You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Persistent, biologically meaningful prostate cancer after 1 year of androgen ablation and docetaxel treatment.
Abstract 1:
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


Title 2:
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
Abstract 2:
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


Title 3:
Improved outcomes with dose escalation in localized prostate cancer treated with precision image-guided radiotherapy.
Abstract 3:
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
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 .