Neoadjuvant Radiochemotherapy and Total Neoadjuvant Therapy in the Management of Locally Advanced Rectal Cancer

Neoadjuvant radiochemotherapy is a key treatment modality for locally advanced rectal cancer (LARC). Total neoadjuvant therapy (TNT) is a relatively new treatment approach consisting of neoadjuvant radiochemotherapy and consolidative or inductive chemotherapy followed by curative resection. In this study, we aimed to assess the treatment outcomes at a tertiary care center, focusing on neoadjuvant treatments, and to compare our results to the available literature.  Methods: This retrospective cohort study included patients with LARC receiving TNT or neoadjuvant radiochemotherapy without postoperative chemotherapy between 2014 and 2023.  Results: A total of 122 patients with LARC, with a median follow-up of 21.4 months, were included. Thirty-one patients received TNT (25.4%). Ninety-one patients (74.6%) received long-course radiochemotherapy. Sixty-eight patients (55.7%) were classified as high-risk. Twenty-six cases of distant metastases (21.3%) and nine cases of local recurrence (7.4%) were observed. Five-year progression-free and distant metastasis-free survival rates were 62.9% and 68.3%, respectively. The five-year local control was 92.7%. Poor post-treatment tumor regression grading (TRG) in the surgical specimen was found to be associated with worse progression-free survival (hazard ratio (HR): 2.55, p=0.028). Tumors in the lower rectum were associated with worse local control (HR: 5.70; p=0.044).  Conclusions: Neoadjuvant radiochemotherapy, including TNT, for the treatment of LARC appears to be a safe and effective treatment option. TRG may play a role in identifying patients at high risk of early progression. Further research is warranted to determine the optimal TNT sequence and to improve patient selection to avoid over- and undertreatment.