***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive and rogen-independent prostate cancer . We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic , hormone-independent prostate cancer . METHODS We r and omly assigned 770 men to one of two treatments , each given in 21-day cycles : 280 mg of estramustine three times daily on days 1 through 5 , 60 mg of docetaxel per square meter of body-surface area on day 2 , and 60 mg of dexamethasone in three divided doses before docetaxel , or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily . The primary end point was overall survival ; secondary end points were progression-free survival , objective response rates , and post-treatment declines of at least 50 percent in serum prostate-specific antigen ( PSA ) levels . RESULTS Of 674 eligible patients , 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone . In an intention-to-treat analysis , the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone ( 17.5 months vs. 15.6 months , P=0.02 by the log-rank test ) , and the corresponding hazard ratio for death was 0.80 ( 95 percent confidence interval , 0.67 to 0.97 ) . The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone ( P<0.001 by the log-rank test ) . PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients , respectively ( P<0.001 ) , and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease , respectively ( P=0.30 ) . Grade 3 or 4 neutropenic fevers ( P=0.01 ) , nausea and vomiting ( P<0.001 ) , and cardiovascular events ( P=0.001 ) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone .  Pain relief was similar in both groups . CONCLUSIONS The improvement in median survival of nearly two months with docetaxel and estramustine , as compared with mitoxantrone and prednisone , provides support for this approach in men with metastatic , and rogen-independent prostate cancer BACKGROUND Abiraterone acetate ( AA ) is an and rogen bio synthesis inhibitor shown to prolong life in patients with castration-resistant prostate cancer ( CRPC ) already treated with chemotherapy .  AA treatment results in dramatic declines in prostate-specific antigen ( PSA ) in some patients and no declines in others , suggesting the presence of molecular determinants of sensitivity in tumors . OBJECTIVE To study the role of transmembrane protease , serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogene homolog ( ERG ) fusion , an and rogen-dependent growth factor , in circulating tumor cells ( CTCs ) as a biomarker of sensitivity to AA . DESIGN , SETTING , AND PARTICIPANTS The predictive value of TMPRSS2-ERG status was studied in 41 of 48 men with postchemotherapy-treated CRPC enrolled in sequential phase 2 AA trials . INTERVENTION Patients received AA 1000 mg daily and continuously . MEASUREMENTS TMPRSS2-ERG status was characterized by a sensitive , analytically valid reverse transcription polymerase chain reaction assay in CTCs enriched from ethylene-diaminetetraacetic acid anticoagulated blood obtained prior to AA treatment . Outcomes were measured by PSA Working Group 1 criteria . RESULTS AND LIMITATIONS St and ard procedures for specimen acquisition , processing , and testing using the vali date d TMPRSS2-ERG assay on a multiplex platform gave intra-assay and interassay coefficients of variation < 7 % . TMPRSS2-ERG fusion was present in 15 of 41 patients ( 37 % ) , who had a median baseline CTC count of 17 ( interquartile range : 7 - 103 cells per 7.5 ml ) . A PSA decline ≥50 % was observed in 7 of 15 patients ( 47 % ) with the fusion and in 10 of 26 patients ( 38 % ) without the fusion . Although limited by the low number of patients , a posttherapy CTC count of less than five per 7.5 ml was prognostic for longer survival relative to a CTC count five or more . TMPRSS2-ERG status did not predict a decline in PSA or other clinical outcomes . CONCLUSIONS Molecular profiles of CTCs with an analytically valid assay identified the presence of the prostate cancer-specific TMPRSS2-ERG fusion but did not predict for response to AA treatment . This finding demonstrates the role of CTCs as surrogate tissue that can be obtained in a routine practice setting . TRIAL REGISTRATION Clinical Trials.gov : NCT00474383 ( COU-AA-003 ) , NCT00485303 ( COU-AA-004 ) Background Treatment response biomarkers are urgently needed for castration-resistant prostate cancer ( CRPC ) . Baseline and post-treatment circulating tumor cell ( CTC ) counts of ≥5 cells/7.5 ml are associated with poor CRPC outcome . Objective To determine the value of a ≥30 % CTC decline as a treatment response indicator . Design , setting , and participants We identified patients with a baseline CTC count ≥5 cells/7.5 ml and evaluable post-treatment CTC counts in two prospect i ve trials . Intervention Patients were treated in the  COU-AA-301 ( abiraterone after chemotherapy )  and  IMMC-38 ( chemotherapy ) trials . Outcome measures and statistical analysis The association between a ≥30 % CTC decline after treatment and survival was evaluated using univariable and multivariable Cox regression models at three l and mark time points ( 4 , 8 , and 12 wk ) . Model performance was evaluated by calculating the area under the receiver operating characteristic curve ( AUC ) and c-indices . Results Overall 486 patients ( 122 in IMMC-38 and 364 in COU-AA-301 ) had a CTC count ≥5 cells/7.5 ml at baseline , with 440 , 380 , and 351 patients evaluable at 4 , 8 , and 12 wk , respectively . A 30 % CTC decline was associated with increased survival at 4 wk ( hazard ratio [ HR ] 0.45 , 95 % confidence interval [ CI ] 0.36–0.56 ; p < 0.001 ) , 8 wk ( HR 0.41 , 95 % CI 0.33–0.53 ; p < 0.001 ) , and 12 wk ( HR 0.39 , 95 % CI 0.3–0.5 ; p < 0.001 ) in univariable and multivariable analyses . Stable CTC count ( < 30 % fall or < 30 % increase ) was not associated with a survival benefit when compared with increased CTC count . The association between a 30 % CTC decline after treatment and survival was independent of baseline CTC count . CTC declines significantly improved the AUC at all time-points . Finally , in the COU-AA-301 trial , patients with CTC ≥5 cells/7.5 ml and a 30 % CTC decline had similar overall survival in both arms . Conclusions A 30 % CTC decline after treatment from an initial count ≥5 cells/7.5 ml is independently associated with CRPC overall survival following abiraterone and chemotherapy , improving the performance of a multivariable model as early as 4 wk after treatment . This potential surrogate must now be prospect ively evaluated . Patient summary Circulating tumor cells ( CTCs ) are cancer cells that can be detected in the blood of prostate cancer patients . We analyzed changes in CTCs after treatment with abiraterone and chemotherapy in two large clinical trials , and found that patients who have a decline in CTC count  have a better survival outcome BACKGROUND And rogen receptor splice variant 7 ( AR-V7 ) in circulating tumor cells ( CTCs ) from patients with metastatic castration-resistant prostate cancer ( mCRPC ) was recently demonstrated to be associated with resistance to abiraterone and enzalutamide . Cabazitaxel might , however , remain effective in AR-V7-positive patients . OBJECTIVE To investigate the association between AR-V7 expression in CTCs and resistance to cabazitaxel . DESIGN , SETTING , AND PARTICIPANTS We selected patients with mCRPC from the multicenter , r and omized , phase 2 , r and omized , open-label , multicenter study in mCRPC on the pharmacodynamic effects of budesonide on cabazitaxel ( Jevtana ) ( CABARESC )  . Before the start of the first and third cabazitaxel cycle , CTCs were enumerated using the Cell Search System . In patients with ≥10 CTCs in 7.5 ml blood at baseline , the expression of AR-V7 was assessed by quantitative polymerase chain reaction . OUTCOME MEASURES AND STATISTICAL ANALYSIS The primary end point was the association between the AR-V7 status and the CTC response rate ( decrease to fewer than five CTCs in 7.5 ml blood during treatment ) . Secondary end points were the prostate-specific antigen ( PSA ) response rate ( RR ) and overall survival ( OS ) . Analyses were performed using chi-square and log-rank tests . RESULTS AND LIMITATIONS AR-V7 was detected in 16 of 29 patients ( 55 % ) with ≥10 CTCs and was more frequently found in  abiraterone  pretreated patients ( 5 of 5 [ 100 % ] treated vs 7 of 20 [ 35 % ] untreated ; p=0.009 ) . We found no differences in CTC and PSA RRs . The presence of AR-V7 in CTCs was not associated with progression-free survival ( hazard ratio [ HR ] : 0.8 ; 95 % confidence interval [ CI ] , 0.4 - 1.8 ) or overall survival ( HR 1 
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EVIDENCE SYNTHESIS Nomograms of prognostic factors ( eg , albumin , lactate dehydrogenase ) enable clinicians to estimate the prognosis of men with mCRPC .
Determination of AR-V7 in CTCs is a big step towards a more personalized treatment approach in mCRPC .
Genomic characterization of liquid biopsies such as CTCs , cfDNA , and circulating RNA are noninvasive tools to further personalize treatment in prostate cancer .
Only by conducting biomarker-driven studies , rather than large one-size-fits-all trials , will we be able to improve prostate cancer treatment .