title: Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer.
abstract: OBJECTIVE
  Tumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect of hypoxia in patients with prostate cancer treated with radiotherapy.
  
  
  METHODS
  Tumor hypoxia was measured in 247 patients with clinically localized prostate cancer before radiotherapy, with or without hormonal therapy. The median pO(2) was 6.8 mm Hg and the median hypoxic percentage less than 10 mm Hg (HP(10)) was 63%. The median follow-up was 6.6 years.
  
  
  RESULTS
  The 5-year biochemical relapse-free rate (bRFR) was 78%. Prostrate-specific antigen and Gleason score were both associated with biochemical relapse and formed a baseline clinical model. The effect of hypoxia was found to vary with the duration of patient follow-up. HP(10), when added to the clinical model, was an independent predictor of early bRFR (P = 0.019). The relationship between hypoxia and early bRFR was more pronounced when the analysis was restricted to 142 patients with bulk tumor at the site of the oxygen measurements (P = 0.004). Hypoxia was the only factor predictive of local recurrence in 70 patients who had biopsies conducted during follow-up (P = 0.043), again with the effect being greatest early after completing treatment.
  
  
  CONCLUSIONS
  This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It shows that hypoxia is associated with early biochemical relapse after radiotherapy and also with local recurrence in the prostate gland.
authors.affiliation: Radiation Medicine Program, Princess Margaret Hospital and Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, ON, Canada M5G 2M9. mike.milosevic@rmp.uhn.on.ca
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.forename: Padraig
authors.initials: P
authors.lastname: Warde
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
authors.forename: Peter
authors.initials: P
authors.lastname: Chung
authors.forename: Ants
authors.initials: A
authors.lastname: Toi
authors.forename: Adrian
authors.initials: A
authors.lastname: Ishkanian
authors.forename: Michael
authors.initials: M
authors.lastname: McLean
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Mary
authors.initials: M
authors.lastname: Gospodarowicz
authors.forename: Charles
authors.initials: C
authors.lastname: Catton
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.forename: Robert
authors.initials: R
authors.lastname: Bristow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D010100:Oxygen / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D017430:Prostate-Specific Antigen; D010100:Oxygen