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 The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND No r and omized trials have compared survival outcomes for men with localized prostate cancer ( PC ) being treated with radical prostatectomy ( RP ) or external beam radiotherapy ( EBRT ) . The goal of the study , therefore , was to estimate the association of RP ( compared with EBRT ) with overall and PC mortality . METHODS We analyzed an observational cohort from the population -based Prostate Cancer Outcomes Study , which included men aged 55 to 74 years diagnosed with localized PC between October 1994 and October 1995 who underwent either RP ( n = 1164 ) or EBRT ( n = 491 ) within 1 year of diagnosis . Patients were followed until death or study end ( December 31 , 2010 ) . Overall and disease-specific mortality were assessed with multivariable survival analysis , with propensity scores to adjust for potential treatment selection confounders ( demographics , comorbidities , and tumor characteristics ) . All statistical tests were two-sided . RESULTS After 15 years of follow-up , there were 568 deaths , including 104 from PC . RP was associated with statistically significant advantages for overall ( hazard ratio [ HR ] = 0.60 , 95 % confidence interval [ CI ] = 0.53 to 0.70 , P < .0001 . ) and disease-specific mortality ( HR = 0.35 , 95 % CI = 0.26 to 0.49 , P < .0001 . ) . Mortality benefits for RP were also observed within treatment propensity quintiles , when subjects were pair-matched on propensity scores , and in subgroup analyses based on age , tumor characteristics , and comorbidity . CONCLUSIONS Population -based observational data on men diagnosed with localized PC in the mid-1990s suggest a mortality benefit associated with RP vs EBRT . Possible explanations include residual selection bias or a true survival advantage . Results might be less applicable for men facing treatment decisions today PURPOSE To assess long-term outcomes of men with favorable-risk prostate cancer in a prospect i ve , active-surveillance program . METHODS Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy . Primary outcomes were overall , cancer-specific , and metastasis-free survival . Secondary outcomes were the cumulative incidence of reclassification and curative intervention . Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model . RESULTS A total of 1,298 men ( median age , 66 years ) with a median follow-up of 5 years ( range , 0.01 to 18.00 years ) contributed 6,766 person-years of follow-up since 1995 .  Overall , cancer-specific , and metastasis-free survival rates were 93 % , 99.9 % , and 99.4 % , respectively , at 10 years and 69 % , 99.9 % , and 99.4 % , respectively , at 15 years . The cumulative incidence of grade reclassification was 26 % at 10 years and was 31 % at 15 years ; cumulative incidence of curative  intervention was 50 % at 10 years and was 57 % at 15 years . The median treatment-free survival was 8.5 years ( range , 0.01 to 18 years ) . Factors associated with grade reclassification were older age ( hazard ratio [ HR ] , 1.03 for each additional year ; 95 % CI , 1.01 to 1.06 ) , prostate-specific antigen density ( HR , 1.21 per 0.1 unit increase ; 95 % CI , 1.12 to 1.46 ) , and greater number of positive biopsy cores ( HR , 1.47 for each additional positive core ; 95 % CI , 1.26 to 1.69 ) . Factors associated with intervention were prostate-specific antigen density ( HR , 1.38 per 0.1 unit increase ; 95 % CI , 1.22 to 1.56 ) and a greater number of positive biopsy cores ( HR , 1.35 for one additional positive core ; 95 % CI , 1.19 to 1.53 ) . CONCLUSION Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention Summary Background Whether the addition of radiation therapy ( RT ) improves overall survival in men with locally advanced prostate cancer managed with and rogen deprivation therapy ( ADT )  is unclear . Our aim was to compare outcomes in such patients with locally advanced prostate cancer . Methods Patients with : locally advanced ( T3 or T4 ) prostate cancer ( n=1057 ) ; or organ-confined disease ( T2 ) with either a prostate-specific antigen ( PSA ) concentration more than 40 ng/mL ( n=119 ) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher ( n=25 ) , were r and omly assigned ( done central ly with stratification and dynamic minimisation , not masked ) to receive lifelong ADT and RT ( 65–69 Gy to the prostate and seminal vesicles , 45 Gy to the pelvic nodes ) . The primary endpoint was overall survival . The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded . All efficacy analyses were done by intention to treat and were based on data from all patients . This trial is registered at controlledtrials.com as IS RCT N24991896 and Clinical trials.gov as NCT00002633 . Results Between 1995 and 2005 , 1205 patients were r and omly assigned ( 602 in the ADT only group and 603 in the ADT and RT group ) ; median follow-up was 6·0 years ( IQR 4·4–8·0 ) . At the time of analysis , a total of 320 patients had died , 175 in the ADT only group and 145 in the ADT and RT group . The addition of RT to ADT  improved overall survival at 7 years ( 74 % , 95 % CI 70–78 vs 66 % , 60–70 ; hazard ratio [ HR ] 0·77 , 95 % CI 0·61–0·98 , p=0·033 ) . Both toxicity and health-related quality -of-life results showed a small effect of RT on late gastrointestinal toxicity ( rectal bleeding grade > 3 , three patients ( 0·5 % ) in the ADT only group , two ( 0·3 % ) in the ADT and RT group ; diarrhoea grade > 3 , four patients ( 0·7 % ) vs eight ( 1·3 % ) ; urinary toxicity grade > 3 , 14 patients ( 2·3 % ) in both groups ) . Interpretation The benefits of combined modality treatment — ADT and RT — should be discussed with all patients with locally advanced prostate cancer . Funding Canadian Cancer Society Research Institute , US National Cancer Institute , and UK Medical Research Council BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy .  Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy  , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) A recent r and omized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival . We report on the quality of life ( QOL ) outcomes for this trial PURPOSE To examine consequences of deferred treatment ( DT ) as initial management of prostate cancer ( PCa ) in a contemporary , prospect i ve cohort of American men diagnosed with PCa . PARTICIPANTS AND METHODS We evaluated deferred treatment for PCa in the Health Professionals Follow-up Study , a prospect i ve study of 51,529 men . Cox proportional hazards models were used to calculate hazard ratios ( H 
    Output:
    
agent
Results The AUA ( American Urological Association ) , ASTRO , and SUO ( Society of Urologic Oncology ) formulated an evidence ‐based guideline based on a risk stratified clinical framework for the management of localized prostate cancer .
***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 The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND No r and omized trials have compared survival outcomes for men with localized prostate cancer ( PC ) being treated with radical prostatectomy ( RP ) or external beam radiotherapy ( EBRT ) . The goal of the study , therefore , was to estimate the association of RP ( compared with EBRT ) with overall and PC mortality . METHODS We analyzed an observational cohort from the population -based Prostate Cancer Outcomes Study , which included men aged 55 to 74 years diagnosed with localized PC between October 1994 and October 1995 who underwent either RP ( n = 1164 ) or EBRT ( n = 491 ) within 1 year of diagnosis . Patients were followed until death or study end ( December 31 , 2010 ) . Overall and disease-specific mortality were assessed with multivariable survival analysis , with propensity scores to adjust for potential treatment selection confounders ( demographics , comorbidities , and tumor characteristics ) . All statistical tests were two-sided . RESULTS After 15 years of follow-up , there were 568 deaths , including 104 from PC . RP was associated with statistically significant advantages for overall ( hazard ratio [ HR ] = 0.60 , 95 % confidence interval [ CI ] = 0.53 to 0.70 , P < .0001 . ) and disease-specific mortality ( HR = 0.35 , 95 % CI = 0.26 to 0.49 , P < .0001 . ) . Mortality benefits for RP were also observed within treatment propensity quintiles , when subjects were pair-matched on propensity scores , and in subgroup analyses based on age , tumor characteristics , and comorbidity . CONCLUSIONS Population -based observational data on men diagnosed with localized PC in the mid-1990s suggest a mortality benefit associated with RP vs EBRT . Possible explanations include residual selection bias or a true survival advantage . Results might be less applicable for men facing treatment decisions today PURPOSE To assess long-term outcomes of men with favorable-risk prostate cancer in a prospect i ve , active-surveillance program . METHODS Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy . Primary outcomes were overall , cancer-specific , and metastasis-free survival . Secondary outcomes were the cumulative incidence of reclassification and curative intervention . Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model . RESULTS A total of 1,298 men ( median age , 66 years ) with a median follow-up of 5 years ( range , 0.01 to 18.00 years ) contributed 6,766 person-years of follow-up since 1995 .  Overall , cancer-specific , and metastasis-free survival rates were 93 % , 99.9 % , and 99.4 % , respectively , at 10 years and 69 % , 99.9 % , and 99.4 % , respectively , at 15 years . The cumulative incidence of grade reclassification was 26 % at 10 years and was 31 % at 15 years ; cumulative incidence of curative  intervention was 50 % at 10 years and was 57 % at 15 years . The median treatment-free survival was 8.5 years ( range , 0.01 to 18 years ) . Factors associated with grade reclassification were older age ( hazard ratio [ HR ] , 1.03 for each additional year ; 95 % CI , 1.01 to 1.06 ) , prostate-specific antigen density ( HR , 1.21 per 0.1 unit increase ; 95 % CI , 1.12 to 1.46 ) , and greater number of positive biopsy cores ( HR , 1.47 for each additional positive core ; 95 % CI , 1.26 to 1.69 ) . Factors associated with intervention were prostate-specific antigen density ( HR , 1.38 per 0.1 unit increase ; 95 % CI , 1.22 to 1.56 ) and a greater number of positive biopsy cores ( HR , 1.35 for one additional positive core ; 95 % CI , 1.19 to 1.53 ) . CONCLUSION Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention Summary Background Whether the addition of radiation therapy ( RT ) improves overall survival in men with locally advanced prostate cancer managed with and rogen deprivation therapy ( ADT )  is unclear . Our aim was to compare outcomes in such patients with locally advanced prostate cancer . Methods Patients with : locally advanced ( T3 or T4 ) prostate cancer ( n=1057 ) ; or organ-confined disease ( T2 ) with either a prostate-specific antigen ( PSA ) concentration more than 40 ng/mL ( n=119 ) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher ( n=25 ) , were r and omly assigned ( done central ly with stratification and dynamic minimisation , not masked ) to receive lifelong ADT and RT ( 65–69 Gy to the prostate and seminal vesicles , 45 Gy to the pelvic nodes ) . The primary endpoint was overall survival . The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded . All efficacy analyses were done by intention to treat and were based on data from all patients . This trial is registered at controlledtrials.com as IS RCT N24991896 and Clinical trials.gov as NCT00002633 . Results Between 1995 and 2005 , 1205 patients were r and omly assigned ( 602 in the ADT only group and 603 in the ADT and RT group ) ; median follow-up was 6·0 years ( IQR 4·4–8·0 ) . At the time of analysis , a total of 320 patients had died , 175 in the ADT only group and 145 in the ADT and RT group . The addition of RT to ADT  improved overall survival at 7 years ( 74 % , 95 % CI 70–78 vs 66 % , 60–70 ; hazard ratio [ HR ] 0·77 , 95 % CI 0·61–0·98 , p=0·033 ) . Both toxicity and health-related quality -of-life results showed a small effect of RT on late gastrointestinal toxicity ( rectal bleeding grade > 3 , three patients ( 0·5 % ) in the ADT only group , two ( 0·3 % ) in the ADT and RT group ; diarrhoea grade > 3 , four patients ( 0·7 % ) vs eight ( 1·3 % ) ; urinary toxicity grade > 3 , 14 patients ( 2·3 % ) in both groups ) . Interpretation The benefits of combined modality treatment — ADT and RT — should be discussed with all patients with locally advanced prostate cancer . Funding Canadian Cancer Society Research Institute , US National Cancer Institute , and UK Medical Research Council BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy .  Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy  , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) A recent r and omized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival . We report on the quality of life ( QOL ) outcomes for this trial PURPOSE To examine consequences of deferred treatment ( DT ) as initial management of prostate cancer ( PCa ) in a contemporary , prospect i ve cohort of American men diagnosed with PCa . PARTICIPANTS AND METHODS We evaluated deferred treatment for PCa in the Health Professionals Follow-up Study , a prospect i ve study of 51,529 men . Cox proportional hazards models were used to calculate hazard ratios ( H 
    Output:
    