Prognostic Value of Survivin in Locally Advanced Prostate Cancer: Study Based on RTOG 8610
Received 16 January 2008; received in revised form 3 June 2008; accepted 4 June 2008. published online 31 October 2008.
Purpose
To examine the prognostic value of nuclear and cytoplasmic survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610.
Methods and Materials
RTOG 8610 was a Phase III randomized study comparing the effect of radiotherapy plus short-term androgen deprivation with radiotherapy alone. Of the 456 eligible patients, 68 patients had suitably stained tumor material for nuclear survivin analysis and 65 patients for cytoplasmic survivin.
Results
Compared with patients with nuclear survivin intensity scores of ≤191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.20–1.00, p = 0.0452). On multivariate analysis, nuclear survivin intensity scores >191.2 were significantly associated with improved overall survival (HR, 0.46; 95% CI, 0.25–0.86; p = 0.0156) and prostate cancer survival (HR, 0.36; 95% CI, 0.16–0.84; p = 0.0173). On univariate analysis, compared with patients with cytoplasmic survivin integrated optical density ≤82.7, those with an integrated optical density >82.7 showed a significantly increased risk of local progression (HR, 2.49; 95% CI, 1.03–6.01; p = 0.0421).
Conclusion
Nuclear overexpression of survivin was associated with improved overall and prostate cancer survival on multivariate analysis, and cytoplasmic overexpression of survivin was associated with increased rate of local progression on univariate analysis in patients with locally advanced prostate cancer treated on RTOG 8610. Our results might reflect the different functions of survivin and its splice variants, which are known to exist in distinct subcellular compartments.
Reprints requests to: Arnab Chakravarti, M.D., Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom St., Cox 3, Boston, MA 02114. Tel: (617) 643-3427; Fax: (617) 643-3229
Supported by Radiation Therapy Oncology Group Grant U10CA21661, Community Clinical Oncology Program Grant U10CA37422, and Grants Stat U10CA32115 from the National Cancer Institute to the Radiation Therapy Oncology Group and the Pennsylvania Department of Health and R01 CA101984-01 (both to A. Pollack).
ABSTRACT