Abstract
Locally advanced rectal cancer (LARC) poses a significant treatment challenge, as conventional chemo-radiotherapy (CRT) frequently results in poor rates of pathological complete response (pCR) and distant metastasis. Total neoadjuvant chemotherapy followed by surgery may have the potential to improve overall outcomes and are coming onto clinical practice. This study aims to compare the efficacy and safety of TNT (Arm A) versus conventional CRT (Arm-B) in achieving pCR and distant metastasis in both the arms. It is an open-labelled randomized controlled trial. Total 172 patients were enrolled in the trial having histologically confirmed LARC (stages T3-T4 or any T stage with lymph node involvement) from June 2021 to June 2023. Patients were randomized to either Arm-A (n = 87) or Arm-B (n = 85). This interim analysis was conducted after two-thirds of the target sample had completed 1-year follow-up. The patients in the Arm A received preoperative radiotherapy with concurrent capecitabine followed by three cycles of capecitabine plus oxaliplatin (CapOx) while those on Arm B received radiotherapy with concurrent capecitabine only followed by 6 cycles of adjuvant CapOx. The primary objective was pCR, being no residual tumor cells (ypT0N0) in the resection specimen. Secondary endpoints were tumor regression score (TRG), circumferential resection margin (CRM) positivity, radicality of the resection margin, local recurrence and distant metastasis, and safety profile. In the interim analysis, which included 150 patients with 75 in each group, pCR was observed in 16.2% of Arm A and 17.4% of Arm-B (p > 0.05). There was no difference in tumor regression scores between the groups. Nonetheless, the TNT group significantly suffered less with distant metastasis at 1 year (6 vs.16 cases; p = 0.040). Local recurrence, CRM positive, or resection margin status did not show any relative difference. There were no significant adverse effects reported in both groups, and toxicity was moderate. This interim analysis suggests that while pCR is comparable in both the groups, TNT may offer superior systemic control by reducing distant metastasis. The findings also suggests the potential of TNT as a preferred treatment strategy in patients with LARC, though completion of the study and a long term follow-up is required to confirm its benefits. Clinical Trials Registry of India: CTRI/2021/05/033642.