***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: Purpose Physicians sometimes make management recommendations on the basis of early results from r and omized controlled trials ( RCTs ) relating to reduced prostate-specific antigen ( PSA ) failure , yet whether this early end point is associated with all-cause mortality ( ACM ) , particularly in men with competing risks , is unknown . Using a vali date d metric in men treated within the context of an RCT , we aim ed to determine whether PSA failure is associated with the risk of ACM stratified by comorbidity score . Patients and Methods Between 1995 and 2001 , 206 men with localized ( T1b to 2b ) intermediate- and high-risk prostate cancer ( PC ) were r and omly assigned to receive radiation therapy or radiation therapy and 6 months of ADT . Cox regression analyses were performed to evaluate whether PSA failure modeled as a time-dependent covariate was associated with an increased risk of ACM among men with Adult Comorbidity Evaluation-27-defined no or minimal versus moderate-to-severe comorbidity adjusting for age , PC prognostic factors , and treatment . Results After a median follow-up of 16.62 years , 156 men ( 76 % ) died , 29 of whom ( 19 % ) died as a result of PC . PSA failure was associated with an increased ACM risk among men with no or minimal ( adjusted hazard ratio , 1.59 ; 95 % CI , 1.03 to 2.46 ; P = .04 ) , but not moderate or severe comorbidity ( adjusted hazard ratio , 1.75 ; 95 % CI , 0.76 to 3.99 ; P = .19 ) . Conclusion Recommending treatment on the basis of reduced PSA failure observed from early results of RCTs is unlikely to prolong survival in men with moderate-to-severe comorbidity but may prolong survival in men with no or minimal comorbidity , providing evidence to support discussing the early results with these men 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 . ) PURPOSE We evaluated predictors of  prostate cancer-specific mortality ( PCSM ) after prostate-specific antigen ( PSA ) failure after radical prostatectomy ( RP ) or radiation therapy ( RT ) . PATIENTS AND METHODS A total of 1,159 men with clinical ly localized prostate cancer treated with RP ( n = 498 ) or RT ( n = 661 ) developed PSA failure , and they formed the study cohort . Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis , including  post-treatment PSA doubling time ( PSA-DT ) , Gleason score , and interval to PSA failure , could also predict time to PCSM after PSA failure . The cumulative incidence method was used to estimate PCSM after PSA failure . RESULTS A post-RP PSA-DT of less than 3 months ( hazard ratio [ HR ] , 54.9 ; 95 % CI , 16.7 to 180 ) , a post-RT PSA-DT of less than 3 months ( HR , 12.8 ; 95 % CI , 7.0 to 23.1 ) , and a biopsy Gleason score of 8 to 10 ( HR , 6.1 ; 95 % CI , 3.4 to 10.7 ) for patients treated with RT were significantly associated with PCSM . Post-RP estimated rates of PCSM 5 years after PSA failure were 31 % ( 95 % CI , 17 % to 45 % ) v 1 % ( 95 % CI , 0 % to 2 % ) for patients with PSA-DT of less than 3 months v > or = 3 months . Post-RT estimated rates of PCSM 5 years after PSA failure were 75 % ( 95 % CI , 59 % to 92 % ) v 35 % ( 95 % CI , 24 % to 47 % ) for patients with a biopsy Gleason score of > or = 8 v < or = 7 , respectively , and PSA-DT of less than 3 months ; these rates were 15 % ( 95 % CI , 0.8 % to 28 % ) v 4 % ( 95 % CI , 1 % to 6 % ) , respectively , for patients with a PSA-DT > or = 3 months . CONCLUSION Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score . These parameters may be useful in identifying patients for a r and omized trial evaluating hormonal therapy with or without docetaxel Background : The optimal management of men with PSA failure following initial prostate cancer ( PC ) therapy stratified by comorbidity is unknown . We investigated the impact that PSA doubling time ( DT ) and comorbidity had on the risk of all-cause mortality ( ACM ) , prostate cancer-specific mortality ( PCSM ) and other-cause mortality ( OCM ) following PSA failure . Methods : Between 1995 and 2001 , 206 men with unfavorable-risk PC were r and omized to receive radiation therapy alone or in combination with 6 months of and rogen deprivation therapy ( ADT ) ; 108 men experienced PSA failure and formed the study cohort . Cox and Fine – Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM , respectively , stratified by comorbidity status using a vali date d metric . Results : After a median follow-up of 13.71 years following PSA failure , 81 of the 108 men ( 75 % ) died . Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal ( adjusted hazard ratio ( AHR ) 0.33 , 95 % confidence interval ( CI ) 0.17–0.65 , P=0.001 ) and moderate/severe comorbidity ( AHR 0.014 , 95 % CI 0.002–0.129 , P=0.0002 ) . However , because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups , increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal ( AHR 0.69 , 95 % CI 0.50–0.96 , P=0.03 ) but not moderate/severe comorbidity ( AHR 0.95 , 95 % CI 0.51–1.78 , P=0.87 ) . Conclusions : Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and /or clinical trial eligibility at the time of PSA failure BACKGROUND Hormonal manipulation concomitant to salvage radiotherapy ( SRT ) given for biochemical recurrence ( BCR ) after radical prostatectomy ( RP ) improved outcomes in two r and omized trials . However , neither of these studies focused on men treated at low prostate-specific antigen ( PSA ) levels . OBJECTIVE To test if the impact of and rogen deprivation therapy ( ADT ) on metastasis in patients undergoing early SRT  varies according to prostate cancer ( PCa ) features . DESIGN , SETTING , AND PARTICIPANTS A total of 525 patients received SRT at PSA levels ≤2ng/ml . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Multivariable Cox regression analyses assessed factors associated with metastasis . We tested the hypothesis that the impact of ADT varied according to the risk of metastasis . An interaction with groups ( concomitant ADT vs no ADT ) and the probability of distant metastasis according to a newly developed model was tested . A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT . RESULTS AND LIMITATIONS Median PSA and radiotherapy dose were 0.42ng/ml and 66Gy , respectively . Overall , 178 ( 34 % ) patients received ADT . At a median follow-up of 104 mo , 71 patients experienced metastasis . Grade group ≥4 ( hazard ratio [ HR ] : 1.66 ; 95 % confidence interval [ CI ] : 1.01 - 3.30 ) , pT3b/4 ( HR : 2.61 ; 95 % CI : 1.51 - 4.52 ) , and dose ( HR : 0.82 ; 95 % CI : 0.76 - 0.89 ) were associated with metastasis . The impact of ADT differed according to the risk of metastasis calculated using a multivariable model ( p=0.01 ) . This was confirmed when considering patients treated with early SRT ( p=0.046 ) , where ADT was associated with a reduction in the rate of metastasis only in eSRT ; patients with more aggressive characteristics ( ie , pT3b/4 and grade group ≥4 , or pT3b/4 and PSA at eSRT ≥0.4ng/ml ) . CONCLUSIONS The beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics , such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP . PATIENT SUMMARY The oncological benefits of concomitant and rogen deprivation therapy ( ADT ) in patients undergoing salvage radiotherapy ( SRT ) vary according to pathological characteristics . Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT . Conversely , the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features BACKGROUND Patients with lymph node (LN)-positive prostate cancer ( PCa ) at radical prostatectomy ( RP ) face a high risk of cancer recurrence . Nevertheless , recurrence patterns of LN-positive PCa and their prognostic significance remain understudied in the literature . OBJECTIVE To analyze a large single-institution series with long-term follow-up to eluci date the various clinical recurrence patterns of LN-positive PCa and their association with oncologic outcomes . DESIGN , SETTING , AND PARTICIPANTS Years 1987 - 2012 
    Output:
    
BCR was associated with worse survival rates , mainly in patients with short prostate-specific antigen doubling time ( PSA-DT ) and a high final Gleason score after RP , or a short interval to biochemical failure ( IBF ) after RT and a high biopsy Gleason score .
BCR has an impact on survival , but this effect appears to be limited to a subgroup of patients with specific clinical risk factors .
Short PSA-DT and a high final Gleason score after RP , and a short IBF after RT and a high biopsy Gleason score are the main factors that have a negative impact on survival .
For many men , rising PSA does not mean that they are at a high risk of death from prostate cancer in the longer term .
Men with PSA that rises shortly after they were treated with radiotherapy or rapidly rising PSA after surgery and a high tumor grade for both treatment modalities are at the highest risk of death .