title: Hypoxic prostate/muscle pO2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings.
abstract: OBJECTIVE
  To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP.
  
  
  METHODS
  Custom-made Eppendorf PO2 microelectrodes were used to obtain approximately 100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio.
  
  
  RESULTS
  With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002).
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Movsas
authors.forename: J Donald
authors.initials: JD
authors.lastname: Chapman
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Hanlon
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Richard E
authors.initials: RE
authors.lastname: Greenberg
authors.forename: Corinne
authors.initials: C
authors.lastname: Stobbe
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hanks
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
mesh_terms: D000368:Aged; D001918:Brachytherapy; D015687:Cell Hypoxia; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010313:Partial Pressure; D016016:Proportional Hazards Models; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen; D010100:Oxygen