***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: OBJECTIVE To describe the incidence , time to onset and extent of anaemia occurring in patients with prostate cancer receiving combined hormone blockade ( CHB )  and the timing and extent of recovery from anaemia in those patients where CHB was discontinued . PATIENTS AND METHODS Patients with prostate cancer were evaluated prospect ively by physical examination and laboratory tests at baseline and at routine intervals while receiving CHB . Of 142 patients who received CHB , 133 were evaluable for the assessment of anaemia ;  CHB was discontinued in 76 patients , of whom 64 were assessable for recovery from their anaemia . RESULTS Haemoglobin levels declined significantly in all patients from a mean baseline of 149 g/L to means of 139 g/L , 132 g/L and 131 g/L at 1 , 2 and 3 months , respectively . Haemoglobin levels continued to decline during CHB to a mean nadir of 123 g/L at a mean of 5.6 months of CHB , representing a mean absolute haemoglobin decline at nadir of 25.4 g/L. In 120 of the 133 ( 90 % ) patients , the relative decline in haemoglobin at nadir was > or = 10 % and was > or = 25 % in 17 ( 13 % ) others , representing a mean absolute haemoglobin decline in this subset of 42.7 g/L. Significant symptoms related to anaemia occurred in 17 patients ( 13 % ) . Anaemia and symptoms in these patients were easily corrected with the subcutaneous administration of recombinant human erythropoietin . CONCLUSIONS The anaemia associated with and rogen deprivation is significant and occurs routinely in men receiving CHB .  It is normochromic , normocytic , temporally-related to the initiation of and rogen blockade and usually resolves after CHB is discontinued . We suggest that patients receiving CHB undergo haematological testing at baseline , 1 - 2 months after initiating CHB and periodically thereafter . Patients developing anaemia should be question ed about symptoms reflecting physiological compromise ( e.g. angina , dyspnoea on exertion ) . In the absence of other causes , CHB should be suspected in the development of anaemia in patients receiving this treatment BACKGROUND We seek to determine if testosterone levels below the accepted castration threshold ( 50 ng/dL ) have an impact on time to progression to castrate-resistant prostate cancer ( CRPC ) . METHODS This is a prospect i ve cohort series of patients undergoing and rogen deprivation therapy ( ADT ) with luteinizing hormone-releasing hormone agonist or antagonist at a tertiary centre from 2006 to 2011 .  Serum testosterone level  was assessed every 3 months . Patients with any testosterone > 50 ng/dL were excluded . Patients were stratified into groups based on those achieving mean testosterone levels < 20 ng/dL and < 32 ng/dL. Progression to CRPC was assessed with the Kaplan-Meier method and compared with the log-rank test . RESULTS A total of 32 patients were included in this study . Mean patient follow-up was 25.7 months . Patients with a 9-month serum testosterone < 32 ng/dL had a significantly increased time to CRPC compared to patients with testosterone 32 to 50 ng/dL ( p = 0.001 , median progression-free survival ( PFS ) 33.1 months [ < 32 ng/dL ] vs. 12.5 months [ > 32 ng/dL ] ) . Patients with first year mean testosterone < 32 ng/dL also had a significantly increased time to CRPC compared to 32 to 50 ng/dL ( p = 0.05 , median PFS 33.1 months [ < 32 ng/dL ] vs. 12.5 months [ 32 - 50 ng/dL ] ) . A testosterone < 20 ng/dL compared to 20 to 50 ng/dL did not significantly predict with time to CRPC . CONCLUSION This study supports a lower testosterone threshold to define optimal medical castration ( T < 32 ng/dL ) than the previously accepted st and ard of 50 ng/dL. Testosterone levels during ADT serve as an early predictor of disease progression and thus should be measured in conjunction with prostate-specific antigen BACKGROUND Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving and rogen-deprivation therapy .  Replacing and rogens before progression of the disease is hypothesized to prolong and rogen dependence . METHODS Men with newly diagnosed , metastatic , hormone-sensitive prostate cancer , a performance status of 0 to 2 , and a prostate-specific antigen ( PSA ) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an anti and rogen agent for 7 months . We then r and omly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent and rogen deprivation  , with patients stratified according to prior or no prior hormonal therapy , performance status , and extent of disease ( minimal or extensive ) . The co primary objectives were to assess whether intermittent  therapy  was noninferior to continuous therapy with respect to survival , with a one-sided test with an upper boundary of the hazard ratio of 1.20 , and whether quality of life differed between the groups 3 months after r and omization . RESULTS A total of 3040 patients were enrolled , of whom 1535 were included in the analysis : 765 r and omly assigned to continuous and rogen deprivation and 770 assigned to intermittent and rogen deprivation . The median follow-up period was 9.8 years . Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group ( hazard ratio for death with intermittent therapy , 1.10 ; 90 % confidence interval , 0.99 to 1.23 ) . Intermittent therapy was associated with better erectile function and mental health ( P<0.001 and P=0.003 , respectively ) at month 3 but not thereafter . There were no significant differences between the groups in the number of treatment-related high- grade adverse events . CONCLUSIONS Our findings were statistically inconclusive . In patients with metastatic hormone-sensitive prostate cancer , the confidence interval for survival exceeded the upper boundary for noninferiority , suggesting that we can not rule out a 20 % greater risk of death with intermittent therapy than with continuous therapy , but too few events occurred to rule out significant inferiority of intermittent therapy . Intermittent therapy result ed in small improvements in quality of life . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00002651 . ) Between 1960 and 1975 , the Veterans Administration Cooperative Urological Research Group conducted a consecutive series of 3 major r and omized clinical trials comparing various endocrine treatments for newly diagnosed prostate cancer patients . Six major conclusions concerning hormonal treatment emerged from these studies : 1 ) increased hazard of cardiovascular death after therapy with 5 mg diethylstilbestrol ( DES ) ; 2 ) orchiectomy plus DES no better than orchiectomy or DES alone ; 3 ) equivalent effect of 1.0 and 5.0 mg DES on cancer ; 4 ) reduced cardiovascular hazard from therapy with 1.0 mg DES ; 5 ) Premarin and Provera no better than 1.0 mg DES at doses studied ; 6 ) decisions about hormone treatment at diagnosis dependent on patient characteristics , mainly age and Gleason grade . In this paper , these studies are review ed briefly and data are presented to support these conclusions . Some tentative treatment recommendations are proposed IMPORTANCE The use of and rogen deprivation therapy ( ADT ) in the treatment of advanced prostate cancer has been shown to delay the clinical progression of the disease . However , the testosterone suppression associated with this therapy may lead to a hypogonadal condition that can have detrimental effects on renal function , thus raising the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury ( AKI ) . OBJECTIVE To determine whether the use of ADT is associated with an increased risk of AKI in patients newly diagnosed with prostate cancer . DESIGN AND SETTING A nested case-control analysis using medical information extracted from the UK Clinical Practice Research Data link linked to the Hospital Episodes Statistics data base . PARTICIPANTS Men newly diagnosed with nonmetastatic prostate cancer between January 1 , 1997 , and December 31 , 2008 , were selected and followed up until December 31 , 2009 . Cases were patients with incident AKI during follow-up who were r and omly matched with up to 20 controls on age , calendar year of prostate cancer diagnosis , and duration of follow-up . MAIN OUTCOMES AND MEASURES Conditional logistic regression was used to estimate odds ratios ( ORs ) with 95 % CIs of AKI associated with the use of ADT . ADT was categorized into 1 of 6 mutually exclusive groups : gonadotropin-releasing hormone agonists , oral anti and rogens , combined and rogen blockade , bilateral orchiectomy , estrogens , and combination of the above . RESULTS A total of 10,250 patients met the study inclusion criteria . During a mean follow-up of 4.1 ( SD , 2.9 ) years , 232 incident cases of AKI were identified ( rate , 5.5/1000 person-years ) . Overall , current use of any ADT was associated with an increased risk of AKI when compared with never use ( OR , 2.48 [ 95 % CI , 1.61 - 3.82 ] ) , generating a rate difference of 4.43/1000 persons per year ( 95 % CI , 1.54 - 7.33 ) . This association was mainly driven by a combined and rogen blockade consisting of gonadotropin-releasing hormone agonists with oral anti and rogens ( OR , 4.50 [ 95 % CI , 2.61 - 7.78 ] ) , estrogens ( OR , 4.00 [ 95 % CI , 1.06 - 15.03 ] ) , other combination therapies ( OR , 4.04 [ 95 % CI , 1.88 - 8.69 ] ) , and gonadotropin-releasing hormone agonists ( OR , 1.93 [ 95 % CI , 1.20 - 3.10 ] ) . CONCLUSIONS AND RELEVANCE In a cohort of patients with newly diagnosed nonmetastatic prostate cancer , the use of ADT was significantly associated with an increased risk of AKI . These findings require replication in other well- design ed studies as well as further investigation of their clinical importance PURPOSE We present a structured debate supporting the premise that immediate hormonal intervention has not been conclusively shown to provide a survival advantage in the management of advanced prostate cancer . MATERIAL S AND METHODS The literature emphasizing r and omized trials was review ed . Recommendations are based solely on a demonstrated advantage in survival . RESULTS In patients with stage Tx Nx Mo or MI disease who did not receive other primary therapy there is no demonstrated survival advantage to immediate hormonal therapy . In men with positive lymph nodes who underwent radical prostatectomy  a relatively small study showed a survival advantage in favor of immediate hormonal treatment compared to deferred treatment . This study did not reach the projected accrual of 240 patients and results have not been supported by other trials . In men with stages T2 - 4 Nx Mx disease who underwent primary treatment with radiotherapy  a survival advantage for early hormonal therapy is primarily limited to high risk subgroups . In patients with biochemical relapse following primary treatment there are no trials . CONCLUSIONS Because hormonal therapy is associated with the development of irreversible resistance in virtually all patients , it does not cure , there is usually a long interval from first prostate specific antigen elevation to the development of metastatic disease , and hormonal therapy has profound side effects and is expensive , delayed treatment is recommended in men with biochemical relapse following surgery or radiotherapy . Patients should be strongly encouraged to enter clinical trials to answer this question Abstract The efficacy of four treatments , placebo , orchiectomy plus placebo , estrogen ( diethylstilbestrol 5.0 mg . daily ) , and orchiectomy plus estrogen , was evaluated in 1,903 Stage III and IV prostatic cancer patients by comparing ( 1 ) survival curves , ( 2 ) causes of death , ( 3 ) clinical response , ( 4 ) development of metastases in Stage III patients , and ( 5 ) incidence of treatment change . Survival curves did not differ significantly for the four treatment groups except in Stage III , in which orchiectomy plus estrogen was worse than placebo , or orchiectomy plus placebo . There were significantly more cancer deaths in the two nonestrogen groups in both stages . Otherwise , there were no appreciable differences between the three hormonal treatments . We conclude that estrogen is more effective than orchiectomy in preventing cancer deaths , and the addition of orchiectomy to estrogen does not offer a clear-cut advantage over either treatment alone . Therefore , if treatment becomes necessary because of cancer symptoms , initial treatment with estrogen is preferred The aim of this study was to compare the efficacy of total intermittent and rogen deprivation ( IAD 
    Output:
    
IADT was found to be non-inferior in the primary setting for non-metastatic prostate cancer as well as in treatment of biochemical recurrence following radiotherapy .
However , these studies overrepresented low risk patients in whom consideration may be given to deferred ADT rather than early treatment with IADT .
In the metastatic prostate cancer setting , IADT was not found to be non-inferior to CADT .
In most trials , castration related symptoms improved with IADT and overall HRQOL results were mixed .
Little data are available on the effect of IADT on long term complications of ADT .
IADT remains a treatment with uncertain outcomes in metastatic prostate cancer and uncertain value over deferring ADT entirely in other prostate cancer clinical states