This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Milosevic, M. Articles by Hill, R. Search for Related Content PubMed PubMed Citation Articles by Milosevic, M. Articles by Hill, R.

Androgen Withdrawal in Patients Reduces Prostate Cancer Hypoxia: Implications for Disease Progression and Radiation Response

¹ Radiation Medicine Program, Departments of ² Medical Imaging, ³ Clinical Study Coordination and Biostatistics, and ⁴ Applied Molecular Oncology, Princess Margaret Hospital and the Ontario Cancer Institute; Departments of ⁵ Radiation Oncology, ⁶ Medical Imaging, ⁷ Public Health Sciences, and ⁸ Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; and ⁹ the Academic Oncology Unit, Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom

Requests for reprints: Michael Milosevic, Radiation Medicine Program, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. Phone: 416-946-2125; Fax: 416-946-6566; E-mail: mike.milosevic{at}rmp.uhn.on.ca.

Hypoxia is a feature of many human malignancies, and leads to aggressive clinical behavior and recurrence after treatment. Here, we show for the first time that androgen withdrawal reduces prostate cancer hypoxia in patients. Oxygen measurements were done in 248 patients with clinically localized prostate cancer prior to radiotherapy, and showed hypoxia of potential biological and clinical significance. In 22 of these patients, prostate oxygen levels were measured both before and after 30 to 145 days of the androgen antagonist bicalutamide. There was a significant reduction in tumor hypoxia with androgen withdrawal (P = 0.005). The median pO₂ increased from 6.4 to 15 mm Hg, and the hypoxic proportion decreased from 40% to 31%. However, the response was heterogeneous, with improvement in 12 patients, stable oxygen readings in 9 patients and worsening hypoxia in 1 patient. Among the responding patients, the median pO₂ increased from 4.9 to 33 mm Hg, and the hypoxic proportion decreased from 51% to 23%. There was no apparent relationship between the change in oxygenation and baseline prostatic volume, T category, Gleason score, prostate-specific antigen levels, the duration of treatment with bicalutamide, or the change in prostate-specific antigen levels with bicalutamide. These results might, in part, explain the improved patient outcome that has been observed in clinical trials of radiotherapy and hormones, and suggest a role for novel therapeutic agents that block the molecular response to hypoxia in prostate cancer either alone or in combination with other established treatments. [Cancer Res 2007;67(13):6022–5]