TY - JOUR
T1 - Prognostic Value of Survivin in Locally Advanced Prostate Cancer
T2 - Study Based on RTOG 8610
AU - Zhang, Min
AU - Ho, Alex
AU - Hammond, Elizabeth H.
AU - Suzuki, Yoshiyuki
AU - Bermudez, R. Scott
AU - Lee, R. Jeffrey
AU - Pilepich, Michael
AU - Shipley, William U.
AU - Sandler, Howard
AU - Khor, Li Yan
AU - Pollack, Alan
AU - Chakravarti, Arnab
N1 - Funding Information:
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).
PY - 2009/3/15
Y1 - 2009/3/15
N2 - 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.
AB - 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.
KW - Prognostic factor
KW - Prostate cancer
KW - Radiotherapy
KW - Survivin
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U2 - 10.1016/j.ijrobp.2008.06.1489
DO - 10.1016/j.ijrobp.2008.06.1489
M3 - Article
C2 - 18977097
AN - SCOPUS:61549127925
VL - 73
SP - 1033
EP - 1042
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
IS - 4
ER -