title: Prognostic significance of disseminated tumor cells in the bone marrow of prostate cancer patients treated with neoadjuvant hormone treatment.
abstract: OBJECTIVE
  To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy.
  
  
  METHODS
  Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients' outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months.
  
  
  RESULTS
  DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014).
  
  
  CONCLUSIONS
  The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Köllermann
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Klaus
authors.initials: K
authors.lastname: Kleinschmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Rau
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D000368:Aged; D000813:Anilides / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D019046:Bone Marrow Neoplasms / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005485:Flutamide / Q000008:administration & dosage; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009570:Nitriles / Q000008:administration & dosage; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D014105:Tosyl Compounds / Q000008:administration & dosage
chemical_list: D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D005485:Flutamide; C053541:bicalutamide; D016729:Leuprolide