In the OPRA trial, 74% of rectal cancer patients had a complete or near-complete response to total neoadjuvant therapy and were offered non-operative management, and roughly half of patients ultimately achieved organ preservation. NO-CUT was another phase 2 trial of nonoperative following TNT. It included 180 patients with state II-III disease in the mid to low rectum. TNT consisted of 4 cycles of CapeOx followed by long course chemoradiation (50-54 Gy in 25 fractions). After assessment at 8 weeks with digital exam, endoscopy, and MRI, 26% had a clinical complete response. NO-CUT was more strict than OPRA and only offered nonoperative management to these complete responders. At 30 months, the primary endpoint of distant relapse free survival was excellent with nonoperative management (95%) and higher than that seen in patients without complete response (74%). | Amatu, Lancet Oncol 2025
