Hypoxic prostate/muscle PO2 ratio predicts for biochemical failure in patients with prostate cancer

Preliminary findings

Benjamin Movsas, J. Donald Chapman, Alexandra L. Hanlon, Eric M. Horwitz, Richard E. Greenberg, Corinne Stobbe, Gerald E. Hanks, Alan Pollack

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Objectives. To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. Methods. Custom-made Eppendorf PO2 microelectrodes were used to obtain ∼100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. Results. With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). Conclusions. To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.

Original languageEnglish
Pages (from-to)634-639
Number of pages6
JournalUrology
Volume60
Issue number4
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

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Prostate
Prostatic Neoplasms
Muscles
Prostate-Specific Antigen
Radiotherapy
Multivariate Analysis
Neoplasm Grading
Partial Pressure
Spinal Anesthesia
Brachytherapy
Microelectrodes
Reading
Hemoglobins
Regression Analysis
Oxygen
Biopsy
Therapeutics
Hypoxia

ASJC Scopus subject areas

  • Urology

Cite this

Hypoxic prostate/muscle PO2 ratio predicts for biochemical failure in patients with prostate cancer : Preliminary findings. / Movsas, Benjamin; Chapman, J. Donald; Hanlon, Alexandra L.; Horwitz, Eric M.; Greenberg, Richard E.; Stobbe, Corinne; Hanks, Gerald E.; Pollack, Alan.

In: Urology, Vol. 60, No. 4, 01.10.2002, p. 634-639.

Research output: Contribution to journalArticle

Movsas, B, Chapman, JD, Hanlon, AL, Horwitz, EM, Greenberg, RE, Stobbe, C, Hanks, GE & Pollack, A 2002, 'Hypoxic prostate/muscle PO2 ratio predicts for biochemical failure in patients with prostate cancer: Preliminary findings', Urology, vol. 60, no. 4, pp. 634-639. https://doi.org/10.1016/S0090-4295(02)01858-7
Movsas, Benjamin ; Chapman, J. Donald ; Hanlon, Alexandra L. ; Horwitz, Eric M. ; Greenberg, Richard E. ; Stobbe, Corinne ; Hanks, Gerald E. ; Pollack, Alan. / Hypoxic prostate/muscle PO2 ratio predicts for biochemical failure in patients with prostate cancer : Preliminary findings. In: Urology. 2002 ; Vol. 60, No. 4. pp. 634-639.
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abstract = "Objectives. To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. Methods. Custom-made Eppendorf PO2 microelectrodes were used to obtain ∼100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. Results. With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31{\%} versus 92{\%}, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). Conclusions. To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.",
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T1 - Hypoxic prostate/muscle PO2 ratio predicts for biochemical failure in patients with prostate cancer

T2 - Preliminary findings

AU - Movsas, Benjamin

AU - Chapman, J. Donald

AU - Hanlon, Alexandra L.

AU - Horwitz, Eric M.

AU - Greenberg, Richard E.

AU - Stobbe, Corinne

AU - Hanks, Gerald E.

AU - Pollack, Alan

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N2 - Objectives. To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. Methods. Custom-made Eppendorf PO2 microelectrodes were used to obtain ∼100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. Results. With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). Conclusions. To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.

AB - Objectives. To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. Methods. Custom-made Eppendorf PO2 microelectrodes were used to obtain ∼100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. Results. With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). Conclusions. To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.

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