Objective: To explore the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with a PD-1 antibody in improving complete clinical response (cCR) and organ preservation in patients with ultra-low rectal cancer. Methods: This was a prospective phase II, single-arm, open-label trial. Patients with confirmed pMMR status T 1-3a N 0-1 M 0 retcal adenocarcinoma were included. Long-course chemoradiotherapy was delivered to a dose of 50 Gy. A PD-1 antibody was added 2 weeks after the first radiotherapy session, and two courses were administered. After chemoradiotherapy, CapeOX plus PD-1 antibody was administered to patients for two cycles. After evaluation, patients with cCR were managed with a watch-and-wait (W&amp;W) approach. Local excision or a W&amp;W approach was performed for patients with near complete clinical response (ncCR) as per multidisciplinary team decision. Radical surgery was recommended for poorly regressed or progressed tumors. Results: Twenty-five patients were enrolled, but two patients withdrew from the study. A total of 23 patients completed the entire neoadjuvant therapy. Ten and five patients achieved cCR and ncCR, respectively, and the rest had a partial clinical response. Patients with cCR were managed with W&amp;W. Four patients with ncCR underwent local excision and were managed using W&amp;W. Eight patients with partial clinical response underwent anus-preserving surgery. At the last follow-up, the rectum and anus preservation rates were 63.4% (14/22) and 95.5% (21/22), respectively. Conclusion: nCRT combined with immunotherapy tended to achieve better cCR and rectum preservation rates with good tolerance in patients.

Safety and clinical efficacy of neoadjuvant chemoradiation therapy with immunotherapy for organ preservation in ultra-low rectal cancer: preliminary results of the CHOICE-I trial: a prospective cohort study