title: Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients.
abstract: BACKGROUND
  Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel.
  
  
  METHODS
  CTC-counts were assessed in 122 serial samples, as continuous or categorical (<5 vs. ≥5 CTCs) variables, at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD), by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods.
  
  
  RESULTS
  Categorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p=0.02) and 18.0 (p=0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p=0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95% CI 1.1-13.8, p=0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95% CI 0.99-1.05, p=0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95% CI 1.6-15.7, p=0.007) and 1.02 (95% CI 1.0-1.040, p=0.04).
  
  
  CONCLUSIONS
  Categorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment.
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. mark.thalgott@lrz.tum.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Thalgott
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum der Ludwig-Maximilians-Universität, Klinikum Innenstadt, Maistrasse 11, 80337, Munich, Germany. Brigitte.Rack@med.uni-muenchen.de.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.affiliation: Department of Radiology, Munich, Germany. matthias.eiber@gmx.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eiber
authors.affiliation: Department of Nuclear Medicine, Munich, Germany. msouvatz@yahoo.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Souvatzoglou
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. m.heck@lrz.tu-muenchen.de.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Heck
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. carokronester@gmx.de.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kronester
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum der Ludwig-Maximilians-Universität, Klinikum Innenstadt, Maistrasse 11, 80337, Munich, Germany. Ulrich.Andergassen@med.uni-muenchen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Andergassen
authors.affiliation: Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. victoria.kehl@tum.de.
authors.forename: Victoria
authors.initials: V
authors.lastname: Kehl
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Rostock, Schillingallee 35, 18057, Rostock, Germany. bernd.krause@uni-rostock.de.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Krause
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. Juergen.Gschwend@lrz.tu-muenchen.de.
authors.forename: Jurgen E
authors.initials: JE
authors.lastname: Gschwend
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. Margitta.Retz@lrz.tu-muenchen.de.
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. Roman.Nawroth@lrz.tu-muenchen.de.
authors.forename: Roman
authors.initials: R
authors.lastname: Nawroth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D057285:Precision Medicine; D011379:Prognosis; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel