title: The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline and survival.
abstract: OBJECTIVE
  There are no known predictive factors of response in men receiving chemotherapy for metastatic castration-resistant prostate cancer (mCRPC). We investigated pre-treatment factors that predicted a 30% PSA decline (30% PSAD) within 3 months of starting chemotherapy, and assessed performance of a risk group classification in predicting PSA declines and overall survival (OS) in men with mCRPC.
  
  
  METHODS
  In TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in two schedules, or mitoxantrone (M), each with prednisone: 989 provided data on PSA decline within 3 months. Predictive factors for a 30% PSAD were identified using multivariable regression in D-treated men (n=656) and validated in M-treated men (n=333).
  
  
  RESULTS
  Four independent risk factors predicted 30% PSAD: pain, visceral metastases, anaemia and bone scan progression. Risk groups (good: 0-1 factors, intermediate: 2 factors and poor: 3-4 factors) were developed with median OS of 25.7, 18.7 and 12.8 months (p<0.0001); 30% PSAD in 78%, 66% and 58% of men (p<0.001); and measurable disease response in 19%, 9% and 5% of men (p=0.018), respectively. In the validation cohort, similar predictive ability was noted for 30% PSAD, tumour response and OS. PCWG2 subtypes were also predictive but resulted in unequal grouping. C-indices were 0.59 and 0.62 for 30% PSAD and OS in the validation dataset, respectively.
  
  
  CONCLUSIONS
  Risk groups have been identified and validated that predict PSAD and OS in men with mCRPC and may facilitate evaluation of new systemic regimens warranting definitive testing in comparison with docetaxel and prednisone. Prospective validation of this classification system is needed.
authors.affiliation: Division of Medical Oncology, Department of Medicine, DUMC, Duke Comprehensive Cancer Center and the Duke Prostate Center, Durham, NC 27715, USA. andrew.armstrong@duke.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Mario
authors.initials: M
authors.lastname: Eisenberger
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D049451:Nomograms; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D012307:Risk Factors; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D011241:Prednisone