***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: In a multicenter trial conducted by the Danish Prostatic Cancer Group , 264 patients with advanced prostate cancer were r and omized either to undergo  bilateral orchiectomy  or to receive combination treatment with goserelin acetate and flutamide . This report is an up date of that study , covering a median follow‐up for survival of 57 months . Of 262 patients who were evaluated , 208 have died . As noted in earlier analyses of this study , no differences in time to progression and cause‐specific and overall survival could be identified between the two treatment groups . In conclusion , the combination of goserelin and flutamide was not clinical ly superior to bilateral orchiectomy in the treatment of advanced prostate cancer OBJECTIVES To compare the efficacy and safety of goserelin and orchiectomy in patients with stage D2 prostate cancer . METHODS A r and omized , open , multicenter study was conducted in 283 patients . Patients were allocated to goserelin , 3.6 mg every 28 days or to orchiectomy . Study end points were endocrine response , objective response , time to treatment failure , survival , and tolerability . Objective response was based on modified criteria of the National Prostate Cancer Project . RESULTS Serum testosterone decreased from baseline to castrate levels by week 4 in each group and remained below castrate levels thereafter . Acid phosphatase and alkaline phosphatase concentrations also decreased in each group . The goserelin and orchiectomy groups had similar results for objective response ( 82 % versus 77 % ) and had similar medial times to treatment failure ( 52 versus 53 weeks ) and survival ( 119 versus 136 weeks ) . No significant interactions between treatments and prognostic factors were observed . Adjusting for baseline testosterone concentration had no effect on survival outcome . Race had no influence on outcome or efficacy end points . Common adverse events in both groups were pain , hot flushes , and lower urinary tract symptoms . CONCLUSIONS Goserelin is well tolerated and as effective as orchiectomy in patients with Stage D2 prostate cancer PURPOSE We assessed the cardiovascular safety profile of degarelix , a new gonadotropin-releasing hormone antagonist . MATERIAL S AND METHODS This is the first report to our knowledge on cardiovascular safety data from a completed 1-year r and omized controlled trial of leuprolide acetate vs degarelix . Outcomes considered in these analyses included the QT interval by central reading and analysis , and cardiovascular adverse events . On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated . RESULTS There were no significant differences between treatment groups for mean change in Fridericia 's correction of QT during the trial . Markedly abnormal Fridericia 's correction of QT values ( 500 milliseconds or greater ) were observed in only a small number of subjects by treatment group , that is 2 ( less than 1 % ) in the pooled degarelix group and 2 ( 1 % ) in the leuprolide group . Supraventricular arrhythmias were the most common type of arrhythmias , affecting 2 % of subjects in the pooled degarelix group and 4 % in the leuprolide group . Other arrhythmias occurred in 1 % or less of subjects by treatment group . The most frequently reported cardiac disorder was ischemic heart disease , which occurred in 4 % of subjects treated with degarelix and 10 % of those on leuprolide . Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age ( p=0.0459 ) and systolic blood pressure ( p=0.0061 ) . CONCLUSIONS In men with prostate cancer  degarelix and leuprolide have similar cardiovascular safety profiles . These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect CONTEXT GnRH agonists markedly increase fat mass in men with prostate cancer , but little is known about the effects of treatment on insulin sensitivity . OBJECTIVE The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity . DESIGN This was a prospect i ve 12-wk study . SETTING The study was conducted at a general clinical research center . PATIENTS OR OTHER PARTICIPANTS We studied 25 men with locally advanced or recurrent prostate cancer , no radiographic evidence of metastases , no history of diabetes mellitus , and no evidence of diabetes mellitus at baseline visit . INTERVENTION Leuprolide depot and bicalutamide were used in the study . MAIN OUTCOME MEASURES Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12 . The primary study outcome was change in insulin sensitivity index . RESULTS Mean ( + /- se ) percentage fat body mass increased by 4.3 + /- 1.3 % from baseline to wk 12 ( P = 0.002 ) . Insulin sensitivity index decreased by 12.9 + /- 7.6 % ( P = 0.02 ) . Insulin sensitivity by homeostatic model assessment decreased by 12.8 + /- 5.9 % ( P = 0.02 ) . Fasting plasma insulin levels increased by 25.9 + /- 9.3 % ( P = 0.04 ) . Mean glycosylated hemoglobin also increased significantly ( P < 0.001 ) . CONCLUSIONS Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer . These observations suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men CONTEXT Patients with cancer often have other medical ailments , referred to as comorbidity . Comorbidity may impact treatment decision-making , prognosis , and quality of care assessment . OBJECTIVE To assess whether comorbidity information can provide important prognostic information in a hospital-based cancer registry . DESIGN , SETTING , AND PARTICIPANTS An observational prospect i ve cohort study using comorbidity data collected by trained hospital-based cancer registrars . Comorbidity was obtained through medical record review using the Adult Comorbidity Evaluation 27 , a vali date d chart-based comorbidity instrument . A total of 17,712 patients receiving care between January 1 , 1995 , and January 31 , 2001 , for the primary diagnosis of new cancer of the prostate , lung ( nonsmall cell ) , breast , digestive system , gynecological , urinary system , or head and neck were included . MAIN OUTCOME MEASURE Duration in months of overall survival . RESULTS A total of 19,268 patients were included in the study ; median duration of follow-up was 31 months . Of these patients , 1556 ( 8.0 % ) were excluded due to missing or unknown data . Severity of comorbidity strongly influenced survival in a dose-dependent fashion and the impact of comorbidity was independent of cancer stage . Compared with patients without comorbidity , the adjusted hazard ratio associated with mild comorbidity was 1.21 ( 95 % confidence interval [ CI ] , 1.13 - 1.30 ) , moderate comorbidity was 1.86 ( 95 % CI , 1.73 - 2.00 ) , and severe comorbidity was 2.56 ( 95 % CI , 2.35 - 2.81 ) . Adjusted Kaplan-Meier survival curves revealed that at any point in time the patients with more severe levels of comorbidity had worse survival ( partial chi2(3 ) due to comorbidity , 523.54 ; P<.001 ) . Model discrimination ranged from 0.71 for head and neck to 0.86 for prostate cancers . CONCLUSIONS Comorbidity is an important independent prognostic factor for patients with cancer . The inclusion of comorbidity in hospital-based cancer registries will increase the value and use of observational research And rogen-deprivation therapy ( ADT ) is a widely used treatment for prostate cancer . Recently , several studies have reported an association between ADT and an increased risk of cardiovascular events , including myocardial infa rct ion and cardiovascular mortality.1 - 5 These reports have led to increased interest and discussion regarding the metabolic effects of ADT and its possible association with increased cardiovascular risk . In addition , likely as a result of these reports , internists , endocrinologists , and cardiologists are now being consulted regarding the evaluation and management of patients in whom ADT is being initiated . Most of these physicians are not aware of the possible effects of ADT on cardiovascular risk factors or the issues regarding ADT and cardiovascular disease . Therefore , this multidisciplinary writing group has been commissioned to review and summarize the metabolic effects of ADT , to evaluate the data regarding a possible relation between ADT and cardiovascular events in patients with prostate cancer , and to generate suggestions regarding the evaluation and management of patients , both with and without known cardiac disease , in whom ADT is being initiated ( Table 1 ) . TABLE 1 Prospect i ve Studies of the Effects of ADT on Cardiac Risk Factors  ADT was first used in prostate cancer for patients with overt metastatic disease,7 and it remains the mainstay of therapy for this group . ADT combined with external-beam radiation therapy is a st and ard of care in the treatment of men with high-risk prostate cancer , on the basis of evidence that shows a survival benefit in multiple r and omized controlled trials.8 - 13 However , ADT is also often used for other prostate cancer states ( eg , for prostate volume reduction in men planning to undergo definitive local therapy with brachytherapy , or in the case of rising prostate-specific antigen after definitive local treatment),14,15 and in these cases , its role in prolonging survival is less certain PURPOSE Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone . Therapy with diethylstilbestrol ( DES ) , leuprolide , or bilateral orchiectomy has been reported to be equivalent . DES is the cheapest preparation , but has the potential for serious cardiovascular or thromboembolic complications .  Flutamide is a novel anti and rogen with fewer side effects . PATIENTS AND METHODS The Eastern Cooperative Oncology Group ( ECOG ) conducted a double-blind , r and omized study to compare the efficacy of flutamide ( 250 mg three times daily ) to DES ( 1 mg three times daily ) as the primary hormonal therapy for patients with stage D2 prostate cancer . Patients were stratified by performance status , disease sites , and history of cardiovascular disease at r and omization . RESULTS Forty-eight patients received DES and 44 flutamide . Patient characteristics were evenly distributed between the two treatments . The overall response rate was similar ( DES , 62 % ; flutamide , 50 % ) . Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3 % of patients on DES and in 17.6 % on flutamide ( P = .051 ) . Other toxicities were similar between the two treatment arms . However , DES produced significantly longer time to treatment failure ( 26.4 v 9.7 months , P = .016 ) and longer survival than flutamide ( 43.2 v 28.5 months , P = .040 ) . CONCLUSION As the primary hormonal therapy for stage D2 prostate cancer , DES caused more serious cardiovascular or thromboembolic complications than flutamide . Despite this , flutamide was not as active an initial agent as DES . However , the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined , and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies OBJECTIVE To evaluate the clinical efficacy and cardiovascular complications of orchidectomy or polyoestradiol phosphate ( PEP ) in the treatment of advanced prostatic cancer . PATIENTS AND METHODS In a prospect i ve , r and omized study 444 patients ( mean age 73 years , range 45 - 91 ) with T3 - 4 M0 or T1 - 4 M1 prostatic cancer were treated either by orchidectomy  ( group 1 , n = 217 ) or  parenteral PEP  ( group 2 , n = 227 ; 240 mg/month ) . The patients were examined at 3 and 6 months after start of the therapy and thereafter every 6 months ; they were also assessed whenever they had symptoms indicating progression . Possible cardiovascular complications included myocardial infa rct ion , cerebrovascular accident , pulmonary embolism and deep vein thrombosis . RESULTS After a follow-up of 2 years there was no statistically significant difference between the groups in progression-free time ; 65 of 217 ( 30 % ) patients in group 1 showed evidence of progression , including seven ( 3 % ) who died from prostate cancer . In group 2 , 64 of 227 ( 28 % ) patients showed progression and eight ( 3.5 % ) died from prostatic cancer . There were 10 ( 5 % ) cardiovascular complications in patients in group 1 , including five ( 2 % ) cardiovascular deaths ; in group 2 there were 24 ( 11 % ) and 14 ( 6 % ) , respectively . During the first year of treatment there were three ( 1.4 % ) cardiovascular complications in 
    Output:
    
Network analysis could only be performed for all-cause mortality and it remains difficult to disentangle benefit ( positive impact on cancer survival ) and risk ( including CV risk ) .