title: Are biochemical recurrence outcomes similar after radical prostatectomy and radiation therapy? Analysis of prostate cancer-specific mortality by nomogram-predicted risks of biochemical recurrence.
abstract: BACKGROUND
  Due to the protracted natural history of the clinical progression of prostate cancer, biochemical recurrence (BCR) is often used to compare treatment modalities. However, BCR definitions and posttreatment prostate-specific antigen kinetics vary considerably among treatments, calling into the question the validity of such comparisons.
  
  
  OBJECTIVE
  To analyze prostate cancer-specific mortality (PCSM) according to treatment-specific nomogram-predicted risk of BCR for men treated by radical prostatectomy (RP), external-beam radiation therapy (EBRT), and brachytherapy.
  
  
  METHODS
  A total of 13 803 men who underwent RP, EBRT, or brachytherapy at two US high-volume hospitals between 1995 and 2008.
  
  
  METHODS
  RP, EBRT, and brachytherapy.
  
  
  METHODS
  The 5-yr progression-free probability (5Y-PFP) was calculated for each patient based on the treatment received using a validated treatment-specific nomogram. Fine and Gray competing risk analysis was then used to estimate PCSM by a patient's predicted 5Y-PFP. Multivariable competing risk regression analysis was used to determine the association of treatment with PCSM after adjusting for nomogram-predicted 5Y-PFP.
  
  
  CONCLUSIONS
  Men receiving EBRT had higher 10-yr PCSM compared with those treated by RP across the range of nomogram-predicted risks of BCR: 5Y-PFP >75%, 3% versus 0.9%; 5Y-PFP 51-75%, 6.8% versus 5.9%; 5Y-PFP 26-50%, 12.2% versus 10.6%; and 5Y-PFP ≤25%, 26.6% versus 21.2%. After adjusting for nomogram-predicted 5Y-PFP, EBRT was associated with a significantly increased PCSM risk compared with RP (hazard ratio: 1.5; 95% confidence interval, 1.1-2.0; p=0.006). No statistically significant difference in PCSM was observed between patients treated by brachytherapy and RP, although patient selection factors and lack of statistical power limited this analysis.
  
  
  CONCLUSIONS
  EBRT patients with similar nomogram-predicted 5Y-PFP appear to have a significantly increased risk of PCSM compared with those treated by RP. Comparison of treatments using nomogram-predicted BCR end points may not be valid.
  
  
  RESULTS
  Biochemical recurrence (BCR) outcomes after external-beam radiation therapy and radical prostatectomy are associated with different risks of subsequent prostate cancer-specific mortality. Physicians and patients should cautiously interpret BCR end points when comparing treatments to make treatment decisions.
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Byron H
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Division of Urologic Surgery, Washington University, St. Louis, MO, USA; Division of Urology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kibel
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Ciezki
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Chandana A
authors.initials: CA
authors.lastname: Reddy
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Changhong
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: stephea2@ccf.org.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000401:mortality*; D057186:Comparative Effectiveness Research; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D061847:Hospitals, High-Volume; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008923:Missouri; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D049451:Nomograms; D009820:Ohio; D011237:Predictive Value of Tests; D011336:Probability; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Brachytherapy; Comparative effectiveness research; Models; Mortality; Nomograms; Observational study; Prospective studies; Prostatectomy; Prostatic neoplasms; Radiotherapy; Statistical; Survival