Prostate cancer hypoxia as a predictor of early biochemical and local failure after radiotherapy.

Abstract

20 Background: Tumor hypoxia is an important determinant of patient outcome in many human malignancies, and has been associated with radioresistance and the development of metastases. The aim of this study was to determine the predictive effect of hypoxia in prostate cancer patients treated with RT. Methods: A total of 256 patients with clinically localized prostate cancer underwent pre-treatment, transrectal, ultrasound-guided measurement of tumor oxygen using a needle electrode. The median pO2 (mpO2) was 6.7 mm Hg and the median hypoxic proportion <10 mm Hg (HP10) was 0.63. Most patients were treated with IMRT to the prostate alone using doses in the range of 75.6-79.8 Gy. Sixty-one received neoadjuvant and concurrent hormonal therapy. The Phoenix definition of biochemical relapse was used, and the median follow-up was 5.4 years. Results: The 5-year bRFR was 78%. High PSA and Gleason score were independently associated with biochemical relapse, and formed the baseline clinical multivariate model. The effect of hypoxia was found to vary with the duration of patient follow- up. HP10, when added to the clinical multivariate model as a time-dependent variable, was a significant, independent predictor of early bRFR (p=0.015). The predictive effect of hypoxia diminished with increasing follow-up and was lost by 36 to 48 months. The relationship between hypoxia and early biochemical recurrence was more pronounced when the analysis was restricted to 144 patients with bulk tumor at the site of the oxygen measurements (p=0.008). Prostate biopsy was performed in 73 patients a median of 36 months after completing RT. Hypoxia was the only factor predictive of local recurrence in this sub-group, with the effect being greatest early in follow-up (p=0.038). Conclusions: This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It suggests that hypoxia in the index tumor increases the risk of recurrence early after completing RT but not at longer times. The results imply a complex interaction between hypoxia and local vs. distant failure, which may be better elucidated with longer follow-up. No significant financial relationships to disclose.