COX-2 expression predicts prostate-cancer outcome

analysis of data from the RTOG 92-02 trial

Li Yan Khor, Kyounghwa Bae, Alan Pollack, M. Elizabeth H Hammond, David Grignon, Varagur M. Venkatesan, Seth A. Rosenthal, Mark A. Ritter, Howard M. Sandler, Gerald E. Hanks, William U. Shipley, Adam P. Dicker

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Background: COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy. Methods: Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immunohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality, overall mortality, and any failure. Findings: 586 patients with sufficient diagnostic tissue for immunohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1·181 [95% CI 1·077-1·295], p=0·0004); biochemical failure by two definitions (ASTRO HR 1·073 [1·018-1·131], p=0·008; Phoenix HR 1·073 [1·014-1·134], p=0·014); and any failure (HR 1·068 [1·015-1·124], p=0·011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD. Interpretation: To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD.

Original languageEnglish
Pages (from-to)912-920
Number of pages9
JournalThe Lancet Oncology
Volume8
Issue number10
DOIs
StatePublished - Oct 2007

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Radiation Oncology
Androgens
Prostatic Neoplasms
Radiotherapy
Staining and Labeling
Neoplasm Metastasis
Multivariate Analysis
Mortality
Cyclooxygenase 2 Inhibitors
Proportional Hazards Models
Radiation

ASJC Scopus subject areas

  • Oncology

Cite this

Khor, L. Y., Bae, K., Pollack, A., Hammond, M. E. H., Grignon, D., Venkatesan, V. M., ... Dicker, A. P. (2007). COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial. The Lancet Oncology, 8(10), 912-920. https://doi.org/10.1016/S1470-2045(07)70280-2

COX-2 expression predicts prostate-cancer outcome : analysis of data from the RTOG 92-02 trial. / Khor, Li Yan; Bae, Kyounghwa; Pollack, Alan; Hammond, M. Elizabeth H; Grignon, David; Venkatesan, Varagur M.; Rosenthal, Seth A.; Ritter, Mark A.; Sandler, Howard M.; Hanks, Gerald E.; Shipley, William U.; Dicker, Adam P.

In: The Lancet Oncology, Vol. 8, No. 10, 10.2007, p. 912-920.

Research output: Contribution to journalArticle

Khor, LY, Bae, K, Pollack, A, Hammond, MEH, Grignon, D, Venkatesan, VM, Rosenthal, SA, Ritter, MA, Sandler, HM, Hanks, GE, Shipley, WU & Dicker, AP 2007, 'COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial', The Lancet Oncology, vol. 8, no. 10, pp. 912-920. https://doi.org/10.1016/S1470-2045(07)70280-2
Khor, Li Yan ; Bae, Kyounghwa ; Pollack, Alan ; Hammond, M. Elizabeth H ; Grignon, David ; Venkatesan, Varagur M. ; Rosenthal, Seth A. ; Ritter, Mark A. ; Sandler, Howard M. ; Hanks, Gerald E. ; Shipley, William U. ; Dicker, Adam P. / COX-2 expression predicts prostate-cancer outcome : analysis of data from the RTOG 92-02 trial. In: The Lancet Oncology. 2007 ; Vol. 8, No. 10. pp. 912-920.
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abstract = "Background: COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy. Methods: Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immunohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality, overall mortality, and any failure. Findings: 586 patients with sufficient diagnostic tissue for immunohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1·181 [95{\%} CI 1·077-1·295], p=0·0004); biochemical failure by two definitions (ASTRO HR 1·073 [1·018-1·131], p=0·008; Phoenix HR 1·073 [1·014-1·134], p=0·014); and any failure (HR 1·068 [1·015-1·124], p=0·011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD. Interpretation: To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD.",
author = "Khor, {Li Yan} and Kyounghwa Bae and Alan Pollack and Hammond, {M. Elizabeth H} and David Grignon and Venkatesan, {Varagur M.} and Rosenthal, {Seth A.} and Ritter, {Mark A.} and Sandler, {Howard M.} and Hanks, {Gerald E.} and Shipley, {William U.} and Dicker, {Adam P.}",
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T2 - analysis of data from the RTOG 92-02 trial

AU - Khor, Li Yan

AU - Bae, Kyounghwa

AU - Pollack, Alan

AU - Hammond, M. Elizabeth H

AU - Grignon, David

AU - Venkatesan, Varagur M.

AU - Rosenthal, Seth A.

AU - Ritter, Mark A.

AU - Sandler, Howard M.

AU - Hanks, Gerald E.

AU - Shipley, William U.

AU - Dicker, Adam P.

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N2 - Background: COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy. Methods: Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immunohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality, overall mortality, and any failure. Findings: 586 patients with sufficient diagnostic tissue for immunohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1·181 [95% CI 1·077-1·295], p=0·0004); biochemical failure by two definitions (ASTRO HR 1·073 [1·018-1·131], p=0·008; Phoenix HR 1·073 [1·014-1·134], p=0·014); and any failure (HR 1·068 [1·015-1·124], p=0·011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD. Interpretation: To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD.

AB - Background: COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy. Methods: Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immunohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality, overall mortality, and any failure. Findings: 586 patients with sufficient diagnostic tissue for immunohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1·181 [95% CI 1·077-1·295], p=0·0004); biochemical failure by two definitions (ASTRO HR 1·073 [1·018-1·131], p=0·008; Phoenix HR 1·073 [1·014-1·134], p=0·014); and any failure (HR 1·068 [1·015-1·124], p=0·011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD. Interpretation: To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD.

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