Hypoxic Prostate/Muscle Po2 Ratio Predicts for Outcome in Patients With Localized Prostate Cancer: Long-Term Results

Abstract

To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. Custom-made Eppendorf PO(2) microelectrodes were used to obtain PO(2) measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO(2), mean PO(2), and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncology (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO(2) ratio on BF. With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO(2) ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO(2) ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. ≥0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02). Hypoxia in prostate cancer (low mean P/M PO(2) ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.