Increasing levels of hypoxia in prostate carcinoma correlate significantly with increasing clinical stage and patient age: an Eppendorf pO(2) study

Abstract

Background: The purpose of this study was to analyze the extent of hypoxia in prostate carcinoma tumors using the Eppendorf pO(2) microelectrode and correlate this with pretreatment characteristics and prognostic factors.

Methods: Custom-made Eppendorf pO(2) microelectrodes were used to obtain pO(2) measurements from the pathologically involved region of the prostate (as determined by the pretreatment sextant biopsies) as well as from a region of normal muscle for comparison. Each set of measurements comprised approximately 100 separate readings of pO(2), for a total of 10,804 individual measurements. Fifty-five patients with localized prostate carcinoma were studied: Forty-one patients received brachytherapy implants, and 14 patients underwent radical prostatectomy. The pO(2) measurements were obtained in the operating room by using a sterile technique under spinal anesthesia for the brachytherapy group and under general anesthesia for the surgery group. The Eppendorf histograms were recorded and described by the median pO(2), mean pO(2), and percentage < 5 mm Hg and < 10 mm Hg. A multivariate mixed-effects analysis for the prediction of tumor oxygenation was performed and included the following covariates: type of tissue (prostate vs. muscle), type of treatment (implant vs. surgery) and/or anesthesia (spinal vs. general), prostate specific antigen level, disease stage, patient age and race, tumor grade, tumor volume, perineural invasion, and hormonal therapy.

Results: Due to differences in patient characteristics and the anesthesia employed, control measurements were obtained from normal muscle (in all but two patients). This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower (average median pO(2), 9.9 mm Hg) compared with the measurements normal muscle (average median pO(2), 28.6 mm Hg; P < 0.0001). A multivariate, linear, mixed analysis demonstrated that, among all of the patients, the significant predictors of oxygenation were tissue (prostate vs. muscle) and anesthesia (spinal vs. general) or treatment (implant vs. surgery). Among the brachytherapy (spinal anesthesia) patients, the significant predictors of pO(2) were tissue type, disease stage, and patient age. There were no significant predictors of oxygenation in the surgical (general anesthesia) group.

Conclusions: This study, employing in vivo electrode oxygen measurements, demonstrated that hypoxia exists in prostate carcinoma tumors. A dramatic effect of anesthesia was observed, likely due to modulation of polarography in the presence of fluorine. Within the group of brachytherapy (spinal anesthesia) patients, increasing levels of hypoxia (within prostatic tissue) correlated significantly with increasing clinical stage and patient age. More patients will be accrued to this prospective study to further correlate the oxygenation status in prostate carcinoma tumors with known prognostic factors and, ultimately, treatment outcome.