Oncological Outcomes and Risk Factors for Local Recurrence and Distant Metastasis After Upfront Surgery in cT3 Rectal Cancer With an Uninvolved Circumferential Resection Margin on Magnetic Resonance Imaging

OBJECTIVE: To evaluate oncological outcomes and potential risk factors for local recurrence (LR) and distant metastasis (DM) after upfront surgery in patients with magnetic resonance imaging (MRI)-defined cT3 rectal cancer, with an uninvolved circumferential resection margin (mrCRM) and no extramural vascular invasion (EMVI), in a Vietnamese cohort. METHODS: A single-center, retrospective-prospective cohort of 144 patients who met these criteria and underwent upfront curative surgery between January 2018 and April 2022 was analyzed. The cumulative incidences of LR and DM were estimated. Univariate Cox regression and penalized regression models (Ridge and LASSO least absolute shrinkage and selection operator) were applied to explore potential risk factors. RESULTS: With a median follow-up of 56 months, LR occurred in 7 patients (4.9%), with 3-, 5-, and 7-year cumulative rates of 3.6%, 5.3%, and 5.3%, respectively. LR was most consistently associated with mesorectal violation, while anastomotic leakage and involved pathological circumferential resection margin (pCRM) showed less stable associations. DM occurred in 15 patients (10.4%), with cumulative incidences of 8.5%, 11.6%, and 11.6% at 3, 5, and 7 years, respectively. Stage III patients had significantly higher DM rates compared with stage II (p = 0.009). Preoperative carcinoembryonic antigen (CEA) ≥ 5 ng/mL and pathological nodal positivity (pN+) were the most consistent predictors of DM, while mesorectal violation and involved pCRM appeared as secondary contributors. CONCLUSION: Upfront surgery yielded favorable outcomes in selected low-risk cT3 rectal cancer patients. Mesorectal violation was most consistently associated with LR, though estimates were limited by the small number of events. DM appeared to be primarily driven by tumor biology (CEA and pN), with mesorectal violation and involved pCRM as possible secondary factors. These findings warrant validation in larger prospective cohorts.