title: Ability of C-reactive protein to complement multiple prognostic classifiers in men with metastatic castration resistant prostate cancer receiving docetaxel-based chemotherapy.
abstract: What's known on the subject? and What does the study add? Serum C-reactive protein (C-reactive protein) is emerging as a potential novel prognostic factor in metastatic castration-resistant prostate cancer (mCRPC). In the present study, a prospective trial was investigated retrospectively and a significant prognostic impact for C-reactive protein that was independent of multiple published prognostic models was identified in men receiving docetaxel-based chemotherapy for mCRPC. Prospective validation is warranted.
  
  
  OBJECTIVE
  • Given the recent emergence of C-reactive protein levels as a novel prognostic factor in men with metastatic castration-resistant prostate cancer (mCRPC), we sought to evaluate the independent prognostic ability of C-reactive protein in the context of published prognostic nomograms, risk grouping and disease state models in men receiving docetaxel-based chemotherapy for mCRPC.
  
  
  METHODS
  • A large randomized phase II trial (CS-205) of mCRPC patients who received docetaxel-prednisone + AT-101 (Bcl-2 inhibitor) or docetaxel-prednisone + placebo was analyzed retrospectively (n= 220). • Overall survival (OS), progression-free survival (PFS) and measures of discriminatory ability were assessed in a hypothesis-generating analysis using Cox regression and concordance probabilities. • Patients from both treatment groups were combined for this analysis because no significant differences in outcomes were observed. • Because some factors used in nomograms were not collected or defined differently, risk was estimated based on slightly modified versions of nomograms.
  
  
  RESULTS
  • C-reactive protein was independently prognostic for OS and PFS (P ≤ 0.002) after adjusting for all modeled risk estimates and classifiers. • C-reactive protein showed a concordance probability of 0.65 for both OS and PFS. • A 10-factor modified prognostic model based on the TAX327 trial had the greatest observed discrimination ability for OS and PFS (concordance probability = 0.623 and 0.603, respectively) among the modified nomograms or classifiers. • Adding the TAX327 model risk estimates to C-reactive protein did not substantially increase discrimination ability over C-reactive protein alone.
  
  
  CONCLUSIONS
  • Current prognostic classifications provide modest discrimination of outcomes in mCRPC receiving docetaxel-based chemotherapy, highlighting the need for improved risk-based models. • Baseline C-reactive protein appears to be an useful, independent prognostic factor and prospective external validation is warranted.
authors.affiliation: Department of Oncology, McMaster University and Ontario Clinical Oncology Group, Hamilton, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Brian A
authors.initials: BA
authors.lastname: Wood
authors.forename: Lance
authors.initials: L
authors.lastname: Leopold
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000556:secondary / Q000628:therapy; D011838:Radiation-Sensitizing Agents; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D002097:C-Reactive Protein