Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer

Michael Milosevic, Padraig Warde, Cynthia Meńard, Peter Chung, Ants Toi, Adrian Ishkanian, Michael McLean, Melania Pintilie, Jenna Sykes, Mary Gospodarowicz, Charles Catton, Richard P. Hill, Robert Bristow

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Purpose: Tumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect of hypoxia in patients with prostate cancer treated with radiotherapy. Experimental Design: Tumor hypoxia was measured in 247 patients with clinically localized prostate cancer before radiotherapy, with or without hormonal therapy. The median pO 2 was 6.8 mm Hg and the median hypoxic percentage less than 10 mm Hg (HP 10) was 63%. The median follow-up was 6.6 years. Results: The 5-year biochemical relapse-free rate (bRFR) was 78%. Prostrate-specific antigen and Gleason score were both associated with biochemical relapse and formed a baseline clinical model. The effect of hypoxia was found to vary with the duration of patient follow-up. HP 10, when added to the clinical model, was an independent predictor of early bRFR (P = 0.019). The relationship between hypoxia and early bRFR was more pronounced when the analysis was restricted to 142 patients with bulk tumor at the site of the oxygen measurements (P = 0.004). Hypoxia was the only factor predictive of local recurrence in 70 patients who had biopsies conducted during follow-up (P = 0.043), again with the effect being greatest early after completing treatment. Conclusions: This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It shows that hypoxia is associated with early biochemical relapse after radiotherapy and also with local recurrence in the prostate gland.

Original languageEnglish (US)
Pages (from-to)2108-2114
Number of pages7
JournalClinical Cancer Research
Volume18
Issue number7
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Prostatic Neoplasms
Radiotherapy
Recurrence
Oxygen
Neoplasms
Neoplasm Grading
Tumor Hypoxia
Hypoxia
Prostate
Research Design
Therapeutics
Neoplasm Metastasis
Biopsy
Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Milosevic, M., Warde, P., Meńard, C., Chung, P., Toi, A., Ishkanian, A., ... Bristow, R. (2012). Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer. Clinical Cancer Research, 18(7), 2108-2114. https://doi.org/10.1158/1078-0432.CCR-11-2711

Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer. / Milosevic, Michael; Warde, Padraig; Meńard, Cynthia; Chung, Peter; Toi, Ants; Ishkanian, Adrian; McLean, Michael; Pintilie, Melania; Sykes, Jenna; Gospodarowicz, Mary; Catton, Charles; Hill, Richard P.; Bristow, Robert.

In: Clinical Cancer Research, Vol. 18, No. 7, 01.04.2012, p. 2108-2114.

Research output: Contribution to journalArticle

Milosevic, M, Warde, P, Meńard, C, Chung, P, Toi, A, Ishkanian, A, McLean, M, Pintilie, M, Sykes, J, Gospodarowicz, M, Catton, C, Hill, RP & Bristow, R 2012, 'Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer', Clinical Cancer Research, vol. 18, no. 7, pp. 2108-2114. https://doi.org/10.1158/1078-0432.CCR-11-2711
Milosevic, Michael ; Warde, Padraig ; Meńard, Cynthia ; Chung, Peter ; Toi, Ants ; Ishkanian, Adrian ; McLean, Michael ; Pintilie, Melania ; Sykes, Jenna ; Gospodarowicz, Mary ; Catton, Charles ; Hill, Richard P. ; Bristow, Robert. / Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 7. pp. 2108-2114.
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AU - McLean, Michael

AU - Pintilie, Melania

AU - Sykes, Jenna

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