title: Circulating tumor cells versus objective response assessment predicting survival in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy.
abstract: OBJECTIVE
  Circulating tumor cell (CTC) counts might display a superior prognostic value for overall survival (OS) compared to objective response criteria (OR) in metastatic castration-resistant prostate cancer (mCRPC) patients.
  
  
  METHODS
  CTCs were detected using the CellSearch™ System out of 122 samples during docetaxel chemotherapy (75 mg/m(2)) at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles, in mCRPC patients (n = 33). OR was evaluated by morphologic RECIST and clinical criteria after 4 (q4) and 10 (q10) cycles.
  
  
  RESULTS
  For OS, analyses revealed a significant prognostic value for categorical (<5 vs. ≥5) CTC counts (q0, p = 0.005; q1, p = 0.001; q4, p < 0.001; q10, p = 0.002), RECIST (q4, p < 0.001; q10, p = 0.02) and clinical criteria (q4, p < 0.001; q10, p = 0.02). Concordance of CTC counts with OR revealed a sensitivity of 83.3-87.5 % and a specificity of 68.0-76.5 % with complementary discriminatory power for OS. Comparing CTC counts with concomitant OR at q4 in multivariate analyses, an independent prognostic value for OS was found for CTC counts (HR 3.3; p = 0.02) similar to clinical (HR 4.9; p = 0.02) and radiologic response (HR 3.4; p = 0.051). Comparing the predictive value for death, early post-treatment CTC counts at q1 demonstrated significant accuracy with an area under the curve of 79.5 % (p = 0.004) similar to CTC counts at q4 (76.7 %; p = 0.009). Radiologic and clinical response at q4 displayed accuracy similar to early CTC counts at q1 (72.2 %; p = 0.03 and 75.0 %; p = 0.02) despite low sensitivities.
  
  
  CONCLUSIONS
  CTC counts appear to be an earlier and more sensitive predictor for survival and treatment response than current OR approaches and may provide complementary information toward individualized treatment strategies.
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany, mark.thalgott@lrz.tum.de.
authors.forename: M
authors.initials: M
authors.lastname: Thalgott
authors.forename: M M
authors.initials: MM
authors.lastname: Heck
authors.forename: M
authors.initials: M
authors.lastname: Eiber
authors.forename: M
authors.initials: M
authors.lastname: Souvatzoglou
authors.forename: G
authors.initials: G
authors.lastname: Hatzichristodoulou
authors.forename: V
authors.initials: V
authors.lastname: Kehl
authors.forename: B J
authors.initials: BJ
authors.lastname: Krause
authors.forename: B
authors.initials: B
authors.lastname: Rack
authors.forename: M
authors.initials: M
authors.lastname: Retz
authors.forename: J E
authors.initials: JE
authors.lastname: Gschwend
authors.forename: U
authors.initials: U
authors.lastname: Andergassen
authors.forename: R
authors.initials: R
authors.lastname: Nawroth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D002452:Cell Count; D000077143:Docetaxel; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel