Preoperative chemoradiotherapy with the TEGAFIRI regimen achieves significant local control in locally advanced rectal cancer.

Purpose: This study aims to evaluate both the short- and long-term outcomes of preoperative chemoradiotherapy (CRT) using the tegafur-uracil/calcium folinate/irinotecan (TEGAFIRI) regimen in patients with locally advanced rectal cancer (LARC). While total neoadjuvant therapy (TNT) is becoming more common, CRT may still be the optimal approach in certain cases to improve prognosis and reduce adverse events.

Methods: This single-center, retrospective cohort study included patients with histologically confirmed nonmetastatic primary adenocarcinoma of the lower rectum treated with preoperative CRT using the TEGAFIRI regimen (TEGAFIRI group). The control group comprised patients treated with tegafur-uracil/calcium folinate (UFT group). The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints included adverse events, overall survival (OS), disease-free survival (DFS), distant recurrence-free survival (DRFS), and local recurrence-free survival (LRFS). The background was adjusted using inverse probability weighting (IPW) calculated with the propensity score.

Results: The TEGAFIRI group consisted of 79 patients, while the UFT group included 264. The standardized pCR rates through the IPW were as follows: TEGAFIRI group: 24.3%, UFT group: 8.8%, and the difference in pCR was 15.4% (P = 0.01). Adverse events of grade 3 or higher were observed in 15.2% vs. 8.7% (adjusted) (13.6% vs. 9.1% crude) in the TEGAFIRI group and the UFT group. The standardized LRFS was significantly higher in the TEGAFIRI group (HR = 0.39, (95% CI 0.16-0.98), P = 0.045). There were no significant differences in OS, DFS, or DRFS between groups.

Conclusions: The TEGAFIRI regimen for preoperative CRT in LARC demonstrated a high pCR rate and reduced local recurrence, with manageable adverse events.