Minimum 18-week chemotherapy improves survival in locally advanced rectal cancer after neoadjuvant radiotherapy: a post hoc analysis of the STELLAR trial
Year: 2026
Type: article
Abstract: BACKGROUND: The survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial. METHODS: This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n = 121), group 2 (3 to 12 weeks, n = 113), group 3 (15 weeks, n = 30), and group 4 (≥ 18 weeks, n = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression. RESULTS: Group 4 achieved the highest 5-year OS (82.1%) and DFS (66.0%) rates. Compared with groups 1 and 2, group 4 demonstrated significantly improved OS (adj. P ≤ 0.001) and improved DFS versus group 1 (HR 0.621, 95% CI 0.443-0.870, adj. P = 0.017). In the TNT cohort, group 4 was associated with significantly improved OS and DFS compared with group 2 (adj. P < 0.01), but not with group 3. Additionally, group 4 showed a significantly lower risk of LRR than group 3. In the CRT cohort, group 4 was associated with improved OS compared with group 1 (adj. P = 0.005); however, this association was not retained in surgical patients. No significant differences in DFS, DM, or LRR were observed across groups in the CRT cohort. CONCLUSIONS: In TNT cohort, minimum 18 weeks of chemotherapy was associated with improved OS and DFS compared to 3 to 12 weeks. The observed OS benefit of minimum 18 weeks versus no chemotherapy in the CRT cohort was not retained among surgical patients. These findings suggest caution in shortening chemotherapy duration, particularly in high-risk patients treated with TNT, and warrant confirmation in prospective TNT-specific trials. TRIAL REGISTRATION: The STELLAR trial was registered at ClinicalTrials.gov (identifier: NCT02533271); however, this post hoc analysis was retrospectively conducted.
Source: BMC Medicine
Authors: Tongzhen Xu, Huiying Ma, Wenjue Zhang, Yongjing Yang, Weiwei Xiao, Ning Li, Haoyue Li, Yuanhong Gao, Shixin Liu, Lichun Wei, Liming Jiang, Jinming Shi, Jiacheng Shuai, Yong Cai, Yongheng Li, Guanghui Cheng, WenGuang Luo, Xin Wang, Ke Liu, Jun Wang, Ningning Lu, Hui Fang, Yueping Liu, Yongwen Song, Wenwen Zhang, Shulian Wang, Yexiong Li, Aiping Zhou, Haitao Zhou, Yihebali Chi, Yuan Tang, Jing Jin
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, State Key Laboratory of Molecular Oncology, Jilin Province Tumor Hospital, Sun Yat-sen University, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Shanxi Medical University, Shanxi Provincial Cancer Hospital, Xijing Hospital, Air Force Medical University, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Peking University Cancer Hospital, Jilin University, University of Science and Technology of China, Sichuan University, West China Hospital of Sichuan University, Hunan Cancer Hospital, Hebei Medical University, Fourth Hospital of Hebei Medical University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Award: G4537962254
OpenAlex ID: W7131357342