Risk factors for distant recurrence in patients with rectal cancer supporting selection for total neoadjuvant therapy

Background and purpose: In locally advanced rectal cancer, distant recurrence remains a major challenge. Total neoadjuvant therapy (TNT) has been implemented to reduce this risk. Identification of risk factors for distant recurrence to support selection of TNT is crucial to avoid excessive treatment. This study aimed to identify magnetic resonance imaging (MRI) features predictive of distant recurrence in patients with rectal cancer. Material and methods: In this national retrospective cohort study, all patients were diagnosed with non-metastatic rectal cancer between 2016 and 2020 and received neoadjuvant radiotherapy followed by surgery. MRI features from the diagnostic report, including cT-stage, cN-stage, clinical extramural vascular invasion (cEMVI), distance to the mesorectal fascia (MRF), and tumor deposit, were registered. The primary endpoint was distant recurrence. Results: A total of 648 patients were included in the study. In multivariate analysis using multiple imputation, risk factors significantly associated with distant recurrence were cT3c/cT3d/cT4-stage (hazard ratio [HR]: 1.8), cEMVI positive tumors (HR: 2.05), and cT3-stage tumors with a distance to MRF of <= 2 mm (HR: 1.51) compared with patients with cT1/cT2/cT3/cT3a/cT3b-stage, cEMVI negative tumors, and cT3-stage tumors with a distance to MRF > 2 mm, respectively. The cN-stage was not significantly associated with distant recurrence. Due to 67% missing data on tumor deposit status, the results regarding this feature cannot be considered conclusive. Interpretation: In this study, cT-stage, cEMVI status, and distance to MRF are prognostic features for risk stratification for patients receiving neoadjuvant radiotherapy. These results may be used for selecting patients for future treatment strategies such as TNT.