title: Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer.
abstract: Little information exists regarding the utility circulating tumor cell (CTC) enumeration in hormone sensitive prostate cancer. We enumerated CTC in 33 consecutive patients undergoing androgren deprivation therapy (ADT) at our institution. Multivariate analysis revealed baseline CTC as the only independent predictor of progression to CRPC. These data suggest that baseline CTC may identify those unlikely to benefit from ADT.
  
  
  BACKGROUND
  Circulating tumor cell (CTC) enumeration by using the Cellsearch platform has established prognostic and predictive value in patients with metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding the clinical utility of CTC enumeration in metastatic hormone-sensitive prostate cancer (mHSPC). The goal of this study was to prospectively determine the relative clinical utility of CTCs in mHSPC.
  
  
  METHODS
  We analyzed serial CTC in conjunction with other classic biomarkers in 33 consecutive patients treated at the Nevada Cancer Institute with HSPC initiating androgen deprivation therapy and correlated these patients with prognostic prostate-specific antigen (PSA) endpoints and onset of CRPC.
  
  
  RESULTS
  Initial CTC correlated positively with lactate dehydrogenase and alkaline phosphatase, and were unrelated to PSA and testosterone. In univariate analysis, baseline CTC, alkaline phosphatase, lactate dehydrogenase, testosterone, and follow-up CTC were individual predictors of progression to CRPC. In a multivariate Cox regression, only baseline CTC retained independent predictive value. Threshold analysis revealed the cutpoint that optimized specificity and sensitivity of the test to be 3 cells per 7.5 mL whole blood. Baseline CTC also correlated well with PSA nadir benchmarks.
  
  
  CONCLUSIONS
  Initial CTC values predict the duration and magnitude of response to hormonal therapy. CTC enumeration may identify patients at risk of progression to CRPC before initiation of androgen deprivation therapy.
authors.affiliation: Department of Clinical Oncology, Nevada Cancer Institute, Las Vegas, 89135, USA. ogoodman@nvcancer.org
authors.forename: Oscar B
authors.initials: OB
authors.lastname: Goodman
authors.forename: James T
authors.initials: JT
authors.lastname: Symanowski
authors.forename: Aida
authors.initials: A
authors.lastname: Loudyi
authors.forename: Louis M
authors.initials: LM
authors.lastname: Fink
authors.forename: David C
authors.initials: DC
authors.lastname: Ward
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002452:Cell Count; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009919:Orchiectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D012372:ROC Curve; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen