title: Androgen deprivation for minimal metastatic disease: threshold for achieving undetectable prostate-specific antigen.
abstract: OBJECTIVE
  To develop objective measures to select systemic therapies for study in large-scale trials for patients with lesser tumor burdens, we explored prostate-specific antigen (PSA) changes after androgen ablation in patients with disease progression after treatment of localized disease. Long-term follow-up of trials incorporating androgen-deprivation with local therapy have shown improved survival relative to local therapy alone. This suggests that the benchmark for treatment of minimal metastatic disease can be cure.
  
  
  METHODS
  Patients with a rising PSA level with or without clinical metastases after local therapy who received androgen deprivation at Memorial Sloan-Kettering Cancer were identified from two institutional databases. The primary outcome was the proportion achieving an undetectable PSA level, and the pretreatment parameters associated with this endpoint were evaluated.
  
  
  RESULTS
  A total of 130 patients who received androgen ablation and were followed up at Memorial Sloan-Kettering Cancer Center were identified. Overall, 31 (57%) of 54 (95% confidence interval 44% to 71%) patients with a rising PSA level alone and 28 (37%) of 76 (95% confidence interval 26% to 47%) patients with a rising PSA level and clinical metastases achieved an undetectable PSA level after androgen ablation (P = 0.02). The PSA level at the start of androgen ablation and the presence of metastases were the most significant predictive factors.
  
  
  CONCLUSIONS
  The probability of achieving an undetectable PSA level varied inversely with the disease extent. Although achieving an undetectable PSA level does not mean that a patient has been cured, it does establish an endpoint that can be used to identify approaches worthy of study in the Phase III setting.
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Beekman
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Susan
authors.initials: S
authors.lastname: Slovin
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilton
authors.forename: Fernando
authors.initials: F
authors.lastname: Bianco
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D019496:Cancer Vaccines; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen