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 Although there is r and omized evidence that radical prostatectomy improves survival , there are few data on how benefit varies by baseline risk . OBJECTIVE We aim ed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient , using stage , grade , prostate-specific antigen , and age as predictors . DESIGN , SETTING , AND PARTICIPANTS A total of 695 men with T1 or T2 prostate cancer participated in the Sc and inavian Prostate Cancer Group 4 trial ( SPCG-4 ) . INTERVENTION Patients in SPCG-4 were r and omized to radical prostatectomy or conservative management . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Competing risk models were created separately for the radical prostatectomy and the watchful waiting group , with the difference between model predictions constituting the estimated benefit for an individual patient . RESULTS AND LIMITATIONS Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics . At 65 yr of age , the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5 % to 17.2 % for low- versus high-risk patients . Little expected benefit was associated with surgery much beyond age 70 . Only about a quarter of men had an individualized benefit within even 50 % of the mean . A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients . CONCLUSIONS Our model suggests that it is hard to justify surgery in patients with Gleason 6 , T1 disease or in those patients much above 70 yr of age . Conversely , surgery seems unequivocally of benefit for patients who have Gleason 8 , or Gleason 7 , stage T2 . For patients with Gleason 6 T2 and Gleason 7 T1 , treatment is more of a judgment call , depending on patient preference and other clinical findings , such as the number of positive biopsy cores and comorbidities BACKGROUND High-intensity focused ultrasound ( HIFU ) is an emerging treatment for select patients with localized prostate cancer ( PCa ) . OBJECTIVES To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter data base . DESIGN , SETTING , AND PARTICIPANTS Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study . Previously irradiated patients were excluded from this analysis . In case of any residual or recurrent PCa , patients were systematic ally offered a second session . Kaplan-Meier analysis was performed to determine disease-free survival rates ( DFSR ) . MEASUREMENTS Prostate-specific antigen ( PSA ) , clinical stage , and pathologic results were measured pre- and post-HIFU . RESULTS AND LIMITATIONS A total of 803 patients from six urologic departments met the inclusion criteria . Stratification according to d'Amico 's risk group was low , intermediate , and high in 40.2 % , 46.3 % , and 13.5 % of patients , respectively . Mean follow-up was 42+/-33 mo . Mean PSA nadir was 1.0+/-2.8 ng/ml with 54.3 % reaching a nadir of < or = 0.3 ng/ml . Control biopsies were negative in 85 % of cases . The overall and cancer-specific survival rates at 8 yr were 89 % and 99 % , respectively . The metastasis-free survival rate at 8 yr was 97 % . Initial PSA value and Gleason score value significantly influence the DFSR . The 5- and 7-yr biochemical-free survival rates ( Phoenix criteria ) were 83 - 75 % , 72 - 63 % , and 68 - 62 % ( p=0.03 ) and the additional treatment-free survival rates were 84 - 79 % , 68 - 61 % , and 52 - 54 % ( p<0.001 ) for low- , intermediate- , and high-risk patients , respectively . PSA nadir was a major predictive factor for HIFU success : negative biopsies , stable PSA , and no additional therapy . CONCLUSIONS Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy ( EBRT ) . The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT 3 Background : Radiotherapy ( RT ) and long term and rogen blockade ( AB ) is st and ard treatment for patients with high risk prostate cancer . However , the optimal duration of AB is not yet defined . The purpose of this r and omized study was to compare outcomes between 36 vs. 18 months of AB in high risk prostate cancer treated with RT ( PCS IV trial , Clinical Trials.gov , # NCT00223171 ) . METHODS PCS IV r and omized patients with node negative high risk prostate cancer ( T3 - 4 , PSA > 20 ng/ml or Gleason score > 7 ) , to pelvic RT ( whole pelvis 44 Gy/4 ½ weeks , prostate 70 Gy/7 weeks ) and 36 ( arm 1 ) vs. 18 months ( arm 2 ) of AB ( neo adjuvant , concomitant , adjuvant ) . AB consisted of bicalutamide 50 mg for one month plus goserelin 10.8 mg every three months for 36 vs. 18 months . Overall survival was the primary end point . Overall and cancer specific survival rates were compared between arms with Kaplan-Meier log rank test and Cox regression . RESULTS From October 2000 to January 2008 , 310 patients were r and omized to arm 1 and 320 to arm 2 . Patients ' characteristics were well balanced between the two arms ( median age 71 years , median PSA 16 ng/ml , median Gleason score 8) . Most patients had T2 - 3 disease . At a median follow-up of 77 months , 71/310 patients ( 22.9 % ) in arm 1 and 76/320 ( 23.8 % ) in arm 2 had died ( p=0.802 ) . Overall , 116 patients died of causes other than prostate cancer . Overall and cancer specific survival hazard ratios were 1.15 ( 0.83 - 1.59 ) , p=0.398 and 1.13 ( 0.61 - 2.08 ) , p=0.153 , respectively . 5 year overall and disease specific survival rates were 92.1 % ( 89.1 - 95.1 ) vs. 86.8 % ( 83.0 - 90.6 ) , p=0.052 and 97.6 % ( 95.9 - 99.4 ) vs. 96.4 % ( 94.2 - 98.6 ) , p=0.473 and 10 year overall and disease specific survival rates were 63.6 % ( 55.7 - 71.5 ) vs. 63.2 % ( 54.7 - 71.7 ) , p=0.429 and 87.2 % ( 81.0 - 93.3 ) vs. 87.2 % ( 80.9 - 93.6 ) , p=0.838 for arm 1 and arm 2 , respectively . There were no significant differences in the rates of biochemical , regional or distant failure between arms . CONCLUSIONS Our study shows that long term AB can be safely reduced from 36 to 18 months without compromising outcomes . Analysis of treatment impact on quality of life is now under review . SOURCE OF FUNDING AstraZeneca Pharmaceuticals Grant . CLINICAL TRIAL INFORMATION Clinical Trials.gov , # NCT00223171 BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) BACKGROUND The optimal upper limit of the normal range for prostate-specific antigen ( PSA ) is unknown . We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less . METHODS Of 18,882 men enrolled in the prevention trial , 9459 were r and omly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination . Among these 9459 men , 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination , had a final PSA determination , and underwent a prostate biopsy after being in the study for seven years . RESULTS Among the 2950 men ( age range , 62 to 91 years ) , prostate cancer was diagnosed in 449 ( 15.2 percent ) ; 67 of these 449 cancers ( 14.9 percent ) had a Gleason score of 7 or higher . The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter , 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter , 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter , 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter , and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter . The prevalence of high- grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter . CONCLUSIONS Biopsy-detected prostate cancer , including high- grade cancers , is not rare among men with PSA levels of 4.0 ng per milliliter or less -- levels generally thought to be in the normal range PURPOSE Active surveillance for favorable risk prostate cancer is an approach that may reduce the risk of overtreatment of clinical ly insignificant prostate cancer . In fact , some patients with favorable risk disease at diagnosis harbor more aggressive disease and may be at risk for prostate cancer mortality despite close monitoring . This is a detailed report of 5 of 453 patients on surveillance who died of prostate cancer . MATERIAL S AND METHODS A large phase 2 prospect i ve trial of active surveillance in patients with favorable risk prostate cancer was initiated in 1995 . Eligible patients had favorable risk prostate cancer ( prostate specific antigen 10 ng/ml or less , Gleason 6 or less , T1c/T2a ) . Epstein criteria for clinical ly insignificant prostate cancer ( a third or less of cores positive , 50 % or less involvement of any 1 core , and prostate specific antigen density less than 0.15 ) were used for men younger than 55 years . Patients were followed with serial prostate specific antigen determinations  every 3 months for 2 years and then every 6 months if stable . Biopsies were performed at 1 year and then every 3 to 4 years . Radical intervention was offered if prostate specific antigen doubling time was less than 3 years or Gleason 3 + 4 pattern disease was identified on repeat biopsy . For the first 5 years of the study patients older than 70 years were eligible if they had Gleason 3 + 4 or less , or prostate specific antigen less than 15 ng/ml . RESULTS The rate of intervention with radiation or surgery  was 38 % at 10 years ( actuarial ) . All  
    Output:
    
agent
Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy .
A biopsy progression indicates the need for active intervention , whereas the role of PSA doubling time is controversial .
In men with locally advanced PCa for whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) , with equivalent oncologic efficacy .
Active treatment is recommended mostly for patients with localized disease and a long life expectancy , with radical prostatectomy ( RP ) shown to be superior to WW in prospect i ve r and omized trials .
Nerve-sparing RP is the approach of choice in organ-confined disease , while neoadjuvant ADT provides no improvement in outcome variables .
For locally advanced disease , adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice .
Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to and rogen-deprivation therapy in locally advanced PCa not requiring immediate local treatment .
***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 Although there is r and omized evidence that radical prostatectomy improves survival , there are few data on how benefit varies by baseline risk . OBJECTIVE We aim ed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient , using stage , grade , prostate-specific antigen , and age as predictors . DESIGN , SETTING , AND PARTICIPANTS A total of 695 men with T1 or T2 prostate cancer participated in the Sc and inavian Prostate Cancer Group 4 trial ( SPCG-4 ) . INTERVENTION Patients in SPCG-4 were r and omized to radical prostatectomy or conservative management . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Competing risk models were created separately for the radical prostatectomy and the watchful waiting group , with the difference between model predictions constituting the estimated benefit for an individual patient . RESULTS AND LIMITATIONS Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics . At 65 yr of age , the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5 % to 17.2 % for low- versus high-risk patients . Little expected benefit was associated with surgery much beyond age 70 . Only about a quarter of men had an individualized benefit within even 50 % of the mean . A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients . CONCLUSIONS Our model suggests that it is hard to justify surgery in patients with Gleason 6 , T1 disease or in those patients much above 70 yr of age . Conversely , surgery seems unequivocally of benefit for patients who have Gleason 8 , or Gleason 7 , stage T2 . For patients with Gleason 6 T2 and Gleason 7 T1 , treatment is more of a judgment call , depending on patient preference and other clinical findings , such as the number of positive biopsy cores and comorbidities BACKGROUND High-intensity focused ultrasound ( HIFU ) is an emerging treatment for select patients with localized prostate cancer ( PCa ) . OBJECTIVES To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter data base . DESIGN , SETTING , AND PARTICIPANTS Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study . Previously irradiated patients were excluded from this analysis . In case of any residual or recurrent PCa , patients were systematic ally offered a second session . Kaplan-Meier analysis was performed to determine disease-free survival rates ( DFSR ) . MEASUREMENTS Prostate-specific antigen ( PSA ) , clinical stage , and pathologic results were measured pre- and post-HIFU . RESULTS AND LIMITATIONS A total of 803 patients from six urologic departments met the inclusion criteria . Stratification according to d'Amico 's risk group was low , intermediate , and high in 40.2 % , 46.3 % , and 13.5 % of patients , respectively . Mean follow-up was 42+/-33 mo . Mean PSA nadir was 1.0+/-2.8 ng/ml with 54.3 % reaching a nadir of < or = 0.3 ng/ml . Control biopsies were negative in 85 % of cases . The overall and cancer-specific survival rates at 8 yr were 89 % and 99 % , respectively . The metastasis-free survival rate at 8 yr was 97 % . Initial PSA value and Gleason score value significantly influence the DFSR . The 5- and 7-yr biochemical-free survival rates ( Phoenix criteria ) were 83 - 75 % , 72 - 63 % , and 68 - 62 % ( p=0.03 ) and the additional treatment-free survival rates were 84 - 79 % , 68 - 61 % , and 52 - 54 % ( p<0.001 ) for low- , intermediate- , and high-risk patients , respectively . PSA nadir was a major predictive factor for HIFU success : negative biopsies , stable PSA , and no additional therapy . CONCLUSIONS Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy ( EBRT ) . The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT 3 Background : Radiotherapy ( RT ) and long term and rogen blockade ( AB ) is st and ard treatment for patients with high risk prostate cancer . However , the optimal duration of AB is not yet defined . The purpose of this r and omized study was to compare outcomes between 36 vs. 18 months of AB in high risk prostate cancer treated with RT ( PCS IV trial , Clinical Trials.gov , # NCT00223171 ) . METHODS PCS IV r and omized patients with node negative high risk prostate cancer ( T3 - 4 , PSA > 20 ng/ml or Gleason score > 7 ) , to pelvic RT ( whole pelvis 44 Gy/4 ½ weeks , prostate 70 Gy/7 weeks ) and 36 ( arm 1 ) vs. 18 months ( arm 2 ) of AB ( neo adjuvant , concomitant , adjuvant ) . AB consisted of bicalutamide 50 mg for one month plus goserelin 10.8 mg every three months for 36 vs. 18 months . Overall survival was the primary end point . Overall and cancer specific survival rates were compared between arms with Kaplan-Meier log rank test and Cox regression . RESULTS From October 2000 to January 2008 , 310 patients were r and omized to arm 1 and 320 to arm 2 . Patients ' characteristics were well balanced between the two arms ( median age 71 years , median PSA 16 ng/ml , median Gleason score 8) . Most patients had T2 - 3 disease . At a median follow-up of 77 months , 71/310 patients ( 22.9 % ) in arm 1 and 76/320 ( 23.8 % ) in arm 2 had died ( p=0.802 ) . Overall , 116 patients died of causes other than prostate cancer . Overall and cancer specific survival hazard ratios were 1.15 ( 0.83 - 1.59 ) , p=0.398 and 1.13 ( 0.61 - 2.08 ) , p=0.153 , respectively . 5 year overall and disease specific survival rates were 92.1 % ( 89.1 - 95.1 ) vs. 86.8 % ( 83.0 - 90.6 ) , p=0.052 and 97.6 % ( 95.9 - 99.4 ) vs. 96.4 % ( 94.2 - 98.6 ) , p=0.473 and 10 year overall and disease specific survival rates were 63.6 % ( 55.7 - 71.5 ) vs. 63.2 % ( 54.7 - 71.7 ) , p=0.429 and 87.2 % ( 81.0 - 93.3 ) vs. 87.2 % ( 80.9 - 93.6 ) , p=0.838 for arm 1 and arm 2 , respectively . There were no significant differences in the rates of biochemical , regional or distant failure between arms . CONCLUSIONS Our study shows that long term AB can be safely reduced from 36 to 18 months without compromising outcomes . Analysis of treatment impact on quality of life is now under review . SOURCE OF FUNDING AstraZeneca Pharmaceuticals Grant . CLINICAL TRIAL INFORMATION Clinical Trials.gov , # NCT00223171 BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) BACKGROUND The optimal upper limit of the normal range for prostate-specific antigen ( PSA ) is unknown . We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less . METHODS Of 18,882 men enrolled in the prevention trial , 9459 were r and omly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination . Among these 9459 men , 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination , had a final PSA determination , and underwent a prostate biopsy after being in the study for seven years . RESULTS Among the 2950 men ( age range , 62 to 91 years ) , prostate cancer was diagnosed in 449 ( 15.2 percent ) ; 67 of these 449 cancers ( 14.9 percent ) had a Gleason score of 7 or higher . The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter , 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter , 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter , 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter , and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter . The prevalence of high- grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter . CONCLUSIONS Biopsy-detected prostate cancer , including high- grade cancers , is not rare among men with PSA levels of 4.0 ng per milliliter or less -- levels generally thought to be in the normal range PURPOSE Active surveillance for favorable risk prostate cancer is an approach that may reduce the risk of overtreatment of clinical ly insignificant prostate cancer . In fact , some patients with favorable risk disease at diagnosis harbor more aggressive disease and may be at risk for prostate cancer mortality despite close monitoring . This is a detailed report of 5 of 453 patients on surveillance who died of prostate cancer . MATERIAL S AND METHODS A large phase 2 prospect i ve trial of active surveillance in patients with favorable risk prostate cancer was initiated in 1995 . Eligible patients had favorable risk prostate cancer ( prostate specific antigen 10 ng/ml or less , Gleason 6 or less , T1c/T2a ) . Epstein criteria for clinical ly insignificant prostate cancer ( a third or less of cores positive , 50 % or less involvement of any 1 core , and prostate specific antigen density less than 0.15 ) were used for men younger than 55 years . Patients were followed with serial prostate specific antigen determinations  every 3 months for 2 years and then every 6 months if stable . Biopsies were performed at 1 year and then every 3 to 4 years . Radical intervention was offered if prostate specific antigen doubling time was less than 3 years or Gleason 3 + 4 pattern disease was identified on repeat biopsy . For the first 5 years of the study patients older than 70 years were eligible if they had Gleason 3 + 4 or less , or prostate specific antigen less than 15 ng/ml . RESULTS The rate of intervention with radiation or surgery  was 38 % at 10 years ( actuarial ) . All  
    Output:
    