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: CRA4504 Background : The impact of radiotherapy on overall survival ( OS ) in men with locally advanced CaP is unclear . The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality . Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. METHODS Patients with T3/T4 ( 1057 ) or T2 , PSA > 40 μ g/l ( 119 ) or T2 PSA > 20 μ g/l and Gleason ≥ 8 ( 25 ) and N0 /NX , M0 prostate adenocarcinoma were r and omized to  lifelong ADT ( bilateral orchiectomy or LHRH agonist ) with or without RT ( 65 - 69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes ) . The primary endpoint was OS and secondary endpoints included disease specific survival ( DSS ) , time to disease progression and quality of life . RESULTS 1205 patients were r and omized from 1995 to 2005 , 602 to ADT and 603 to ADT+RT  ( well balanced with respect to baseline characteristics ) . A protocol specified second interim analysis on OS was performed in Aug 2009 ( data cut-off Dec 31 2008 ) . The DSMC recommended release of the results to the Trial Committee for publication . The median follow-up is 6.0 years and 320 patients have died ( 175 ADT and 145 ADT+RT ) . 10 % of patients had no follow-up data beyond 2006 . The addition of RT to ADT  significantly reduced the risk of death ( hazard ratio [ HR ] 0.77 , 95 % CI 0.61 - 0.98 , p=0.033 ) . 140 patients died of disease and /or treatment ( 89 on ADT and 51 on ADT+RT ) The disease specific survival HR was 0.57 ( 95 % CI 0.41 - 0.81 , p=0.001 ) favoring ADT+RT  . The 10 year cumulative disease specific death rates were estimated at 15 % with ADT+ RT and 23 % with ADT  alone . Grade ≥2 late GI toxicity rates were similar in both arms ( proctitis , 1.3 % ADT alone , 1.8 % ADT+RT ) . CONCLUSIONS The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach ( ADT+RT ) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity . In view of this data combined modality therapy ( ADT+RT ) should be the st and ard treatment approach for these patients . Supported by NCI-US Grant # 5U10CA077202 - 12 , CCSRI Grant # 15469 . No significant financial relationships to disclose 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 5 patients had a prostate specific antigen doubling time of 1.6 years or less triggering a recommendation of radical therapy . Radical intervention was performed in 3 of the 5 patients . Patients 1 and 4 received radiation and patient 3 underwent radical prostatectomy . Of the 2 patients who did not receive definitive treatment 1 was lost to followup ( patient 2 ) and was treated conservatively by his family doctor . Patient 5 elected and  rogen deprivation therapy  rather than  radical treatment . CONCLUSIONS The low prostate cancer mortality in our surveillance cohort provides support for an active surveillance approach to favorable risk prostate cancer . Only 1 of the 5 patients presented with favorable disease and experienced a theoretically preventable death . The absence of preventable deaths suggests that the basic approach is sound . Two patients had a trigger for intervention but did not receive it . This reinforces the importance of close monitoring and of definitive treatment for those in whom disease is reclassified as higher risk over time PURPOSE To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy ( IMRT ) to a dose of 86.4 Gy for localized prostate cancer . METHODS AND MATERIAL S Between August 1997 and March 2004 , 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique . To adhere to normal tissue constraints , the mean D95 and V100 for the planning target volume were 83 Gy and 87 % , respectively . Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0 . Freedom from biochemical relapse was calculated . The median follow-up was 53 months . RESULTS Thirty-seven patients ( 8 % ) experienced acute Grade 2 gastrointestinal ( GI ) toxicity . There was no acute Grade 3 or 4 GI toxicity . One hundred and five patients ( 22 % ) experienced acute Grade 2 genitourinary ( GU ) toxicity and three patients ( 0.6 % ) had Grade 3 GU toxicity . There was no acute Grade 4 GU toxicity . Sixteen patients ( 3 % ) developed late Grade 2 GI toxicity and two patients ( < 1 % ) developed late Grade 3 GI toxicity . Sixty patients ( 13 % ) had late Grade 2 GU toxicity and 12 ( <3 % ) experienced late Grade 3 GU toxicity . The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98 % , 85 % and 70 % for the low , intermediate , and high risk NCCN prognostic groups . CONCLUSION This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer . Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging BACKGROUND Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer . To assess the effect of radiotherapy , we did an open phase III study comparing endocrine therapy with and without local radiotherapy , followed by castration on progression . METHODS This r and omised trial included men from 47 centres in Norway , Sweden , and Denmark . Between February , 1996 , and December , 2002 , 875 patients with locally advanced prostate cancer ( T3 ; 78 % ; PSA<70 ; N0 ; M0 ) were central ly r and omly assigned by computer to endocrine treatment alone ( 3 months of total and rogen blockade followed by continuous endocrine treatment using flutamide ; 439 patients ) , or to the same endocrine treatment combined with radiotherapy ( 436 patients ) . The primary endpoint was prostate-cancer-specific survival , and analysis was by intention to treat . This study is registered as an international st and ard r and omised controlled trial , number IS RCT N01534787 . FINDINGS After a median follow-up of 7.6 years , 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer . The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9 % in the endocrine alone group and 11.9 % in the endocrine plus radiotherapy group ( difference 12.0 % , 95 % CI 4.9 - 19.1 % ) , for a relative risk of 0.44 ( 0.30 - 0.66 ) . At 10 years , the cumulative incidence for overall mortality was 39.4 % in the endocrine alone group and 29.6 % in the endocrine plus radiotherapy group ( difference 9.8 % , 0.8 - 18.8 % ) , for a relative risk of 0.68 ( 0.52 - 0.89 ) . Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group ( 74.7%vs 25.9 % , p<0.0001 ; HR 0.16 ; 0.12 - 0.20 ) . After 5 years , urinary , rectal , and sexual problems were slightly more frequent in the endocrine plus radiotherapy group . INTERPRETATION In patients with locally advanced or high-risk local prostate cancer , addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality , and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone . In the light of these data , endocrine treatment plus radiotherapy should be the new st and ard Prostate biopsy is usually performed without anesthesia . We evaluated the patient ’s perception of pain/discomfort experienced during the procedure in terms of the type of anesthesia used : periprostatic infiltration with 2 % lidocaine , or intrarectal instillation of lidocaine-prilocain cream . A total of 198 patients were divided into three groups : group 1 ( control group , n=40 ) received sonographic gel intrarectally prior to biopsy , group 2 ( n=75 ) were given intrarectal instillation of lidocaine-prilocain cream , and group 3 ( n=80 ) received periprostatic anesthesia by injecting 10 ml of 2 % lidocaine .  Pain after each biopsy was assessed using an 11-point linear visual analog pain scale . The mean pain scores were 5.1 in group 1 , 4.8 in group 2 , and 2.5 in group 3 , result ing in a significant difference between group 3 and both groups 1 and 2 , but not between groups 1 and 2 . The incidence of biopsy-related adverse events did not differ among groups . Transrectal ultrasonographic guided periprostatic anesthesia is superior to intarectal instillation of lidocaine-prilocain cream BACKGROUND 
    Output:
    
agent
Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy .
PSA doubling time in < 3 yr or a biopsy progression indicates the need for active intervention .
In men with locally advanced PCa in 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 mostly recommended for patients with localised disease and a long life expectancy  with  radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial .
Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables .
For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice .
***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: CRA4504 Background : The impact of radiotherapy on overall survival ( OS ) in men with locally advanced CaP is unclear . The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality . Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. METHODS Patients with T3/T4 ( 1057 ) or T2 , PSA > 40 μ g/l ( 119 ) or T2 PSA > 20 μ g/l and Gleason ≥ 8 ( 25 ) and N0 /NX , M0 prostate adenocarcinoma were r and omized to  lifelong ADT ( bilateral orchiectomy or LHRH agonist ) with or without RT ( 65 - 69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes ) . The primary endpoint was OS and secondary endpoints included disease specific survival ( DSS ) , time to disease progression and quality of life . RESULTS 1205 patients were r and omized from 1995 to 2005 , 602 to ADT and 603 to ADT+RT  ( well balanced with respect to baseline characteristics ) . A protocol specified second interim analysis on OS was performed in Aug 2009 ( data cut-off Dec 31 2008 ) . The DSMC recommended release of the results to the Trial Committee for publication . The median follow-up is 6.0 years and 320 patients have died ( 175 ADT and 145 ADT+RT ) . 10 % of patients had no follow-up data beyond 2006 . The addition of RT to ADT  significantly reduced the risk of death ( hazard ratio [ HR ] 0.77 , 95 % CI 0.61 - 0.98 , p=0.033 ) . 140 patients died of disease and /or treatment ( 89 on ADT and 51 on ADT+RT ) The disease specific survival HR was 0.57 ( 95 % CI 0.41 - 0.81 , p=0.001 ) favoring ADT+RT  . The 10 year cumulative disease specific death rates were estimated at 15 % with ADT+ RT and 23 % with ADT  alone . Grade ≥2 late GI toxicity rates were similar in both arms ( proctitis , 1.3 % ADT alone , 1.8 % ADT+RT ) . CONCLUSIONS The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach ( ADT+RT ) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity . In view of this data combined modality therapy ( ADT+RT ) should be the st and ard treatment approach for these patients . Supported by NCI-US Grant # 5U10CA077202 - 12 , CCSRI Grant # 15469 . No significant financial relationships to disclose 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 5 patients had a prostate specific antigen doubling time of 1.6 years or less triggering a recommendation of radical therapy . Radical intervention was performed in 3 of the 5 patients . Patients 1 and 4 received radiation and patient 3 underwent radical prostatectomy . Of the 2 patients who did not receive definitive treatment 1 was lost to followup ( patient 2 ) and was treated conservatively by his family doctor . Patient 5 elected and  rogen deprivation therapy  rather than  radical treatment . CONCLUSIONS The low prostate cancer mortality in our surveillance cohort provides support for an active surveillance approach to favorable risk prostate cancer . Only 1 of the 5 patients presented with favorable disease and experienced a theoretically preventable death . The absence of preventable deaths suggests that the basic approach is sound . Two patients had a trigger for intervention but did not receive it . This reinforces the importance of close monitoring and of definitive treatment for those in whom disease is reclassified as higher risk over time PURPOSE To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy ( IMRT ) to a dose of 86.4 Gy for localized prostate cancer . METHODS AND MATERIAL S Between August 1997 and March 2004 , 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique . To adhere to normal tissue constraints , the mean D95 and V100 for the planning target volume were 83 Gy and 87 % , respectively . Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0 . Freedom from biochemical relapse was calculated . The median follow-up was 53 months . RESULTS Thirty-seven patients ( 8 % ) experienced acute Grade 2 gastrointestinal ( GI ) toxicity . There was no acute Grade 3 or 4 GI toxicity . One hundred and five patients ( 22 % ) experienced acute Grade 2 genitourinary ( GU ) toxicity and three patients ( 0.6 % ) had Grade 3 GU toxicity . There was no acute Grade 4 GU toxicity . Sixteen patients ( 3 % ) developed late Grade 2 GI toxicity and two patients ( < 1 % ) developed late Grade 3 GI toxicity . Sixty patients ( 13 % ) had late Grade 2 GU toxicity and 12 ( <3 % ) experienced late Grade 3 GU toxicity . The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98 % , 85 % and 70 % for the low , intermediate , and high risk NCCN prognostic groups . CONCLUSION This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer . Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging BACKGROUND Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer . To assess the effect of radiotherapy , we did an open phase III study comparing endocrine therapy with and without local radiotherapy , followed by castration on progression . METHODS This r and omised trial included men from 47 centres in Norway , Sweden , and Denmark . Between February , 1996 , and December , 2002 , 875 patients with locally advanced prostate cancer ( T3 ; 78 % ; PSA<70 ; N0 ; M0 ) were central ly r and omly assigned by computer to endocrine treatment alone ( 3 months of total and rogen blockade followed by continuous endocrine treatment using flutamide ; 439 patients ) , or to the same endocrine treatment combined with radiotherapy ( 436 patients ) . The primary endpoint was prostate-cancer-specific survival , and analysis was by intention to treat . This study is registered as an international st and ard r and omised controlled trial , number IS RCT N01534787 . FINDINGS After a median follow-up of 7.6 years , 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer . The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9 % in the endocrine alone group and 11.9 % in the endocrine plus radiotherapy group ( difference 12.0 % , 95 % CI 4.9 - 19.1 % ) , for a relative risk of 0.44 ( 0.30 - 0.66 ) . At 10 years , the cumulative incidence for overall mortality was 39.4 % in the endocrine alone group and 29.6 % in the endocrine plus radiotherapy group ( difference 9.8 % , 0.8 - 18.8 % ) , for a relative risk of 0.68 ( 0.52 - 0.89 ) . Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group ( 74.7%vs 25.9 % , p<0.0001 ; HR 0.16 ; 0.12 - 0.20 ) . After 5 years , urinary , rectal , and sexual problems were slightly more frequent in the endocrine plus radiotherapy group . INTERPRETATION In patients with locally advanced or high-risk local prostate cancer , addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality , and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone . In the light of these data , endocrine treatment plus radiotherapy should be the new st and ard Prostate biopsy is usually performed without anesthesia . We evaluated the patient ’s perception of pain/discomfort experienced during the procedure in terms of the type of anesthesia used : periprostatic infiltration with 2 % lidocaine , or intrarectal instillation of lidocaine-prilocain cream . A total of 198 patients were divided into three groups : group 1 ( control group , n=40 ) received sonographic gel intrarectally prior to biopsy , group 2 ( n=75 ) were given intrarectal instillation of lidocaine-prilocain cream , and group 3 ( n=80 ) received periprostatic anesthesia by injecting 10 ml of 2 % lidocaine .  Pain after each biopsy was assessed using an 11-point linear visual analog pain scale . The mean pain scores were 5.1 in group 1 , 4.8 in group 2 , and 2.5 in group 3 , result ing in a significant difference between group 3 and both groups 1 and 2 , but not between groups 1 and 2 . The incidence of biopsy-related adverse events did not differ among groups . Transrectal ultrasonographic guided periprostatic anesthesia is superior to intarectal instillation of lidocaine-prilocain cream BACKGROUND 
    Output:
    