title: Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer.
abstract: OBJECTIVE
  To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer.
  
  
  METHODS
  A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy.
  
  
  RESULTS
  The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months.
  
  
  CONCLUSIONS
  In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. zelefskm@mskcc.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
authors.forename: Leah
authors.initials: L
authors.lastname: Ben-Porat
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Heather M
authors.initials: HM
authors.lastname: Chan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fearn
authors.forename: Zvi Y
authors.initials: ZY
authors.lastname: Fuks
authors.forename: Steven A
authors.initials: SA
authors.lastname: Leibel
authors.forename: E S
authors.initials: ES
authors.lastname: Venkatraman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies
chemical_list: D017430:Prostate-Specific Antigen