title: A prostate-specific antigen doubling time of <6 months is prognostic for metastasis and prostate cancer-specific death for patients receiving salvage radiation therapy post radical prostatectomy.
abstract: BACKGROUND
  The ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established. We sought to assess what PSADT threshold is most clinically prognostic in this setting.
  
  
  METHODS
  575 patients who received SRT at a single institution for biochemical recurrence after radical prostatectomy were retrospectively reviewed. We assessed the impact of pre-SRT PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). Kaplan-Meier methods, hazard ratio (HR) assessment, and Cox Proportional Hazard models were used to assess the discriminatory ability of various PSADT thresholds.
  
  
  RESULTS
  Sufficient data to calculate PSADTs were available for 277 patients. PSADT was prognostic for BF, DM, PCSM, and OM on univariate analysis regardless of threshold. HR assessment identified 6 months as a strong threshold. No statistically significant difference was observed in BF, DM, PCSM, or OM between patients with PSADT <3 (n=40) and 3-6 months (n=61) or between 6-10 (n=62) and >10 months (n=114). However significant differences were seen in BF (HR:2.2, [95%CI: 1.4-3.5], p<0.01) and DM (HR:2.2, [95%CI: 1.2-4.3], p=0.02) between a PSADT of 3-6 and 6-10 months. On multivariate analysis a PSADT <6 months predicted BF (HR:2.0, [95%CI: 1.4-2.9], p=0.0001), DM (HR:2.0, [95%CI: 1.2-3.4], p=0.01), and PCSM (HR:2.6, [95%CI: 1.1-5.9], p=0.02).
  
  
  CONCLUSIONS
  A pre-SRT PSADT <6 months was a strong predictor of outcomes in our data set, including PCSM. The most common nomogram for SRT uses a 10-month PSADT threshold for assigning points used to assess BF following SRT. If validated, our findings suggest that a PSADT threshold of <6 months should be considered for stratification of patients in future clinical trials in this setting.
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48105, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Jackson
authors.forename: Skyler B
authors.initials: SB
authors.lastname: Johnson
authors.forename: Darren
authors.initials: D
authors.lastname: Li
authors.forename: Corey
authors.initials: C
authors.lastname: Foster
authors.forename: Benjamin
authors.initials: B
authors.lastname: Foster
authors.forename: Yeohan
authors.initials: Y
authors.lastname: Song
authors.forename: Matthew
authors.initials: M
authors.lastname: Schipper
authors.forename: Mark
authors.initials: M
authors.lastname: Shilkrut
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: Todd M
authors.initials: TM
authors.lastname: Morgan
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000368:Aged; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods* / Q000401:mortality*
chemical_list: D017430:Prostate-Specific Antigen