human
***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 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 . ) BACKGROUND We report the long-term results of a trial of immediate postoperative irradiation versus a wait- and -see policy in patients with prostate cancer extending beyond the prostate , to confirm whether previously reported progression-free survival was sustained . METHODS This r and omised , phase 3 , controlled trial recruited patients aged 75 years or younger with untreated cT0 - 3 prostate cancer ( WHO performance status 0 or 1 ) from 37 institutions across Europe . Eligible patients were r and omly assigned central ly ( 1:1 ) to postoperative irradiation ( 60 Gy of conventional irradiation to the surgical bed for 6 weeks ) or to a wait- and -see policy until biochemical progression ( increase in prostate-specific antigen > 0·2 μg/L confirmed twice at least 2 weeks apart ) . We analysed the primary endpoint , biochemical progression-free survival , by intention to treat ( two-sided test for difference at α=0.05 , adjusted for one interim analysis ) and did exploratory analyses of heterogeneity of effect . This trial is registered with Clinical Trials.gov , number NCT00002511 . FINDINGS 1005 patients were r and omly assigned to a wait- and -see policy ( n=503 ) or postoperative irradiation ( n=502 ) and were followed up for a median of 10·6 years ( range 2 months to 16·6 years ) . Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait- and -see policy ( 198 [ 39·4 % ] of 502 patients in postoperative irradiation group vs 311 [ 61·8 % ] of 503 patients in wait- and -see group had biochemical or clinical progression or died ; HR 0·49 [ 95 % CI 0·41 - 0·59 ] ; p<0·0001 ) . Late adverse effects ( any type of any grade ) were more frequent in the postoperative irradiation group than in the wait- and -see group ( 10 year cumulative incidence 70·8 % [ 66·6 - 75·0 ] vs 59·7 % [ 55·3 - 64·1 ] ; p=0.001 ) . INTERPRETATION Results at median follow-up of 10·6 years show that conventional postoperative irradiation  significantly improves biochemical progression-free survival and local control compared with a wait- and -see policy , supporting results at 5 year follow-up ; however , improvements in clinical progression-free survival were not maintained . Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins , but could have a detrimental effect in patients aged 70 years or older . FUNDING Ligue Nationale contre le Cancer ( Comité de l'Isère , Grenoble , France ) and the European Organisation for Research and Treatment of Cancer ( EORTC ) Charitable Trust Prostate cancer is a common malignancy worldwide , and in Canada , it is the most frequently diagnosed cancer in men . The stratification of prostate cancer into risk categories has allowed for improved counselling of patients and provides guidance for treatment selection . However , the exact definition of high-risk prostate cancer remains controversial , and that lack of consensus remains a barrier to assessing available data from various institutions and from clinical trials . The proportion of patients with locally advanced high-risk disease has fallen in the last 20 years largely because of screening for prostate-specific antigen , but management in this population continues to be an important clinical problem . A factor that has emerged in recent years is the importance of local disease control , with data from multiple r and omized trials suggesting that local therapy improves progression-free survival , disease-free survival , and overall survival . Further research in this population is necessary to improve outcomes BACKGROUND Local failure after radical prostatectomy ( RP ) is common in patients with cancer extending beyond the capsule . Three prospect ively r and omized trials demonstrated an advantage for adjuvant radiotherapy ( ART ) compared with a wait- and -see ( WS ) policy . OBJECTIVE To determine the efficiency of ART after a 10-yr follow-up in the ARO 96 - 02 study . DESIGN , SETTING , AND PARTICIPANTS After RP , 388 patients with pT3 pN0 prostate cancer ( PCa ) were r and omized to WS or three-dimensional conformal ART with 60 Gy . The present analysis focuses on intent-to-treat patients who achieved an undetectable prostate-specific antigen after RP ( ITT2 population ) --that is , 159  WS plus 148  ART  men . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point of the study was progression-free survival ( PFS ) ( events : biochemical recurrence , clinical recurrence , or death ) . Outcomes were compared by log-rank test . Cox regression analysis served to identify variables influencing the course of disease . RESULTS AND LIMITATIONS The median follow-up was 111 mo for ART and 113 mo for WS . At 10 yr , PFS was 56 % for ART and 35 % for WS ( p<0.0001 ) . In pT3b and R1 patients , the rates for WS even dropped to 28 % and 27 % , respectively . Of all 307 ITT2 patients , 15 died from PCa , and 28 died for other or unknown reasons . Neither metastasis-free survival nor overall survival was significantly improved by ART . However , the study was underpowered for these end points . The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity . No grade 4 events occurred . CONCLUSIONS Compared with WS , ART reduced the risk of ( biochemical ) progression with a hazard ratio of 0.51 in pT3 PCa . With only one grade 3 case of late toxicity , ART was safe . PATIENT SUMMARY Pre caution ary radiotherapy counteracts relapse after surgery for prostate cancer with specific risk factors 
    Output:
    
agent
***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 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 . ) BACKGROUND We report the long-term results of a trial of immediate postoperative irradiation versus a wait- and -see policy in patients with prostate cancer extending beyond the prostate , to confirm whether previously reported progression-free survival was sustained . METHODS This r and omised , phase 3 , controlled trial recruited patients aged 75 years or younger with untreated cT0 - 3 prostate cancer ( WHO performance status 0 or 1 ) from 37 institutions across Europe . Eligible patients were r and omly assigned central ly ( 1:1 ) to postoperative irradiation ( 60 Gy of conventional irradiation to the surgical bed for 6 weeks ) or to a wait- and -see policy until biochemical progression ( increase in prostate-specific antigen > 0·2 μg/L confirmed twice at least 2 weeks apart ) . We analysed the primary endpoint , biochemical progression-free survival , by intention to treat ( two-sided test for difference at α=0.05 , adjusted for one interim analysis ) and did exploratory analyses of heterogeneity of effect . This trial is registered with Clinical Trials.gov , number NCT00002511 . FINDINGS 1005 patients were r and omly assigned to a wait- and -see policy ( n=503 ) or postoperative irradiation ( n=502 ) and were followed up for a median of 10·6 years ( range 2 months to 16·6 years ) . Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait- and -see policy ( 198 [ 39·4 % ] of 502 patients in postoperative irradiation group vs 311 [ 61·8 % ] of 503 patients in wait- and -see group had biochemical or clinical progression or died ; HR 0·49 [ 95 % CI 0·41 - 0·59 ] ; p<0·0001 ) . Late adverse effects ( any type of any grade ) were more frequent in the postoperative irradiation group than in the wait- and -see group ( 10 year cumulative incidence 70·8 % [ 66·6 - 75·0 ] vs 59·7 % [ 55·3 - 64·1 ] ; p=0.001 ) . INTERPRETATION Results at median follow-up of 10·6 years show that conventional postoperative irradiation  significantly improves biochemical progression-free survival and local control compared with a wait- and -see policy , supporting results at 5 year follow-up ; however , improvements in clinical progression-free survival were not maintained . Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins , but could have a detrimental effect in patients aged 70 years or older . FUNDING Ligue Nationale contre le Cancer ( Comité de l'Isère , Grenoble , France ) and the European Organisation for Research and Treatment of Cancer ( EORTC ) Charitable Trust Prostate cancer is a common malignancy worldwide , and in Canada , it is the most frequently diagnosed cancer in men . The stratification of prostate cancer into risk categories has allowed for improved counselling of patients and provides guidance for treatment selection . However , the exact definition of high-risk prostate cancer remains controversial , and that lack of consensus remains a barrier to assessing available data from various institutions and from clinical trials . The proportion of patients with locally advanced high-risk disease has fallen in the last 20 years largely because of screening for prostate-specific antigen , but management in this population continues to be an important clinical problem . A factor that has emerged in recent years is the importance of local disease control , with data from multiple r and omized trials suggesting that local therapy improves progression-free survival , disease-free survival , and overall survival . Further research in this population is necessary to improve outcomes BACKGROUND Local failure after radical prostatectomy ( RP ) is common in patients with cancer extending beyond the capsule . Three prospect ively r and omized trials demonstrated an advantage for adjuvant radiotherapy ( ART ) compared with a wait- and -see ( WS ) policy . OBJECTIVE To determine the efficiency of ART after a 10-yr follow-up in the ARO 96 - 02 study . DESIGN , SETTING , AND PARTICIPANTS After RP , 388 patients with pT3 pN0 prostate cancer ( PCa ) were r and omized to WS or three-dimensional conformal ART with 60 Gy . The present analysis focuses on intent-to-treat patients who achieved an undetectable prostate-specific antigen after RP ( ITT2 population ) --that is , 159  WS plus 148  ART  men . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point of the study was progression-free survival ( PFS ) ( events : biochemical recurrence , clinical recurrence , or death ) . Outcomes were compared by log-rank test . Cox regression analysis served to identify variables influencing the course of disease . RESULTS AND LIMITATIONS The median follow-up was 111 mo for ART and 113 mo for WS . At 10 yr , PFS was 56 % for ART and 35 % for WS ( p<0.0001 ) . In pT3b and R1 patients , the rates for WS even dropped to 28 % and 27 % , respectively . Of all 307 ITT2 patients , 15 died from PCa , and 28 died for other or unknown reasons . Neither metastasis-free survival nor overall survival was significantly improved by ART . However , the study was underpowered for these end points . The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity . No grade 4 events occurred . CONCLUSIONS Compared with WS , ART reduced the risk of ( biochemical ) progression with a hazard ratio of 0.51 in pT3 PCa . With only one grade 3 case of late toxicity , ART was safe . PATIENT SUMMARY Pre caution ary radiotherapy counteracts relapse after surgery for prostate cancer with specific risk factors 
    Output:
    