title: Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer.
abstract: OBJECTIVE
  To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy.
  
  
  METHODS
  The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity.
  
  
  RESULTS
  At 2 years, 33% of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes.
  
  
  CONCLUSIONS
  Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.
authors.affiliation: Massachusetts General Hospital, Cox 640, 100 Blossom St, Boston, MA 02114, USA. smith.matthew@mgh.harvard.edu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Marc C
authors.initials: MC
authors.lastname: Gittelman
authors.forename: David L
authors.initials: DL
authors.lastname: Bilhartz
authors.forename: Chris
authors.initials: C
authors.lastname: Wynne
authors.forename: Robin
authors.initials: R
authors.lastname: Murray
authors.forename: Norman R
authors.initials: NR
authors.lastname: Zinner
authors.forename: Claude
authors.initials: C
authors.lastname: Schulman
authors.forename: Ronald
authors.initials: R
authors.lastname: Linnartz
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Carsten
authors.initials: C
authors.lastname: Goessl
authors.forename: Yong-Jiang
authors.initials: YJ
authors.lastname: Hei
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Richard
authors.initials: R
authors.lastname: Cook
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen