ESTRO 2025 - Abstract Book

S1199

Clinical – Lower GI

ESTRO 2025

Cancer Hospital and Institute, Beijing, China. 5 Department of Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China. 6 Department of Radiation Oncology, China-Japan Union Hospital, Jilin University, Changchun, China. 7 Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu, China. 8 Department of Radiation Oncology, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China. 9 Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, China. 10 Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China. 11 Department of Radiation Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. 12 Department of Radiation Oncology, Sichuan Provincial Cancer Hospital, Chengdu, China. 13 Department of Radiation Oncology, Qinghai Red Cross Hospital, Qinghai, China. 14 Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China. 15 Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA. 16 Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, China. 17 Department of Radiation Oncology, Jilin Provincial Cancer Hospital, Changchun, China. 18 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. 19 Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China Purpose/Objective: In the multicenter, open-label, phase III STELLAR trial, we previously reported 3-year results showing that preoperative short-course radiotherapy followed by chemotherapy is not inferior to the standard long-course chemoradiotherapy in disease-free survival (DFS) for patients with locally advanced rectal cancer (LARC) and is even superior in overall survival (OS). Here, we present updated 5-year results to assess whether the DFS non-inferiority and OS benefit was sustained, and to evaluate long-term quality of life (QoL) and anorectal function. Material/Methods: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX in the TNT group or six cycles of CAPOX in the CRT group. The primary end point was DFS, with a noninferiority margin of HR=1.43 at 1-sided alpha of 0.05. Results: A total of 591 patients were evaluable for the analysis of long-term outcomes (TNT group: 298, CRT group: 293). DFS and OS events occurred in 248 and 178 patients (TNT: 119 DFS, 80 OS; CRT: 129 DFS, 98 OS; Table 1). At a median follow-up of 68.7 months, the 5-year DFS was 62.0% and 58.7% in the TNT and CRT groups (HR, 0.849; 90% CI, 0.689 to 1.046; P <0.001 for non-inferiority; Figure 1). The previously reported OS benefit favoring TNT over CRT was sustained at 5 years, with OS rates of 78.1% versus 69.7% (HR, 0.739; 95% CI, 0.550 to 0.993; P =0.044). No significant difference was observed in the incidences of distant metastasis (HR, 0.826; P=0.220) or locoregional recurrence (HR, 0.814; P=0.417) at 5 years. Subgroup analysis revealed no significant differences on DFS between TNT and CRT; however, TNT group demonstrated a significant OS benefit in patients aged ≤ 55 years (HR, 0.644; P=0.047), with MRF-positive status (HR 0.676, P=0.039) or with EMVI-positive status (HR 0.659, P=0.033). Of the 413 surviving patients, 196 (47.5%) completed QoL and anorectal function survey. No significant differences in QoL or anorectal function were observed between treatment groups.