Association Between Clinical Tumor Stage and Response to Total Neoadjuvant Therapy in Rectal Cancer: Outcomes in cT3...

Total neoadjuvant therapy (TNT) is standard for managing locally advanced rectal cancer (LARC), enabling organ preservation in patients who achieve a complete clinical response (cCR). However, the influence of clinical tumor stage (cT) on response rates and long-term outcomes remains incompletely defined.

A total of 121 patients with cT3 or cT4 rectal adenocarcinoma treated with TNT between 2019 and 2024 at a single tertiary care center were analyzed. Rates of cCR, tumor regrowth, distant metastasis, and mortality were compared between cT3 and cT4 groups. Multivariable logistic regression was used to identify factors associated with cCR in the overall cohort and among patients with cT4 specifically.

Overall, 32.8% of patients achieved a cCR: 38% patients with cT3 disease and 23% with cT4 (p = 0.09). In adjusted analysis, cT4 disease was independently associated with a reduced odds of achieving cCR (odds ratio, 0.31; 95% CI, 0.11-0.88). Among patients achieving cCR, 86.8% pursued organ preservation, with no significant differences in regrowth (27% cT3 versus 17% cT4; p = 0.75) or mortality. Among patients with cT4, no independent predictors of cCR were identified. Time to metastatic disease and mortality did not differ significantly between groups.

Patients with cT4 rectal cancer are significantly less likely to achieve a cCR following TNT compared with those with cT3 tumors. However, among those who do achieve cCR, rates of regrowth and long-term outcomes are comparable. Clinical tumor stage may aid in counseling patients on the likelihood of nonoperative management after TNT.