***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: PURPOSE Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases . However , no formal study on the merits of this approach has been reported . We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment . PATIENTS AND METHODS Patients with locally advanced or lymph node-metastatic prostate cancer underwent 1 year of and rogen ablation and three cycles of docetaxel therapy , followed by prostatectomy .  All specimens were characterized for stage by accepted criteria . Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high- grade prostate cancer . Marker expression was divided into three groups : intracellular signaling pathways , stromal-epithelial interaction pathways , and angiogenesis . RESULTS Forty patients were enrolled , 30 ( 75 % ) of whom underwent prostatectomy and two ( 5 % ) who underwent cystoprostatectomy .  Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray . Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17 , SRD5A1 , and Hedgehog pathway components , and modulations of the insulin-like growth factor I pathway . CONCLUSION A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy ; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression 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 AND PURPOSE Dose-escalated radiotherapy ( DE ) improves outcomes in localized prostate cancer ( PCa ) . The impact of DE in the context of image-guided radiotherapy ( IGRT ) remains unknown . Herein , we determined outcomes of three sequential cohorts treated with progressive DE-IGRT . MATERIAL S AND METHODS We analyzed data from 1998 to 2012 . Patients treated with radical radiotherapy were included , with three sequential institutional schedules : ( A ) 75.6Gy , ( B ) 79.8Gy , ( C ) 78Gy , with 1.8 , 1.9 and 2Gy/fraction , respectively . IGRT consisted of fiducial markers and daily EPID ( A , B ) or CBCT ( C ) . RESULTS 961 patients were included , with median follow-up of 6.1y . 30.5 % , 32.6 % and 36.9 % were treated in A , B and C , respectively . Risk category distribution was 179 ( 18.6 % ) low- , 653 ( 67.9 % ) intermediate- and 129 ( 13.5 % ) high-risk . PSA , T-category , and rogen deprivation use and risk distribution were similar among groups . BCR ( biochemical recurrence ) was different ( p<0.001 ) between A , B and C with 5-year rates of 23 % , 17 % and 9 % , respectively ( HR 2.68 [ 95 % CI 1.87 - 3.85 ] and 1.92 [ 95 % CI 1.33 - 2.78 ] for A and B compared to C , respectively ) . Findings were most significant in the intermediate-risk category . Metastasis , cause-specific-death and toxicities were not different between cohorts . CONCLUSION Our findings suggest continuous BCR improvement with progressive DE-IGRT . Prospect i ve validation considering further DE with IGRT seems warranted 
    Output:
    
Data from cancer registries , multi-institutional data bases and a single institutional case-control study indicate a possible benefit of combined cytoreduction and hormonal therapy compared to hormonal therapy alone .