title: Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy.
abstract: BACKGROUND
  Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy.
  
  
  METHODS
  Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n = 507) and testing (n = 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC).
  
  
  RESULTS
  The nine prognostic variables in the final model were Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormonal use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70 (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively.
  
  
  CONCLUSIONS
  A prognostic model of OS in the postdocetaxel, second-line chemotherapy, mCRPC setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed.
authors.affiliation: Affiliations of authors: Department of Biostatistics and Bioinformatics, (SH, C-YL, EK), and Alliance Statistics and Data Center (SH), Duke University, Durham, NC; Departments of Medicine and Urology, University of California-San Francisco, San Francisco, CA (EJS); Division of Medical Oncology, Duke Prostate Center and the Duke Cancer Institute, Durham, NC (AJA); Departments of Medical Oncology and Urology, Yale University Cancer Center, New Haven, CT (DP); Department of Medical Oncology, San Camillo and Forlanini Hospital, Rome, Italy (CNS); Sanofi, Malvern, PA (LS); Department of Medical Oncology, Georges Pompidou European Hospital, Paris, France (SO); Department of Clinical Studies, Royal Marsden Hospital and Institute of Cancer Research, Surrey, United Kingdom (JdB); Urology Department, Tulane Cancer Center, New Orleans, LA (OS).
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Chen-Yen
authors.initials: CY
authors.lastname: Lin
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Kaplan
authors.forename: Daniel
authors.initials: D
authors.lastname: Petrylak
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Liji
authors.initials: L
authors.lastname: Shen
authors.forename: Stephane
authors.initials: S
authors.lastname: Oudard
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015233:Models, Statistical; D015999:Multivariate Analysis; D049451:Nomograms; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010146:Pain / Q000209:etiology; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D012680:Sensitivity and Specificity; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D006454:Hemoglobins; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C552428:cabazitaxel; C081294:satraplatin; D008942:Mitoxantrone; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; D011241:Prednisone