title: The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up.
abstract: OBJECTIVE
  To describe metastasis-free survival (MFS) in men with prostate-specific antigen (PSA) recurrence following radical prostatectomy, and to define clinical prognostic factors modifying metastatic risk.
  
  
  METHODS
  We conducted a retrospective analysis of 450 men treated with prostatectomy at a tertiary hospital between July 1981 and July 2010 who developed PSA recurrence (≥0.2 ng/mL) and never received adjuvant or salvage therapy before the development of metastatic disease. We estimated MFS using the Kaplan-Meier method, and investigated factors influencing the risk of metastasis using Cox proportional hazards regression.
  
  
  RESULTS
  Median follow-up after prostatectomy was 8.0 years, and after biochemical recurrence was 4.0 years. At last follow-up, 134 of 450 patients (29.8%) had developed metastases, while median MFS was 10.0 years. Using multivariable regressions, two variables emerged as independently predictive of MFS: PSA doubling time (<3.0 vs 3.0-8.9 vs 9.0-14.9 vs ≥15.0 months) and Gleason score (≤6 vs 7 vs 8-10). Using these stratifications of Gleason score and PSA doubling time, tables were constructed to predict median, 5- and 10-year MFS after PSA recurrence. In different patient subsets, median MFS ranged from 1 to 15 years.
  
  
  CONCLUSIONS
  In men undergoing prostatectomy, MFS after PSA recurrence is variable and is most strongly influenced by PSA doubling time and Gleason score. These parameters serve to stratify men into different risk groups with respect to metastatic progression. Our findings may provide the background for appropriate selection of patients, treatments and endpoints for clinical trials.
authors.affiliation: Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center, Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21231, USA. eantona1@jhmi.edu
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Feng
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Humphreys
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000097:blood / Q000556:secondary* / Q000601:surgery; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen