title: Individualized estimation of the benefit of radical prostatectomy from the Scandinavian Prostate Cancer Group randomized trial. Multicentric oncologic outcomes of high-intensity focused ultrasound for localized prostate cancer in 803 patients. High-risk prostate cancer treated with pelvic radiotherapy and 36 versus 18 months of androgen blockade: Results of a phase III randomized study. Prostate-cancer mortality at 11 years of follow-up. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. Prostate cancer death of men treated with initial active surveillance: clinical and biochemical characteristics. Results from the Scandinavian Prostate Cancer Group Trial Number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting. Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis. Radical prostatectomy versus observation for localized prostate cancer. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial Pain during transrectal ultrasonography guided prostate biopsy: a randomized prospective trial comparing periprostatic infiltration with lidocaine with the intrarectal instillation of lidocaine-prilocain cream Competing event risk stratification may improve the design and efficiency of clinical trials: secondary analysis of SWOG 8794. Mortality results from a randomized prostate-cancer screening trial. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911) A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. Optimal approach for prostate cancer detection as initial biopsy: prospective randomized study comparing transperineal versus transrectal systematic 12-core biopsy. Complications after prostate biopsy: data from SEER-Medicare. A prospective randomized comparison of diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy Prediction of seminal vesicle invasion in prostate cancer: incremental value of adding endorectal MR imaging to the Kattan nomogram. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. PCA3: a molecular urine assay for predicting prostate biopsy outcome. Intermediate-term potency, continence, and survival outcomes of radical prostatectomy for clinically high-risk or locally advanced prostate cancer. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. Addition of radiotherapy to long-term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial. Radical retropubic prostatectomy plus orchiectomy versus orchiectomy alone for pTxN+ prostate cancer: a matched comparison. Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy. Antibiotic prophylaxis for transrectal needle biopsy of the prostate: a randomized controlled study A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lack of benefit for the addition of androgen deprivation therapy to dose-escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer. Role of androgen deprivation therapy for node-positive prostate cancer. Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77-06. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. 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. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Duration of androgen suppression in the treatment of prostate cancer. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. Combination of adjuvant hormonal and radiation therapy significantly prolongs survival of patients with pT2-4 pN+ prostate cancer: results of a matched analysis.
abstract: BACKGROUND Although there is r and omized evidence that radical prostatectomy improves survival , there are few data on how benefit varies by baseline risk . OBJECTIVE We aim ed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient , using stage , grade , prostate-specific antigen , and age as predictors . DESIGN , SETTING , AND PARTICIPANTS A total of 695 men with T1 or T2 prostate cancer participated in the Sc and inavian Prostate Cancer Group 4 trial ( SPCG-4 ) . INTERVENTION Patients in SPCG-4 were r and omized to radical prostatectomy or conservative management . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Competing risk models were created separately for the radical prostatectomy and the watchful waiting group , with the difference between model predictions constituting the estimated benefit for an individual patient . RESULTS AND LIMITATIONS Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics . At 65 yr of age , the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5 % to 17.2 % for low- versus high-risk patients . Little expected benefit was associated with surgery much beyond age 70 . Only about a quarter of men had an individualized benefit within even 50 % of the mean . A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients . CONCLUSIONS Our model suggests that it is hard to justify surgery in patients with Gleason 6 , T1 disease or in those patients much above 70 yr of age . Conversely , surgery seems unequivocally of benefit for patients who have Gleason 8 , or Gleason 7 , stage T2 . For patients with Gleason 6 T2 and Gleason 7 T1 , treatment is more of a judgment call , depending on patient preference and other clinical findings , such as the number of positive biopsy cores and comorbidities 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 3 Background : Radiotherapy ( RT ) and long term and rogen blockade ( AB ) is st and ard treatment for patients with high risk prostate cancer . However , the optimal duration of AB is not yet defined . The purpose of this r and omized study was to compare outcomes between 36 vs. 18 months of AB in high risk prostate cancer treated with RT ( PCS IV trial , Clinical Trials.gov , # NCT00223171 ) . METHODS PCS IV r and omized patients with node negative high risk prostate cancer ( T3 - 4 , PSA > 20 ng/ml or Gleason score > 7 ) , to pelvic RT ( whole pelvis 44 Gy/4 ½ weeks , prostate 70 Gy/7 weeks ) and 36 ( arm 1 ) vs. 18 months ( arm 2 ) of AB ( neo adjuvant , concomitant , adjuvant ) . AB consisted of bicalutamide 50 mg for one month plus goserelin 10.8 mg every three months for 36 vs. 18 months . Overall survival was the primary end point . Overall and cancer specific survival rates were compared between arms with Kaplan-Meier log rank test and Cox regression . RESULTS From October 2000 to January 2008 , 310 patients were r and omized to arm 1 and 320 to arm 2 . Patients ' characteristics were well balanced between the two arms ( median age 71 years , median PSA 16 ng/ml , median Gleason score 8) . Most patients had T2 - 3 disease . At a median follow-up of 77 months , 71/310 patients ( 22.9 % ) in arm 1 and 76/320 ( 23.8 % ) in arm 2 had died ( p=0.802 ) . Overall , 116 patients died of causes other than prostate cancer . Overall and cancer specific survival hazard ratios were 1.15 ( 0.83 - 1.59 ) , p=0.398 and 1.13 ( 0.61 - 2.08 ) , p=0.153 , respectively . 5 year overall and disease specific survival rates were 92.1 % ( 89.1 - 95.1 ) vs. 86.8 % ( 83.0 - 90.6 ) , p=0.052 and 97.6 % ( 95.9 - 99.4 ) vs. 96.4 % ( 94.2 - 98.6 ) , p=0.473 and 10 year overall and disease specific survival rates were 63.6 % ( 55.7 - 71.5 ) vs. 63.2 % ( 54.7 - 71.7 ) , p=0.429 and 87.2 % ( 81.0 - 93.3 ) vs. 87.2 % ( 80.9 - 93.6 ) , p=0.838 for arm 1 and arm 2 , respectively . There were no significant differences in the rates of biochemical , regional or distant failure between arms . CONCLUSIONS Our study shows that long term AB can be safely reduced from 36 to 18 months without compromising outcomes . Analysis of treatment impact on quality of life is now under review . SOURCE OF FUNDING AstraZeneca Pharmaceuticals Grant . CLINICAL TRIAL INFORMATION Clinical Trials.gov , # NCT00223171 BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) BACKGROUND The optimal upper limit of the normal range for prostate-specific antigen ( PSA ) is unknown . We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less . METHODS Of 18,882 men enrolled in the prevention trial , 9459 were r and omly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination . Among these 9459 men , 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination , had a final PSA determination , and underwent a prostate biopsy after being in the study for seven years . RESULTS Among the 2950 men ( age range , 62 to 91 years ) , prostate cancer was diagnosed in 449 ( 15.2 percent ) ; 67 of these 449 cancers ( 14.9 percent ) had a Gleason score of 7 or higher . The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter , 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter , 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter , 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter , and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter . The prevalence of high- grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter . CONCLUSIONS Biopsy-detected prostate cancer , including high- grade cancers , is not rare among men with PSA levels of 4.0 ng per milliliter or less -- levels generally thought to be in the normal range PURPOSE Active surveillance for favorable risk prostate cancer is an approach that may reduce the risk of overtreatment of clinical ly insignificant prostate cancer . In fact , some patients with favorable risk disease at diagnosis harbor more aggressive disease and may be at risk for prostate cancer mortality despite close monitoring . This is a detailed report of 5 of 453 patients on surveillance who died of prostate cancer . MATERIAL S AND METHODS A large phase 2 prospect i ve trial of active surveillance in patients with favorable risk prostate cancer was initiated in 1995 . Eligible patients had favorable risk prostate cancer ( prostate specific antigen 10 ng/ml or less , Gleason 6 or less , T1c/T2a ) . Epstein criteria for clinical ly insignificant prostate cancer ( a third or less of cores positive , 50 % or less involvement of any 1 core , and prostate specific antigen density less than 0.15 ) were used for men younger than 55 years . Patients were followed with serial prostate specific antigen determinations  every 3 months for 2 years and then every 6 months if stable . Biopsies were performed at 1 year and then every 3 to 4 years . Radical intervention was offered if prostate specific antigen doubling time was less than 3 years or Gleason 3 + 4 pattern disease was identified on repeat biopsy . For the first 5 years of the study patients older than 70 years were eligible if they had Gleason 3 + 4 or less , or prostate specific antigen less than 15 ng/ml . RESULTS The rate of intervention with radiation or surgery  was 38 % at 10 years ( actuarial ) . All 5 patients had a prostate specific antigen doubling time of 1.6 years or less triggering a recommendation of radical therapy . Radical intervention was performed in 3 of the 5 patients . Patients 1 and 4 received radiation and patient 3 underwent radical prostatectomy . Of the 2 patients who did not receive definitive treatment 1 was lost to followup ( patient 2 ) and was treated conservatively by his family doctor . Patient 5 elected and  rogen deprivation therapy  rather than  radical treatment . CONCLUSIONS The low prostate cancer mortality in our surveillance cohort provides support for an active surveillance approach to favorable risk prostate cancer . Only 1 of the 5 patients presented with favorable disease and experienced a theoretically preventable death . The absence of preventable deaths suggests that the basic approach is sound . Two patients had a trigger for intervention but did not receive it . This reinforces the importance of close monitoring and of definitive treatment for those in whom disease is reclassified as higher risk over time In the Sc and inavian Prostate Cancer Group Trial Number 4 ( SPCG-4 ) , 347 men were r and omly assigned to  radical prostatectomy  and 348 to  watchful waiting .  In the most recent analysis ( median follow-up time = 12.8 years ) , the cumulative mortality curves had been stable over the follow-up . At 15 years , the absolute risk reduction of dying from prostate cancer was 6.1 % following r and omization to radical prostatectomy , compared with watchful waiting . Hence , 17 need to be r and omized to operation to avert one death . Data on self-reported symptoms , stress from symptoms , and quality of life were collected at 4 and 12.2 years of median follow-up . These question naire studies show an intricate pattern of symptoms evolving after surgery , hormonal treatments , signs of tumor progression , and also from natural aging . This article discusses some of the main findings of the SPCG-4 study BACKGROUND Previous r and omised trials demonstrated that adjuvant radiation therapy ( aRT ) improves cancer control in patients with pT3 prostate cancer ( PCa ) . However , there is currently no evidence supporting early salvage radiation therapy ( eSRT ) as equivalent to aRT in improving freedom from biochemical recurrence ( BCR ) after radical prostatectomy ( RP ) . OBJECTIVE To evaluate BCR-free survival for aRT versus observation followed by eSRT in cases of relapse in patients undergoing RP for pT3pN0 , R0-R1 PCa . DESIGN , SETTING , AND PARTICIPANTS Using a European multi-institutional cohort , 890 men with pT3pN0 , R0-R1 PCa were identified . INTERVENTION All patients underwent RP . Subsequently , patients were stratified into two groups : aRT versus initial observation followed by eSRT in cases of relapse . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES : Propensity-matched analysis was employed , and patients were stratified into two groups : aRT versus observation and eventual eSRT , defined as RT given at a postoperative serum prostate-specific antigen ( PSA ) ≤ 0.5 ng/ml at least 6 mo after RP . BCR , defined as PSA > 0.20 ng/ml and rising after administration of RT , was compared between aRT and initial observation followed by eSRT in cases of relapse using Kaplan-Meier and Cox regression methods . RESULTS AND LIMITATIONS Overall , 390 ( 43.8 % ) and 500 ( 56.2 % ) patients were treated with aRT and initial observation , respectively . Within the latter group , 225 ( 45.0 % ) patients experienced BCR and underwent eSRT . In the postpropensity-matched cohort , the 2- and 5-yr BCR-free survival rates were 91.4 % and 78.4 % in aRT versus 92.8 % and 81.8 % in patients who underwent initial observation and eSRT in cases of relapse , respectively ( p=0.9 ) . No differences in the 2- and 5-yr BCR-free survival rates were found , even when patients were stratified according to pT3 substage and surgical margin status ( all p ≥ 0.4 ) . These findings were also confirmed in multivariable analyses ( p=0.6 ) . Similar results were achieved when the cut-off to define eSRT was set at 0.3 ng/ml ( all p ≥ 0.5 ) . CONCLUSIONS The current study suggests that timely administration of eSRT is comparable to aRT in improving BCR-free survival in the majority of pT3pN0 PCa patients .  Therefore , eSRT may not compromise cancer control but significantly reduces overtreatment associated with aRT 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 . ) BACKGROUND Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer . To assess the effect of radiotherapy , we did an open phase III study comparing endocrine therapy with and without local radiotherapy , followed by castration on progression . METHODS This r and omised trial included men from 47 centres in Norway , Sweden , and Denmark . Between February , 1996 , and December , 2002 , 875 patients with locally advanced prostate cancer ( T3 ; 78 % ; PSA<70 ; N0 ; M0 ) were central ly r and omly assigned by computer to endocrine treatment alone ( 3 months of total and rogen blockade followed by continuous endocrine treatment using flutamide ; 439 patients ) , or to the same endocrine treatment combined with radiotherapy ( 436 patients ) . The primary endpoint was prostate-cancer-specific survival , and analysis was by intention to treat . This study is registered as an international st and ard r and omised controlled trial , number IS RCT N01534787 . FINDINGS After a median follow-up of 7.6 years , 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer . The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9 % in the endocrine alone group and 11.9 % in the endocrine plus radiotherapy group ( difference 12.0 % , 95 % CI 4.9 - 19.1 % ) , for a relative risk of 0.44 ( 0.30 - 0.66 ) . At 10 years , the cumulative incidence for overall mortality was 39.4 % in the endocrine alone group and 29.6 % in the endocrine plus radiotherapy group ( difference 9.8 % , 0.8 - 18.8 % ) , for a relative risk of 0.68 ( 0.52 - 0.89 ) . Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group ( 74.7%vs 25.9 % , p<0.0001 ; HR 0.16 ; 0.12 - 0.20 ) . After 5 years , urinary , rectal , and sexual problems were slightly more frequent in the endocrine plus radiotherapy group . INTERPRETATION In patients with locally advanced or high-risk local prostate cancer , addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality , and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone . In the light of these data , endocrine treatment plus radiotherapy should be the new st and ard Prostate biopsy is usually performed without anesthesia . We evaluated the patient ’s perception of pain/discomfort experienced during the procedure in terms of the type of anesthesia used : periprostatic infiltration with 2 % lidocaine , or intrarectal instillation of lidocaine-prilocain cream . A total of 198 patients were divided into three groups : group 1 ( control group , n=40 ) received sonographic gel intrarectally prior to biopsy , group 2 ( n=75 ) were given intrarectal instillation of lidocaine-prilocain cream , and group 3 ( n=80 ) received periprostatic anesthesia by injecting 10 ml of 2 % lidocaine .  Pain after each biopsy was assessed using an 11-point linear visual analog pain scale . The mean pain scores were 5.1 in group 1 , 4.8 in group 2 , and 2.5 in group 3 , result ing in a significant difference between group 3 and both groups 1 and 2 , but not between groups 1 and 2 . The incidence of biopsy-related adverse events did not differ among groups . Transrectal ultrasonographic guided periprostatic anesthesia is superior to intarectal instillation of lidocaine-prilocain cream BACKGROUND Composite endpoints can be problematic in the presence of competing risks when a treatment does not affect events comprising the endpoint equally . METHODS We conducted secondary analysis of SWOG 8794 trial of adjuvant radiation therapy ( RT ) for high-risk post-operative prostate cancer . The primary outcome was metastasis-free survival ( MFS ) , defined as time to first occurrence of metastasis or death from any cause ( competing mortality ( CM ) ) . We developed separate risk scores for time to metastasis and CM using competing risks regression . We estimated treatment effects using Cox models adjusted for risk scores and identified an enriched subgroup of 75 patients at high risk of metastasis and low risk of CM . RESULTS The mean CM risk score was significantly lower in the RT arm vs. control arm ( p=0.001 ) . The effect of RT on MFS ( HR 0.70 ; 95 % CI , 0.53 - 0.92 ; p=0.010 ) was attenuated when controlling for metastasis and CM risk ( HR 0.76 ; 95 % CI , 0.58 - 1.00 ; p=0.049 ) , and the effect of RT on overall survival ( HR 0.73 ; 95 % CI , 0.55 - 0.96 ; p=0.02 ) was no longer significant when controlling for metastasis and CM risk ( HR 0.80 ; 95 % CI , 0.60 - 1.06 ; p=0.12 ) . Compared to the whole sample , the enriched subgroup had the same 10-year incidence of MFS ( 40 % ; 95 % CI , 22 - 57 % ) , but a higher incidence of metastasis ( 30 % ( 95 % CI , 15 - 47 % ) vs. 20 % ( 95 % CI , 15 - 26 % ) ) . A r and omized trial in the subgroup would have achieved 80 % power with 56 % less patients ( 313 vs. 709 , respectively ) . CONCLUSION Stratification on competing event risk may improve the efficiency of clinical trials BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . Summary Background Whether the addition of radiation therapy ( RT ) improves overall survival in men with locally advanced prostate cancer managed with and rogen deprivation therapy ( ADT )  is unclear . Our aim was to compare outcomes in such patients with locally advanced prostate cancer . Methods Patients with : locally advanced ( T3 or T4 ) prostate cancer ( n=1057 ) ; or organ-confined disease ( T2 ) with either a prostate-specific antigen ( PSA ) concentration more than 40 ng/mL ( n=119 ) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher ( n=25 ) , were r and omly assigned ( done central ly with stratification and dynamic minimisation , not masked ) to receive lifelong ADT and RT ( 65–69 Gy to the prostate and seminal vesicles , 45 Gy to the pelvic nodes ) . The primary endpoint was overall survival . The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded . All efficacy analyses were done by intention to treat and were based on data from all patients . This trial is registered at controlledtrials.com as IS RCT N24991896 and Clinical trials.gov as NCT00002633 . Results Between 1995 and 2005 , 1205 patients were r and omly assigned ( 602 in the ADT only group and 603 in the ADT and RT group ) ; median follow-up was 6·0 years ( IQR 4·4–8·0 ) . At the time of analysis , a total of 320 patients had died , 175 in the ADT only group and 145 in the ADT and RT group . The addition of RT to ADT  improved overall survival at 7 years ( 74 % , 95 % CI 70–78 vs 66 % , 60–70 ; hazard ratio [ HR ] 0·77 , 95 % CI 0·61–0·98 , p=0·033 ) . Both toxicity and health-related quality -of-life results showed a small effect of RT on late gastrointestinal toxicity ( rectal bleeding grade > 3 , three patients ( 0·5 % ) in the ADT only group , two ( 0·3 % ) in the ADT and RT group ; diarrhoea grade > 3 , four patients ( 0·7 % ) vs eight ( 1·3 % ) ; urinary toxicity grade > 3 , 14 patients ( 2·3 % ) in both groups ) . Interpretation The benefits of combined modality treatment — ADT and RT — should be discussed with all patients with locally advanced prostate cancer . Funding Canadian Cancer Society Research Institute , US National Cancer Institute , and UK Medical Research Council 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 A recent r and omized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival . We report on the quality of life ( QOL ) outcomes for this trial PURPOSE Radiation Therapy Oncology Group ( RTOG ) Protocol 92 - 02 was a r and omized trial testing long-term ( LT ) adjuvant and rogen deprivation ( AD ) after initial AD with external-beam radiotherapy ( RT ) in patients with locally advanced prostate cancer ( PC ; T2c-4 ) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS Patients received a total of 4 months of goserelin and flutamide , 2 months before and 2 months during RT . A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes . Patients were r and omly assigned to receive no additional therapy ( short-term [ST]AD-RT ) or 24 months of goserelin ( LTAD-RT ) ; 1,554 patients were entered onto the study . RESULTS The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival ( OS ; 80.0 % v 78.5 % at 5 years , P = .73 ) , compared with the STAD-RT arm . In a subset of patients not part of the original study design , with tumors assigned Gleason scores of 8 to 10 by the contributing institutions , the LTAD-RT arm had significantly better OS ( 81.0 % v 70.7 % , P = .044 ) . There was a small but significant increase in the frequency of late radiation grade s 3 , 4 , and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm ( 2.6 % v 1.2 % at 5 years , P = .037 ) , the cause of which is not clear . CONCLUSION The RTOG 92 - 02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC . In the exploratory subset analysis of patients with Gleason scores 8 to 10 , LT adjuvant AD result ed in a survival advantage 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 PURPOSE More than 1 million prostate biopsies are performed annually among Medicare beneficiaries . We determined the risk of serious complications requiring hospitalization . We hypothesized that with emerging multidrug resistant organisms there may be an increasing risk of infectious complications . MATERIAL S AND METHODS In a 5 % r and om sample of Medicare participants in SEER ( Surveillance , Epidemiology and End Results ) regions from 1991 to 2007 we compared 30-day hospitalization rates and ICD-9 primary diagnosis codes for admissions between 17,472 men who underwent prostate biopsy and a r and om sample of 134,977 controls . Multivariate logistic and Poisson regression were used to examine the risk and predictors of serious infectious and noninfectious complications with time . RESULTS The 30-day hospitalization rate was 6.9 % within 30 days of prostate biopsy , which was substantially higher than the 2.7 % in the control population . After adjusting for age , race , SEER region , year and comorbidities prostate biopsy was associated with a 2.65-fold ( 95 % CI 2.47 - 2.84 ) increased risk of hospitalization within 30 days compared to the control population ( p < 0.0001 ) . The risk of infectious complications requiring hospitalization after biopsy was significantly greater in more recent years ( p(trend ) = 0.001 ) . Among men undergoing biopsy , later year , nonwhite race and higher comorbidity scores were significantly associated with an increased risk of infectious complications . CONCLUSIONS The risk of hospitalization within 30 days of prostate biopsy was significantly higher than in a control population . Infectious complications after prostate biopsy have increased in recent years while the rate of serious noninfectious complications is relatively stable . Careful patient selection for prostate biopsy is essential to minimize the potential harms 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 To retrospectively determine whether endorectal magnetic resonance ( MR ) imaging findings contribute incremental value to the Kattan nomogram for predicting seminal vesicle invasion ( SVI ) in patients with prostate cancer . MATERIAL S AND METHODS The institutional review board issued a waiver of authorization , which included a waiver of informed consent , for this HIPAA-compliant study . From October 2000 through January 2005 , 573 patients ( mean age , 58.3 years ; age range , 36 - 86 years ) underwent endorectal MR imaging before prostate cancer surgery .  The endorectal MR imaging results had been prospect ively interpreted by seven radiologists , and the likelihood of SVI was retrospectively scored on the basis of radiologists ' written reports . MR imaging findings , individual clinical variables ( serum prostate-specific antigen [ PSA ] level , Gleason grade , clinical stage , greatest percentage of cancer in all biopsy cores , percentage of positive cores in all biopsy cores , and perineural invasion ) , and the Kattan nomogram were evaluated with respect to SVI prediction ; surgical pathologic analysis was used as the reference st and ard . Logistic regression and receiver operating characteristic ( ROC ) curve analyses were performed . RESULTS At pathologic analysis , 28 ( 4.9 % ) of 573 patients had SVI . At univariate analysis , endorectal MR imaging results and all clinical variables except the percentage of positive biopsy cores were significantly associated with SVI ( P<.02 ) ; endorectal MR imaging ( 0.76 ) had a larger area under the ROC curve ( AUC ) than any clinical variable ( 0.62 - 0.73 ) . At multivariate analysis , endorectal MR imaging results , Gleason grade , PSA level , and the percentage of cancer in all biopsy cores were significantly associated with SVI ( P < or=.02 ) . The Kattan nomogram plus endorectal MR imaging ( 0.87 ) had a significantly larger ( P<.05 ) AUC than either endorectal MR imaging alone ( 0.76 ) or the Kattan nomogram alone ( 0.80 ) . CONCLUSION The addition of endorectal MR imaging contributes significant incremental value to the Kattan nomogram for predicting SVI PURPOSE To assess the benefit and toxicity and quality -of-life ( QOL ) outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients . PATIENTS AND METHODS Between December 1998 and June 2004 , 444 patients with T1b-T3 , N0 pNx , M0 prostate carcinoma were r and omly assigned to either pelvic and prostate radiotherapy or prostate radiotherapy only .  Patients were stratified according to the prognostic factor of lymph node involvement ( LNI ) . Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for patients in the high-risk group . The pelvic dose was 46 Gy . The total dose recommended to the prostate was changed during the course of the study from 66 Gy to 70 Gy . Criteria for progression-free survival ( PFS ) included biologic prostate-specific antigen recurrences or a local or metastatic evolution . Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group and Late Effects in Normal Tissues Subjective , Objective , Management , and Analytic scales , respectively . The QOL outcome was recorded with the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 , the International Prostatic Symptom Score , and the Sexual Function Index scales . RESULTS With a 42.1-month median follow-up time , the 5-year PFS and overall survival were similar in the two treatment arms for the whole series and for each stratified group . On multivariate analysis , low LNI risk and hormonal therapy were statistically associated with increased PFS . However , subgroup analyses based on these factors did not show any benefit for pelvic irradiation . There were no significant differences in acute and late digestive toxicities and in QOL outcomes . CONCLUSION Pelvic node irradiation was well tolerated but did not improve PFS 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 OBJECTIVES Controversy exists about the preferred treatment of patients with high-risk or locally advanced prostate cancer . We examined the intermediate-term cancer control and quality -of-life outcomes after  radical retropubic prostatectomy ( RRP ) in selected patients . METHODS From 1984 to 2003 , 288 men with Stage cT2b ( Gleason score 8 to 10 or a prostate-specific antigen level greater than 15 ng/mL ) or T3 disease underwent RRP by a single surgeon . The 7 and 10-year actuarial progression-free survival ( PFS ) , cancer-specific survival ( CSS ) , overall survival ( OS ) , potency , and continence rates were recorded . RESULTS The actuarial 7-year PFS , CSS , and OS rate after surgery was 39 % , 92 % , and 91 % , respectively . The corresponding actuarial 10-year rates were 35 % , 88 % , and 74 % . Only OS differed significantly by age group . On multivariate analysis , the pathologic stage was a significant independent predictor of progression . Ultimately , 31 men ( 11 % ) required hormonal therapy , 58 ( 20 % ) underwent postoperative radiotherapy , and 67 ( 23 % ) received both . Potency and continence were preserved in 64 % and 92 % , respectively . CONCLUSIONS Overall , RRP offers excellent intermediate-term cancer control for selected men of all ages who present with high-risk or locally advanced disease . The PFS was significantly greater for men with high-risk Stage cT2b than for those with cT3 disease , but the CSS and OS were similar . Both continence and potency were preserved in most patients , although the potency rates were significantly greater for the younger men . RRP with appropriate postoperative radiotherapy and /or hormonal therapy is a reasonable treatment option for selected men with high-risk or locally advanced disease PURPOSE Local failure after radical prostatectomy ( RP ) is common in patients with cancer extending beyond the capsule . Two r and omized trials demonstrated an advantage for adjuvant radiotherapy ( RT ) compared with a wait- and -see policy . We conducted a r and omized , controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen ( PSA ) level after RP . METHODS After RP , 192 men were r and omly assigned to a wait- and -see policy , and 193 men were assigned to immediate postoperative RT . Eligible patients had pT3 pN0 tumors . Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to r and om assignment ( n = 78 ; 20 % ) . Of the remaining 307 patients , 34 patients on the RT arm did not receive RT and five patients on the wait- and -see arm received RT . Therefore , 114 patients underwent RT and 154 patients were treated with a wait- and -see policy . The primary end point was biochemical progression-free survival . RESULTS Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group ( 72 % ; 95 % CI , 65 % to 81 % ; v 54 % , 95 % CI , 45 % to 63 % ; hazard ratio = 0.53 ; 95 % CI , 0.37 to 0.79 ; P = .0015 ) . On univariate analysis , Gleason score more than 6 and less than 7 , PSA before RP , tumor stage , and positive surgical margins were predictors of outcome . The rate of grade 3 to 4 late adverse effects was 0.3 % . CONCLUSION Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression . Further follow-up is needed to assess the effect on metastases-free and overall survival BACKGROUND Radiotherapy combined with and rogen-deprivation therapy ( ADT ) is superior to radiotherapy alone in localised prostate cancer ; however , data comparing ADT alone are somewhat limited . OBJECTIVE To compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients . DESIGN , SETTING , AND PARTICIPANTS A multicentre r and omised open controlled phase 3 trial in 264 histologically confirmed T3 - 4 or pT3N0M0 prostate cancer patients r and omised from March 2000 to December 2003 . INTERVENTION ADT ( 11.25 mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr ) plus external-beam radiotherapy or ADT alone . Flutamide ( 750 g/d ) was administered for 1 mo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary objective was 5 yr progression-free survival ( PFS ) according to clinical or biologic criteria , using the American Society for Therapeutic Radiology and Oncology ( ASTRO ) and the newer ( Phoenix ) definition ( nadir plus 2 ng/ml ) , by intention to treat . Secondary objectives included time to locoregional recurrence and distant metastases , and overall and disease-specific survival . Our Analyses : intent-to-treat analysis , multivariate analyses using a Cox model with a 5 % threshold from univariate analysis , and Kaplan-Meier estimates . RESULTS AND LIMITATIONS  ADT alone was administered to 130 patients and combined therapy to 133 . With a median follow-up of 67 mo , 5-yr PFS was 60.9 % for combined therapy versus 8.5 % with ADT alone ( ASTRO ; p<0.0001 ) , and 64.7 % versus 15.4 % , respectively , for Phoenix ( p<0.0011 ) . Locoregional progression was reported in 9.8 % of combined-therapy patients versus 29.2 % with ADT alone ( p<0.0001 ) and metastatic progression in 3.0 % versus 10.8 % , respectively ( p<0.018 ) . Overall survival was 71.4 % with combined therapy versus 71.5 % with ADT alone ; disease-specific survival was 93.2 % versus 86.2 % . Limitations included the relatively small population and a relatively short follow-up period . CONCLUSIONS Combined therapy strongly favoured improved PFS , locoregional control , and metastasis-free survival . Longer follow-up is needed to assess the potential survival impact PURPOSE Untreated stage pTxN+ prostate cancer is associated with a poor outcome . Monotherapy ( surgery , radiation , hormonal therapy ) alone is associated with a high progression rate . We evaluate whether radical prostatectomy and pelvic lymphadenectomy plus early adjuvant orchiectomy impart a survival advantage compared to pelvic lymphadenectomy and orchiectomy alone in a matched cohort of patients . MATERIAL S AND METHODS Between 1966 and 1995 , 382 and 79 patients with stage pTxN+ prostate cancer underwent pelvic lymphadenectomy and radical prostatectomy plus early adjuvant orchiectomy ( within 3 months of prostatectomy ) , and pelvic lymphadenectomy and orchiectomy only  , respectively . We selected 79 matched controls from the prostatectomy plus orchiectomy group for the orchiectomy group . Patients were matched according to the number of positive nodes , clinical grade , clinical stage , age , year of surgery and preoperative prostate specific antigen ( after 1987 ) . The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate overall and cause specific survival for the 2 groups . RESULTS There was an overall survival advantage at 10 years for the prostatectomy plus orchiectomy ( 66+/-6 % ) compared to the orchiectomy ( 28+/-6 % ) group ( p < 0.001 , risk ratio 0.36 , 95 % confidence interval 0.20 to 0.66 ) . There was also an advantage in cause specific survival at 10 years in the prostatectomy plus orchiectomy ( 79+/-5 % ) versus the orchiectomy ( 39+/-7 % ) group ( p < 0.001 , relative risk 0.28 , 95 % confidence interval 0.13 to 0.59 ) . After 1987 , when matched on preoperative prostate specific antigen , the apparent survival advantage at 5 years with radical prostatectomy was smaller ( 79+/-8 versus 63+/-9 % orchiectomy ) and not significant ( p = 0.19 ) . CONCLUSIONS This retrospective study of patients with stage pTxN+ PC suggests that radical prostatectomy with early adjuvant orchiectomy may provide a significant advantage in overall and cause specific survival compared to orchiectomy alone PURPOSE Controversy exists as to whether current pretreatment prostate-specific antigen ( PSA ) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer . We assessed whether pretreatment PSA velocity ( PSAV ) or doubling time ( PSADT ) predicted outcome in men undergoing radical prostatectomy  and whether any definition enhanced accuracy of an outcome prediction model . PATIENTS AND METHODS The cohort included 2,938 patients with two or more PSA values before radical prostatectomy .  Biochemical recurrence ( BCR ) occurred in 384 patients , and metastases occurred in 63 patients . Median follow-up for patients without BCR was 2.1 years . We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis . Predictive accuracy was assessed using the concordance index . RESULTS On univariate analysis , two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis ( P < .05 ) . One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone , and four PSAV definitions improved prediction of metastasis . However , the improvements in predictive accuracy were small , associated with wide CIs , and markedly reduced if additional predictors of stage and grade were included alongside PSA . Modeling with r and om variables suggests that similar results would be expected by chance . CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone Objectives To determine the effect of antibiotic prophylaxis on infective complications after transrectal needle biopsy of the prostate Localized prostate cancer can be treated several different ways , but head‐to‐head comparisons of treatments are infrequent . The authors of this report conducted a r and omized , unblinded , noninferiority trial to compare cryoablation with external beam radiotherapy in these patients 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 Assessment of and rogen deprivation therapy ( ADT ) benefits for prostate cancer treated with dose-escalated radiotherapy ( RT ) . METHODS AND MATERIAL S From 1991 to 2004 , 1,044 patients with intermediate- ( n = 782 ) or high-risk ( n = 262 ) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital . Patients received external-beam RT ( EBRT ) alone , brachytherapy ( high or low dose rate ) , or high dose rate brachytherapy plus pelvic EBRT .  Intermediate-risk patients had Gleason score 7 , prostate-specific antigen ( PSA ) 10.0 - 19.9 ng/mL , or Stage T2b-T2c . High-risk patients had Gleason score 8 - 10 , PSA ≥20 , or Stage T3 . Patients were additionally divided specifically by Gleason score , presence of palpable disease , and PSA level to further define subgroups benefitting from ADT . RESULTS Median follow-up was 5 years ; 420 patients received ADT + dose-escalated RT , and 624 received dose-escalated RT alone . For all patients , no advantages in any clinical endpoints at 8 years were associated with ADT administration . No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately . Patients with palpable disease plus Gleason ≥8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT . Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given . CONCLUSION Benefits of ADT in the setting of dose-escalated RT remain poorly defined . This question must continue to be addressed in prospect i ve study PURPOSE To determine the impact of adjuvant and rogen deprivation therapy ( ADT ) for patients who have node-positive prostate cancer in the prostate-specific antigen ( PSA ) era . PATIENTS AND METHODS We used linked Surveillance , Epidemiology and End Results -Medicare data to construct a cohort of men who underwent radical prostatectomy ( RP ) between 1991 and 1999 and who had positive regional lymph nodes . We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP , and we compared them to the men who had not received adjuvant ADT . We used propensity scores to balance potential confounders of receiving adjuvant ADT ( ie , tumor characteristics , extent of nodal disease , demographics , receipt of radiation therapy ) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival ( OS ) , stratified by propensity score quintile . We conducted a sensitivity analysis that used 90 , 150 , 180 , and 365 days as the definition for adjuvant ADT . RESULTS A total of 731 men were identified , 209 of whom received ADT within 120 days of RP . There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group ( HR , 0.97 ; 95 % CI , 0.71 to 1.27 ) . There was no statistically significant survival difference with 90 , 150 , 180 , and 365 days as the adjuvant ADT definition . CONCLUSION Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival . Because observational studies should be considered hypothesis-generating studies , these results should be vali date d in a prospect i ve fashion in a similar patient population From 1978 to 1983 the Radiation Therapy Oncology Group conducted a study to evaluate the role of elective pelvic lymph node irradiation in carcinoma of the prostate . Eligible patients were those with clinical Stage A2 ( occult disease with more than 3 positive chips and poorly differentiated tumor ) and Stage B without clinical ( lymphangiogram ) or biopsy evidence of lymph node involvement . The patients were r and omized to receive 6.5 weeks of either prostatic bed irradiation only 6500 cGy at 180 - 200 cGy per treatment or pelvic node irradiation to 4500 cGy with a boost of 2000 cGy to the prostatic bed bringing the total dose to 6500 cGy . As of February , 1988 , the median follow up has been 7 years and there were 445 analyzable cases who were evaluated for local control , incidence of distant metastases , ned ( no evidence of disease ) survival and survival . The results of the study revealed no statistically significant benefit of elective pelvic irradiation 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 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 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 initial report of the Selenium and Vitamin E Cancer Prevention Trial ( SELECT ) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer . OBJECTIVE To determine the long-term effect of vitamin E and selenium on risk of prostate cancer  in relatively healthy men . DESIGN , SETTING , AND PARTICIPANTS A total of 35,533 men from 427 study sites in the United States , Canada , and Puerto Rico were r and omized between August 22 , 2001 , and June 24 , 2004 . Eligibility criteria included a prostate-specific antigen ( PSA ) of 4.0 ng/mL or less , a digital rectal examination not suspicious for prostate cancer , and age 50 years or older for black men and 55 years or older for all others . The primary analysis included 34,887 men who were r and omly assigned to 1 of 4 treatment groups : 8752 to receive selenium ; 8737 , vitamin E ; 8702 , both agents , and 8696 , placebo . Analysis reflect the final data collected by the study sites on their participants through July 5 , 2011 . INTERVENTIONS Oral selenium ( 200 μg/d from L-selenomethionine ) with matched vitamin E placebo , vitamin E ( 400 IU/d of all rac-α-tocopheryl acetate ) with matched selenium placebo , both agents , or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years . MAIN OUTCOME MEASURES Prostate cancer incidence . RESULTS This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report . Compared with the placebo ( referent group ) in which 529 men developed prostate cancer , 620 men in the vitamin E group developed prostate cancer ( hazard ratio [ HR ] , 1.17 ; 99 % CI , 1.004 - 1.36 , P = .008 ) ; as did 575 in the selenium group ( HR , 1.09 ; 99 % CI , 0.93 - 1.27 ; P = .18 ) , and 555 in the selenium plus vitamin E group ( HR , 1.05 ; 99 % CI , 0.89 - 1.22 , P = .46 ) . Compared with placebo , the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E , 0.8 for selenium , and 0.4 for the combination . CONCLUSION Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00006392 BACKGROUND The combination of radiotherapy plus long-term medical suppression of and rogens ( > or = 2 years ) improves overall survival in patients with locally advanced prostate cancer . We compared the use of radiotherapy plus short-term and rogen suppression with the use of radiotherapy plus long-term and rogen suppression in the treatment of locally advanced prostate cancer . METHODS We r and omly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of and rogen suppression  to two groups , one to receive no further treatment ( short-term suppression ) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist ( long-term suppression ) . An outcome of noninferiority of short-term and rogen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival , with a one-sided alpha level of 0.05 . An interim analysis showed futility , and the results are presented with an adjusted one-sided alpha level of 0.0429 . RESULTS A total of 1113 men were registered , of whom 970 were r and omly assigned , 483 to short-term suppression and 487 to long-term suppression . After a median follow-up of 6.4 years , 132 patients in the short-term group and 98 in the long-term group had died ; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group . The 5-year overall mortality for short-term and long-term suppression was 19.0 % and 15.2 % , respectively ; the observed hazard ratio was 1.42 ( upper 95.71 % confidence limit , 1.79 ; P=0.65 for noninferiority ) . Adverse events in both groups included fatigue , diminished sexual function , and hot flushes . CONCLUSIONS The combination of radiotherapy plus 6 months of and rogen suppression provides inferior survival as compared with radiotherapy plus 3 years of and rogen suppression in the treatment of locally advanced prostate cancer . ( Clinical Trials.gov number , NCT00003026 . CONTEXT Comorbidities may increase the negative effects of specific anticancer treatments such as and rogen suppression therapy ( AST ) . OBJECTIVES To compare 6 months of AST and radiation therapy ( RT ) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality . DESIGN , SETTING , AND PATIENTS At academic and community-based medical centers in Massachusetts , between December 1 , 1995 , and April 15 , 2001 , 206 men with localized but unfavorable-risk prostate cancer were r and omized to receive RT alone or RT and AST combined .  All-cause mortality estimates stratified by r and omized treatment group and further stratified in a postr and omization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test . MAIN OUTCOME MEASURE Time to all-cause mortality . RESULTS As of January 15 , 2007 , with a median follow-up of 7.6 ( range , 0.5 - 11.0 ) years , 74 deaths have occurred . A significant increase in the risk of all-cause mortality ( 44 vs 30 deaths ; hazard ratio [ HR ] , 1.8 ; 95 % confidence interval [ CI ] , 1.1 - 2.9 ; P = .01 ) was observed in men r and omized to RT compared with RT and AST . However , the increased risk in all-cause mortality appeared to apply only to men r and omized to RT with no or minimal comorbidity ( 31 vs 11 deaths ; HR , 4.2 ; 95 % CI , 2.1 - 8.5 ; P < .001 ) . Among men with moderate or severe comorbidity , those r and omized to RT alone vs RT and AST did not have an increased risk of all-cause mortality ( 13 vs 19 deaths ; HR , 0.54 ; 95 % CI , 0.27 - 1.10 ; P = .08 ) . CONCLUSIONS The addition of 6 months of AST to RT result ed in increased overall survival in men with localized but unfavorable-risk prostate cancer . This result may pertain only to men without moderate or severe comorbidity , but this requires further assessment in a clinical trial specifically design ed to assess this interaction . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116220 BACKGROUND Previous prospect i ve r and omised trials have shown a positive impact of adjuvant radiation therapy ( RT ) in patients with locally advanced prostate cancer . However , none of these trials included patients with lymph node invasion ( LNI ) . OBJECTIVE The aim of this study was to assess the impact of combination adjuvant hormonal therapy ( HT ) and RT on the survival of patients with prostate cancer and histologically documented lymph node metastases ( pN+ ) . DESIGN , SETTING , AND PARTICIPANTS Data on 703 consecutive patients with LNI treated with radical prostatectomy , pelvic lymph node dissection , and adjuvant treatments between September 1986 and November 2002 at two large academic institutions were review ed . MEASUREMENTS For study purpose s , patients treated with adjuvant HT plus RT and patients treated with adjuvant HT alone were matched for age at surgery , pathologic T stage and Gleason score , number of nodes removed , surgical margin status , and length of follow-up . Differences in cancer-specific survival ( CSS ) and overall survival ( OS ) were compared using the Kaplan-Meier method and life table analyses . RESULTS AND LIMITATIONS Following the matching process , 117 pT2 - 4 pN1 patients of 171 ( 68.4 % ) treated with adjuvant HT plus RT ( group 1 ) were compared with 247 pT2 - 4 pN1 patients of 532 ( 46.4 % ) receiving adjuvant HT alone ( group 2 ) . After matching , the two groups of patients were comparable in terms of pre- and postoperative characteristics ( all p ≥ 0.07 ) . Mean follow-up was 100.8 mo ( median : 95.1 mo ; range : 3.5 - 229.3 mo ) . Overall , prostate CSS and OS rates at 5 , 8 , and 10 yr were 90 % , 82 % , and 75 % , and 85 % , 70 % , and 60 % , respectively . Patients treated with adjuvant RT plus HT had significantly higher CSS and OS rates compared with patients treated with HT alone at 5 , 8 , and 10 yr after surgery ( 95 % , 91 % , and 86 % vs 88 % , 78 % , and 70 % , and 90 % , 84 % , and 74 % vs 82 % , 65 % , and 55 % , respectively ; p = 0.004 and p<0.001 , respectively ) . Similarly , higher survival rates associated with the combination of HT plus RT were found when patients were stratified according to the extent of nodal invasion ( namely , two or fewer vs more than two positive nodes ; all p ≤ 0.006 ) . Lack of st and ardised HT and RT protocol s represents the main limitations of our retrospective study . CONCLUSIONS Adjuvant RT plus HT significantly improved CSS and OS of pT2 - 4 pN1 patients , regardless of the extent of nodal invasion . These results reinforce the need for a multimodal approach in the treatment of node-positive prostate cancer
target: 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 .
  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 .
  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 .
background: 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 .
  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 .
  CONCLUSIONS Knowledge in the field of PCa is rapidly changing .