Neoadjuvant Chemotherapy Versus Upfront Surgery for cT2N1 or cT3a-bN0-1 Middle-High Rectal Cancer

The optimal treatment strategy for patients with middle-high rectal cancer staged as cT2N1 or cT3a-bN0-1 without mesorectal fascia (MRF) involvement remains uncertain. Although guidelines suggest that neoadjuvant chemotherapy (NCT) or upfront surgery may be considered, the survival outcomes of NCT compared with upfront surgery remain unclear. This retrospective cohort study included patients with middle-high rectal cancer staged as cT2N1 or cT3a-bN0-1 without MRF involvement who were treated at West China Hospital between January 2016 and June 2023. The primary endpoints were disease-free survival (DFS) and metastasis-free survival (MFS); secondary endpoints were overall survival (OS) and local recurrence-free survival (LRFS). Propensity score matching (PSM) was used to reduce baseline confounding. 514 patients were included (262 in the upfront surgery group and 252 in the NCT group). After PSM, 201 pairs were matched. NCT followed by surgery was associated with improved DFS (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.30-0.83; p = 0.008) and MFS (HR, 0.50; 95% CI, 0.28-0.86; p = 0.01). The 3-year DFS rates were 90.5% and 81.6%, respectively, and the corresponding 3-year MFS rates were 92.0% and 84.0%. OS and LRFS were similar between groups. In this selected retrospective cohort of patients with middle-high rectal cancer staged as cT2N1 or cT3a-bN0-1 without MRF involvement, NCT followed by surgery was associated with improved DFS and MFS, whereas OS and LRFS did not differ significantly. Given the nonrandomized treatment allocation, differences in systemic therapy exposure, and potential unmeasured confounding, these findings require prospective randomized validation before routine practice change.