Abstract Background: Colorectal cancer (CRC) incidence among patients under age 50 has increased drastically over the past few decades. Given that increased cancer-related distress is associated with worse oncologic outcomes, studies are needed to assess the psychosocial wellbeing of CRC survivors across the shifting demographic and socioeconomic landscape. Methods: The ColoCare Study is a prospective cohort study of newly-diagnosed CRC patients enrolled across six US and European sites. We analyzed ColoCare data from the Washington University site, which has high accrual of Non-Hispanic Black (NHB) patients. Cancer-related distress was measured using a validated Cancer and Treatment Distress (CTXD) tool with 4-point Likert scales ranging from 0-3 with higher scores indicating greater distress. Covariate-adjusted linear regression analyses were used to evaluate sociodemographic, lifestyle, and clinical factors as predictors of cancer-related distress 12 months following CRC diagnosis. Results: This analysis included 156 participants enrolled from April 2017 to September 2022 who completed a 12-month CTXD questionnaire: 51.4% male; mean age 55.3 (SD 13.1) years; 64.8% Non-Hispanic White; 33.1% NHB; mean 12-month CTXD score 0.75 (SD 0.70). In covariate-adjusted models, predictors of increased distress at 12 months (Table 1) included recurrence or new metastasis (regression coefficient (β)=0.63, 95% confidence interval (CI)=0.35-0.91), stage II ((β=0.49, 95% CI=0.15-0.84) or stage III (β=0.37, 95% CI=0.02-0.72) disease, current smoking (β=0.33, 95% CI=0.10-0.56), female gender (β=0.22, 95% CI=0.00-0.44) and age (β= -0.01, 95% CI -0.02-0.00). Race and social vulnerability index were not predictors of distress in this analysis. Conclusion: Among CRC survivors, those with younger age, female gender, active smoking, advanced stage, and disease progression may benefit from targeted cancer-related distress assessment and interventions. Multiple Linear Regression Analysis Estimating 12-Month CTXD Scores Variable Regression Coefficients 95% Lower CI 95% Upper CI P-value Age -0.01 -0.02 0.00 *0.015 Gender: Female vs. Male 0.22 0.00 0.44 *0.050 Race: Black vs. White 0.01 -0.26 0.29 0.933 Race: Other vs. White -0.17 -0.91 0.57 0.650 Social Vulnerability Index 0.15 -0.26 0.56 0.463 BMI 0.00 -0.02 0.02 0.908 Smoking Status: Current vs. Former/Never 0.33 0.10 0.56 *0.006 Stage II vs. Stage I 0.49 0.15 0.84 *0.006 Stage III vs. Stage I 0.37 0.02 0.72 *0.040 Stage IV vs. Stage I 0.41 -0.08 0.91 0.100 Neoadjuvant Treatment: Yes vs. No 0.09 -0.19 0.38 0.510 Adjuvant Treatment: Yes vs. No -0.23 -0.53 0.07 0.133 Stoma at 6 months: Yes vs. No -0.21 -0.68 0.25 0.364 Recurrence or New Metastasis: Yes vs. No 0.63 0.35 0.91 *<0.001 Citation Format: Catherine N. Zivanov, Rachel Kalbfell, Jorge Zarate Rodriguez, Shaleen Sathe, Joel Vetter, Myung Jeon, Dante Chao, Kerri A. Ohman, Jennifer Ose, Biljana Gigic, Erin M. Siegel, David Shibata, Christopher I. Li, Jane C. Figueiredo, Cornelia M. Ulrich, Adetunji T. Toriola. Predictors of cancer related distress among patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3471.