Abstract 120 Background: Both environmental radiation exposure and use of therapeutic radiation (XRT) in primary solid tumor malignancies increase the risk of secondary MDS. No data exist on the risk of developing secondary MDS in prostate cancer patients (pts) being treated with radiotherapy. Establishing this risk has important clinical implications, as prostate cancer is the leading cancer in men and radiation therapy has increasingly become the preferred modality for treatment of localized prostate cancer. Methods: We performed a prospective case control study of 11,015 pts with localized prostate adenocarcinoma newly diagnosed between 1986 and 2011 at Cleveland Clinic who underwent treatment with either radical prostatectomy (control group) or definitive radiotherapy (external beam radiotherapy [EBRT] or prostate interstitial brachytherapy [PI] – case group), to investigate the risk of radiation-related MDS. Data on demographics, surgery, radiation treatment, and follow-up were collected from merged prostate cancer and MDS databases. Cytogenetic risk groups were per International Prognostic Scoring System (IPSS) for MDS. Univariate and multivariate analyses were performed using the Fine and Gray competing risk model with MDS as a time-dependent endpoint (which incorporates differences in duration of follow-up) and death from any cause as the competing event, comparing radiotherapy groups to the surgical cohort as the reference group, controlling for age and follow-up frequency. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Results: For all pts, median age was 64 years (yrs, range, 37 – 88) at the time of prostate cancer diagnosis: 69 yrs in EBRT, 67 yrs in PI, and 60 yrs in surgery pts, respectively (p Conclusions: Pts who underwent definitive radiation treatment for localized prostate cancer did not appear to have a significantly increased risk of subsequent MDS, in analyses that controlled for age and incorporated length of follow-up. A trend for MDS development was present for those undergoing XRT with PI. These findings are encouraging for both patients and providers who have concerns about the potential effects of XRT on development of MDS. Disclosures: Maciejewski: Celgene: Membership on an entity9s Board of Directors or advisory committees. Sekeres: Celgene: Consultancy, Honoraria, Speakers Bureau.