Chen Po-Chuan, Yang Avery Shuei-He, Fichera Alessandro, Tsai Mu-Hung, Wu Yuan-Hua, Yeh Yu-Min, Shyr Yu, Lai Edward Chia-Cheng, Lai Chao-Han
Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
JAMA Netw Open. 2025 May 1;8(5):e259049. doi: 10.1001/jamanetworkopen.2025.9049.
Guidelines for resectable locally advanced rectal cancer (LARC) advocate for neoadjuvant radiotherapy (NRT) followed by surgery as the standard approach. However, recent trials have reported no oncological benefits of NRT-based therapy for middle or lower rectal cancer, raising the question of whether NRT followed by surgery remains the optimal treatment approach for resectable LARC overall.
To compare the outcomes of NRT followed by surgery vs up-front surgery for resectable LARC.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study, using a target trial emulation framework with nationwide registries in Taiwan, included patients undergoing curative resection for resectable LARC (cT1-2N1-2, cT3Nany) between January 1, 2014, and December 31, 2017, with follow-up until December 31, 2020. Data were analyzed from January 1, 2024, to February 15, 2025.
NRT.
The primary outcomes were overall survival (OS) and local recurrence (LR). The secondary outcome was intraoperative diverting stoma outcomes.
A total of 4099 patients were analyzed, including 1436 patients undergoing NRT followed by surgery (median [IQR] age, 62.0 [53.0-71.0] years; 1036 [72.1%] male) and 2663 patients undergoing up-front surgery (median [IQR] age, 65.0 [56.0-74.0] years; 1626 [61.1%] male). NRT followed by surgery, compared with up-front surgery, was associated with higher 3-year OS rates (88.5% vs 85.2%; hazard ratio [HR], 0.74; 95% CI, 0.59-0.92) but higher permanent diverting stoma rates (20.6% vs 11.1%; relative risk [RR], 1.91; 95% CI, 1.62-2.25); LR rates were not significantly different (5.7% vs 6.6%; HR, 0.78; 95% CI, 0.55-1.11). Subgroup analysis revealed that compared with up-front surgery, NRT followed by surgery was associated with improved outcomes in middle or lower rectal cancer but not upper rectal cancer (OS: HR, 1.54; 95% CI, 0.82-2.90; LR: HR, 1.08; 95% CI, 0.23-5.00). NRT followed by surgery was associated with significantly increased risks of permanent diverting stomas across different tumor heights, particularly in upper rectal cancer (RR, 3.54; 95% CI, 1.44-8.69).
In this cohort study of nationwide registries in Taiwan, NRT followed by surgery was associated with improved oncological outcomes for overall resectable LARC, with excessive diverting stoma nonreversal as the trade-off. However, the benefits of NRT were not observed for upper rectal cancer. These findings raise concerns about potential harm from NRT and advise caution when performing NRT for upper rectal cancer.
可切除的局部晚期直肠癌（LARC）指南提倡新辅助放疗（NRT）后手术作为标准方法。然而，最近的试验报告称，基于NRT的治疗对中低位直肠癌无肿瘤学益处，这引发了对于NRT后手术是否仍然是整体可切除LARC的最佳治疗方法的质疑。
比较NRT后手术与直接手术治疗可切除LARC的结局。
设计、设置和参与者：这项队列研究采用目标试验模拟框架和台湾的全国性登记系统，纳入了2014年1月1日至2017年12月31日期间接受可切除LARC（cT1-2N1-2，cT3Nany）根治性切除的患者，并随访至2020年12月31日。数据分析时间为2024年1月1日至2025年2月15日。
NRT。
主要结局为总生存期（OS）和局部复发（LR）。次要结局为术中转流造口结局。
共分析了4099例患者，其中1436例接受NRT后手术（中位[IQR]年龄，62.0[53.0-71.0]岁；1036例[72.1%]为男性），2663例接受直接手术（中位[IQR]年龄，65.0[56.0-74.0]岁；1626例[61.1%]为男性）。与直接手术相比，NRT后手术的3年OS率更高（88.5%对85.
