Milosevic M et al. (2007) Androgen withdrawal in patients reduces prostate cancer hypoxia: implications for disease progression and radiation response. Cancer Res 67: 6022–6025

Around one-quarter of patients who receive radical treatment for prostate cancer subsequently develop progressive disease. The mechanisms underlying this malignant progression are, however, poorly elucidated. Recently, Milosevic and co-workers have investigated the effects of androgen withdrawal on prostate cancer hypoxia. Androgen withdrawal is known to result in tumor regression in the majority of patients, and is effective in combination with radiotherapy.

Tumor hypoxia is associated with aggressive tumor behavior and the development of progressive disease. The researchers measured pretreatment tumor oxygen concentrations in 248 patients using an ultrasound-guided needle-electrode technique, and detected potentially clinically and biologically significant levels of hypoxia. In total, 22 of these patients received the androgen antagonist bicalutamide (150 mg/day) and consented to a second set of oxygen measurements (performed after 30–145 days). Relative to pretreatment measurements, a significant reduction in prostate hypoxia was observed in these patients after androgen withdrawal (P = 0.005), although there was considerable variation in individual response. Tumor hypoxia improved in twelve patients and remained stable in a further nine. Changes in oxygenation were not associated with baseline tumor characteristics, PSA level or duration of bicalutamide treatment.

The authors conclude that induced improvements in levels of hypoxia might explain the favorable patient outcomes observed after treatment with androgen withdrawal plus radiotherapy. Therapeutic agents that block the response to hypoxia might be useful for treating and preventing prostate cancer.