PurposeTo evaluate the association of computed tomography (CT) texture features of locally advanced rectal cancer with neoadjuvant chemoradiotherapy (CRT) response and disease-free survival (DFS).Methods and findingsThe institutional review board approved this retrospective study. 95 patients who received neoadjuvant CRT, followed by surgery, for locally advanced rectal cancer were included. Texture features (entropy, uniformity, kurtosis, skewness, and standard deviation) were assessed in pretreatment CT images and obtained without filtration and with Laplacian of Gaussian spatial filter of various filter values (1.0, 1.5, 2.0, and 2.5). Dworak pathologic grading was used for treatment response assessment. Independent t-test was used to compare each texture feature between the treatment responder and non-responder groups. DFS was assessed with Kaplan-Meier method, and differences were compared with log-rank test. Cox proportional hazards models were constructed to predict prognosis based on stage, age, and each texture feature. Treatment responders (n = 32) showed significantly lower entropy, higher uniformity, and lower standard deviation in no filtration, fine (1.0), and medium (1.5) filter values. Entropy, uniformity, and standard deviation without filtration showed significant difference in DFS in Kaplan-Meier analysis (P = 0.015, 0.025, and 0.038). Homogeneous texture features (≤ 6.7 for entropy, > 0.0118 for uniformity, and ≤ 28.06 for standard deviation) were associated with higher DFS. Entropy, uniformity, and standard deviation were independent texture features in predicting DFS (P = 0.017, 0.03, and 0.036)ConclusionsHomogeneous texture features are associated with better neoadjuvant CRT response and higher DFS in patients with locally advanced rectal cancer.