***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: Accurate prognostic parameters in prostate biopsies are needed to better counsel individual patients with prostate cancer . We evaluated the prognostic impact of morphologic and immunohistochemical parameters in preoperative prostate cancer biopsies . A consecutive series of prostate biopsies of 279 men ( 72 % with clinical stage T1c and 23 % with T2 ) who subsequently underwent radical prostatectomy  was prospect ively analysed for Gleason score , number and percentage of positive cores ( NPC , PPC ) , total percentage of biopsy tissue with tumour ( TPT ) , maximum tumour percentage per core ( MTP ) , and expression of Ki67 , Bcl‐2 and p53 . All biopsy features were significantly associated with at least one feature of the radical prostatectomy specimen . pT stage was independently predicted by PSA , seminal vesicle invasion by Ki67 LI , positive margins by PSA and MTP , large tumour diameter by PSA and PPC , and Gleason score by biopsy Gleason score , MTP , and Ki67 LI , respectively . Biopsy Gleason score , NPC ( 1 vs. > 1 ) , TPT ( < 7 vs. ≥7 % ) , and Ki67 LI ( < 10 vs. ≥10 % ) were significant predictors of biochemical recurrence after radical prostatectomy ( p < 0.01 , each ) . KI67 LI was the only independent prognostic factor in case of a low TPT ( < 7 % ) or low Gleason score ( < 7 ) , the hazard ratio being 6.76 and 6.44 , respectively . In summary , preoperative Gleason score , NPC , TPT and Ki67 LI significantly predict the risk of recurrence after radical prostatectomy , and Ki67 is an independent prognosticator in biopsies with low‐volume or low‐ grade prostate cancer . Analysis of Ki67 LI in these biopsies may help to better identify patients with clinical ly insignificant prostate cancer . © 2008 Wiley‐Liss , BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free survival ( 3.42 [ 1.96 - 5.98 ] , p<0.0001 ) . Of 49 histopathology slides received ( 19 immediate ADT , 30 observation ) , 16 were down grade d from the original Gleason score ( between groups < or = 6 , 7 , and > or = 8) and five were up grade d. We recorded similar proportions of score changes in each group ( p=0.68 ) , and no difference in score distribution by treatment ( p=0.38 ) . After adjustment for score , associations were still significant between treatment and survival ( overall , p=0.02 ; disease-specific , p=0.002 ; progression-free survival , p<0.0001 ) . INTERPRETATION Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy , compared with those who receive deferred treatment . The beneficial effects of early ADT , rather than an imbalance in risk factors , are likely to explain the differences in outcomes between treatments 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 BACKGROUND Optimum management of clinical ly localised prostate cancer presents unique challenges because of the highly variable and often indolent natural history of the disease . To predict disease aggressiveness , clinicians combine clinical variables to create prognostic models , but the models have limited accuracy . We assessed the prognostic value of a predefined  cell cycle progression  ( CCP ) score in two cohorts of patients with prostate cancer . METHODS We measured the expression of 31 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumour sample s , and created a predefined score and assessed its usefulness in the prediction of disease outcome . The signature was assessed retrospectively in a cohort of patients from the USA who had undergone radical prostatectomy , and in a cohort of r and omly selected men with clinical ly localised prostate cancer diagnosed by use of a transurethral resection of the prostate ( TURP ) in the UK who were managed conservatively . The primary endpoint was time to biochemical recurrence for the cohort of patients who had radical prostatectomy , and time to death from prostate cancer for the TURP cohort . FINDINGS After prostatectomy , the CCP score was useful for predicting biochemical recurrence in the univariate analysis ( hazard ratio for a 1-unit change [ doubling ] in CCP 1·89 ; 95 % CI 1·54 - 2·31 ; p=5·6 × 10(-9 ) ) and the best multivariate analysis ( 1·77 , 1·40 - 2·22 ; p=4·3 × 10(-6 ) ) . In the best predictive model ( final multivariate analysis ) , the CCP score and prostate-specific antigen ( PSA ) concentration were the most important variables and were more significant than any other clinical variable . In the TURP cohort , the CCP score was the most important variable for prediction of time to death from prostate cancer in both univariate analysis ( 2·92 , 2·38 - 3·57 , p=6·1 × 10(-22 ) ) and the final multivariate analysis ( 2·57 , 1·93 - 3·43 ; p=8·2 × 10(-11 ) ) , and was stronger than all other prognostic factors , although PSA concentration also added useful information . Heterogeneity in the hazard ratio for the CCP score was not noted in any case for any clinical variables . INTERPRETATION The results of this study provide strong evidence that the CCP score is a robust prognostic marker , which , after additional validation , could have an essential role in determining the appropriate treatment for patients with prostate cancer . FUNDING Cancer Research UK , Queen Mary University of London , Orchid Appeal , US National Institutes of Health , and Koch Foundation 
    Output:
    
High Ki-67 was strongly associated with worse clinical outcomes .
High Ki-67 expression in localized PCa is a factor of poor prognosis for DSS , biochemical failure-free survival , DFS , DM , and OS after curative-intent treatments .