title: Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: an analysis of Radiation Therapy Oncology Group Protocol 92-02.
abstract: OBJECTIVE
  We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint.
  
  
  METHODS
  We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level <150 ng/mL), treated and monitored prospectively on Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995, men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation therapy (n = 761), or in combination with 24 months of adjuvant androgen deprivation (n = 753). Using an adjusted Cox proportional hazards model, we tested if PSADT was prognostic and independent of randomized treatment in this cohort. The endpoints were time to PSADT (assuming first-order kinetics for a minimum of 3 rising PSA measurements) and cancer-specific survival (CSS).
  
  
  RESULTS
  After a median follow-up time of 5.9 years, randomized treatment was a significant predictor for CSS (p(Cox) = 0.002), PSADT <6 months (p(Cox) < 0.001), PSADT <9 months (p(Cox) < 0.001), and PSADT <12 months (p(Cox) < 0.001) but not for PSADT <3 (p(Cox) = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (p(Cox)< 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment.
  
  
  CONCLUSIONS
  Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT.
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA. Richard.Valicenti@mail.tju.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Valicenti
authors.forename: Michelle
authors.initials: M
authors.lastname: DeSilvio
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hanks
authors.forename: Arthur
authors.initials: A
authors.lastname: Porter
authors.forename: Harmar
authors.initials: H
authors.lastname: Brereton
authors.forename: Seth A
authors.initials: SA
authors.lastname: Rosenthal
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000401:mortality* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D017430:Prostate-Specific Antigen