Total neoadjuvant treatment in locally advanced rectal cancer: A retrospective multicentre cohort analysis in three cancer centres in Brazil.

Abstract

77 Background: Total neoadjuvant therapy (TNT) improves overall survival (OS) while maintaining local recurrence-free survival (LRFS) in locally advanced rectal cancer (LARC). Real-world data are essential to refine patient selection and outcomes. Methods: Multicentre retrospective study of LARC patients treated with TNT in three Brazilian cancer centres. Outcomes: sphincter preservation and survival endpoints. Kaplan–Meier estimated survival; log-rank compared groups; Cox regression identified prognostic factors. Results: A total of 281 patients were analyzed (median age 58 [22–83], follow-up 31 [6–69 months]). Key baseline characteristics: T4 19%, N2 28%, extramural vascular invasion (EMVI) 15%, positive MRF (MRF+) 29%, lower rectum 64%, grade 3 tumors 5%, signet-ring 4%; treatment: IMRT 66%, 3D-CRT 34%, short-course radiotherapy (SCRT) 50%, long-course radiotherapy (LCRT) 50%; neoadjuvant chemotherapy regimens included CAPOX 61%, FOLFOX 35%, FOLFIRINOX 3%, and capecitabine monotherapy 1%. Overall, 212 (76%) underwent surgery and 65 (23%) were managed with watch-and-wait (WW). Pathological complete response (pCR) was achieved in 21%. Sphincter preservation was 78%. Absence of pCR (HR 3.14, 95% CI 1.32–7.47, p=0.009) and MRF+ (HR 2.14, 95% CI 1.21–3.77, p=0.009) predicted worse RFS; WW (HR 0.45, 95% CI 0.21–0.96, p=0.038) and mid- vs. lower-rectal tumors (HR 0.51, 95% CI 0.26–0.99, p=0.046) predicted improved RFS. Absence of pCR (HR 3.67, 95% CI 1.43–9.46, p=0.007) and MRF+ (HR 2.43, 95% CI 1.34–4.41, p=0.004) were associated with worse distant disease-free survival (DDFS). Grade 3 tumors and signet-ring histology were associated with worse LRFS. Three-year RFS, DDFS, LRFS, and OS were 74%, 75%, 93%, and 89%, respectively. No difference in LRFS or OS was observed between SCRT and LCRT (HR for OS 2.0, 95% CI 0.93–4.32, p=0.072). Radiotherapy technique (IMRT vs 3D-CRT) did not affect LRFS. Prognostic factors for worse OS included signet-ring histology, MRF+, EMVI, grade 3 tumors, and distal tumor location. Conclusions: TNT in Brazilian LARC patients achieved outcomes consistent with international series. pCR and MRF were key prognostic factors. No LRFS or OS difference was observed between SCRT and LCRT, supporting the adoption of different TNT strategies in clinical practice.