Background: Our pilot study, hich analyzed DAB2IP expression in 46 patientsx0027; biopsies and had short follo up, shoed that DAB2IP reduction correlates ith orse outcome in patients ith high-risk prostate cancer treated ith radiation therapy and androgen deprivation. With longer follo up and increased sample size, e hypothesized that pretreatment tumor status of DAB2IP ould also predict orse prostate cancer-specific survival  PCSS . Methods: Immunohistochemistry of pretreatment biopsies as scored by an expert genitourinary pathologist. PCSS as defined as death due to prostate cancer, radiation toxicity, or unknon cause ith distant metastasis or castration resistance. Other endpoints analyzed include freedom from biochemical failure  FFBF , castration resistance-free survival  CRFS , and distant metastasis-free survival  DMFS . Results: 79 patients ith NCCN-defined high-risk prostate cancer treated ith radiotherapy from 2005-2012 at our institution ere evaluated. 28 percent  2279  of pretreatment biopsies revealed DAB2IP-reduction hile 72 percent  5779  retained DAB2IP expression. The median follo up times ere 4.8 years and 5.3 years for patients in the DAB2IP-reduced group and DAB2IP-retained group, respectively. Patients ith reduced DAB2IP ere statistically more likely to have higher T stage  p = 0.0149 , pretreatment PSA  p = 0.0379 , and Gleason scores  p = 0.0048 . Patients ith reduced DAB2IP also demonstrated orse outcome compared to patients retaining DAB2IP, including FFBF  4-year: 34 percent vs. 92 percent; p lt 0.0001 , CRFS  4-year: 58 percent vs. 96 percent; p = 0.0039 , DMFS  4-year: 58 percent vs. 100 percent; p = 0.0006 , and PCSS  5-year: 83 percent vs. 100 percent; p = 0.0102 . Univariate analysis shoed T stage, N stage, and Gleason score ere statistically significant variables. Pretreatment tumor DAB2IP status remained significant in the multivariable analysis. Conclusions: This study suggests that about one-fourth of men ith high-risk prostate cancer have decreased DAB2IP tumor expression. This subpopulation ith reduced DAB2IP has a suboptimal response and orse PCSS folloing radiation therapy and androgen deprivation. Further study into improving treatment response and survival in this subpopulation is arranted.,J Clin Oncol 34, 2016  suppl; abstr e16553 ,Publication Only Genitourinary  Prostate  Cancer