title: Intergroup randomized phase III study of androgen deprivation therapy (ADT) plus radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633). 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. Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Screening and prostate-cancer mortality in a randomized European study. Patient-reported long-term outcomes after conventional and high-dose combined proton and photon radiation for early prostate cancer. Pain during transrectal ultrasonography guided prostate biopsy: a randomized prospective trial comparing periprostatic infiltration with lidocaine with the intrarectal instillation of lidocaine-prilocain cream Mortality results from a randomized prostate-cancer screening trial. Optimal approach for prostate cancer detection as initial biopsy: prospective randomized study comparing transperineal versus transrectal systematic 12-core biopsy. 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. Antibiotic prophylaxis for transrectal needle biopsy of the prostate: a randomized controlled study Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 M0 prostate cancer not suitable for local curative treatment (EORTC 30891). Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Role of androgen deprivation therapy for node-positive prostate cancer. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. Prostate cancer mortality in screen and clinically detected prostate cancer: estimating the screening benefit.
abstract: CRA4504 Background : The impact of radiotherapy on overall survival ( OS ) in men with locally advanced CaP is unclear . The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality . Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. METHODS Patients with T3/T4 ( 1057 ) or T2 , PSA > 40 μ g/l ( 119 ) or T2 PSA > 20 μ g/l and Gleason ≥ 8 ( 25 ) and N0 /NX , M0 prostate adenocarcinoma were r and omized to  lifelong ADT ( bilateral orchiectomy or LHRH agonist ) with or without RT ( 65 - 69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes ) . The primary endpoint was OS and secondary endpoints included disease specific survival ( DSS ) , time to disease progression and quality of life . RESULTS 1205 patients were r and omized from 1995 to 2005 , 602 to ADT and 603 to ADT+RT  ( well balanced with respect to baseline characteristics ) . A protocol specified second interim analysis on OS was performed in Aug 2009 ( data cut-off Dec 31 2008 ) . The DSMC recommended release of the results to the Trial Committee for publication . The median follow-up is 6.0 years and 320 patients have died ( 175 ADT and 145 ADT+RT ) . 10 % of patients had no follow-up data beyond 2006 . The addition of RT to ADT  significantly reduced the risk of death ( hazard ratio [ HR ] 0.77 , 95 % CI 0.61 - 0.98 , p=0.033 ) . 140 patients died of disease and /or treatment ( 89 on ADT and 51 on ADT+RT ) The disease specific survival HR was 0.57 ( 95 % CI 0.41 - 0.81 , p=0.001 ) favoring ADT+RT  . The 10 year cumulative disease specific death rates were estimated at 15 % with ADT+ RT and 23 % with ADT  alone . Grade ≥2 late GI toxicity rates were similar in both arms ( proctitis , 1.3 % ADT alone , 1.8 % ADT+RT ) . CONCLUSIONS The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach ( ADT+RT ) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity . In view of this data combined modality therapy ( ADT+RT ) should be the st and ard treatment approach for these patients . Supported by NCI-US Grant # 5U10CA077202 - 12 , CCSRI Grant # 15469 . No significant financial relationships to disclose 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 PURPOSE To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy ( IMRT ) to a dose of 86.4 Gy for localized prostate cancer . METHODS AND MATERIAL S Between August 1997 and March 2004 , 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique . To adhere to normal tissue constraints , the mean D95 and V100 for the planning target volume were 83 Gy and 87 % , respectively . Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0 . Freedom from biochemical relapse was calculated . The median follow-up was 53 months . RESULTS Thirty-seven patients ( 8 % ) experienced acute Grade 2 gastrointestinal ( GI ) toxicity . There was no acute Grade 3 or 4 GI toxicity . One hundred and five patients ( 22 % ) experienced acute Grade 2 genitourinary ( GU ) toxicity and three patients ( 0.6 % ) had Grade 3 GU toxicity . There was no acute Grade 4 GU toxicity . Sixteen patients ( 3 % ) developed late Grade 2 GI toxicity and two patients ( < 1 % ) developed late Grade 3 GI toxicity . Sixty patients ( 13 % ) had late Grade 2 GU toxicity and 12 ( <3 % ) experienced late Grade 3 GU toxicity . The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98 % , 85 % and 70 % for the low , intermediate , and high risk NCCN prognostic groups . CONCLUSION This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer . Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging BACKGROUND The European R and omized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen ( PSA ) testing on death rates from prostate cancer . METHODS We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study . The men were r and omly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening . The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years . The primary outcome was the rate of death from prostate cancer . Mortality follow-up was identical for the two study groups and ended on December 31 , 2006 . RESULTS In the screening group , 82 % of men accepted at least one offer of screening . During a median follow-up of 9 years , the cumulative incidence of prostate cancer was 8.2 % in the screening group and 4.8 % in the control group . The rate ratio for death from prostate cancer in the screening group , as compared with the control group , was 0.80 ( 95 % confidence interval [ CI ] , 0.65 to 0.98 ; adjusted P=0.04 ) . The absolute risk difference was 0.71 death per 1000 men . This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer . The analysis of men who were actually screened during the first round ( excluding subjects with noncompliance ) provided a rate ratio for death from prostate cancer of 0.73 ( 95 % CI , 0.56 to 0.90 ) . CONCLUSIONS PSA-based screening reduced the rate of death from prostate cancer by 20 % but was associated with a high risk of overdiagnosis . ( Current Controlled Trials number , IS RCT N49127736 . CONTEXT Increased radiation doses improve prostate cancer control but also increase toxicity to adjacent normal tissue . Proton radiation may attenuate adverse effects . OBJECTIVE To determine long-term , patient-reported , dose-related toxicity . DESIGN , SETTING , AND PATIENTS We performed a post hoc cross-sectional survey of surviving participants in the Proton Radiation Oncology Group ( PROG ) 9509 - -a r and omized trial comparing 70.2 Gy vs 79.2 Gy of combined photon and proton radiation for 393 men with clinical ly localized prostate cancer ( stage T1b-T2b , prostate-specific antigen < 15 ng/mL , and no radiographic evidence of metastasis ) . The estimated 10-year biochemical progression rate for patients receiving st and ard dose was 32 % ( 95 % confidence interval , 26%-39 % ) compared with 17 % ( 95 % confidence interval , 11%-23 % ) for patients receiving high dose ( P < .001 ) . We surveyed 280 of the surviving 337 patients ( 83 % ) from April 2007 to September 2008 . MAIN OUTCOME MEASURES Prostate Cancer Symptom Indices , a vali date d measure of urinary incontinence , urinary obstruction and irritation , bowel problems , and sexual dysfunction , and related quality -of-life instruments . RESULTS At a median of 9.4 years after treatment ( range , 7.4 - 12.1 years ) , participants ' demographic and clinical characteristics were similar . Patient-reported outcomes were reported as mean ( SD ) scale score for st and ard dose vs high dose : urinary obstruction/irritation ( 23.3 [ 13.7 ] vs 24.6 [ 14.0 ] ; P = .36 ) , urinary incontinence ( 10.6 [ 17.7 ] vs 9.7 [ 15.8 ] ; P = .99 ) , bowel problems ( 7.7 [ 7.8 ] vs 7.9 [ 9.1 ] ; P = .70 ) , sexual dysfunction ( 68.2 [ 34.6 ] vs 65.9 [ 34.7 ] ; P = .65 ) , and most other outcomes were also similar , although patients receiving st and ard dose whose cancers had more often progressed expressed less confidence that their cancers were under control ( mean [ SD ] scale score for st and ard dose , 76.0 [ 25.4 ] vs high dose , 86.2 [ 17.9 ] ; P < .001 ) . Many patients characterized their urinary and bowel function as normal despite reporting symptoms that , for other prostate cancer patients before and early after cancer treatment , caused substantial distress . CONCLUSION Among men with clinical ly localized prostate cancer , treatment with higher-dose radiation compared with st and ard dose was not associated with an increase in patient-reported prostate cancer symptoms after a median of 9.4 years 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 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 . 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 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 Objectives To determine the effect of antibiotic prophylaxis on infective complications after transrectal needle biopsy of the prostate PURPOSE To determine whether a dose of 78 Gy improves outcome compared with a conventional dose of 68 Gy for prostate cancer patients treated with three-dimensional conformal radiotherapy .  PATIENTS AND METHODS Between June 1997 and February 2003 , stage T1b-4 prostate cancer patients were enrolled onto a multicenter r and omized trial comparing 68 Gy with 78 Gy . Patients were stratified by institution , age , (neo)adjuvant hormonal therapy ( HT ) , and treatment group . Four treatment groups ( with specific radiation volumes ) were defined based on the probability of seminal vesicle involvement . The primary end point was freedom from failure ( FFF ) . Failure was defined as clinical failure or biochemical failure , according to the American Society of Therapeutic Radiation Oncology definition . Other end points were freedom from clinical failure ( FFCF ) , overall survival ( OS ) , and toxicity . RESULTS Median follow-up time was 51 months . Of the 669 enrolled patients , 664 were included in the analysis . HT was prescribed for 143 patients .  FFF was significantly better in the 78-Gy arm compared with the 68-Gy arm ( 5-year FFF rate , 64 % v 54 % , respectively ) , with an adjusted hazard ratio of 0.74 ( P = .02 ) . No significant differences in FFCF or OS were seen between the treatment arms . There was no difference in late genitourinary toxicity of Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer grade 2 or more and a slightly higher nonsignificant incidence of late gastrointestinal toxicity of grade 2 or more . CONCLUSION This multicenter r and omized trial shows a significantly improved FFF in prostate cancer patients treated with a higher dose of radiotherapy 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 OBJECTIVE EORTC trial 30891 compared immediate versus deferred and rogen-deprivation therapy ( ADT ) in T0 - 4 N0 - 2 M0 prostate cancer ( PCa ) . Many patients r and omly assigned to deferred ADT did not require ADT because they died before becoming symptomatic . The question arises whether serum prostate-specific antigen ( PSA ) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment . METHODS PSA data at baseline , PSA doubling time ( PSADT ) in  patients receiving no ADT  , and time to PSA relapse ( > 2 ng/ml ) in patients whose PSA declined to < 2 ng/ml within the first year after immediate ADT  were analyzed in 939 eligible patients r and omly assigned to immediate ( n=468 ) or deferred ADT ( n=471 ) . RESULTS In both arms , patients with a baseline PSA>50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA < or=8 ng/ml . If baseline PSA was between 8 and 50 ng/ml , the risk of PCa death was approximately 7.5-fold higher in patients with PSADT<12 mo than in patients with PSADT>12 mo . Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA , suggesting that baseline PSA may also reflect disease aggressiveness . CONCLUSIONS Patients with a baseline PSA>50 ng/ml and /or a PSADT<12 mo were at increased risk to die from PCa and might have benefited from immediate ADT , whereas patients with a baseline PSA<50 ng/ml and a slow PSADT ( > 12 mo ) were likely to die of causes unrelated to PCa , and thus could be spared the burden of immediate ADT PURPOSE This study ( EORTC 30891 ) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred and rogen ablation .  PATIENTS AND METHODS We r and omly assigned 985 patients with newly diagnosed prostate cancer T0 - 4 N0 - 2 M0 to receive and rogen deprivation either immediately ( n = 493 ) or on symptomatic disease progression or occurrence of serious complications ( n = 492 ) . RESULTS Baseline characteristics were well balanced in the two groups . Median age was 73 years ( range , 52 to 81 ) . At a median follow-up of 7.8 years , 541 of 985 patients had died , mostly of prostate cancer ( n = 193 ) or cardiovascular disease ( n = 185 ) . The overall survival hazard ratio was 1.25 ( 95 % CI , 1.05 to 1.48 ; noninferiority P > .1 ) favoring immediate treatment , seemingly due to fewer deaths of nonprostatic cancer causes ( P = .06 ) . The time from r and omization to progression of hormone refractory disease did not differ significantly , nor did prostate-cancer specific survival . The median time to the start of deferred treatment after study entry was 7 years . In this group 126 patients ( 25.6 % ) died without ever needing treatment ( 44 % of the deaths in this arm ) . CONCLUSION Immediate and rogen deprivation result ed in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival . This must be weighed on an individual basis against the adverse effects of life-long and rogen deprivation , which may be avoided in a substantial number of patients with a deferred treatment policy 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 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 BACKGROUND The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one r and omized trial . In 2005 , we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up . We now report results after 3 more years of follow-up . METHODS From October 1 , 1989 , through February 28 , 1999 , 695 men with clinical ly localized prostate cancer were r and omly assigned to radical prostatectomy ( n = 347 ) or watchful waiting ( n = 348 ) . Follow-up was complete through December 31 , 2006 , with histopathologic review and blinded evaluation of causes of death . Relative risks ( RRs ) were estimated using the Cox proportional hazards model . Statistical tests were two-sided . RESULTS During a median of 10.8 years of follow-up ( range = 3 weeks to 17.2 years ) , 137 men in the surgery group and 156 in the watchful waiting group died ( P = .09 ) . For 47 of the 347 men ( 13.5 % ) who were r and omly assigned to surgery and 68 of the 348 men ( 19.5 % ) who were not , death was due to prostate cancer . The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up . At 12 years , 12.5 % of the surgery group and 17.9 % of the watchful waiting group had died of prostate cancer ( difference = 5.4 % , 95 % confidence interval [ CI ] = 0.2 to 11.1 % ) , for a relative risk of 0.65 ( 95 % CI = 0.45 to 0.94 ; P = .03 ) . The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up . At 12 years , 19.3 % of men in the surgery group and 26 % of men in the watchful waiting group had been diagnosed with distant metastases ( difference = 6.7 % , 95 % CI = 0.2 to 13.2 % ) , for a relative risk of 0.65 ( 95 % CI = 0.47 to 0.88 ; P = .006 ) . Among men who underwent radical prostatectomy  , those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it ( RR = 14.2 , 95 % CI = 3.3 to 61.8 ; P < .001 ) . CONCLUSION Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery 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 BACKGROUND To estimate the benefits of prostate-specific antigen ( PSA ) screening on prostate cancer ( Pca ) metastasis and Pca-specific mortality , we compared two population s with a well-defined difference in intensity of screening . METHODS Between 1997 and 1999 , a total of 11,970 men , aged 55 - 74 years , were included in the intervention arm of the European R and omised Study of Screening for Prostate Cancer ( ERSPC ) section Rotterdam . Control population consisted of 133,287 men , aged 55 - 74 years , between 1998 and 1999 in Northern Irel and ( NI ) . Men were followed for Pca incidence , Pca metastasis and cause of death until 31st December 2006 . RESULTS Median age in both groups was 63 years at study entry ( p=0.184 ) . In Rotterdam 94.2 % of men and in NI 6 % of men underwent PSA testing . In Rotterdam , 1153 men ( 9.6 % ) were diagnosed with Pca with median baseline PSA of 5.1 ng/ml . In NI , 3962 men ( 3.0 % , p<0.001 ) were diagnosed with Pca with median baseline PSA of 18.0 ng/ml ( p<0.001 ) . The relative risk of Pca metastasis during observation in the intervention population compared to control population was 0.47 ( 95 % confidence interval ( CI ) , 0.35 - 0.63 ; p<0.001 ) . The relative risk of Pca-specific mortality was also lower in the intervention population compared to the control population after a median follow-up of 8.5 years : 0.63 ( 95 % CI , 0.45 - 0.88 ; p=0.008 ) ; absolute mortality reduction was 1.8 deaths per 1000 men . CONCLUSIONS A relative reduction in Pca metastasis of 53 % and Pca mortality of 37 % was observed in the intervention population after 8.5 years of observation . The impact of overdiagnosis , quality of life benefits and cost-effectiveness need to be assessed before population -based PSA screening can be recommended
target: Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy .
  PSA doubling time in <3 yr or a biopsy progression indicates the need for active intervention .
  In men with locally advanced PCa in whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) with equivalent oncologic efficacy .
  Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial .
  Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables .
  For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice .
background: OBJECTIVE Our aim was to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the screening , diagnosis , and treatment of clinical ly localised cancer of the prostate ( PCa ) .
  Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa .
  A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method .