title: Increased survival with enzalutamide in prostate cancer after chemotherapy. 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. Prostate Gland Lengths and Iceball Dimensions Predict Micturition Functional Outcome Following Salvage Prostate Cryotherapy in Men with Radiation Recurrent Prostate Cancer New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial Intermittent versus continuous androgen deprivation in prostate cancer. Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Importance of continued testicular suppression in hormone-refractory prostate cancer. Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report. Salvage lymph node dissection for prostate cancer nodal recurrence detected by 11C-choline positron emission tomography/computerized tomography. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. 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). Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Optimal Starting Time for Flutamide to Prevent Disease Flare in Prostate Cancer Patients Treated with a Gonadotropin-Releasing Hormone Agonist A Phase II study of salvage high-dose-rate brachytherapy for the treatment of locally recurrent prostate cancer after definitive external beam radiotherapy AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.
abstract: BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) 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 Introduction Tissue cryoablation is a potential curative option for solid malignancies , including radiation recurrent prostate cancer ( RRPC ) . Case series of salvage cryotherapy ( SCT ) in RRPC have reported promising disease free survival ( DFS ) outcomes and acceptable toxicity profile . While many men receive SCT , no predictive factors for treatment induced side effects are known . The aim of this study is to vali date the oncologic outcome of SCT in a large multi-centre patient cohort and to identify potential parameters associated with an increased risk of micturition symptoms . Patients and Methods In this retrospective analysis , we studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres ( between 2001 and 2011 ) .  Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites . We analysed clinico-pathological factors against tumour response . Functional outcomes were assessed by continence status and IPSS question naire . Predictive factors for SCT-induced micturition symptoms were analysed in a sub-group ( n = 42 ) of consecutive cases . Results We found that nadir post-SCT PSA levels strongly associated with DFS . The DFS rates at 12- and 36-month were 84 % and 67 % for the ≤1 ng/ml group and 56 % and 14 % for the > 1 ng/ml group , respectively ( p<0.001 ) . Correlative analysis revealed highly significant association between patients ' post-SCT micturition status with prostate gl and and iceball lengths following SCT . Finally , in a reduction model , both gl and length and maximal length of iceball were highly associated with patients ' IPSS outcome ( p<0.001 ) . Conclusion We report the largest European patient cohort treated with SCT for RRPC . Oncologic outcome guided by nadir PSA of < 1 ng/ml is consistent with earlier single-centre series . For the first time , we identified physical parameters to predict micturition symptoms following SCT . Our data will directly assist on-going and future trial design in cryotherapy in prostate cancer BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as " new lesions " or " no new lesions , " changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit Purpose The aim of this retrospective two-centre study was to investigate the clinical impact of 11C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer ( rPCa ) after radical therapy .  Methods Enrolled in this retrospective study were 150 patients ( 95 from Bologna , 55 from Würzburg ) with rPCa and biochemical relapse ( PSA mean ± SD 4.3 ± 5.5 ng/mL , range 0.2–39.4 ng/mL ) after radical therapy .  The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative and rogen deprivation therapy ( ADT ) in 55 patients . The effective clinical impact of 11C-choline PET/CT was rated as major ( change in therapeutic approach ) , minor ( same treatment , but modified therapeutic strategy ) or none . Multivariate binary logistic regression analysis included PSA level , PSA kinetics , ongoing ADT , Gleason score , TNM , age and time to relapse . Results Changes in therapy after 11C-choline PET/CT were implemented in 70 of the 150 patients ( 46.7 % ) . A major clinical impact was observed in 27 patients ( 18 % ) and a minor clinical impact in 43 ( 28.7 % ) . 11C-choline PET/CT  was positive in 109 patients ( 72.7 % ) detecting local relapse ( prostate bed and /or iliac lymph nodes and /or pararectal lymph nodes ) in 64 patients ( 42.7 % ) . Distant relapse ( paraaortic and /or retroperitoneal lymph nodes and /or bone lesions ) was seen in 31 patients ( 20.7 % ) , and both local and distant relapse in 14 ( 9.3 % ) . A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients ( p < 0.05 ) . In multivariate analysis , PSA level , PSA doubling time and ongoing ADT were significant predictors of a positive scan ( p < 0.05 ) . In statistical analysis no significant differences were observed between the Bologna and Würzburg patients ( p > 0.05 ) . In both centres the same criteria to vali date PET-positive findings were used : in 17.3 % of patients by histology and in 82.7 % of patients by correlative imaging and /or clinical follow-up ( follow-up mean 20.5 months , median 18.3 months , range 6.2–60 months ) . Conclusion 11C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients . It led to an overall change in 46.7 % of patients , with a major clinical change implemented in 18 % of patients . Further prospect i ve studies are needed to evaluate the effect of such treatment changes on patient survival Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy .  We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy  , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing  long-term hormone  therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research BACKGROUND Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving and rogen-deprivation therapy .  Replacing and rogens before progression of the disease is hypothesized to prolong and rogen dependence . METHODS Men with newly diagnosed , metastatic , hormone-sensitive prostate cancer , a performance status of 0 to 2 , and a prostate-specific antigen ( PSA ) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an anti and rogen agent for 7 months . We then r and omly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent and rogen deprivation  , with patients stratified according to prior or no prior hormonal therapy , performance status , and extent of disease ( minimal or extensive ) . The co primary objectives were to assess whether intermittent  therapy  was noninferior to continuous therapy with respect to survival , with a one-sided test with an upper boundary of the hazard ratio of 1.20 , and whether quality of life differed between the groups 3 months after r and omization . RESULTS A total of 3040 patients were enrolled , of whom 1535 were included in the analysis : 765 r and omly assigned to continuous and rogen deprivation and 770 assigned to intermittent and rogen deprivation . The median follow-up period was 9.8 years . Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group ( hazard ratio for death with intermittent therapy , 1.10 ; 90 % confidence interval , 0.99 to 1.23 ) . Intermittent therapy was associated with better erectile function and mental health ( P<0.001 and P=0.003 , respectively ) at month 3 but not thereafter . There were no significant differences between the groups in the number of treatment-related high- grade adverse events . CONCLUSIONS Our findings were statistically inconclusive . In patients with metastatic hormone-sensitive prostate cancer , the confidence interval for survival exceeded the upper boundary for noninferiority , suggesting that we can not rule out a 20 % greater risk of death with intermittent therapy than with continuous therapy , but too few events occurred to rule out significant inferiority of intermittent therapy . Intermittent therapy result ed in small improvements in quality of life . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00002651 . ) OBJECTIVE To demonstrate the safety and efficacy of up to 5 years of degarelix treatment and the effects of crossing over from leuprolide to degarelix in the extension phase of a phase III pivotal 1-year trial . METHODS Patients receiving degarelix who completed the 1-year trial continued on 80 mg ( n = 125 ) or 160 mg ( n = 126 ) maintenance doses . Patients who received leuprolide were rer and omized to degarelix 240/80 mg ( n = 69 ) or 240/160 mg ( n = 65 ) . Safety and tolerability were assessed ( primary end point ) , as well as testosterone and prostate-specific antigen levels and prostate-specific antigen progression-free survival ( secondary end points ) . RESULTS Adverse event frequency was similar between both the groups . Adverse events included initial injection site reactions , hot flushes , and increased weight . Testosterone and prostate-specific antigen values during the extension study were similar to those seen during the 1-year trial in patients who continued on degarelix or crossed over from leuprolide . The prostate-specific antigen progression-free survival hazard rate was decreased significantly after the crossover in the leuprolide to degarelix group ( from 0.20 to 0.09 ; P = .002 ) , whereas in patients who continued on degarelix , the rate did not change significantly . In patients with baseline prostate-specific antigen > 20 ng/mL , the same hazard rate change pattern was observed on crossover ( from 0.38 to 0.19 ; P = .019 ) . CONCLUSION Degarelix was well tolerated ; no safety concerns were identified . The significant prostate-specific antigen progression-free survival benefit established for degarelix over leuprolide during year 1 remained consistent at 5 years PURPOSE Patients in whom prostate cancer progresses despite testicular and rogen ablation  are generally said to have cancers that have become resistant to hormonal maneuvers . If and rogen suppression has been pharmacologic , this therapy is often stopped before consideration of other systemic treatments . This exploratory study sought clinical correlates of experimental evidence that there may be substantial acceleration of tumor growth after cessation of and rogen suppression . MATERIAL S AND METHODS A retrospective multivariate analysis was performed on survival data for 341 patients treated on four clinical trials of secondary therapy for hormone-refractory prostate cancer . Factors included in the model were recent weight loss , age , performance status , disease site ( soft tissue v bone-dominant ) , prior radiotherapy , and continued and rogen suppression v discontinued exogenous endocrine therapy . RESULTS Recent weight loss , age , performance status , and disease site were important prognostic factors for survival duration in hormone-refractory prostate cancer . Correcting for these factors , continued testicular and rogen suppression was also an important predictor of survival duration in all data sets examined . CONCLUSION This retrospective study showed a modest advantage in survival duration for men with hormone-refractory prostate cancer who continued to receive testicular and rogen suppression .  The hypothesis that continued hormonal maneuvers can still affect survival in this group warrants examination in prospect i ve trials PURPOSE Gonadotropin-releasing hormone agonists decrease bone mineral density , lean mass , and muscle size and increase fat mass in men with prostate cancer . Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition . PATIENTS AND METHODS In a 12-month , open-label study , we r and omly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide ( 150 mg by mouth daily ) . Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography . RESULTS Mean ( + /- st and ard error ) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5 % + /- 0.5 % in the leuprolide group and increased by 2.5 + /- 0.5 in the bicalutamide group from baseline to 12 months ( P < .001 ) . Mean changes in bone mineral density of the total body , total hip , femoral neck , and trabecular bone of the lumbar spine also differed significantly between groups ( P < or = .003 for each comparison ) . Fat mass increased by 11.1 % + /- 1.3 % in the leuprolide group and by 6.4 % + /- 1.1 % in the bicalutamide group ( P = .01 ) . Changes in lean mass , muscle size , and muscle strength were similar between the groups . Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group . Fatigue , loss of sexual interest , and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group . CONCLUSION In men with prostate cancer , bicalutamide monotherapy increases bone mineral density , lessens fat accumulation , and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily  and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone CONTEXT Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy , but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival , and if so , the subgroup of men most likely to benefit . OBJECTIVES To quantify the relative improvement in prostate cancer-specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy , and to identify subgroups for whom salvage treatment is most beneficial . DESIGN , SETTING , AND PATIENTS Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982 - 2004 , followed up through December 28 , 2007 , who experienced biochemical and /or local recurrence and received no salvage treatment ( n = 397 ) , salvage radiotherapy alone ( n = 160 ) , or salvage radiotherapy combined with hormonal therapy ( n = 78 ) . MAIN OUTCOME MEASURE Prostate cancer-specific survival defined from time of recurrence until death from disease . RESULTS With a median follow-up of 6 years after recurrence and 9 years after prostatectomy , 116 men ( 18 % ) died from prostate cancer , including 89 ( 22 % ) who received no salvage treatment , 18 ( 11 % ) who received salvage radiotherapy alone , and 9 ( 12 % ) who received salvage radiotherapy and hormonal therapy . Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer-specific survival relative to those who received no salvage treatment ( hazard ratio [ HR ] , 0.32 [ 95 % confidence interval { CI } , 0.19 - 0.54 ] ; P<.001 ) . Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer-specific survival ( HR , 0.34 [ 95 % CI , 0.17 - 0.69 ] ; P = .003 ) . The increase in prostate cancer-specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established prognostic factors . Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer-specific survival .  Men whose prostate-specific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer-specific survival .  Salvage radiotherapy also was associated with a significant increase in overall survival . CONCLUSIONS Salvage radiotherapy administered within 2 years of biochemical recurrence was associated with a significant increase in prostate cancer-specific survival among men with a prostate-specific antigen doubling time of less than 6 months , independent of other prognostic features such as pathological stage or Gleason score . These preliminary findings should be vali date d in other setting s , and ultimately , in a r and omized controlled trial PURPOSE To assess the impact of prognostic factors , including continued ( orchiectomy ) versus discontinued and rogen-suppression ( nonorchiectomy ) therapy , on  chemotherapy response and survival of patients with hormone-refractory prostate cancer . METHODS Analysis of five consecutive Southwest Oncology Group ( SWOG ) phase II chemotherapy trials was undertaken . RESULTS Two hundred five hormone-refractory patients were evaluated . Eighty-four percent had been orchiectomized . The median survival duration s for the nonorchiectomy and orchiectomy patients were 6 and 7 months , respectively ( P = .73 ) . In a univariate analysis , orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy  ( 1.1 v 0.1 years , P = .003 ) , were more likely to have had chemotherapy initiated > or = 2 years from diagnosis ( 75 % v 56 % , P = .03 ) , had a lower incidence of liver metastases ( 16 % v 30 % , P = .05 ) , and had lower likelihood of being black ( 8 % v 18 % , P = .05 ) when compared with the nonorchiectomy group . Orchiectomy patients had a marginally significant longer median time from initial hormone treatment , more prior endocrine manipulations , lower median baseline alkaline phosphatase levels , and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group . Absence of liver metastases ( P = .004 ) , hemoglobin level > or = 10 g/dL ( P < .001 ) , acid phosphatase level > or = 1.2 IU/L ( P = .05 ) , response to chemotherapy ( P = .001 ) , and > or = 2 years from initial hormone treatment ( P = .01 ) are important factors for survival . CONCLUSION This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression . A prospect i ve r and omized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy PURPOSE We report salvage lymph node dissections for prostate cancer nodal recurrence detected by (11)C-choline positron emission tomography/computerized tomography in the setting of increasing prostate specific antigen after radical prostatectomy . MATERIAL S AND METHODS Retrospective chart review was performed for all patients who underwent salvage lymph node dissection for prostate cancer nodal recurrence . Only patients previously treated with radical prostatectomy were included in the study and those with evidence of local recurrence were excluded from analysis . Primary end points included biochemical recurrence , systemic progression and cancer specific mortality . RESULTS From 2009 to 2013 , 52 men underwent salvage lymph node dissection .  Before salvage lymph node dissection  78.8 % ( 41 of 52 ) had some form of therapy after radical prostatectomy . Median age at salvage lymph node dissection was 60 years and median prostate specific antigen was 2.2 ng/ml ( IQR 1.4 - 3.7 ) . The median number of lymph nodes dissected was 21.5 ( IQR 16 - 30 ) and the median number of positive nodes was 3.5 ( IQR 1.2 - 6.5 ) . Since salvage lymph node dissection 46.2 % of the men ( 24 of 52 ) have had no further treatment , 34.6 % ( 18 of 52 ) are on hormonal therapy and 19.2 % ( 10 of 52 ) have received multiple different treatments . At the last followup at a median of 20 months ( IQR 8 - 33 ) , 57.7 % ( 30 of 52 ) had prostate specific antigen remain less than 0.2 ng/ml , 75 % ( 39 of 52 ) remained free of systemic progression and 96.2 % of the men ( 50 of 52 ) were alive . Two patients died of prostate cancer . Three-year biochemical recurrence-free , systemic progression-free and cancer specific survival was 45.5 % , 46.9 % and 92.5 % , respectively . CONCLUSIONS This represents the largest U.S. series of salvage lymph node dissection in the setting of lymph node metastatic prostate cancer after radical prostatectomy . Although followup was short and the study lacked a r and omized control group , salvage lymph node dissection may represent a valid treatment option BACKGROUND Docetaxel administered every 3 weeks is a st and ard treatment for castration-resistant advanced prostate cancer . We hypothesised that 2-weekly administration of docetaxel would be better tolerated than 3-weekly docetaxel in patients with castration-resistant advanced prostate cancer , and did a prospect i ve , multicentre , r and omised , phase 3 study to compare efficacy and safety . METHODS Eligible patients had advanced prostate cancer ( metastasis , a prostate-specific-antigen test result of more than 10·0 ng/mL , and WHO performance status score of 0 - 2 ) , had received no chemotherapy ( except with estramustine ) , had undergone surgical or chemical castration , and had been referred to a treatment centre in Finl and , Irel and , or Sweden . Enrolment and treatment were done between March 1 , 2004 , and May 31 , 2009 . R and omisation was done central ly and stratified by centre and WHO performance status score of 0 - 1 vs 2 . Patients were assigned 75 mg/m(2 ) docetaxel intravenously on day 1 of a 3-week cycle , or 50 mg/m(2 ) docetaxel intravenously on days 1 and 15 of a 4-week cycle . 10 mg oral prednisolone was administered daily to all patients . The primary endpoint was time to treatment failure ( TTTF ) . We assessed data in the per- protocol population . This study is registered with Clinical Trials.gov , number NCT00255606 . FINDINGS 177 patients were r and omly assigned to the 2-weekly docetaxel  group and 184 to the 3-weekly group . 170 patients in the 2-weekly group and 176 in the 3-weekly group were included in the analysis . The 2-weekly administration was associated with significantly longer TTTF than was 3-weekly administration ( 5·6 months , 95 % CI 5·0 - 6·2 vs 4·9 months , 4·5 - 5·4 ; hazard ratio 1·3 , 95 % CI 1·1 - 1·6 , p=0·014 ) . Grade 3 - 4 adverse events occurred more frequently in the 3-weekly than in the 2-weekly administration group , including neutropenia ( 93 [ 53 % ] vs 61 [ 36 % ] ) , leucopenia ( 51 [ 29 % ] vs 22 [ 13 % ] ) , and febrile neutropenia ( 25 [ 14 % ] vs six [ 4 % ] ) . Neutropenic infections were reported more frequently in patients who received docetaxel every 3 weeks ( 43 [ 24 % ] vs 11 [ 6 % ] , p=0·002 ) . INTERPRETATION Administration of docetaxel every 2 weeks seems to be well tolerated in patients with castration-resistant advanced prostate cancer and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated . FUNDING Sanofi 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 To up date the Potentially Curable Pancreatic Cancer : American Society of Clinical Oncology Clinical Practice Guideline published on May 31 , 2016 . The October 2016 up date focuses solely on new evidence that pertains to clinical question 4 of the guideline : What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor ? Methods The recently published results of a r and omized phase III study prompted an up date of this guideline . The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations . Results The ESPAC-4 study , a multicenter , international , open-label r and omized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma .  Median overall survival was improved in the doublet arm to 28.0 months ( 95 % CI , 23.5 to 31.5 months ) versus 25.5 months ( 95 % CI , 22.7 to 27.9 months ) for gemcitabine alone ( hazard ratio , 0.82 ; 95 % CI , 0.68 to 0.98 ; P = .032 ) . Grade 3 and 4 adverse events were similar in both arms , although higher rates of h and -foot syndrome and diarrhea occurred in patients r and omly assigned to the doublet arm . Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications . The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance ; alternatively , monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered . Adjuvant treatment should be initiated within 8 weeks of surgical resection , assuming complete recovery . The remaining recommendations from the original 2016 ASCO guideline are unchanged BACKGROUND The management of patients with clinical recurrence of prostate cancer after radical prostatectomy ( RP ) remains challenging . OBJECTIVE To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography ( PET/CT ) scan may have an impact on the prognosis of patients with biochemical recurrence ( BCR ) and nodal recurrence after RP . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan . INTERVENTION Patients underwent salvage lymph node dissection ( LND ) . MEASUREMENTS Biochemical response ( BR ) to treatment was defined as prostate-specific antigen ( PSA ) < 0.2 ng/ml at 40 d after salvage LND . Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence ( CR ) after salvage LND , respectively . RESULTS AND LIMITATIONS Overall , 56.9 % of patients achieved BR . Mean and median follow-up after LND were 39.4 and 39.8 mo , respectively . The 5-yr BCR-free survival rate was 19 % . Preoperative PSA < 4 ng/ml ( hazard ratio [ HR ] : 0.12 ; p = 0.005 ) , time to BCR < 24 mo ( HR : 7.52 ; p = 0.005 ) , and negative lymph nodes at previous RP ( HR : 0.19 ; p=0.04 ) represented independent predictors of BR . Overall , 5-yr CR-free and cancer-specific survival were 34 % and 75 % , respectively . At multivariable analyses , only PSA > 4 ng/ml ( HR : 2.13 ; p=0.03 ) and the presence of retroperitoneal uptake at PET/CT scan ( HR=2.92 ; p=0.004 ) represented independent preoperative predictors of CR . Similarly , the presence of pathologic nodes in the retroperitoneum ( HR : 2.78 ; p=0.02 ) , higher number of positive lymph nodes ( HR : 1.04 ; p=0.006 ) , and complete BR to salvage LND ( HR : 0.31 ; p=0.002 ) represented postoperative independent predictors of CR . Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses . CONCLUSIONS Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan . Biochemical response after surgery can be achieved in a consistent proportion of patients . Although most patients invariably progressed to BCR after surgery at longer follow-up , 35 % of patients showed the absence of CR at 5 yr OBJECTIVES Based on methods introduced in the late 1960s and no longer used ,  serum testosterone level in men after surgical castration was reported to be 50 ng/dL or less . Radioimmunoassay and , subsequently , chemiluminescent methods have supplanted the early analytic methods because of their improved accuracy and ease of testing . The purpose of this study was to define the castrate testosterone level in the era of chemiluminescent testing . METHODS After bilateral orchiectomy , serum testosterone ( total ) levels were measured prospect ively in 35 prostate cancer patients . RESULTS The median testosterone value in this patient cohort was 15 ng/dL ( 0.5 nmol/L ; 95 % confidence interval 12 to 17 ng/dL ) . CONCLUSIONS In a contemporary series , castrate testosterone should be defined as less than 20 ng/dL ( 0.7 nmol/L ) . The important biologic and economic implication s are discussed Objective : Flare-up phenomena , such as an increase in prostate-specific antigen ( PSA ) and /or deterioration of symptoms , are observed in some patients undergoing gonadotropin-releasing hormone ( GnRH ) agonist therapy .  This study was carried out to determine the optimal time for starting the administration of flutamide to prevent flare-up phenomena . Patients and Methods : Twenty-six patients with prostate cancer and elevated serum levels of PSA were r and omly assigned to 5 groups . Group A patients ( n = 6 ) were treated with a subcutaneous injection of 3.75 mg leuprorelin acetate depot alone . Group B , C , D and E patients ( 5 patients in each group ) were treated with 375 mg/day of orally administered flutamide combined with leuprorelin . Flutamide was initiated on the day of leuprorelin injection in group B , and at 1 , 2 and 4 weeks before leuprorelin injection in groups C , D and E , respectively . Serum PSA and testosterone levels were measured in each patient . Results : Pretreatment with flutamide increased the serum testosterone level , but the testosterone surge after leuprorelin administration was almost the same in all 5 treatment groups . In patients who had been treated with flutamide in combination with leuprorelin , the mean PSA level did not exceed the pretreatment levels after leuprorelin administration . The rate of decrease in PSA in the group receiving simultaneous administration of flutamide with leuprorelin showed a decline comparable to that during the period before leuprorelin administration in the flutamide pretreatment groups . Conclusion : Simultaneous administration of flutamide with a GnRH agonist is sufficient to prevent flare-up phenomena PURPOSE We report the toxicity and biochemical tumor control outcome of a prospect i ve Phase II study using high-dose-rate brachytherapy ( HDR ) alone as a salvage therapy for recurrent disease after external beam radiotherapy ( EBRT ) . METHODS Forty-two patients with biopsy-proven recurrence were enrolled on a Phase II study of salvage HDR monotherapy using iridium-192 . Median pretreatment EBRT dose was 8100 cGy ( 6840–8640 cGy ) and the median time from completion of EBRT to salvage HDR was 73 months . The protocol prescription dose of 3200 cGy was delivered in four fractions over 30 hours in a single insertion . Median followup after salvage HDR was 36 months ( 6–67 months ) . RESULTS The actuarial prostate-specific antigen biochemical relapse-free survival and distant metastases-free survival rates at 5 years were 68.5 % and 81.5 % , respectively . Cause-specific survival was 90.3 % . Late genitourinary Grade 1 and 2 toxicities were found in 38 % and 48 % , respectively , and one patient developed Grade 3 urinary incontinence . Late Grade 1 and 2 gastrointestinal toxicity was noted in 17 % and 8 % of patients , respectively . Three patients ( 7 % ) developed Grade 2 late urinary toxicity ( urethral stricture ) , which were corrected with urethral dilatation , and one patient developed Grade 3 urinary incontinence . No Grade 4 toxicities were observed . CONCLUSIONS Genitourinary toxicity was the most commonly encountered toxicity observed after salvage HDR but severe toxicities were uncommon . Salvage HDR is an effective and well-tolerated modality for locally recurrent prostate cancer and should be considered even for patients who have previously been treated with ultra-high dose levels of EBRT BACKGROUND The and rogen-receptor isoform encoded by splice variant 7 lacks the lig and -binding domain , which is the target of enzalutamide and abiraterone , but remains constitutively active as a transcription factor . We hypothesized that detection of and rogen-receptor splice variant 7 messenger RNA ( AR-V7 ) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone . METHODS We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospect ively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone .  We examined associations between AR-V7 status ( positive vs. negative ) and prostate-specific antigen ( PSA ) response rates ( the primary end point ) , freedom from PSA progression ( PSA progression-free survival ) , clinical or radiographic progression-free survival , and overall survival . RESULTS A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled , of whom 39 % and 19 % , respectively , had detectable AR-V7 in circulating tumor cells . Among men receiving enzalutamide  , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 53 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.4 months vs. 6.0 months ; P<0.001 ) , clinical or radiographic progression-free survival ( median , 2.1 months vs. 6.1 months ; P<0.001 ) , and overall survival ( median , 5.5 months vs. not reached ; P=0.002 ) . Similarly , among men receiving abiraterone  , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 68 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.3 months vs. not reached ; P<0.001 ) , clinical or radiographic progression-free survival ( median , 2.3 months vs. not reached ; P<0.001 ) , and overall survival ( median , 10.6 months vs. not reached , P=0.006 ) . The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length and rogen receptor messenger RNA . CONCLUSIONS Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone . These findings require large-scale prospect i ve validation . ( Funded by the Prostate Cancer Foundation and others . ) A previously reported , double‐blind , r and omized , multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined and rogen blockade ( CAB ) with luteinizing hormone‐releasing hormone agonist ( LHRH‐A ) plus bicalutamide 80 mg versus LHRH‐A plus bicalutamide‐matching placebo ( LHRH‐A monotherapy ) . The analysis at a median follow‐up of 2.4 years indicated that CAB significantly ( P < .001 ) prolonged the time to progression and the time to treatment failure . In the current report , survival data from a long‐term follow‐up ( median , 5.2 years ) were analyzed BACKGROUND How best to treat rising prostate-specific antigen ( PSA ) concentration after radical prostatectomy is an urgent clinical question . Salvage radiotherapy delays the need for more aggressive treatment such as long-term and rogen suppression , but fewer than half of patients benefit from it . We aim ed to establish the effect of adding short-term and rogen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy . METHODS This open-label , multicentre , phase 3 , r and omised controlled trial , was done in 43 French study centres . We enrolled men ( aged ≥18 years ) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate ( but no previous and rogen deprivation therapy or pelvic radiotherapy ) , and who had stage pT2 , pT3 , or pT4a ( bladder neck involvement only ) in patients who had rising PSA of 0·2 to less than 2·0 μg/L following radical prostatectomy , without evidence of clinical disease . Patients were r and omly assigned ( 1:1 ) central ly via an interactive web response system to st and ard salvage radiotherapy ( three-dimensional [ 3D ] conformal radiotherapy or intensity modulated radiotherapy , of 66 Gy in 33 fractions 5 days a week for 7 weeks ) or radiotherapy plus short-term and rogen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later . R and omisation was stratified using a permuted block method according to investigational site , radiotherapy modality , and prognosis . The primary endpoint was progression-free survival , analysed in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00423475 . FINDINGS Between Oct 19 , 2006 , and March 30 , 2010 , 743 patients were r and omly assigned , 374 to radiotherapy  alone and 369 to radiotherapy plus goserelin . Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years ( 80 % [ 95 % CI 75 - 84 ] vs 62 % [ 57 - 67 ] ; hazard ratio [ HR ] 0·50 , 95 % CI 0·38 - 0·66 ; p<0·0001 ) . No additional late adverse events occurred in patients receiving short-term and rogen suppression compared with those who received radiotherapy alone . The most frequently occuring acute adverse events related to goserelin were hot flushes , sweating , or both ( 30 [ 8 % ] of 366 patients had a grade 2 or worse event ; 30 patients [ 8 % ] had hot flushes and five patients [ 1 % ] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group ) . Three ( 8 % ) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group . The most common late adverse events of grade 3 or worse were genitourinary events ( 29 [ 8 % ] in the radiotherapy alone group vs 26 [ 7 % ] in the radiotherapy plus goserelin group ) and sexual disorders ( 20 [ 5 % ] vs 30 [ 8 % ] ) . No treatment-related deaths occurred . INTERPRETATION Adding short-term and rogen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable . Radiotherapy combined with short-term and rogen suppression could be considered as a reasonable option in this population . FUNDING French Ministry of Health , AstraZeneca , and La Ligue Contre le Cancer
target: Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications .
  PATIENT SUMMARY In men with a rise in their PSA levels after prior local treatment for prostate cancer only , it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients .
background: OBJECTIVE To present a summary of the 2016 version of the European Association of Urology ( EAU ) - European Society for Radiotherapy & Oncology ( ESTRO ) - International Society of Geriatric Oncology ( SIOG ) Guidelines on the treatment of relapsing , metastatic , and castration-resistant prostate cancer ( CRPC ) .
  EVIDENCE SYNTHESIS Relapse after local therapy is defined by a rising prostate-specific antigen ( PSA ) level > 0.2ng/ml following radical prostatectomy ( RP ) and > 2ng/ml above the nadir after radiation therapy ( RT ) .
  And rogen deprivation therapy ( ADT ) remains the basis for treatment of men with metastatic prostate cancer ( PCa ) .
  Level 1 evidence for the treatment of metastatic CRPC ( mCRPC ) includes , abiraterone acetate plus prednisone ( AA/P ) , enzalutamide , radium 223 ( Ra 223 ) , docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel , AA/P , enzalutamide , and radium are approved for second-line treatment of CRPC following docetaxel .
  CONCLUSIONS The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly .