Huddart Robert, Hafeez Shaista, Griffin Clare, Choudhury Ananya, Foroudi Farshad, Syndikus Isabel, Hindson Benjamin, Webster Amanda, McNair Helen, Birtle Alison, Varughese Mohini, Henry Ann, McLaren Duncan B, Parikh Omi, Nikapota Ashok, Tang Colin, Patel Emma, Miles Elizabeth, Warren-Oseni Karole, Kron Tomas, Hill Courtney, Philipps Lara, Vassallo-Bonner Catalina, Cheung Ka Ching, Gribble Hannah, Lewis Rebecca, Hall Emma
The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK.
The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK.
Eur Urol. 2025 Jan;87(1):60-70. doi: 10.1016/j.eururo.2024.09.006. Epub 2024 Oct 7.
Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule.
RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART.
A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy.
Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts.
对膀胱进行放射治疗具有挑战性，因为膀胱是一个可移动、可变形的结构。剂量递增的自适应图像引导放射治疗可能会改善治疗效果。RAIDER试验旨在证明这种治疗方案的安全性。
RAIDER是一项国际2期非对照随机对照试验（ISRCTN26779187）。单灶性T2-T4a期尿路上皮膀胱癌患者被随机分组（1:1:2），分别接受标准全膀胱放疗（WBRT）、标准剂量自适应放疗（SART）或剂量递增自适应放疗（DART）。独立招募了两种分割（f）方案。WBRT和SART的剂量为55 Gy/20次或64 Gy/32次，DART的剂量为60 Gy/20次或70 Gy/32次。对于SART和DART，每天选择一个放射治疗计划（小、中或大）。主要终点是放疗相关的晚期不良事件通用术语标准≥3级毒性反应的患者比例；该试验旨在排除DART方案毒性反应>20%的情况。
2015年10月至2020年4月期间，共有345例患者被随机分组：20次/32次分割队列中分别有41/46例WBRT、41/46例SART和81/90例DART患者。中位年龄为72/73岁；78%/85%患有T2期肿瘤，46%/52%接受过新辅助化疗，70%/71%接受过放射增敏治疗。中位随访时间为42.1/38.2个月。计划接受DART治疗的77例20次分割参与者中有66例（8
