***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 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 1.6 ; 95 % CI , 0.6 - 4.4 ) . CONCLUSIONS The response to cabazitaxel seems to be independent of the AR-V7 status of CTCs from mCRPC patients . Consequently , cabazitaxel might be a valid treatment option for patients with AR-V7-positive CTCs . PATIENT SUMMARY Tools are needed to select specific treatments for specific patients at specific times . The presence of the gene AR-V7 in CTCs has been associated with resistance to anti- and rogen receptor treatments . We investigated whether this holds true for cabazitaxel , but we found cabazitaxel to be effective independent of the presence of AR-V7 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 Importance A critical decision in the management of metastatic castration-resistant prostate cancer ( mCRPC ) is when to administer an and rogen receptor signaling ( ARS ) inhibitor or a taxane . Objective To determine if pretherapy nuclear and rogen-receptor splice variant 7 ( AR-V7 ) protein expression and localization on circulating tumor cells ( CTCs ) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes . Design , Setting , and Participants For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center , 265 men with progressive mCRPC undergoing a change in treatment were considered ; 86 were excluded because they were not initiating ARS or taxane therapy ; and 18 were excluded for processing time constraints , leaving 161 patients for analysis . Between December 2012 and March 2015 , blood was collected and processed from patients with progressive mCRPC immediately prior to new line of systemic therapy . Patients were followed up to 3 years . Main Outcomes and Measures Prostate-specific antigen ( PSA ) response , time receiving therapy , radiographic progression-free survival ( rPFS ) , and overall survival ( OS ) . Results Overall , of 193 prospect ively collected blood sample s from 161 men with mCRPC , 191 were evaluable ( 128 pre-ARS inhibitor and 63 pretaxane ) . AR-V7-positive CTCs were found in 34 sample s ( 18 % ) , including 3 % of first-line , 18 % of second-line , and 31 % of third- or greater line sample s. Patients whose sample s had AR-V7-positive CTCs before ARS inhibition had resistant posttherapy PSA changes ( PTPC ) , shorter rPFS , shorter time on therapy , and shorter OS than those without AR-V7-positive CTCs . Overall , resistant PTPC were seen in 65 of 112 sample s ( 58 % ) without detectable AR-V7-positive CTCs prior to ARS inhibition . There were statistically significant differences in OS but not in PTPC , time on therapy , or rPFS for patients with or without pretherapy AR-V7-positive CTCs treated with a taxane . A multivariable model adjusting for baseline factors associated with survival showed superior OS with taxanes relative to ARS inhibitors when AR-V7-positive CTCs were detected pretherapy ( hazard ratio , 0.24 ; 95 % CI , 0.10 - 0.57 ; P = .035 ) . Conclusions and Relevance The results vali date CTC nuclear expression of AR-V7 protein in men with mCRPC as a treatment-specific biomarker that is associated with superior survival on taxane therapy over ARS-directed therapy in a clinical practice setting . Continued examination of this biomarker in prospect i ve studies will further aid clinical utility 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 . ) 
    Output:
    
AR-V7-positive proportion was significantly higher in CRPC than that in newly diagnosed PCa .
AR-V7 positive HSPC patients portend worse prognosis of first-line hormonal therapy and prostatectomy .