title: Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations.
abstract: OBJECTIVE
  To examine the natural history of patients who have received definitive radiation therapy alone for clinically localized prostate cancer and have an increasing prostate-specific antigen (PSA) profile.
  
  
  METHODS
  One hundred fifty-one men with an increasing PSA profile after definitive radiotherapy were identified. The subsequent natural history of these men, including local recurrence, distant metastasis, and survival, was examined. In 119 men, posttreatment PSA doubling times (PSADT) were calculated using linear regression. Cox regression models were used to examine the effect of clinical and treatment variables on clinical failure and survival.
  
  
  RESULTS
  Patients with high pretreatment PSA values, high Gleason scores, and T3 tumors were more likely to develop a PSA elevation. The median calculated post-treatment PSADT was 13 months, and 95% of patients had posttreatment PSADT of less than 3 years. PSADT was correlated with tumor stage and Gleason score. Five years after PSA elevation, the estimated rate of clinical local recurrence is 26% and the estimated rate of distant metastases is 47%. Rapid PSADT (< 12 months) and a short interval from the end of treatment to PSA elevation (< 12 months) were significant independent predictors of distant metastases. The estimated rates of overall and cause-specific survival 5 years after PSA elevation are 65% and 76%, respectively. Gleason grade is the only significant independent predictor of overall and cause-specific survival after PSA elevation.
  
  
  CONCLUSIONS
  The natural history of men who have an increasing PSA profile following definitive radiotherapy is heterogeneous. In the absence of salvage therapy, at least three quarters of men will have clinical evidence of recurrent disease 5 years after a PSA elevation is detected. Men with a rapid posttreatment PSADT and a short interval from the end of treatment to an increasing PSA profile are at a very high risk of developing distant metastasis within 5 years of PSA elevation.
authors.affiliation: Department of Radiation Therapy, Fox Chase Cancer Center, Philadelphia, PA, USA. wrlee@bgsm.edu
authors.forename: W R
authors.initials: WR
authors.lastname: Lee
authors.forename: G E
authors.initials: GE
authors.lastname: Hanks
authors.forename: A
authors.initials: A
authors.lastname: Hanlon
mesh_terms: D000206:Actuarial Analysis / Q000379:methods*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000401:mortality; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D012044:Regression Analysis; D016019:Survival Analysis
chemical_list: D009363:Neoplasm Proteins; D017430:Prostate-Specific Antigen