Statewide analysis of outcomes in patients with early-stage rectal cancer undergoing standard-of-care upfront resection

BACKGROUND: Patients with early-stage (cT2-3N0) rectal cancer undergoing standard care upfront resection remain a poorly studied patient group with limited literature reporting the impact of adverse pathological features and surgical complications. This study aimed to characterise outcomes in patients with early-stage rectal cancer undergoing upfront Total Mesorectal Excision (TME). METHODS: This is a retrospective, multi-centre, statewide study of patients with cT2-3N0 rectal adenocarcinoma without high-risk clinical staging characteristics (extramural vascular invasion [EMVI] or threatened/involved mesorectal fascia on MRI) undergoing upfront TME from 2013 to 2025 in South Australia. The main outcome measure was a composite of adverse pathological features, defined as: R1 resection, pT4 disease, nodal upstaging, or EMVI. Operative and oncological outcomes were collected and used to determine rates of Textbook Outcome (TO). The impact of adverse pathological features on 3-year disease-free survival (DFS) and overall survival (OS) was analysed. RESULTS: Among 120 patients with cT2-3N0 rectal cancer undergoing upfront surgery, at least one adverse pathological feature was present in 35.8% of patients, increasing to 50% in patients with low rectal cancer. 3-year DFS rates were 84% (95% CI 75-93) without adverse pathological features, and 72% (95% CI 57-87) in patients with at least one adverse pathological feature (p = 0.167). 3-year OS rates were 94% (95% CI 88-100) without adverse pathological features, and 92% (95% CI 83-100) in patients with at least one adverse pathological feature (p = 0.617). TO was achieved in 57.5%, and 39.2% of patients experienced an ideal short term outcome (no adverse pathological features and TO achieved). CONCLUSION: There is a considerable margin, nodal and EMVI upstaging rate in patients with early-stage rectal cancer undergoing standard care upfront TME, particularly those with low tumours. This highlights the limitations of current clinical staging in rectal cancer, leading to early-staged patients potentially being undertreated.