 μg/L confirmed twice at least 2 weeks apart ) . We analysed the primary endpoint , biochemical progression-free survival , by intention to treat ( two-sided test for difference at α=0.05 , adjusted for one interim analysis ) and did exploratory analyses of heterogeneity of effect . This trial is registered with Clinical Trials.gov , number NCT00002511 . FINDINGS 1005 patients were r and omly assigned to a wait- and -see policy ( n=503 ) or postoperative irradiation ( n=502 ) and were followed up for a median of 10·6 years ( range 2 months to 16·6 years ) . Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait- and -see policy ( 198 [ 39·4 % ] of 502 patients in postoperative irradiation group vs 311 [ 61·8 % ] of 503 patients in wait- and -see group had biochemical or clinical progression or died ; HR 0·49 [ 95 % CI 0·41 - 0·59 ] ; p<0·0001 ) . Late adverse effects ( any type of any grade ) were more frequent in the postoperative irradiation group than in the wait- and -see group ( 10 year cumulative incidence 70·8 % [ 66·6 - 75·0 ] vs 59·7 % [ 55·3 - 64·1 ] ; p=0.001 ) . INTERPRETATION Results at median follow-up of 10·6 years show that conventional postoperative irradiation  significantly improves biochemical progression-free survival and local control compared with a wait- and -see policy , supporting results at 5 year follow-up ; however , improvements in clinical progression-free survival were not maintained . Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins , but could have a detrimental effect in patients aged 70 years or older . FUNDING Ligue Nationale contre le Cancer ( Comité de l'Isère , Grenoble , France ) and the European Organisation for Research and Treatment of Cancer ( EORTC ) Charitable Trust OBJECTIVES Transperineal and transrectal prostate biopsy are both used for prostate cancer detection . However , which approach is superior remains unknown . In this study , we performed a prospect i ve r and omized study to compare the efficacy of transperineal versus transrectal 12-core initial prostate biopsy . METHODS From May 2003 to October 2005 , a prospect i ve r and omized study of  transperineal versus transrectal 12-core biopsy ( 126 and 120 patients , respectively ) was conducted in 246 patients with a prostate-specific antigen level of 4.0 to 20.0 ng/mL. All procedures were performed with the patient in the lithotomy position , with the transperineal and transrectal approach performed with spinal anesthesia ( 0.5 % bupivacaine ) or a caudal block ( 1 % lidocaine ) , respectively . With both approaches , eight biopsy specimens were obtained systematic ally from the peripheral zone , including the apex , and four from the transition zone . RESULTS The cancer detection rate was 42.1 % ( 53 of 126 patients ) with the transperineal approach and 48.3 % ( 58 of 120 patients ) with the transrectal approach ( P = 0.323 ) . For all patients undergoing transperineal and transrectal biopsy , the cancer core rate ( cancer core number/biopsy core number ) was 13.7 % ( 207 of 1512 cores ) and 14.4 % ( 208 of 1440 cores ) , respectively ( P = 0.566 ) . Apart from headache , presumably related to the spinal anesthesia , no significant differences were found in the complications between the two groups . CONCLUSIONS No significant differences were found in the cancer detection rate , cancer core rate , or complications between the two approaches . We believe that the preferred approach as an initial prostate biopsy is the transrectal approach , which does not require spinal anesthesia or another burdensome process OBJECTIVES To assess whether the proportion of men with clinical ly significant prostate cancer ( PCa ) is higher among men r and omized to multiparametric magnetic resonance imaging (mp-MRI)/biopsy vs. those r and omized to transrectal ultrasound (TRUS)-guided biopsy . METHODS In total , 1,140 patients with symptoms highly suggestive of PCa were enrolled and divided in 2 groups of 570 patients to follow 2 different diagnostic algorithms . Group A underwent a TRUS-guided r and om biopsy . Group B underwent an mp-MRI and a TRUS-guided targeted+r and om biopsy . The accuracy of mp-MRI in the diagnosis of PCa was calculated using prostatectomy as the st and ard of reference . RESULTS In group A , PCa was detected in 215 patients . The remaining 355 patients underwent an mp-MRI : the findings were positive in 208 and unremarkable in 147 patients . After the second r and om+targeted biopsy , PCa was detected in 186 of the 208 patients . In group B , 440 patients had positive findings on mp-MRI , and PCa was detected in 417 at first biopsy ; 130 group B patients had unremarkable findings on both mp-MRI and biopsy . In the 130 group B patients with unremarkable findings on mp-MRI and biopsy , a PCa Gleason score of 6 or precancerous lesions were detected after saturation biopsy . mp-MRI showed an accuracy of 97 % for the diagnosis of PCa . CONCLUSIONS The proportion of men with clinical ly significant PCa is higher among those r and omized to mp-MRI/biopsy vs. those r and omized to TRUS-guided biopsy ; moreover , mp-MRI is a very reliable tool to identify patients to schedule in active surveillance The aim of this study is to eluci date the diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy for prostate cancer . We prospect ively r and omized 200 consecutive men into two groups to undergo  systematic prostate biopsy .  Overall positivity for cancer was similar ( 47 % by transperineal and 53 % by transrectal ; P=0.480 ) . However , in case with ‘ gray zone ’ PSA ( from 4.1 to 10.0 ng/ml ) , significantly more cores were positive when approach was transperineal , especially among transition zone cores . Therefore , urologist preferences are sufficient for choosing an approach , except for a possible small advantage of transperineal biopsy when PSA is in gray zone PURPOSE Conventional radiotherapy ( C-RT ) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks . Pre clinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes . This trial was design ed to assess whether the efficacy of a hypofractionated radiotherapy ( H-RT ) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer . PATIENTS AND METHODS A total of 1,115 men with low-risk prostate cancer were r and omly assigned 1:1 to C-RT ( 73.8 Gy in 41 fractions over 8.2 weeks ) or to H-RT ( 70 Gy in 28 fractions over 5.6 weeks ) . This trial was design ed to establish ( with 90 % power and an α of .05 ) that treatment with H-RT results in 5-year disease-free survival ( DFS ) that is not worse than C-RT by more than 7.65 % ( H-RT/C-RT hazard ratio [ HR ] < 1.52 ) . RESULTS A total of 1,092 men were protocol eligible and had follow-up information ; 542 patients were assigned to C-RT  and 550 to H-RT . Median follow-up was 5.8 years . Baseline characteristics were not different according to treatment assignment . The estimated 5-year DFS was 85.3 % ( 95 % CI , 81.9 to 88.1 ) in the C-RT arm and 86.3 % ( 95 % CI , 83.1 to 89.0 ) in the H-RT  arm . The DFS HR was 0.85 ( 95 % CI , 0.64 to 1.14 ) , and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met ( P < .001 ) . Late grade 2 and 3 GI and genitourinary adverse events were increased ( HR , 1.31 to 1.59 ) in patients who were treated with H-RT . CONCLUSION In men with low-risk prostate cancer , the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks , although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes . PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen < /= 15 ng/mL were r and omly assigned to a total dose of either 70.2 Gray equivalents ( GyE ; conventional ) or 79.2 GyE ( high ) . No patient received and rogen suppression therapy with radiation .  Local failure ( LF ) , biochemical failure ( BF ) , and overall survival ( OS ) were outcomes . Results A total of 393 men were r and omly assigned , and median follow-up was 8.9 years . Men receiving high-dose radiation therapy were significantly less likely to have LF , with a hazard ratio of 0.57 . The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4 % for conventional-dose and 16.7 % for high-dose radiation therapy ( P < .0001 ) . This difference held when only those with low-risk disease ( n = 227 ; 58 % of total ) were examined : 28.2 % for conventional and 7.1 % for high dose ( P < .0001 ) . There was a strong trend in the same direction for the intermediate-risk patients ( n = 144 ; 37 % of total ; 42.1 % v 30.4 % , P = .06 ) . Eleven percent of patients subsequently required and rogen deprivation for recurrence after conventional dose compared with 6 % after high dose ( P = .047 ) . There remains no difference in OS rates between the treatment arms ( 78.4 % v 83.4 % ; P = .41 ) . Two percent of patients in both arms experienced late grade > /= 3 genitourinary toxicity , and 1 % of patients in the high-dose arm experienced late grade > /= 3 GI toxicity . CONCLUSION This r and omized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation . This was achieved without an increase in grade > /= 3 late urinary or rectal morbidity PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 PURPOSE To report long-term failure patterns and survival in a r and omized radiotherapy dose escalation trial for prostate cancer . MATERIAL S AND METHODS A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years .  Failure patterns and survival were compared between dose levels . The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors . RESULTS Patients with pretreatment prostate-specific antigen ( PSA ) > 10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy . These patients also had a significantly higher risk of dying of prostate cancer .  Patients < 70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy , whereas those treated to 78 Gy died of other causes more frequently . Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes , and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up . In regression analysis , factors predicting for death from prostate cancer were pretreatment PSA > 10.5 ng/mL , Gleason score 9 and 10 , recurrence within 2.6 years of radiation , and doubling time of < 3.6 months at the time of recurrence . CONCLUSIONS Moderate dose escalation ( 78 Gy ) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA > 10 ng/mL or high-risk disease Objectives The Swedish Family-Cancer Data base has been the major source of population -based prospect i ve data on familial risks on most cancers , including prostate cancer . In the present review , I focus on three lines of family studies with novel results . Methods The covered studies originate from the same data base with publication date s spanning a period of somewhat over 3 years . Age-specific hazard ratios ( HRs ) of incident prostate cancer and fatal prostate cancer were determined according to the number of affected relatives . Cumulative risks for incidence and death were calculated for the various types of families . Finally , data on the familial association of prostate cancer with some other cancers were review ed . Results If the father had prostate cancer , the HR for sons was 2.1 and it increased to 17.7 when three brothers were affected . The highest HR ( 23 ) was observed for men before age 60 years with three affected brothers . The patterns for fatal familial prostate cancer were similar . Other review ed sets of data showed evidence for the familial concordance of good and poor survival in prostate cancer . Familial risks were somewhat higher for fatal than for incident prostate cancer , suggesting that fatal prostate cancers may be a genetic subgroup . Conclusions Considering the high familial risks in fatal prostate cancer , family history remains an important prognostic piece of information useful for clinical genetic counseling . Obviously , preventive measures for at-risk men are needed but these are beyond the present paper . Starting screening before any prostate cancers are diagnosed in a family appears counterproductive BACKGROUND Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging ( MRI ) and transrectal ultrasound ( TRUS ) images ( MRI group ) has not yet been compared with 12-core r and om biopsy ( RB ; control group ) in a r and omized controlled trial ( RCT ) . OBJECTIVE To compare the rate of detection of clinical ly significant prostate cancer ( csPCa ) between the two groups . DESIGN , SETTING , AND PARTICIPANTS This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer , r and omized to an MRI group ( n=86 ) and a control group ( n=89 ) between September 2011 and June 2013 . INTERVENTION In the MRI group , two-core targeted biopsy ( TB ) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB . In the control group , both two-core TB for abnormal digital rectal examination ( DRE ) and /or TRUS-suspicious lesions and 12-core RB were performed . In patients with normal MRI or DRE/TRUS , only 12-core RB was performed . OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB . RESULTS AND LIMITATIONS Detection rates for any cancer ( MRI group 51/86 , 59 % ; control group 48/89 , 54 % ; p=0.4 ) and csPCa ( 38/86 , 44 % vs 44/89 , 49 % ; p=0.5 ) did not significantly differ between the groups . Detection of csPCa was comparable between two-core MRI/TRUS-TB ( 33/86 , 38 % ) and 12-core RB in the control group ( 44/89 , 49 % ; p=0.2 ) . In a subset analysis of patients with normal DRE , csPCa detection was similar between two-core MRI/TRUS-TB ( 14/66 , 21 % ) and 12-core RB in the control group ( 15/60 , 25 % ; p=0.7 ) . Among biopsy-proven csPCas in MRI group , 87 % ( 33/38 ) were detected by MRI/TRUS-TB . The definition of csPCa was only based on biopsy outcomes . CONCLUSION Overall csPCa detection was similar between the MRI and control groups . Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection . PATIENT SUMMARY Our r and omized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging ( MRI ) and transrectal ultrasound ( TRUS ) and 12-core r and om biopsy . The traditional 12-core r and om biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinical ly significant prostate cancer PURPOSE To compare the subjective Likert score to the Prostate Imaging Reporting and Data System ( PIRADS ) and morphology-location-signal intensity ( MLS ) scores for categorization of prostate lesions as benign or malignant at multiparametric magnetic resonance ( MR ) imaging . MATERIAL S AND METHODS Two hundred fifteen patients who underwent T2-weighted , diffusion-weighted , and dynamic contrast material -enhanced multiparametric MR imaging of the prostate before radical prostatectomy  were included in a prospect i ve data base after they signed the institutional review board-approved forms . Senior readers 1 and 2 prospect ively noted the location , shape , and signal intensity of lesions on MR images from individual pulse sequences and scored each for likelihood of malignancy by using a Likert scale ( range , 1 - 5 ) . A junior reader ( reader 3 ) retrospectively review ed the data base and did the same analysis . The MLS score ( range , 1 - 13 ) was computed by using the readers ' descriptions of the lesions . Then , the three readers again scored the lesions they described by using the PIRADS score ( range , 3 - 15 ) . MLS and PIRADS scores were compared with the Likert score by using their areas under the receiver operating characteristic curves . RESULTS Areas under the receiver operating characteristic curves of the Likert , MLS , and PIRADS scores were 0.81 , 0.77 ( P = .03 ) , and 0.75 ( P = .01 ) for reader 1 ; 0.88 , 0.74 ( P < .0001 ) , and 0.76 ( P < .0001 ) for reader 2 ; and 0.81 , 0.78 ( P = .23 ) , and 0.75 ( P = .01 ) for reader 3 . For diagnosing cancers with Gleason scores greater than or equal to 7 , the Likert score was significantly more accurate than the others , except for the MLS score for reader 3 . Weighted κ values were 0.470 - 0.524 , 0.405 - 0.430 , and 0.378 - 0.441 for the Likert , MLS , and PIRADS scores , respectively . CONCLUSION The Likert score allowed significantly more accurate categorization of prostate lesions on MR images than did the MLS and PIRADS scores BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free survival ( 3.42 [ 1.96 - 5.98 ] , p<0.0001 ) . Of 49 histopathology slides received ( 19 immediate ADT , 30 observation ) , 16 were down grade d from the original Gleason score ( between groups < or = 6 , 7 , and > or = 8) and five were up grade d. We recorded similar proportions of score changes in each group ( p=0.68 ) , and no difference in score distribution by treatment ( p=0.38 ) . After adjustment for score , associations were still significant between treatment and survival ( overall , p=0.02 ; disease-specific , p=0.002 ; progression-free survival , p<0.0001 ) . INTERPRETATION Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy , compared with those who receive deferred treatment . The beneficial effects of early ADT , rather than an imbalance in risk factors , are likely to explain the differences in outcomes between treatments PURPOSE We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology . MATERIAL S AND METHODS A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy  were included in this prospect i ve , institutional review board approved pilot study . Using magnetic resonance imaging-ultrasound fusion , tissue was obtained from a 12-point systematic grid ( mapping biopsy ) and from regions of interest detected by multiparametric magnetic resonance imaging ( targeted biopsy ) . A single radiologist read all magnetic resonance imaging , and a single pathologist independently re review ed all biopsy and whole mount pathology , blinded to prior interpretation and matched specimen . Gleason score concordance between biopsy and prostatectomy was the primary end point . RESULTS Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml .  Final Gleason score at prostatectomy was 6 ( 13 % ) , 7 ( 70 % ) and 8 - 9 ( 17 % ) . A tertiary pattern was detected in 17 ( 31 % ) men . Of 45 high suspicion ( image grade 4 - 5 ) magnetic resonance imaging targets 32 ( 71 % ) contained prostate cancer . The per core cancer detection rate was 20 % by systematic mapping biopsy and 42 % by targeted biopsy . The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54 % , targeted biopsy in 54 % and a combination in 81 % of cases . Overall 17 % of cases were up grade d from fusion biopsy to final pathology and 1 ( 2 % ) was down grade d. The combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy . CONCLUSIONS In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods ( 81 % vs 40 % to 65 % ) . If confirmed , these results will have important clinical implication BACKGROUND Local failure after radical prostatectomy ( RP ) is common in patients with cancer extending beyond the capsule . Three prospect ively r and omized trials demonstrated an advantage for adjuvant radiotherapy ( ART ) compared with a wait- and -see ( WS ) policy . OBJECTIVE To determine the efficiency of ART after a 10-yr follow-up in the ARO 96 - 02 study . DESIGN , SETTING , AND PARTICIPANTS After RP , 388 patients with pT3 pN0 prostate cancer ( PCa ) were r and omized to WS or three-dimensional conformal ART with 60 Gy . The present analysis focuses on intent-to-treat patients who achieved an undetectable prostate-specific antigen after RP ( ITT2 population ) --that is , 159  WS plus 148  ART  men . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point of the study was progression-free survival ( PFS ) ( events : biochemical recurrence , clinical recurrence , or death ) . Outcomes were compared by log-rank test . Cox regression analysis served to identify variables influencing the course of disease . RESULTS AND LIMITATIONS The median follow-up was 111 mo for ART and 113 mo for WS . At 10 yr , PFS was 56 % for ART and 35 % for WS ( p<0.0001 ) . In pT3b and R1 patients , the rates for WS even dropped to 28 % and 27 % , respectively . Of all 307 ITT2 patients , 15 died from PCa , and 28 died for other or unknown reasons . Neither metastasis-free survival nor overall survival was significantly improved by ART . However , the study was underpowered for these end points . The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity . No grade 4 events occurred . CONCLUSIONS Compared with WS , ART reduced the risk of ( biochemical ) progression with a hazard ratio of 0.51 in pT3 PCa . With only one grade 3 case of late toxicity , ART was safe . PATIENT SUMMARY Pre caution ary radiotherapy counteracts relapse after surgery for prostate cancer with specific risk factors BACKGROUND Early risk-stratified chemotherapy is a st and ard treatment for breast , colorectal , and lung cancers , but not for high-risk localised prostate cancer . Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer . We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer . METHODS We did this r and omised phase 3 trial at 26 hospitals in France . We enrolled patients with treatment-naive prostate cancer and at least one risk factor ( ie , stage T3-T4 disease , Gleason score of ≥8 , prostate-specific antigen concentration > 20 ng/mL , or pathological node-positive ) . All patients underwent a staging pelvic lymph node dissection . Patients were r and omly assigned ( 1:1 ) to either and rogen deprivation therapy ( ADT ; goserelin 10·8 mg every 3 months for 3 years ) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2 ) and estramustine 10 mg/kg per day on days 1 - 5 , every 3 weeks , or ADT only . The r and omisation was done central ly by computer , stratified by risk factor . Local treatment was administered at 3 months . Neither patients nor investigators were masked to treatment allocation . The primary endpoint was relapse-free survival in the intention-to-treat population . Follow-up for other endpoints is ongoing . This study is registered with Clinical Trials.gov , number NCT00055731 . FINDINGS We r and omly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group . Median follow-up was 8·8 years ( IQR 8·1 - 9·7 ) . 88 ( 43 % ) of 207 patients in the ADT plus docetaxel and estramustine group had an event ( relapse or death ) versus 111 ( 54 % ) of 206 in the ADT only group . 8-year relapse-free survival was 62 % ( 95 % CI 55 - 69 ) in the ADT plus docetaxel and estramustine group versus 50 % ( 44 - 57 ) in the ADT only group ( adjusted hazard ratio [ HR ] 0·71 , 95 % CI 0·54 - 0·94 , p=0·017 ) . Of patients who were treated with radiotherapy and had data available , 31 ( 21 % ) of 151 in the ADT plus docetaxel and estramustine group versus 26 ( 18 % ) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect ( p=0·61 ) . We recorded no excess second cancers ( 26 [ 13 % ] of 207 vs 22 [ 11 % ] of 206 ; p=0·57 ) , and there were no treatment-related deaths . INTERPRETATION Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer . Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival . FUNDING Ligue Contre le Cancer , Sanofi-Aventis , AstraZeneca , Institut National du Cancer Objective To determine the relative risks of prostate cancer incidence , metastasis , and mortality associated with screening by serum prostate specific antigen ( PSA ) levels at age 60 . Design Population based cohort study . Setting General male population of Sweden taking part in a screening trial in Gothenburg or participating in a cardiovascular study , the Malmö Preventive Project . Participants The screened group consisted of 1756 men aged 57.5 - 62.5 participating in the screening arm of the Gothenburg r and omized prostate cancer screening trial since 1995 . The unscreened group consisted of 1162 men , born in 1921 , participating in the Malmö Preventive Project , with PSA levels measured retrospectively in stored blood sample s from 1981 . Intervention PSA screening versus no screening . Main outcome measures Incidence rate ratios for the effect of screening on prostate cancer diagnosis , metastasis , and death by PSA levels at age 60 . Results The distribution of PSA levels was similar between the two cohorts . Differences in benefits by baseline PSA levels were large . Among men with baseline levels measured , 71.7 % ( 1646/2295 ) had a PSA level < 2 ng/mL. For men aged 60 with PSA level < 2 ng/mL , there was an increase in incidence of 767 cases per 10 000 without a decrease in prostate cancer mortality . For men with PSA levels ≥2 ng/mL , the reduction in cancer mortality was large , with only 23 men needing to be screened and six diagnosed to avoid one prostate cancer death by 15 years . Conclusions The ratio of benefits to harms of PSA screening varies noticeably with blood PSA levels at age 60 . For men with a PSA level < 1 ng/mL at age 60 , no further screening is recommended . Continuing to screen men with PSA levels > 2 ng/mL at age 60 is beneficial , with the number needed to screen and treat being extremely favourable . Screening men with a PSA level of 1 - 2 ng/mL is an individual decision to be based on a discussion between patient and doctor OBJECTIVES More-extensive pelvic lymph node dissection ( PLND ) may be associated with a higher rate of complications and a longer hospital stay than more limited PLND . METHODS Before radical retropubic prostatectomy , PLNDs were performed in 963 patients . Of these , 767 ( 79.6 % ) had > or=10 lymph nodes removed and examined ( extended PLND [ ePLND ] ) , while 1 - 9 nodes ( limited PLND [ lPLND ] ) were removed in the remaining 196 ( 20.4 % ) . Limits included external iliac , obturator , internal iliac , and iliac bifurcation . PLND-related  complications and the length of hospital stay were recorded prospect ively and analyzed according to the extent of PLND . RESULTS In patients subjected to ePLND , the overall rate of complications was 19.8 % versus 8.2 % in those treated with lPLND ( p<0.001 ) . In individual analyses of specific complications , only the lymphocele rate was significantly higher after ePLND ( 10.3 % vs 4.6 % ; p=0.01 ) . Similarly , ePLND translated into a longer hospital stay ( 9.9 vs 8.2 d ; p<0.001 ) . These differences persisted when adjustment was made for prostate-specific antigen and either clinical or pathologic tumor characteristics . CONCLUSIONS Our data indicate that , even in the h and s of experienced urologic surgeons , ePLNDs are associated with higher complication rates and longer hospital stay . These detriments need to be taken into account when the staging benefit associated with ePLND is considered 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 Although there is no evidence that testosterone therapy increases the risk of prostate cancer , there is a paucity of long-term data . We determined whether the incidence of prostate cancer is increased in hypogonadal men receiving long-term testosterone therapy .  MATERIAL S AND METHODS In 3 parallel , prospect i ve , ongoing , cumulative registry studies 1,023 hypogonadal men received testosterone therapy .  Two study cohorts were treated by urologists ( since 2004 ) and 1 was treated at an academic and rology center ( since 1996 ) . Patients were treated when  total testosterone was 12.1 nmol/l or less ( 350 ng/dl ) and symptoms of hypogonadism were present . Maximum followup was 17 years ( 1996 to 2013 ) and median followup was 5 years . Mean baseline patient age in the urological setting s was 58 years and in the and rology setting it was 41 years . Patients received testosterone undecanoate injections in 12-week intervals . Pretreatment examination of the prostate and monitoring during treatment were performed . Prostate biopsies were performed according to EAU guidelines . RESULTS Numbers of positive and negative biopsies were assessed . The incidence of prostate cancer and post-prostatectomy outcomes was studied . A total of 11 patients were diagnosed with prostate cancer in the 2 urology setting s at proportions of 2.3 % and 1.5 % , respectively . The incidence per 10,000 patient-years was 54.4 and 30.7 , respectively . No prostate cancer was reported by the and rology center . Limitations are inherent in the registry design without a control group . CONCLUSIONS Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer . If guidelines for testosterone therapy are properly applied , testosterone treatment is safe in hypogonadal men PURPOSE We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen ( PSA ) , or histologic progression as treatment indications for clinical ly localized prostate cancer . PATIENTS AND METHODS This was a prospect i ve , single-arm , cohort study . Patients were managed with an initial expectant approach . Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years , Gleason score progression ( to 4 + 3 or greater ) , or unequivocal clinical progression .  Survival analysis and Cox proportional hazard model were applied to the data . Results A total of 450 patients have been observed with active surveillance . Median follow-up was 6.8 years ( range , 1 to 13 years ) . Overall survival was 78.6 % . The 10-year prostate cancer actuarial survival was 97.2 % . Overall , 30 % of patients have been reclassified as higher risk and have been offered definitive therapy . Of 117 patients treated radically , the PSA failure rate was 50 % , which was 13 % of the total cohort . PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years ( P < .0001 ) . The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years . CONCLUSION We observed a low rate of prostate cancer mortality . Among the patients who were reclassified as higher risk and who were treated , PSA failure was relatively common . Other-cause mortality accounted for almost all of the deaths . Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis PURPOSE We determined whether the characteristics of patients undergoing prostate needle biopsies and prostate needle biopsy results changed after the U.S. Preventive Services Task Force recommendation in 2012 against prostate specific antigen based screening for prostate cancer for men of any age . MATERIAL S AND METHODS A prospect i ve data base of patients undergoing prostate needle biopsies at Virginia Mason from 2004 to 2014 was review ed . Welch 's t-test and chi-square tests were used to compare patients seen before to those seen after the USPSTF recommendation . Relative risks and corresponding confidence intervals were estimated by general linear regression . RESULTS Patients in the post-USPSTF group ( 310 ) had a higher prostate specific antigen ( p < 0.001 ) , were more likely to be diagnosed with higher clinical stage ( 2b , p=0.003 ; 2c-3a , p=0.027 ) and D'Amico high risk prostate cancer ( p=0.036 ) , with an adjusted relative risk for high risk prostate cancer of 1.25 ( 95 % CI 1.02 - 1.52 ) compared to those in the pre-USPSTF group ( 1,416 ) . Limiting the pre-USPSTF group to the 30 months before the draft guidelines ( 448 patients ) yielded similar results . The absolute number of biopsies performed decreased by 31 % , with the majority of the decrease occurring in the detection of intermediate risk tumors . CONCLUSIONS In the 2 and a half years after the USPSTF recommendation against prostate specific antigen based screening , patients undergoing prostate needle biopsies were significantly more likely to be diagnosed with high risk disease . However , a reduction in the number of prostate needle biopsies performed occurred concomitantly with a decrease in the detection of intermediate risk , potentially curable prostate cancer . Future focus on informed application of screening techniques may prevent the reversal of decades of improvement in the prostate cancer mortality rate PURPOSE This trial was design ed to test the hypothesis that total and rogen suppression and whole pelvic radiotherapy ( WPRT ) followed by a prostate boost improves progression-free survival ( PFS ) by > or = 10 % compared with total and rogen suppression and prostate only RT ( PORT ) . This trial was also design ed to test the hypothesis that neoadjuvant hormonal therapy ( NHT ) followed by concurrent total and rogen suppression and RT improves PFS compared with RT followed by adjuvant hormonal therapy ( AHT ) by > or = 10 % . METHODS AND MATERIAL S Patients eligible for the study included those with clinical ly localized adenocarcinoma of the prostate and an elevated prostate-specific antigen level of < 100 ng/mL. Patients were stratified by T stage , prostate-specific antigen level , and Gleason score and were required to have an estimated risk of lymph node involvement of > 15 % . RESULTS The difference in overall survival for the four arms was statistically significant ( p = 0.027 ) . However , no statistically significant differences were found in PFS or overall survival between NHT vs. AHT and WPRT compared with PORT . A trend towards a difference was found in PFS ( p = 0.065 ) in favor of the WPRT + NHT arm compared with the PORT + NHT and WPRT + AHT arms . CONCLUSIONS Unexpected interactions appear to exist between the timing of hormonal therapy and radiation field size for this patient population . Four Phase III trials have demonstrated better outcomes when NHT was combined with RT compared with RT alone . The Radiation Therapy Oncology Group 9413 trial results have demonstrated that when NHT is used in conjunction with RT , WPRT yields a better PFS than does PORT . It also showed that when NHT + WPRT results in better overall survival than does WPRT + short-term AHT . Additional studies are warranted to determine whether the failure to demonstrate an advantage for NHT + WPRT compared with PORT + AHT is chance or , more likely , reflects a previously unrecognized biologic phenomenon
target: Moderate hypofractionation is safe and effective , but longer-term data are still lacking .
  Brachytherapy represents an effective way to increase the delivered dose .
background: OBJECTIVE To present a summary of the 2016 version of the European Association of Urology ( EAU ) - European Society for Radiotherapy & Oncology ( ESTRO ) - International Society of Geriatric Oncology ( SIOG ) Guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly localised prostate cancer ( PCa ) .
  EVIDENCE SYNTHESIS BRCA2 mutations have been added as risk factors for early and aggressive disease .
  Systematic screening is still not recommended .
  An early prostate-specific antigen test , the use of a risk calculator , or one of the promising biomarker tools are being investigated and might be able to limit the overdetection of insignificant PCa .
  Breaking the link between diagnosis and treatment may lower the overtreatment risk .
  Multiparametric magnetic resonance imaging using st and ardised reporting can not replace systematic biopsy , but robustly nested within the diagnostic work-up , it has a key role in local staging .
  In Northern and Western Europe , the number of men diagnosed with PCa has been on the rise .