COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial.
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.


RESULTS
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.


CONCLUSIONS
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.
Khor
Li-Yan
LY
Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Bae
Kyounghwa
K
Pollack
Alan
A
Hammond
M Elizabeth H
ME
Grignon
David J
DJ
Venkatesan
Varagur M
VM
Rosenthal
Seth A
SA
Ritter
Mark A
MA
Sandler
Howard M
HM
Hanks
Gerald E
GE
Shipley
William U
WU
Dicker
Adam P
AP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000032:analysis*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000532:radiotherapy*; D016896:Treatment Outcome
D000726:Androgen Antagonists; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2