Abstract Background The standard treatment for early‐stage (cT2‐3N0) rectal adenocarcinoma is upfront Total Mesorectal Excision (TME), but the desire for organ preservation has seen the increasing use of neoadjuvant therapy in these patients. Owing to its likely higher complete response rate, Total Neoadjuvant Therapy (TNT) is an attractive but understudied option. This study aimed to determine outcomes in patients with early‐stage rectal cancer undergoing TNT. Methods This was a retrospective study of patients with cT2‐3N0M0 rectal adenocarcinoma who underwent TNT instead of upfront surgery from 2019 to 2025 in South Australia. TNT comprised long‐course chemoradiotherapy followed by up to 8 cycles of FOLFOX or 6 cycles of CAPOX. Patients with cCR were offered watch and wait (W none experienced a LR and three had a DR. The 3‐year DFS in the overall cohort was 94.1% (95% CI 86.3%–100%) and all patients were alive up to 3 years of follow‐up. The rate of Grade 3 or higher chemotherapy‐related toxicity was 25.6% and there were no deaths. Conclusion Patients receiving TNT for early‐stage rectal cancer had a very high cCR rate and associated high organ preservation rate. This approach has potential quality of life advantages compared with surgery, with acceptable oncological and toxicity profiles.
Bunjo et al. (2026) studied this question.