Safety and efficacy of individualized modified total neoadjuvant therapy for low locally advanced rectal cancer

Various studies have confirmed the benefits of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). Nevertheless, preoperative intensive treatment and a long waiting period can lead to significant side effects. This may result in surgical difficulties and a higher complication rate. The individualized modified TNT (mTNT) model might lessen the side effects without influencing the curative effect. The clinical data of LARC with short-course neoadjuvant radiotherapy and chemotherapy in the same attending group of colorectal surgery at Fujian Cancer Hospital were retrospectively examined from January 2017 to October 2023. An analysis was carried out on aspects such as the adverse reaction of chemoradiotherapy, postoperative complications, pathological withdrawal, and long-term outcomes of the data. 62 cases were enrolled, including 16 cases of induction chemotherapy mode (IC group), 20 cases of consolidation chemotherapy mode (CC group), and 26 cases of induction + consolidation chemotherapy sandwich mode (IC + CC group). In all three groups, the neoadjuvant therapy compliance rate reached 100%. No grade 4-5 toxicity was found, and the perioperative complication rate of 12.90% was within an acceptable range, including major complications, 4 cases of anastomotic leakage and one case of abdominal bleeding. Delayed complications including ileus and rectovaginal fistula occured in 5 patients, all of whom received consolidation chemotherapy and had BMI less than 21. There was a total pathological complete remission (pCR) rate of 24.19%, including IC group 18.75%, CC group 25.00%, and IC + CC group 26.92%. The downstaging rate of IC + CC group was significantly higher than that of IC group and CC group (P = 0.037). In comparison with those in the CC or IC + CC group, patients in the IC group, had lower Locoregional relapse-free survival (LRFS) rate (81.3%vs.82.5% and 92.9%, respectively, P = 0.292), and higher Distant metastasis-free survival (DMFS) rate (93.8% vs.73.1% and 82.4%, respectively, P = 0.365), however, these variances were not of significance. The initial outcomes of the individualized modified TNT model are promising. Sequencing adjusted according to the disease risk upon presentation might be the best way to balance local and distant disease control and treatment toxicity.