title: Time to second prostate-specific antigen failure is a surrogate endpoint for prostate cancer death in a prospective trial of therapy for localized disease.
abstract: OBJECTIVE
  The most relevant endpoint in comparing the efficacy of curative therapies for prostate cancer is cancer-specific death. Prospective trials need to mature for a least a decade to yield meaningful cancer death data due to the long natural history of the disease amd the use of salvage androgen suppression. This delay may be long enough that the tested treatments are outdated by the time of reporting; thus, there is a need for reliable early surrogate endpoints for cancer survival.
  
  
  METHODS
  This report evaluates 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer. Patients were accrued between 1982 and 1992 and received radical irradiation to either a standard dose of 67.2 Gy or a higher dose of 75.6 Gy. Median follow-up was 5.4 years. A total 76 men have received androgen suppression or orchiectomy for salvage following relapse. Of this group, 35 experienced a second relapse heralded by a rise in the serum prostate-specific antigen (PSA).
  
  
  RESULTS
  The median survival from the time of second biochemical relapse (defined as a progression with a rise in serum PSA more than 10% above the nadir after androgen suppression) was 27 months. Kaplan-Meier analysis projected a 0% survival for this group at 4 years. All those dying after second biochemical failure died of the prostate cancer.
  
  
  CONCLUSIONS
  Second PSA failure (or PSA progression on hormonal therapy) has potential as a surrogate for impending cancer death and its use as an endpoint in prospective studies could allow earlier reporting by 2 to 4 years.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston 02114, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Zietman
authors.forename: K C
authors.initials: KC
authors.lastname: Dallow
authors.forename: P A
authors.initials: PA
authors.lastname: McManus
authors.forename: N M
authors.initials: NM
authors.lastname: Heney
authors.forename: W U
authors.initials: WU
authors.lastname: Shipley
mesh_terms: D000206:Actuarial Analysis; D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality* / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality* / Q000628:therapy; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000628:therapy; D018714:Radiotherapy, Adjuvant; D016879:Salvage Therapy; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D017430:Prostate-Specific Antigen