title: Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.
abstract: BACKGROUND
  The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial.
  
  
  METHODS
  Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided.
  
  
  RESULTS
  At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria.
  
  
  CONCLUSIONS
  Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.
authors.affiliation: Radiology Associates of Appleton, Appleton, WI 54911, USA. michael.ray@thedacare.org
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ray
authors.forename: Kyounghwa
authors.initials: K
authors.lastname: Bae
authors.forename: Maha H A
authors.initials: MH
authors.lastname: Hussain
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hanks
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D023381:Endpoint Determination / Q000379:methods; D005485:Flutamide / Q000008:administration & dosage; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D012107:Research Design; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D017273:Goserelin; D005485:Flutamide; D017430:Prostate-Specific Antigen