Effectiveness of the total neo-adjuvant therapy in rectal cancer treatment. Results of the randomized trial

To ASSESS effectiveness of total neoadjuvant therapy (TNT) for patients with rectal carcinoma.Patients and methods: patients with histologically proven rectal carcinoma were randomly assigned in two groups: in the TNT group after the neoadjuvant CRT 50-54 Gy with capecitabine 3 consolidation courses of XELOX were done, in the CTR group - conventional neoadjuvant CRT 50-54 Gy with capecitabine. At the end of the treatment, effect was assessed by MRI using the mrTRG scale. For patients with a full clinical response, who have refused surgery, «watch&wait» approach was used. For other patients effect of neoadjuvant therapy was evaluated by pathomorphological study using the Ryan scale. The primary endpoint of study was the complete response rate (clinical and pathomorphological). Secondary endpoints of study: frequency and structure of intraoperative and postoperative complications, the rate of grade 3–4 toxicity of radiotherapy and chemotherapy, R0-resection rates. The study was registered on the ClinicalTrials.gov (NCT04747951)RESULTS: between October 2020 and October 2023, 183 patients were enrolled in the randomized study: 91 patients in the TNT group and 92 patients in the CRT group. At median (Q1, Q3) follow-up period 24 (14; 28) months, complete clinical response observed in 23% (14/60) of TNT patients and in 7% (5/71) of THL patients (p=0.008). The pCR rate was 20% (9/45) in the TNT group and 8% (5/66) in the CRT group (p=0.05). The frequency of development of toxic reactions of degree 3-4, the frequency and structure of intra- and postoperative complications, as well as the frequency of R0 resection of the group did not differ statistically significantly. The total rate of Grade 3–4 toxicity, rate of intra- and postoperative complications, R0-resections rate did not differ between two groups.CONCLUSION: preliminary results of a randomized study demonstrated the effectiveness and safety of total neo-adjuvant therapy in rectal cancer treatment.