Background: ASCO/NCCN guidelines recommend screening for multifactorial distress in cancer patients. Understanding predictors of cancer related distress can lead to early intervention and improve clinical outcomes, symptom management, and operational efficiency. Through electronic distress screening (EDS), patient reported outcomes (PRO) were collected across 42 practice locations. Methods: EDS has 39 questions related to cancer related distress including: distress, cancer symptoms/side effects, malnutrition, depression, anxiety, social/family support, financial, and spiritual concerns. 27,106 patients completed screens between 2017-2018. Multivariate analysis and logistic regressions determined predictors of distress for completed screens overall, registry matched, and within 60 days of diagnosis. Results: Median age was 59 (IQR 18-101) and 65% were female. Five symptoms consistently predicted clinically significant distress ≥ 4: anxiety, fatigue, pain, poor emotional coping, and sleep. Diagnosis (dx), staging at time of dx, and timing of screen did not independently predict distress. Factors predicting clinically significant distress varied across geographic regions. Conclusions: In large patient population, five key PROs are predictive of clinically significant distress and could potentially impact clinical outcomes. Early PROs predictive of distress were consistent along the continuum, thus the importance of early symptom identification. EDS can help custom tailor supportive oncology programs to mitigate symptoms related to cancer distress.

*p<.0002**all test variables not included in chart but will be included in presentation