***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 Intermediate or surrogate endpoints for survival can shorten time lines for drug approval . We aim ed to assess circulating tumour cell ( CTC ) count as a prognostic factor for survival in patients with progressive , metastatic , castration-resistant prostate cancer receiving first-line chemotherapy . METHODS We identified patients with progressive metastatic castration-resistant prostate cancer starting first-line chemotherapy in the IMMC38 trial .  CTCs were isolated by immunomagnetic capture from blood sample s at baseline and after treatment . Baseline variables , including CTC count , titre of prostate-specific antigen ( PSA ) , and concentration of lactate dehydrogenase ( LDH ) , and post-treatment variables ( change in CTCs and PSA ) were tested for association with survival with Cox proportional hazards models . Concordance probability estimates were used to gauge discriminatory strength of the informative factors in identifying patients at low-risk and high-risk of survival . FINDINGS Variables associated with high risk of death were high LDH concentration ( hazard ratio 6.44 , 95 % CI 4.24 - 9.79 ) , high CTC count ( 1.58 , 1.41 - 1.77 ) , and high PSA titre ( 1.26 , 1.10 - 1.45 ) , low albumin ( 0.10 , 0.03 - 0.39 ) , and low haemoglobin ( 0.72 , 0.64 - 0.81 ) at baseline . At 4 weeks , 8 weeks , and 12 weeks after treatment , changes in CTC number were strongly associated with risk , whereas changes in PSA titre were weakly or not associated ( p>0.04 ) . The most predictive factors for survival were LDH concentration and CTC counts ( concordance probability estimate 0.72 - 0.75 ) . INTERPRETATION CTC number , analysed as a continuous variable , can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials . Prospect i ve recording of CTC number as an intermediate endpoint of survival in r and omised clinical trials is warranted Purpose : To detect insulin-like growth factor-IR ( IGF-IR ) on circulating tumor cells ( CTC ) as a biomarker in the clinical development of a monoclonal human antibody , CP-751,871 , targeting IGF-IR . Experimental Design : An automated sample preparation and analysis system for enumerating CTCs ( CellTracks ) was adapted for detecting IGF-IR – positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871 . This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was vali date d using cell lines and blood sample s from healthy volunteers and patients with metastatic carcinoma . Results : There was no interference between the analytic and therapeutic antibodies . Eighty patients were enrolled on phase I studies of CP-751,871 , with 47 ( 59 % ) patients having CTCs detected during the study . Before treatment , 26 patients ( 33 % ) had CTCs  , with 23 having detectable IGF-IR – positive CTCs . CP-751,871 alone , and CP-751,871 with cytotoxic chemotherapy , decreased CTCs and IGF-IR – positive CTCs ; these increased toward the end of the 21-day cycle in some patients , falling again with retreatment . CTCs were commonest in advanced hormone refractory prostate cancer ( 11 of 20 ) . Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by > 50 % ( 6 of 10 versus 2 of 8 patients ) . A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by > 50 % . Conclusions : IGF-IR expression is detectable by immunofluorescence on CTCs . These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection , particularly in advanced prostate cancer In clinical ly organ-confined prostate cancer patients , bloodstream tumour cell dissemination generally occurs , and may be enhanced by surgical prostate manipulation . To evaluate cancer-cell seeding impact upon patient recurrence-free survival , 155 patients were prospect ively enrolled then followed . Here , 57 patients presented blood prostate cell shedding preoperatively and intraoperatively ( group I ) . Of the 98 preoperatively negative patients , 53 ( 54 % ) remained negative ( group II ) and 45 ( 46 % ) became intraoperatively positive ( group III ) . Median biological and clinical recurrence-free time was far shorter in group I ( 36.2 months , P<0.0001 ) than in group II ( 69.6 months ) but did not significantly differ in group II and III ( 69.6 months vs 65.0 ) . Such 5-year follow-up data show that preoperative circulating prostate cells are an independent prognosis factor of recurrence . Moreover , tumour h and ling induces cancer-cell seeding but surgical blood dissemination does not accelerate cancer evolution BACKGROUND The purpose of this study was to evaluate the association of  circulating tumour cell ( CTC ) counts  , before and after commencing treatment , with overall survival ( OS ) in patients with castration-resistant prostate cancer ( CRPC ) . EXPERIMENTAL DESIGN A 7.5 ml of blood was collected before and after treatment in 119 patients with CRPC .  CTCs were enumerated using the Cell Search System . RESULTS Higher CTC counts associated with baseline characteristics portending aggressive disease . Multivariate analyses indicated that a CTC > or=5 was an independent prognostic factor at all time points evaluated . Patients with baseline CTC > or=5 had shorter OS than those with < 5 [ median OS 19.5 versus > 30 months , hazard ratio ( HR ) 3.25 , P=0.012 ] ; patients with CTC > 50 had a poorer OS than those with CTCs 5 - 50 ( median OS 6.3 versus 21.1 months , HR 4.1 , P<0.001 ) . Patients whose CTC counts reduced from > or=5 at baseline to < 5 following treatment had a better OS compared with those who did not . CTC counts showed a similar , but earlier and independent , ability to time to disease progression to predict OS . CONCLUSION  CTC counts  predict OS and provide independent prognostic information to time to disease progression ; CTC dynamics following therapy need to be evaluated as an intermediate end point of outcome in r and omised phase III trials Purpose : The TAX-327 study r and omized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel , weekly docetaxel , or mitoxantrone , each with prednisone . Experimental Design : We used the TAX-327 data base to address ( a ) the relationship between quality of life ( QoL ) and pain ; ( b ) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL ; ( c ) the relationships between prostate-specific antigen ( PSA ) response , pain response , and QoL response ; ( d ) the times at which these responses are first observed ; and ( e ) whether PSA , pain , and /or QoL response predict for overall survival . Results : At baseline , 374 of 815 men assessed for QoL had major pain ; of these , 92 % had substantial impairment of QoL compared with 75 % without major pain ( P < 0.001 ) . Men with minimal symptoms had prolonged survival ( median , 25.6 months ) compared with symptomatic patients ( median , 17.1 months ; P = 0.009 ) ; they were more likely to have initial deterioration of QoL if treated with weekly docetaxel .  PSA response and pain response , but not QoL response , were independently associated with survival in l and mark analysis . Median times to PSA and pain response were 44 and 27 days , respectively ; some men had initial increase in serum PSA before subsequent decline . Conclusions : Symptoms other than pain contribute to impaired QoL in men with hormone-refractory prostate cancer . Those with minimal symptoms have prolonged survival . Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies . Early increases in serum PSA ( up to 12 weeks ) should be ignored when determining response or progression PURPOSE We report a prospect i ve study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction ( RT-PCR ) for prostate-specific antigen ( PSA ) and prostate-specific membrane antigen ( PSM ) to predict pathologic stage and biochemical recurrence in patients with clinical ly localized prostate cancer treated with radical prostatectomy .  PATIENTS AND METHODS One hundred forty-one patients were entered onto the study . Preoperative evaluation included clinical T stage , serum PSA , biopsy Gleason score , and serum RT-PCR for PSA/PSM . Univariate and multivariate logistic regression models , Kaplan-Meier estimates , and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure . RESULTS Seventy-three patients ( 51.8 % ) were RT-PCR positive for PSA , PSM , or both . In the multivariate logistic regression model , only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease ( odds ratio [ OR ] , 1.06 ; 95 % confidence interval [ CI ] , 1.00 to 1.13 ; P = .026 ) or organ-/specimen-confined disease ( OR , 1.09 ; 95 % CI , 1.02 to 1.16 ; P = .009 ) . Overall Kaplan-Meier biochemical relapse-free survival ( bRFS ) was 85 % at 59 months . Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA ( OR , 1.05 ; 95 % CI , 1.02 to 1.09 ; P = .004 ) and biopsy Gleason score ( OR , 3.57 ; 95 % CI , 1.37 to 9.58 ; P = .009 ) were independent predictors of biochemical failure . RT-PCR status did not predict pathologic stage or biochemical failure . Repeat analysis excluding 27 patients who received preoperative and rogen-deprivation therapy did not change the results . CONCLUSION Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy . This assay has no clinical utility in this patient population The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies PURPOSE We previously reported evidence of hematogenous dissemination of prostate cells during radical retropubic prostatectomy , and we now provide clinical and molecular reverse transcriptase-polymerase chain reaction ( RT-PCR ) followup of that patient cohort . MATERIAL S AND METHODS A total of 101 men with clinical ly localized prostate cancer were prospect ively enrolled in the study . The prostate specific antigen ( PSA ) RT-PCR assay was performed on peripheral venous blood sample s preoperatively in 101 , during surgery in 29 , during and up to 12 weeks after surgery in 50 and at least 1 year postoperatively in 65 patients . Correlation with clinical ( PSA ) indicators of recurrence was performed . RESULTS Of the 101 patients 9 demonstrated biochemical evidence of prostate cancer progression ( median followup 22 months ) . Of the 50 men with perioperative molecular results the RT-PCR positive rate increased from 22 % preoperatively in 11 to 48 % in 24 ( p = 0.02 ) and then decreased to 10 % in 4 of 40 men at 1 year postoperatively ( p = 0.07 ) . Molecular followup at a minimum of 1 year after radical retropubic prostatectomy was obtained in  
    Output:
    
Initially , reverse transcriptase polymerase chain reaction ( RT-PCR ) based methods were utilized with weak correlation between their positive detection and patients ' outcome .
More recent immunological techniques have indicated a reproducible correlation with outcome .