title: Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel.
abstract: OBJECTIVE
  We investigated whether serum markers of angiogenesis endothelin-1 (ET-1) and tissue factor (TF), and/or markers of vascular damage such as circulating endothelial cells (CECs), or their relative changes during treatment, were prognostic for overall survival (OS) in castration resistant prostate cancer (CRPC) patients. Additionally, we combined these markers with circulating tumour cells (CTCs) to construct a predictive nomogram for treatment outcome.
  
  
  METHODS
  One hundred and sixty two CRPC patients treated with a docetaxel containing regimen had blood drawn before and at 2-5 weeks and 6-8 weeks after treatment start. Prospectively determined CTC and CEC levels, and retrospectively measured serum concentrations of ET-1 (pg/mL) and TF (pg/mL) were evaluated to determine their prognostic value for OS.
  
  
  RESULTS
  Baseline CEC, TF and ET-1 were not prognostic for OS. A > or = 3.8-fold increase in CEC 2-5 weeks after treatment initiation was associated with decreased OS (median 10.9 versus 16.8 months; P=0.015), as was any decrease in TF levels compared to baseline levels (median 11.9 versus 21.5 months; P=0.0005). As previously published, baseline and CTC counts > or = 5 at 2-5 weeks were also predictive of decreased OS. Combining CTC with changes in TF and CEC 2-5 weeks after treatment initiation yielded four groups differing in OS (median OS 24.2 versus 16.0 versus 11.4 versus 6.1 months; P<0.0001).
  
  
  CONCLUSIONS
  CEC, CTC and TF levels alone and combined can predict early on OS in CRPC patients treated with docetaxel-based therapy. A prospective study to confirm the use of these markers for patient management is needed.
authors.affiliation: Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Strijbos
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.forename: P I M
authors.initials: PI
authors.lastname: Schmitz
authors.forename: C
authors.initials: C
authors.lastname: Rao
authors.forename: W
authors.initials: W
authors.lastname: Onstenk
authors.forename: G V
authors.initials: GV
authors.lastname: Doyle
authors.forename: M C
authors.initials: MC
authors.lastname: Miller
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: L W M M
authors.initials: LW
authors.lastname: Terstappen
authors.forename: S
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000077143:Docetaxel; D019332:Endothelin-1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D009389:Neovascularization, Pathologic; D009919:Orchiectomy; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D013925:Thromboplastin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019332:Endothelin-1; D043823:Taxoids; D000077143:Docetaxel; D013925:Thromboplastin