Background: DSRCT is a rare, aggressive, and poorly understood neoplasm characterized by the EWS-WT1 translocation. Prognosis is poor despite upfront multimodality therapy with surgery, radiation (RT), and high-dose chemotherapy. We performed a retrospective review of patients (pts) with DSRCT at Memorial Sloan Kettering Cancer Center (MSKCC) to assess the association between overall survival (OS) and various clinical and therapeutic variables. Methods: We collected demographic/clinical data on pts diagnosed with DSRCT from 1995-2011 who had pathologic review and ≥1 oncologic consultation at MSKCC. Living pts were censored at time of last contact. First-line therapies were classified as follows: optimal (R0/R1) vs suboptimal (R2) surgery; consolidative RT; auto transplant; and chemotherapy: high-dose cyclophosphamide (HDCy) vs. standard Ewing’s regimen [sER] vs other. Univariate (UVA) and multivariate (MVA) analyses were performed. Results: 191 patients were identified; 152 (80%) male, median age 22.6 years (yr) (range 4-62), 67% Caucasian. Most common primary site was abdomen and pelvis (A/P, 94%). Pts had disease (dz) present in A/P only (40%) or A/P plus: liver/spleen (21%), extra-abdominal (17%), or multiple distant sites (21%). Median OS (mOS) was 2.4 yr (range 0.04-12) with a median f/u 6.5 yr. UVA revealed mOS varied by site of dz, with A/P alone superior to A/P plus liver/spleen or multiple distant sites (2.8 vs 2.5 vs 2.3 yr, p=0.001). Age was not associated with mOS (p=0.90). MVA for mOS in 148 pts with complete covariates identified: optimal surgery vs suboptimal (3.2 vs 2.4 yr; HR 0.48, CI 0.29-0.78, p=0.003); consolidative RT vs no RT (3.2 vs 2.4 yr; HR 0.53, CI 0.31-0.91, p=0.021); and sER chemotherapy vs HDCy (2.7 vs 2.4 yr; HR 0.59, 0.38 – 0.93, p=0.024) as associated with improved OS. Conclusions: This is the largest DSRCT case series reported to date and represents the first MVA of the impact of multimodality therapy. Although overall prognosis remains dismal, R0/1 surgery and consolidative RT were associated with improved OS. sER was associated with improved OS over HDCy, but the magnitude of benefit was small. Further research and collaborations are needed to improve outcomes in these patients.