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Bcl-2 and Bax Expression Predict Prostate Cancer Outcome in Men Treated with Androgen Deprivation and Radiotherapy on Radiation Therapy Oncology Group Protocol 92-02

Authors' Affiliations: Departments of ¹ Radiation Oncology, and ² Pathology, Fox Chase Cancer Center; ³ Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania; ⁴ Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, Utah; ⁵ Radiation Oncology, University of Western Ontario, London, Ontario, Canada; ⁶ Radiological Associates of Sacramento Medical Group, Inc., Sacramento, California; ⁷ Radiation Oncology, University of Wisconsin, Madison, Wisconsin; ⁸ Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan; and ⁹ Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts

Requests for reprints: Alan Pollack, Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. Phone: 215-728-2940; Fax: 215-728-2868; E-mail: Alan.Pollack{at}FCCC.EDU.

Purpose: Bcl-2 is antiapoptotic, and its overexpression has been associated with resistance to androgen deprivation and poor outcome in some patients treated with radiotherapy. Bax is proapoptotic, regulating Bcl-2 through heterodimer formation. In a prior study, Bcl-2 and Bax were not related to outcome in locally advanced patients treated with radiotherapy or short-term androgen deprivation + radiotherapy (STAD+RT) on another Radiation Therapy Oncology Group trial (86-10). A follow-up investigation was carried out here in more contemporary high-risk men treated on Radiation Therapy Oncology Group 92-02 with STAD+RT or long-term AD+RT (LTAD+RT).

Experimental Design: Adequate tissue was available to be analyzed immunohistochemically in 502 patients for Bcl-2 and 343 patients for Bax. Univariate and multivariate analyses by Cox proportional hazards models were applied to end points of failure.

Results: Bcl-2 was positive in 45.6% cases, and Bax expression altered in 53.9% cases. Abnormal Bcl-2 was not related to any of the failure end points tested. Altered Bax expression was significantly associated with any failure (P = 0.023) and marginally with biochemical failure (P = 0.085). The combination of negative Bcl-2/normal Bax expression seemed more robust, being significantly related to reduced biochemical failure (P = 0.036) and any failure (P = 0.046). The predictive value of negative Bcl-2/normal Bax was most pronounced in those who received STAD+RT, as opposed to LTAD+RT.

Conclusions: Normal Bax expression was associated with significantly more favorable outcome. The combination of negative Bcl-2 and normal Bax was more consistently significant, particularly when STAD+RT was the treatment administered. These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed.

Commentary

"No Turning Bax" in the Combined Battle against Prostate Cancer:

Ramji R. Rajendran and Gary D. Kao
Clin. Cancer Res. 2007 13: 3435-3438. [Full Text] [PDF]

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