title: Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916.
abstract: OBJECTIVE
  Prostate-specific antigen progression (PSA-P) is an indicator of progression in hormone-sensitive (HS) and castration-resistant (CR) prostate cancer (PC). We evaluated different definitions of PSA-P as predictors of overall survival (OS).
  
  
  METHODS
  A total of 1,078 patients with HSPC who were on hormones (Southwest Oncology Group [SWOG] trial 9346 [S9346]) and 597 patients with CRPC who were treated with chemotherapy (SWOG trial 9916 [S9916]) were eligible for this analysis. PSA-P definitions tested included the following: PSA Working Group, Prostate Cancer Working Group (PCWG 2008), and other definitions. A time-varying approach analyzed associations between PSA-P at any time and OS. A landmark analysis examined the relationship between PSA-P status at 7 months for S9346, or 3 months for S9916, and subsequent OS.
  
  
  RESULTS
  In the time-varying analysis, both working groups definitions were strongly associated with OS (P < .001) in both study settings. In patients enrolled onto S9346, both definitions predicted a 2.4-fold increased risk of death (ROD) and a greater than four-fold increased ROD if PSA-P occurred in the first 7 months. In S9916, they predicted a 40% increase in ROD and a two-fold increase in ROD if PSA-P occurred at 3 months. In landmark analyses of patients on S9346 by using the PCWG 2008 definition of PSA-P, median subsequent OS was 10 months versus 44 months in patients who did or did not have PSA-P by 7 months, respectively; in S9916, data were 11 months versus 18 months for patients who did or did not have PSA-P by 3 months, respectively.
  
  
  CONCLUSIONS
  PSA-P, defined as an increase of > or = 25% greater than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in HSPC and CRPC and may be a suitable end point for phase II studies in these settings.
authors.affiliation: University of Michigan, Ann Arbor, MI 48109-0946, USA. mahahuss@umich.edu
authors.forename: Maha
authors.initials: M
authors.lastname: Hussain
authors.forename: Bryan
authors.initials: B
authors.lastname: Goldman
authors.forename: Cathy
authors.initials: C
authors.lastname: Tangen
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Atif M
authors.initials: AM
authors.lastname: Akdas
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Donnelly
authors.forename: Subramanian Kanaga
authors.initials: SK
authors.lastname: Sundram
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Burch
authors.forename: Robert S
authors.initials: RS
authors.lastname: Dipaola
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009570:Nitriles / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D014105:Tosyl Compounds / Q000008:administration & dosage
chemical_list: D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009570:Nitriles; D043823:Taxoids; D014105:Tosyl Compounds; D017273:Goserelin; D000077143:Docetaxel; D004961:Estramustine; C053541:bicalutamide; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D011241:Prednisone